Ministry of Health of Ukraine National University of Pharmacy Department of Industrial Technology of Drugs

Methodical instructions to implement the course work in industrial technology of drugs for IV year students specialty "Pharmacy"

Утверждено ЦМК НФаУ (Протокол № от 2014 г.)

Kharkiv 2014 2 UDC 615.451: 615.451.16: 615: 453

Authors: Ruban O.А. Khokhlova L.M. Bobritska L.O. Kovalevska I.V. Maslij J.S. Slipchenko G.D. Spiridonov S.V. Zaporozhska S.M. Rubachuk V.D. Tkach Т. O. Pulayev D.S.

Methodical instructions (guidelines) to implement the coursework

Methodical instructions are tailored introduction of modern technologies and equipment in manufacturing drugs according to the requirements of international standards (GMP). The purpose of guidelines - to help the student in performing and writing term papers , development of technology and equipment in the production of biologically active substances, finished drugs and monitoring their quality.

Reviewers: Gladuh E.V, Doctor of Pharmacy, professor, head of the Department of Industrial Pharmacy NUPh.

3 Содержание 1. General Provisions 5 2. Guidelines for implementation of student work 6 2.1. Making coursework 6 2.2. Making the cover sheet 8 3. Topics of coursework 9 Topic № 1 Main directions of intensification in the production of liqueurs 9 (tinctures) Topic № 2 Main directions of intensification in the production of liquid 10 extracts Topic № 3 New technologies in the production of thick and dry extracts 11 Topic № 4 Production newgalenic preparations containing alkaloids 12 Topic № 5 Production newgalenic preparations containing cardiac 14 glycosides Topic № 6 Production newgalenic preparations containing flavonoids 15 Topic № 7 Modern trends in the production of tablets by the method of 17 direct compression. Topic № 8 Using the method of granulation in the manufacture of tablets 18 Topic № 9 Using of different polymers in the preparation of coated tablets 19 Topic № 10 Preparation of solid dosage forms with prolonged action 21 Topic №11 Industrial production of chewable tablets 22 Topic № 12 Industrial production of drugs in capsules 23 Topic № 13 Pharmaceutical solutions 24 Topic № 14 Methods of sterilization of injection solutions 25 Topic № 15 Industrial production of infusion solutions 27 Topic № 16 Карпулы – a new dosage form for parenteral use 28 Topic № 17 Production of suspensions and emulsions for parenteral use 30 Topic № 18 Solutions for injection in pre-filled syringes 31 Topic №19 Production of sterile ophthalmic preparations 33 Topic № 20 Injectable solutions for non-aqueous solvents. Lyophilized 34 preparations of parenteral administration. Topic № 21 Structural - mechanical (rheological) properties of soft drugs 35 Topic № 22 Production of drugs in the form of gels 36 Topic № 23 Pharmaceutical and biological aspects of ointments 37 Topic № 24 Medicinal preparations in the form of suppositories 38 Topic № 25 Fundamentals and excipients used in the manufacture of 39 4 suppositories Topic № 26 Modern approaches to creating aerosol systems in 41 manufacturing preparations under the pressure Topic № 27 Current approaches to child formulations 42 Topic № 28 Role of excipients in the stability of drugs 44 Topic № 29 Nasal drugs 45 Topic №30 Manufacture of medical fees (herbal teas) 47 Topic № 31 The role of biotechnology in the creation of drugs 48 Topic № 32 Application of nanotechnology in the development of drugs 50 technologies Topic №33 Manufacture of essential oils and their use in pharmacy. 51 Literature 53

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1. General Provisions The main priorities of the pharmaceutical industry of Ukraine is the issue of drugs and medicines of domestic production in accordance with the requirements of the World Health Organization (WHO) international standards GMP. The purpose of guidelines - to help students analyze, synthesize and consolidate theoretical knowledge and practical skills in drug technology in industrial production. The main objective of the course work - forming the students more knowledge on a selected topic related to the preparation of medicaments in an industrial environment, making the technological scheme of production, quality control, intermediate products and finished product. When writing a term paper a student should acquire the following practical skills in solving technological issues: • pick up information material in accordance with the plan of the theme - job; • analyze the existing production technology of medicines in accordance with the requirements of GMP; • find ways to solve situational problems in the organization of the production process; • Develop a technological scheme of production of finished drugs; • summarize information material relating to the job with suggestions for practical implementation in pharmacy. 6

2. Guidelines for implementation of student work

Quest for the job at the Department of the student receives the instructor leading this academic group. In some cases the department can suggest the performance of work on scientific subjects of the department. Work is performed under the supervision of an instructor. Consultants work can be teachers of other departments, if the subject of a complex. During execution of the recommended plan may specify her or modified, but it has to include all the issues associated with the development of the theme, and the changes agreed with the teacher. Scope of work - up to 30 pages of standard sheets, including visual material, conclusions and references (application in the amount of work not included). Protection of passes at the department in a timely manner. A student who has not executed the work can not be certified.

2.1. Making coursework Work should contain the following sections: title page; table of contents (TOC); introduction; a literature review; experimental (or calculated) part where the drug is given technology or the finished product (FPP) and the corresponding equipment; conclusions and recommendations; bibliography. In the table of contents should reveal the structure of work, name of chapters, sections and subsections, include all headings of work. Headlines contents must accurately repeat titles in the text. Against each title name must specify the page number, which begins in the text of this section. In the introduction, it is necessary to reveal the relevance of the theme based on the objectives practical pharmacy, set out the purpose and objectives of the study. A review of literature on the issue studied should show modern scientific advances in the theory and practice of pharmacy, to summarize the material (based on his critical evaluation), and to draw conclusions on the topic studied. In writing 7 it used literature recommended on this topic, as well as informative sources internet. Particular attention in the literature review should be paid to the theoretical substantiation of technology production SFS questions biopharmaceutical nature, possible ways to improve formulations, Apparatus and equipment for operations in stages of drug technology and other issues relating to the topic. In the experimental (calculated) at the direction of the student teacher is working copybook to produce the necessary number of SFS, leads his block diagram and related equipment. This section also indicates the range of products relating to course work, produced by pharmaceutical company. Work necessary to finish presenting the findings and evidence-based recommendations arising from the review of the material presented. Objective findings - in a compressed form to convey the basic content of the obtained results, as well as capture the essence and value of the research. Must outline specific practical recommendations to improve the technology of proprietary medicines. In the list of recommended literature lead all used literary sources in alphabetical order in the following pattern: • For journal articles - source number, surname and initials of authors, title, journal name, year, issue, page; • For the books - the name and initials of the authors, book titles, city and year of publication, publisher cited page; In applications placed circuits, block diagrams, drawings devices. After selection and in-depth study on the question of literary sources and the factual data necessary to systematize it in accordance with the work plan. Digital material must be made into a table. If several tables, they should be numbered in Arabic numerals in the entire text, themed table header placed in the center of the page and write with a capital without a point at the end. Illustrations in the text should be presented in the form of diagrams, drawings, graphs, photographs. 8 Coursework should be typed on a computer, or handwrite clearly legible handwriting on one side of standard sizes and stitch into the cover. Left page field should be at least 3 cm and 1 cm to the right, 2 cm above and 3 cm below. Not allowed all sorts of statements and additions that are placed on separate pages or the reverse side of the sheet. Each chapter should begin on a new page (this rule applies to other structural parts: introduction, the list of references); headings and subheadings - separated from the main text by using a different font or otherwise. The title page should be formalized work in accordance with the model number the pages. All the results in text citations and statistics should perform appropriate references to the sources from which they are taken, the source noted in parentheses after the quotation figure. Text citations need to be quoted. Work must be carefully checked, paying particular attention to the figures, quotations, names and initials. Work performed must sign, specify the date of execution and deliver the head. 9

2.2. Making the cover sheet Title page - this is the first sheet of a text document. Perform a cover sheet in accordance with GOST 2.105. - 99. It can be made in hard copy (in the form of form with places to fill) or manually (handwritten way) black ink. Cover sheet is performed on sheet A4 size paper in the format shown in Figure 1. Figure 1. Sample of cover page.

20 mm

Form № N - 6.01 National University of Pharmacy (full name of Higher Education) Department of Industrial Technology of Drugs (full name of the department, cyclic commission)

COURSEWORK for Industrial Technology of drugs (name of the discipline) on the topic: "Pharmaceutical and biological aspects of ointments" 10 30 mm mm

Student 4 course 8 group Training direction Pharmacy Speciality Pharmacy Artamonova V.A. (Full name) Head (Supervisor): Candidate of Pharmaceutical Sciences, Associate Professor, J.S. Masliy. (position, title, academic degree, name) National Scale ______Points: ______Mark: ECTS ______

Members of the commission: ______(Signature) (Name) ______(Signature) (Name) ______(Signature) (Name)

Kharkiv – 2014

25 mm

10

3. Coursework topics Topic № 1 Main directions of intensification in the production of tinctures. Introduction. The role of phytochemical preparations in medicine and pharmacy. 1. Review of the literature. 1.1. Current state of tincture production in Ukraine. 1.2. Methods of preparation of tinctures. Their comparative characteristics. 1.3. Main directions of intensification of the extraction process in the production of tinctures. 1.3.1. Vortex extraction. 1.3.2. Extraction with forced circulation of extractant. 1.3.3. Countercurrent extraction with simultaneous movement of the extractant and feedstock. 1.4. Regeneration of alcohol from raw material meal. 1.4.1. Washing with water recovery. 1.4.2. Recovery steam distillation. 1.4.3. Distillation of ethanol. Design and operation of distillation columns. 1.5. Quality Control infusions according to SPU. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of tinctures produced by the leading pharmaceutical companies of Ukraine. 2.3. Make working copybook for the required number of tinctures, guided by the data in Table 1 (job number indicates the teacher). Make flowchart of production of tinctures, specify equipment used on each step and described technology of manufacturing of this tincture. Table № 1 № Drug Name Required Absorption factor The

volume, l of raw material concentration of used ethanol,% 1 2 3 4 5 1 Valerian tincture 350 2,9 93 2 Tincture of lily-of-the- 400 2,5 90 11

valley 3 Motherwort tincture 200 2,0 92 4 Hawthorn tincture 250 1,8 80 5 Ginseng tincture 400 1,5 95 6 Mint tincture 300 2,4 95 7 Calendula tincture 650 3,0 85 8 Hypericum tincture 1200 1,6 75 9 Tincture of belladonna 900 2,5 85 10 Tincture Schisandra 700 3,0 96

3. Conclusions. Prospects for the development of technology of tinctures in the domestic pharmaceutical industry.

Topic № 2 Main directions of intensification in the production of liquid extracts. Introduction. Current state of production of liquid extracts in Ukraine. 1. Review of the literature. 1.1. Methods of liquid extracts producing. Their comparative characteristics. 1.1.1. Methods of extraction of plant raw materials, providing subsequent evaporation of extracts. 1.1.2. Methods of extraction of raw materials without subsequent evaporation of extracts. 1.3. Main directions of intensification of the extraction process in the production of liquid extracts. 1.3.1. Extraction using a rotor- pulsation apparatus (RPA). 1.3.2. Extraction with electrohydraulic effect. 1.3.3. Ultrasonic extraction. 1.3.4. Extraction using electroplasmolysis, electrodialysis. 1.4. Quality control of liquid extracts of the SPof U. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of liquid extracts manufactured by the leading pharmaceutical companies in Ukraine. 12 2.3. Create a working copybook for the required amount of liquid extract, guided by the data in Table 1 (job number indicates the teacher). Make flowchart (technological scheme) of production of liquid extract, specify equipment used on each step and described technology of manufacturing of this liquid extract. Table № 1 № Drug name Necessary Coefficient of Number of The volume, l absorption of volumes of concentration raw extractant for of used materials total ethanol,% exhaustion of raw materials 1 2 3 4 5 6 1 Liquid extract of 600 2,5 4 92 belladonnae 2 Liquid extract of hawthorn 200 1,8 8 80 3 Liquid extract water pepper 750 2,0 4 95 4 Liquid extract of alder 1500 1,5 8 75 buckthorn 5 Liquid extract of great nettle 800 2,8 4 70 6 Liquid extract Yarrow 1200 2,5 5 80 7 Liquid extract of 100 1,7 10 75 Eleutherococcus 8 Liquid extract leuzeae 800 1,9 6 96 9 Liquid extract of thyme 250 2,8 6 70 10 Liquid extract of shepherd's 900 2,4 3 85 purse

3.Conclusions. Prospects for the development of technology of liquid extract in the domestic pharmaceutical industry.

Topic № 3 New technologies in the production of thick and dry extracts. Introduction. Current state of production of thick and dry extracts in Ukraine. 1. Review of the literature. 1.1. The extractants used in the preparation of thick and dry extracts. Requirements to extractants, their comparative characteristics. 1.2. Theoretical Foundations of evaporation and drying processes. 1.3. New technologies in the production of thick and dry extracts. 13 1.3.1. Extraction by the liquefied gases. Its advantages and hardware design. Comparative characteristics of liquefied gases as extractants. 1.3.2. Supercritical fluid extraction. Concept of supercritical fluids, their advantages as extractants. 1.3.3. Extraction by biphasic systems of solvents. 1.4. Modern equipment for evaporation and drying hoods, their mechanism and operation. 1.5. Quality Control of dense and dry extracts of the SPU. Determination of residual amounts of solvents in the formulations. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of thick and dry extracts produced by the leading Ukraine pharmaceutical companies. 2.3. Create a working copybook for the required amount of extract, guided by the data in Table 1 (job number indicates the teacher). Make flowchart (technological scheme) of production of the extract, indicate equipment used at each stage and describe the technology of its receipt. Table № 1 № Drug name The Coefficient Amount of Number Aver- required of extractives, of volumes age amount, absorption %, of specific kg of in raw extractant consum raw material for total ption material exhaustio n of raw materials 1 2 3 4 5 6 7 1 Thick extract of belladonna 10,0 2,4 20,0 7 1,125 2 Male fern thick extract 15,0 1,7 18,0 9 1,134 3 Wormwood thick extract 18,0 2,9 17,5 8 1,095 4 Thick extract of Licorice 20,0 1,5 21,0 10 1,010 5 Dandelion thick extract 25,0 1,6 22,0 9 1,015 6 Trefoil water thick extract 15,0 2,0 20,0 7 1,127 7 Dry extract of rhubarb 12,0 1,2 22,0 10 1,015 8 Licorice root dry extract 22,0 1,5 21,0 10 1,010 9 Belladonna dry extract 30,0 2,4 20,0 7 1,125 10 Dry extract of Helichrysum 40,0 1,3 24,0 6 1,163 14 3. Conclusions. Prospects for the development of technology of tinctures in the domestic pharmaceutical industry.

Topic № 4 Production of newgalenic preparations containing alkaloids Introduction. Meaning of alkaloids containing preparations for medicine and pharmacy. 1. Review of literature. 1.1. Classification of alkaloids. Nomenclature of alkaloids containing drugs produced by the domestic industry. 1.2. Methods used for the isolation of alkaloids from the raw materials. Used extractants. 1.3. Methods for purification of extracts in the production of primary products containing alkaloids. 1.3.1. Extraction of a liquid - liquid system. Used equipment. 1.3.2. Sorption. Kinds of adsorbents. 1.3.3. Chromatographic purification methods. Column, ion-exchange chromatography. 1.3.4. Crystallization. 1.4. Features proprietary technology newgalenic preparations containing alkaloids. 1.4.1. Production technology of raunatin. 1.4.2. Technology of production of drugs based on tropane alkaloids (atropine, scopolamine). 1.4.3. Technology of production of drugs on the basis of purine alkaloids (caffeine, theophylline). 1.4.4. Technology of production of drugs based on isoquinoline alkaloids (morphine, berberine). 1.5. Standardization of alkaloid-containing drugs. 2. Experimental (calculated) part. 2.1. Objects and methods. 15 2.2. Name the range of newgalenic preparations containing alkaloids produced by the leading pharmaceutical companies in Ukraine. 2.3. Calculate the mass of the loaded raw materials needed for producing a given amount of alkaloid substances, guided by the data in Table 1 (job number indicates the teacher). Make flowchart of production of newgalenic substances, indicate equipment used in each step and describe the process of its production. Table 1 № Name of The required Humidity Alkaloid Consumabl Consumables substance amount of of raw content in es odds. at odds. to Art. substance, kg material, absolutely the stage of purification % dry raw preparatio of total material,% n of raw alkaloids materials 1 2 3 4 5 6 8 1 Atropine 1,2 11,5 0,35 1,03 1,12 2 Morphine 0,8 12,0 1,15 1,05 1,14 3 Raunatin 0,85 14,0 0,85 1,02 1,09 4 Caffeine 5,4 10,8 2,70 1,01 1,11 5 Ergotal 0,75 11,2 0,20 1,06 1,15 6 Ajmaline 1,1 12,5 0,95 1,05 1,27 7 Theophylline 4,2 13,3 1,40 1,05 1,25 8 Ephedrine 2,9 9,1 1,25 1,08 1,10 9 Berberine 3,7 8,5 3,15 1,05 1,27 10 Glaucine 1,5 10,7 1,05 1,02 1,21

3. Conclusions. Advances in the development of new technologies of newgalenic preparations.

Topic № 5 Production of newgalenic preparations containing cardiac glycosides Introduction. The pharmacological activity of the preparations of cardiac glycosides and their use in medicine. 1. Review of the literature. 1.1. Physico-chemical characteristics of cardiac glycosides. Range of domestic and foreign products, presented at the Ukrainian market. 1.2. Features of the process of cardiac glycosides extraction from the raw materials. Used extractants. Meaning of the stage of feedstock fermentation. 16 1.3. Methods for cleaning primary extracts in the manufacture of preparations containing cardiac glycosides. 1.3.1. Extraction of a liquid - liquid system. Used equipment. 1.3.2. Sorption. Kinds of adsorbents. 1.3.3. Chromatographic purification methods. 1.3.4. Crystallization. 1.4. Features proprietary technology newgalenic preparations containing cardiac glycosides. 1.4.1. Technology of adonizid production. 1.4.2. Technology of lantosidum production. 1.4.3. Technology of cordigita production. 1.4.4. Technology of strophantine production. 1.4.5. Technology of erizimina production. 1.5. Features of standardization of cardiac glycosides. 1.5.1. Biological methods of standardization. 1.5.2. Chemical methods of standardization. 1.5.3. Instrumental methods of standardization. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of newgalenic preparations containing cardiac glycosides produced by the leading Ukrainian pharmaceutical companies. 2.3. Calculate the mass of the loaded raw materials needed for producing given amount of substances of cardiac glycosides, guided by the data in Table 1 (job number indicates the teacher). Make flowchart of production of newgalenic preparations, indicate equipment used in each step and describe the technology of its receipt. 17

Table 1 № Name of The Activity Activity of Consumpti Consumption substance required of materials, on of raw of the amount of substance Frog unit materials in purification the frog unit preparatio step amount substance, in 1 g n glycosides kg (l) (ml) 1 2 3 4 5 6 8 1 Adonizid 80 24 55 1,03 1,14 2 Dry adonizid 0,5 15000 60 1,04 1,27 3 Lantosidum 50 11 65 1,07 1,12 4 Corglyconum 0,25 22000 135 1,05 1,10 5 Digitoxin 0,35 9000 60 1,06 1,22 6 Digoxin 0,5 14000 62 1,02 1,21 7 Tselanid 0,4 16000 62 1,06 1,28 8 Digalen-neo 120 6 65 1,02 1,16 9 Strophanthine 0,15 45000 150 1,01 1,27 10 Erizimin 0,2 22000 120 1,06 1,25

3. Conclusions. Role of newgalenic preparations in drug therapy of heart disease.

Topic № 6 Production of newgalenic preparations containing flavonoids Introduction. Meaning of flavonoids containing preparations for medicine and pharmacy. 1. Review of the literature. 1.1. Classification of flavonoids. Range of domestic and foreign newgalenic drugs based on flavonoids. 1.2. Development of domestic technologies for creating flavonoid drugs. 1.3. Current methods of extraction and purification of substances in the production of flavonoids. 1.3.1. Supercritical fluid extraction. The used equipment. 1.3.2. Ultrasonic extraction capabilities to highlight the amount of flavonoids. 1.3.3. Chromatographic methods of flavonoids purification. Adsorption, ion exchange chromatography. 1.4. Features of proprietary technology of flavonoid drugs. 1.4.1. Production technology of Flamen. 1.4.2. Production technology of Silibor. 18 1.4.3. Technology of production of Quercetin. 1.4.4. Technology of production of Liquiriton. 1.4.5. Technology of production of Flavanobol. 1.5. Quality control of preparations based on flavonoids. 1.5.1. Chemical methods of analysis. 1.5.2. Instrumental methods of analysis. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of newgalenic preparations containing flavonoids produced by the leading Ukrainian pharmaceutical companies. 2.3. Calculate the mass of the loaded raw materials needed to produce a given amount of flavonoids substances, guided by the data in Table 1 (job number indicates the teacher). Make flow chart production of newgalenic preparations, are in use at each stage of the equipment and describe the technology of its receipt. Table 1 № Name of The Humidity Flavonoid Consumpti Consumption substance required of raw content in on of raw of in the amount of materials absolutely materials in purification substance, ,% dry raw preparatio step of total kg material,% n flavonoid

1 2 3 4 5 6 8 1 Silibor 4,0 11,0 2,85 1,05 1,26 2 Flamen 5,2 9,8 2,07 1,07 1,17 3 Quercetin 2,4 12,2 6,12 1,04 1,20 4 Convaflavin 1,7 10,5 1,72 1,04 1,15 5 Caleflon 1,8 9,2 1,28 1,02 1,11 6 Skuteks 1,2 12,4 0,82 1,07 1,24 7 Liquiriton 3,3 10,3 3,45 1,08 1,21 8 Flacarbin 4,9 9,5 2,73 1,08 1,17 9 Flavanabol 2,1 11,2 1,44 1,09 1,16 10 Kamilofan 1,6 10,4 1,15 1,03 1,25 3. Conclusion (Conclusions). Improved methods of cleaning newgalenic preparations.

Topic № 7 19

Modern directions of tablet production by the method of direct compression Introduction. State of the industry in the domestic production of tablet pharmacy. 1. Review of literature. 1.1. Description of tablets as a medicinal form. Advantages and disadvantages. 1.2. Methods for producing tablets. 1.3. Describe direct compression. Rationale for using this method. 1.4. Optimal conditions to carry out the method of direct compression. 1.4.1. Technological characteristics of drug substances used in direct compression. 1.4.2. New excipients used in direct compression. 1.5. Direction of direct compression. 1.5.1. Direct compression with added excipients. 1.5.2. Direct compression with forced feed compressible substance in the matrix. 1.5.3. Direct compression with previous lydirectional crystallization compressible material. 1.6. The equipment used in direct compression tablets. 1.7. Direct compression, its advantages and disadvantages. 1.8. The quality control of tablets according to the SPhU. 2. Experimental (calculated) part. 2.1. Objects and Methods 2.2. Name the range of tablets produced by the leading pharmaceutical companies in Ukraine. 2.3. Using the data table 1 (directed by the head of the course work), make a working copybook for the manufacture of tablets by direct compression. (Values consumption ratios conventionally considered the same for all components of prescription). Make a flow chart of the production of the drug in accordance with the requirements of GMP, describe the technology and specify the equipment used. Table № 1 № Name of drug The Consumpti Consump Consump Consum amount of on factors tion tion ption (packing) preparatio factors factors factors n of raw the step of tableting at the materials, producing step stage of a tablet filling weight and packing 1 2 3 4 5 6 7 1 Tablets of sodium chloride 800 1,004 1,011 1,005 1,014 20

0,9g №10 2 Tablets zolpidem 0,01g №20 1550 1,001 1,010 1,010 1,006 3 Tablets Ledibon 0,0025g № 2000 1,005 1,011 1,007 1,008 28 4 Tablets «Bikarmintae» №20 1650 1,007 1,009 1,009 1,007 5 Tablets cinnarizine 0,0025 g 600 1,006 1,009 1,006 1,010 №50 6 Tablets calcex №10 1200 1,010 1,010 1,015 1,012 7 Tablets Aspekard 0,1g № 24 1800 1,003 1,011 1,012 1,002 8 Tablets aspivit №10 1250 1,011 1,010 1,011 1,007 9 Tablets acetylsalicylic acid 1500 1,009 1,003 1,008 1,005 0,1 g №20 10 Tablets Vitamin C 500 by 0,5 1600 1,002 1,004 1,013 1,009 g №30 3. Conclusion. Prospects of development of the technology of tablets by direct compression in domestic pharmacy.

Topic № 8 Tablet production by the using method preliminary granulation.

Introduction. Modern state of the pharmaceutical industry in the production of tablets preliminary granulation method. 1. Review of literature. 1.1. Advantages and disadvantages using method preliminary granulation. 1.2. The purpose of granulation in manufacture of tablets. The influence of physico-chemical and technological properties on the process of tabletting and the choice of technology for obtaining tablets. 1.4. The main types of granulation, equipment used. 1.4.1. Wet granulation. Advantages and disadvantages of this process. 1.4.2. Dry granulation. 1.4.3. Methods of structural granulation. 1.4.4. Mixed granulation. 1.5. Binders and their assortment. 2. Experimental (calculated) part. 2.1.Objects and Methods 2.2. Name the range of tablets obtained by the method of granulation, which are produced by the leading pharmaceutical companies in Ukraine. 2.3. Using the data table 1 (directed by the head of the course work), make a working copybook for the manufacture of tablets by preliminary granulation. (Values consumption ratios conventionally considered the same for all components of prescription). Make a flow chart of the production of the drug in accordance 21 with the requirements of GMP, describe the technology and specify the equipment used. Table № 1 № Name of drug The Consum Consump Consump Consum amount ption tion tion ption of factors factors factors factors (packing) prepara the step tableting at the tion of of step stage of raw producin filling materia g a tablet and ls, weight packing 1 2 3 4 5 6 7 1 Tablets analginum 0,5 g №10 700 1,004 1,030 1,005 1,014 2 Tablets streptocide 0,3 g №10 550 1,001 1,033 1,010 1,006 3 Tablets amitriptyline 0,025 g 1650 1,005 1,035 1,007 1,008 №10 4 Tablets Riboxin 0,2 g №30 1200 1,007 1,039 1,009 1,007 5 Tablets of activated Carbon 2000 1,006 1,036 1,006 1,010 0,25 g №10 6 Tablets «Tripharmacon» 0,5g 600 1,010 1,031 1,015 1,012 №10 7 Tablets mukaltin 0,05 g №10 1600 1,003 1,034 1,012 1,002 8 Tablets bisacodyl 0,005g №30 1800 1,011 1,037 1,011 1,007 9 Tablets Atorvastatin 0,04 g 1250 1,009 1,032 1,008 1,005 №30 10 Tablets loratadine 0,01 g №10 1500 1,002 1,038 1,013 1,009 3. Conclusion. Prospects of development of the technology of tablets by preliminary granulation in domestic pharmacy.

Topic № 9 The use of different polymers for preparation of coated tablets

Introduction. The purpose of tablet coating. Biopharmaceutical aspects of determining the compositions and technologies of solid medicinal forms. Types of coatings and methods of their application. 1. Review of literature. 1.1. Manufacture of coated tablets. Advantages and disadvantages of this process. 1.2. Requirements for the geometric form of tablets-cores. 1.3. Methods of producing the coated tablets. 1.3.1. Auxiliary substances used in manufacturing dragee, technology of their obtaining. 22 1.3.2. Film coating. Types and properties. Methods of application. An apparatus for closed loop for film coating. Its structure, advantages and principles of operation. 1.3.3. New polymers for coating. Their benefits. 1.4. The quality control of tablets according to the SPhU. 2. Experimental (calculated) part. 2.1.Objects and Methods 2.2. Name the range of coated tablets, manufactured by leading pharmaceutical companies in Ukraine. 2.3 Using the data table 1 (directed by the head of the course work), make a working copybook for the manufacture of tablets by coated tablets. (Values consumption ratios conventionally considered the same for all components of prescription). Make a flow chart of the production of the drug in accordance with the requirements of GMP, describe the technology and specify the equipment used. Table № 1 № Name of drug The Consumpt Consumpt Consum Consum amount of ion ion ption ption (packing) factors factors factors factors preparati the step of tabletin at the on of raw producing g step stage of materials, a tablet filling weight and packing 1 2 3 4 5 6 7 1 Tablets «Vitaftor» 0,5g 2000 1,004 1,030 1,005 1,014 №10 2 Tablets «Propolin» 0,01g 600 1,001 1,033 1,010 1,006 №50 3 Tablets aspirin cardio 0,3g 1650 1,005 1,035 1,007 1,008 №20 4 Tablets atenolol 0,05g №20 550 1,007 1,039 1,009 1,007

5 Tablets afenoksina 0,25g 700 1,006 1,036 1,006 1,010 №10 6 Tablets Tsiprobay 0,25g 1250 1,010 1,031 1,015 1,012 №10 7 Tablets diklonat retard 0,1 g 1500 1,003 1,034 1,012 1,002 №20 8 Tablets Aleron 0,005 g №30 1200 1,011 1,037 1,011 1,007

9 Tablets «Hofitol» 0,35 g 1800 1,009 1,032 1,008 1,005 №60 10 Tablets Neovir 0,125 g №12 1600 1,002 1,038 1,013 1,009

3. Conclusion. Prospects of development of the technology of tablets of coated tablets in domestic pharmacy. 23

Topic 10 Manufacturing solid dosage form prolonged action

Introduction. The actual of developing drugs with a modified release of active ingredients. 1. Review of the literature. 1.1. Advantages of a modified release medicaments 1.2. Historical aspects of sustained release drug. 1.3. Methods of prolongation and technological aspects of prolonged preparations. 1.4. The coatings to modify the release of active substances and their nomenclature. 1.5. Types and properties of matrix-polymers. 1.6. Microcapsulation is a process for preparing prolonged preparations. 1.7. Innovative forms of release preparations of prolonged 1.8. Standardization solid dosage form with modified release of active substances. 2. Experimental part. 2.1. Objects and methods. 2.2. Name the range of tablets with prolonged action is allowed on the leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (on the instructions of the head of the course work), make a recipe of working for production of sustained-release tablet. Make a flowchart of the production of the drug according to the requirements of GMP, give description of technology and specify equipment.

Table 1 Number Drug Name The Красх step Красх step Красх Красх amount preparation obtaining step step of of raw tablet masse tableting pre- (packing) materials packing and packing 1 Tablets Glucophage 1000 1,004 1,003 1,005 1,004 Long 500mg №30 2 Tablets Сordipin 2000 1,001 1,033 1,010 1, 006 XL 40mg tablets №20 3 Tablets Lorvas SR 1250 1,007 1,002 1,001 1,002 1,5 mg №30 4 Tablets Ambroxol 1200 1,003 1,003 1,008 1,004 retard 0,075 № 12 5 Tablets Indapamide 1450 1,005 1,001 1,005 1,001 retard 0.15 mg № 30 6 Tablets Neofillin 2200 1,004 1,003 1,005 1,004 300mg № 50 24

7 Tablets Preductal 1500 1,003 1,004 1,002 1,002 MR 35mg № 60 8 Tablets Dalfuzin 1250 1,001 1,033 1,010 1, 006 5mg № 30 9 Tablets Diltiazem 3000 1,004 1,005 1,002 1,001 retard 90mg № 20 10 Tablets Betalok 800 1,003 1,006 1,004 1,005 ZOК 25mg №14

3. Conclusion. Prospects for the development of new medicaments with prolonged release of active substances.

Topic 11 Industrial production of chewable tablets Introduction. Current state of production of chewable tablets. 1. Review of the literature. 1.1. Characteristics of chewable tablets as dosage form. Its advantages and disadvantages. 1.2. Methods for preparing of chewable tablets. 1.3. Excipients used for the preparation of chewable tablets. 1.4. Features of improving taste in technology of chewable tablets. 1.5. Direct compression in the production of chewable tablets. 1.6. Quality control of chewable tablets according to the requirements of European Pharmacopoeia. 1.7. The validation and control of production processes of tablets. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of tablets produced by the leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (on the instructions of the head of the course work), make a working formula for the production of chewable tablets. Make a flowchart of the production of the medicine according to the requirements of GMP, please give a description and specify the used equipment. Table № 1 № Name of medicine Quantity F on F on stage F on stage F on (packs.) stage of of mixing of stage of prepara tabletting packing tion of raw materia l 1 2 3 4 5 6 7 1 Tablets "Vitamin C 500» № 30 700 1,004 1,030 1,005 1,014 25

2 Tablets "Maalox» № 10 550 1,001 1,033 1,010 1,006 3 Tablets "Multivit» № 90 1650 1,005 1,035 1,007 1,008 4 Tablets "Multi-tabs ® with 1200 1,007 1,039 1,009 1,007 Vitamin C» № 30 5 Tablets "Sennalaks» № 30 2000 1,006 1,036 1,006 1,010 6 Tablets "Ferrum Lek ®» № 20 600 1,010 1,031 1,015 1,012 7 Tablets "Etoksidol ®» № 1600 1,003 1,034 1,012 1,002 8 Tablets "Ferestal ®» № 20 1900 1,002 1,054 1,052 1,042 9 Tablets "Digestal ®» № 30 1200 1,001 1,014 1,022 1,012 10 Tablets "Penzital» № 50 1350 1,008 1,024 1,032 1,022 3. Conclusion: Prospects for the development of production of chewable tablets in Ukraine. Topic number 12 Industrial production of drugs in capsules Introduction. Value of encapsulated drugs in medical therapy. 1. Literature review. 1.1. Modern classification of capsules. Advantages and disadvantages of the dosage form. 1.2. The main and auxiliary substances capsules. 1.2.1. Shaping materials (gelatin, cellulose derivatives). 1.2.2. Film-forming high molecular weight compounds. 1.2.3. Plasticizers. 1.2.4. Stabilizers. 1.2.5. Preservatives. 1.2.6. Flavorants, colorants and pigments. 1.3. Production methods capsules. 1.3.1. Drip method. 1.3.2. Pressure method. 1.3.3. Dip method. 1.4. Machines for encapsulation. Modern methods of filling of hard and soft capsules. 1.5. Quality control of capsules. 1.6. Factors affecting the bioavailability of drugs from capsules. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Name the range of capsules produced by the leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (at the direction of the head of the course work) make a prescription for the production of gelatine capsules (does consumption ratios equal for all components prescriptions). Make the 26 technological scheme of production preparation, description of the technology and equipment used. Table 1 № Drug name Number Coefficient Coefficient Coefficient of expendable expendable expendable packages masses in on on labeling preparation encapsulatin and for g step packaging encapsulation stage 1 2 3 4 5 6 1 Dicloberl retard 0,1 № 50 600 1,011 1,013 1,009 2 Linex 0,025 № 16 250 1,010 1,012 1,010 3 Enterolum 0,25 №20 180 1,008 1,009 1,011 4 Antifrontum № 30 220 1,011 1,009 1,010 5 Prostanolum 0,32 № 30 180 1,013 1,012 1,014 6 Persen № 20 220 1,019 1,018 1,012 7 Florised № 20 130 1,007 1,006 1,005 8 Phezam № 20 140 1,009 1,010 1,008 9 Artichoke № 20 190 1,011 1,009 1,010 10 Essentiale forte 0,3 № 30 220 1,012 1,011 1,009 3. Conclusions. Prospects of development of the technology of drugs in capsules. Topic № 13 Pharmaceutical solutions

Introduction. The role and place of pharmaceutical solutions in drug therapy. 1. Review of the literature. 1.1. Characterization and classification of solutions. 1.2. Theoretical foundations of dissolution. 1.2.1. Solids solution. 1.2.2. Solutions liquids. 1.2.3. Solutions of gaseous substances. 1.3. Main types of dissolution and hydration theory. 1.4. Characteristics of the solvents used in the technology of liquid dosage forms. 1.5. Effect of various process factors to rate of the process dissolution (temperature, the hydrodynamic conditions change, etc.). 1.6. Role biopharmaceutical factors in changing the therapeutically active substances in solution (selection medium, additive electrolytes, HMS, surfactants, etc.). 2. Experimental (calculated) part. 2.1. Object s and methods. 2.2. Name the range of solutions produced by leading pharmaceutical and maceutical factorys of Ukraine. 27 2.3. Using the data in Table 1, make a recipe of working for pharmaceutical solutions (job number is indicated by teacher). Make a flowchart of the production of the drug, a description and specify the technology used equipment in accordance with the requirements of GMP. Table number 1 Number Drug Name Amount К расх К расх К расх (pcs.) step step compiled Stage preparation by a solution shovels and of raw packaging 1 2 3 4 5 6 1 Sol. hydrogen peroxide - 250 1.0 10 1.0 09 1.00 9 100 ml 2 Formalin - 100ml 200 1,011 1,010 1.0 11 3 Sol. boric acid alcohol - 360 1.0 16 1 0 13 1.0 13 25 ml 4 Sol. iodine alcohol 5% - 420 1.0 18 1 0 20 1.0 22 20 ml 5 Sol. iodine alcohol 10% - 410 1.0 20 1 0 18 1.0 20 20 ml 6 Sol. brilliant green 500 1.0 21 1,020 1.0 22 alcohol - 20 ml 7 Sol. camphor alcohol - 25 650 1.0 24 1 0 22 1.0 19 ml 8 Sol. acid salitsylovoy 450 1,022 1 0 21 1.0 24 alcohol - 25 ml 9 Sol. Lugol - 100 ml 350 1.0 26 1 0 21 1.0 26 10 Sol. camphor oil - 25 ml 260 1,025 1,022 1.0 25 3. Conclusion (Conclusions). Prospects for the development of technology solutions in the domestic pharmacy.

Topic № 14 Methods of sterilization of injection solutions Introduction. Control of microbial purity in production of medicines. 1. Review of the literature. 1.1. WHO requirements for microbial purity of sterile and non-sterile pharmaceutical products. 1.2. GMP requirements for the purity of sterile dosage forms and ways of its achievement. 1.3. Methods of sterilization in technology of parenteral dosage forms. 1.3.1. Physical methods of sterilization (heat or thermal, radiation, ultrasound, plasma, high-frequency currents, etc.), its advantages and disadvantages; equipment used. 1.3.2. Mechanical methods of sterilization (sterile filtration). Depth and membrane filters, and their comparative characteristics. 28 1.3.3. Chemical methods of sterilization, gas sterilization; addition of chemical preservatives. 1.4. Validation and control of sterilization processes in technology of parenteral dosage forms. 1.5. Methods of control of microbiological purity of sterile dosage forms. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of tablets produced by the leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (on the instructions of the head of the course work), make a working formula for the production of injectable solutions. Make a flowchart of the production of the medicine according to the requirements of GMP, please give a description and specify the used equipment. Table № 1 № Name of medicine Quantit F on stage F on F on F on F on y of stage of stage of stage stage of (packs) preparatio prepara filling of packing n of raw tion of ampoul sterili material solution es zation 1 2 3 4 5 6 7 8 1 Sol. dimedrola 1% amp. 1 1900 1,011 1,005 1,011 1,009 1,003 ml 2 Sol. dioksidina 1% amp. 1 1700 1,010 1,003 1,004 1,010 1,004 ml 3 Sol. mezatona 1% amp. 1 1800 1,008 1,007 1,008 1,009 1,003 ml 4 Sol. calcium chloride 10% 1000 1,009 1,006 1,010 1,010 1,005 in amp. 2 ml 5 Sol. magnesium sulfate 1900 1,008 1,008 1,011 1,009 1,004 25% in amp. 2 ml 6 Glutargin - 4% solution in 1500 1,007 1,009 1,010 1,010 1,003 ampoules. 5 ml. 7 Dikloksin - sol. in amp. 2 1700 1,006 1,010 1,011 1,009 1,004 ml 8 Sol. eufillina 2.4% solution 1500 1,009 1,011 1,0009 1,011 1,005 in ampoules. 2 ml. 9 Sol. hexamethylene 1900 1,010 1,012 1,012 1,012 1,004 tetramine 40% amp. 2 ml. 10 Sol. 20% camphor oil in 1300 1,019 1,018 1,009 1,012 1,002 amp. 2 ml 3. Conclusion: Justify the choice of the method of sterilization and its effect on the quality of pharmaceutical products. 29

Subject number 15 Industrial production of infusion solutions

Introduction. The role and place of infusion solutions in a group of medicines for parenteral use. 1. Literature review. 1.1. Requirements for infusion solutions (isotonic, isohydricity, izoionichnost, osmolarity osmolality required viscosity of the medium, etc.). 1.2. Excipients used in the technology of infusion solutions and their meaning. 1.3. Technology of production of infusion drugs. 1.3.1. Class clean room production of infusion solutions. Methods for preparation of air, equipment and inventory, personnel and workwear. 1.3.2. Preparation of infusion solutions and equipment used. 1.3.3. Quality Control infusion solutions according to HFCs and European Pharmacopoeia. 1.4. Types of containers and closures used in the manufacture of infusion. Use of polymeric materials. Prepare containers and closures. 1.5. Physico-chemical and pharmaceutical ingredients in the complex compatibility infusion system. . Experimental (calculated) part. 2.1. Subjects and methods. 2.2. Name the range of infusion solutions produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (at the direction of the head of the course work), make a recipe of working to produce the required amount of infusion solution (value consumption ratios conventionally considered the same for all components of the recipe ) . Make a flow chart of the production of the drug in accordance with the GMP requirements and specify the equipment used. Table number 1

№ Name of drug The C расх. C C расх. C расх. C расх. amoun raw расх. filling sterilizin he step t of material at the and g the of drug preparatio stage capping solution marking (packi n step, the of and ng) solvent prepar packing and the ation material of the solutio n 1 2 3 4 5 6 7 8 30

1 Sol. sodium chloride 0.9 % 200 1,018 1,007 1,009 1,003 1,003 - 100 ml 2 Sol. glucose 10% - 200 ml 250 1,015 0,006 1,008 1,002 1,004 3 Sol. glucose 40 % - 200 ml 300 1,015 0,007 1,009 1,003 1,003 4 Sol. Ringer - 200 ml 450 450 1,014 0,008 1,008 1,004 1,005 5 Sol. Ringer- Locke - 200 500 1,019 0,007 1,007 1,002 1,004 ml 6 P- p " Disol " - 200 ml 150 1,018 0,008 1,006 1,002 1,003 7 P- p " Disol " - 200 ml 250 1,019 0,007 1,007 1,003 1,004 8 " Kvartasol " - 200 ml 200 1,018 0,006 1,005 1,002 1,005 9 Poliglyukin - 400 ml 400 1,020 0,010 1,006 1,006 1,004 10 Reopoligljukin 10 - 400 ml 500 1,019 0,009 1,007 1,003 1,002

3. (Conclusions). Prospects for the development of technology infusion of medicines in Ukraine.

Subject number 16 The cartridges - a new dosage form for parenteral use Introduction. Role and location of preparations for parenteral use in medical therapy. 1. Literature review. 1.1. Role and location of preparations for parenteral use in medical therapy. Historical data on the establishment of a new dosage form the cartridges. 1.2. The cartridge advantages over other types of preparations for parenteral use. 1.3. Scope of aplications cartridges. 1.4. Device the cartridge injection system. 1.5. Manufacture of mortars in the cartridge. 1.5.1. The cleanliness class of production facilities of the cartridge ensuring their quality. 1.5.2. Schematic production technology of drugs in the cartridge. 1.5.3. Quality control of drugs in the cartridge. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Name the range of cartridges produced by the leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (at the direction of the head of the course work), make a recipe of working to produce injectable in the cartridge (does consumption ratios equal for all components prescriptions). Make the 31 technological scheme of production preparation in accordance with the GMP requirements and equipment used. Table 1 № Drug name Number Coefficient Coefficien Coefficient Coefficie Coeff of expendable t expendable at nt icient packages on the expendab the stage of expendab expen preparation le on sterilizing le on dable raw preparati filtration encapsul on materials, on stage ating labeli solvent and of step ng the solution and materials packa ging stage 1 2 3 4 5 6 7 8 1 Articainum+ 150 1,011 1,009 1,008 1,009 1,010 Epinephrinum cartridge 1,8 ml № 50 2 Articainum+ 200 1,011 1,010 1,007 1,010 1,011 Epinephrinum cartridge 1,7 ml № 50 3 Insuman Rapid 150 1,013 0,010 1,009 1,012 1,011 100 IU/ml cartridge for OptiPen 3 ml № 5 4 Insuman Basal 150 1,009 1,009 1,010 1,011 1,012 cartridge for OptiPen 3 ml № 5 5 Ultracain D-S forte 100 1,010 1,008 1,011 1,010 1,011 cartridge 1,7 ml № 100 6 Ultracain D-S 250 1,009 1,008 1,009 1,012 1,011 cartridge 1,7 ml № 100 7 Ultracain forte 500 1,010 1,009 1,010 1,010 1,011 cartridge 1,7 ml № 100 8 Ubistesin cartridge 600 1,011 1,009 1,010 1,011 1,011 1,7 ml № 100 9 Septanest 4% 200 1,009 0,011 1,013 1,009 1,007 cartridge 1,7 ml № 100 32

10 Septanest 4% SP 170 1,012 1,010 1,011 1,010 1,008 cartridge 1,7 ml № 100 3. Conclusions. Prospects of development of the technology of drugs in cartridges.

Topic № 17. Manufacture of suspensions and emulsions for parenteral use. Introduction. General characteristics of medicinal products for parenteral use. 1. Literature review. 1.1. Manufacture of suspensions for injection on pharmaceutical plants. 1.1.1 .Activities to maintain aseptic production. Classes of clean room. Cleaning the air. 1.1.2. Technological features of manufacture injection for suspensions. Ensuring their sterility. 1.1.3. Using excipients in technology suspensions, increase their stability. 1.1.4. Quality control suspensions for injections. 1.1.5. Assortment of suspensions for injection (suspension of insulin, hydrocortisone, etc.). 1.2. Emulsions for parenteral use. Their purpose, benefits, classification. Technology features. 1.2.1. Emulsion for parenteral nutrition (fat emulsion). Their meaning and use. Composition. Ensuring stability of ultraemulsion. Drugs of fat emulsions. 1.2.2. Antihemolytic emulsion. Composition. Using, advantage of application. 1.2.3. Emulsions for blood replacement. Composition, application, using of emulsifiers. 1.2.4. Ensuring sterility emulsions for parenteral nutrition and their quality control. 1.2.5. Drugs of fat emulsions used in medical practice. 1.3. Validation and control of production processes drugs for parenteral nutrition. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Assortment of emulsions and suspensions, produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (at the direction of the head of the course work), make a working prescription for production of medicines for parenteral use. (Does consumption ratios equal for all components prescriptions). Make a flow chart of manufacture of the drug in accordance with the GMP requirements and specify the equipment used. Tabl № 1 № Drug name Quantit Cons. Cons. Cons. Cons. Cons. y Factor Factor Factor Factor Factor (packing at the at the at the at the at the ) stage of stage of stage of stage stage prepara prepara at the of of tion of tion of stage of sterili labeli 33

raw the filling zation ng materia solution and packa ls, sealing ging 1 2 3 4 5 6 7 8 1 Lipidyn – fl. 200 ml. 600 1,012 1,011 1,011 1,003 1,002 2 Introlipid – fl. 200 ml. 550 1,012 1,010 1,012 1,004 1,004 3 Lipofundin – fl. 200 мл. 300 1,011 1,011 1,011 1,003 1,003 4 Aminofosfatid– fl. 200 ml. 450 1,013 1,009 1,009 1,004 1,002 5 Hydrocortisone acetate 600 1,013 1,009 1,008 1,002 1,003 suspension for injection 2.5% - Amp. 2 ml. 6 Insulin-protamine suspension 1200 1,010 1,010 1,009 1,002 1,003 for injection - fl. 5 ml. 7 The suspension of amorphous 900 1,011 1,011 1,010 1,003 1,002 zinc-insulin for injection - fl. 5 ml. 8 Protamine zinc insulin for 650 1,010 1,010 1,009 1,004 1,003 injection - fl. 5 ml. 9 Insulin zinc suspension for 700 1,009 1,003 1,010 1,007 1,002 injection - fl. 10 ml. 10 Suspension of zinc insulin 600 1,009 1,004 1,010 1,007 1,003 crystalline for injection - fl. 5 ml.

3. Conclusions. Problems of industrial production of suspensions and emulsions for injection in Ukraine. Ways to overcome them.

Topic № 18. Solutions for injection in pre-filled syringes Introduction. The role and place of injection solutions in pre-filled syringes in a group of drugs for parenteral use. 1. Literature review. 1.1. Preconditions of creation prefilled syringes. Their advantages over injection solutions in ampoules. 1.2. Basic elements of pre-filled syringes. 1.3. Manufacture of injection solutions in prefilled syringes. 1.3.1. The main technological steps of obtaining pre-filled syringes. 1.3.2. The essence of siliconization surface pre-filled syringes. Its advantages. 1.3.3. Classes of clean room for the production of injection solutions in prefilled syringes. Air purification system, ventilation. Preparing the equipment and inventory, personnel and special clothing. 1.3.4. Quality control of injection solutions in pre-filled syringes. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Select the assortment of injection solutions in pre-filled syringes. 2.3. Using the data in Table 1 (at the direction of the head of the course work), make a working prescription to produce the required amount of solution for 34 injection in pre-filled syringes (values of consumption ratios conventionally considered the same for all components of the prescription). Make a flow chart of manufacture of the drug in accordance with the requirements of GMP, give a description and specify the technology used equipment. Table № 1 № Drug name Quantit Cons. Cons. Cons. Cons. Cons. y Factor at Factor Factor Factor Factor (packin the stage at the at the at the at the g) of stage stage of stage of stage of preparati of at the steriliza labeling on of raw prepa stage of tion packagi materials, ration filling ng of the and solutio sealing n 1 2 3 4 5 6 7 8 1 Epostim, srg., 1 ml. 50 1,020 1,008 1,011 1,003 1,001 2 Alflutol, srg., 2 ml 100 1,018 0,007 1,010 1,002 1,001 3 Noltrex, srg. 1 ml 100 1,016 0,009 1,012 1,003 1,002 4 Fraxiparin, srg., 1 ml 100 1,017 0,011 1,009 1,004 1,001 5 Pharmaglobulin, srg., 1 50 1,021 1,007 1,008 1,002 1,001 ml 6 Alfa-globulin, srg., 1 ml 50 1,009 0,009 1,005 1,002 1,002 7 Interleykin, srg., 2 ml 50 1,023 1,007 1,005 1,001 1,001 8 Vitakan, srg., 1 ml 200 1,025 0,006 1,006 1,002 1,002 9 Sertobek, srg., 2 ml 200 1,028 0,010 1,009 1,006 1,002 10 Eralfon, srg., 0,5 ml 150 1,021 0,009 1,008 1,003 1,003

3. Conclusion. Perspectives of technology development of injection solutions in pre-filled syringes.

Topic № 19 Production of sterile ophthalmic preparations Introduction. State of the industry ophthalmic preparations domestic pharmacy. 1. Review of the literature. 1.1. Classification of ophthalmic formulations 1.2. Requirements to forms used in ophthalmology 1.3. Excipients used for the preparation of ocular dosage forms 1.4. Liquid ophthalmological dosage forms 1.5. The main steps of preparing eye drops 1.6. Types of packaging for eye drops. 1.7. Ophthalmic ointment. Types of ointment bases. 1.8. Classification and benefits of eye inserts. 1.9. Eye film and lamellae. Using and range. 1.10. Technology for producing eye films. 2. Experimental part. 2.1. Objects and methods of research. 35 2.2. Name assortment ophthalmology drugs are prodused by leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (job number is indicated by teacher) make a recipe of working to produce the drug in the form of eye drops. Make a flow chart of the production of the drug according to the requirements of GMP, please give a description and specify the technology used equipment. Table number 1. Number Drug Name Amount К расх К расх К расх (pcs.) . step step step preparation compiled by packaging of raw a solution of finished materials products

1 Dex-Ghentamzin 5ml 1000 1,004 1,003 1,004

2 Maksideks 0.1% - 5ml 2000 1,001 1,033 1, 006 3 Lekrolin 20mg/ml -10ml 1250 1,007 1,002 1,002

4 Niklofen 0.1% - 5ml 1200 1,003 1,003 1,004 5 Alergokrom 2%-10 ml 1450 1,005 1,001 1,001 6 Artificial tears 15ml 2200 1,004 1,003 1,004

7 Betoptik 0.25%- 5ml 1500 1,003 1,004 1,002 8 Okoferon 0.1% - 5ml 1250 1,001 1,033 1, 006 9 Lanotan 0.05 mg - 2.5 ml 3000 1,004 1,005 1,001 10 Taufon 4% - 10ml 800 1,003 1,006 1,005 3. Conclusions. The prospect of the development of new ophthalmic drugs and expand their range of domestic producers.

Topic № 20. Solutions for injections on the non-aqueous solvents. Lyophilized drugs for parenteral administration. Introduction. Comparative analysis of drugs for parenteral use domestic pharmaceutical industry and abroad. 1. Literature review. 1.1. Manufacture of injection solutions on the non-aqueous solvents. 1.1.1. Field of application of non-aqueous solvents in the manufacture of preparations for parenteral use and requirements to them. 1.1.2. Classification and characteristics of the main groups of non-aqueous solvents. Individual and mixed solvents. 1.1.3. Technological features of non-aqueous parenteral preparations manufacturing. 1.1.4. Quality control of nonaqueous parenteral preparations. 1.2. Production of lyophilized powders for parenteral administration. 1.2.1. The essence of lyophilization processes or cold sublimation. 1.2.2. Construction and principle of operation of the plant for freeze-drying. 36 1.2.3. Lyophilization - effective way to improve the stability of low-stability and heat-sensitive drugs. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Assortment of injection solutions, manufactured on the leading pharmaceutical companies in Ukraine. 2.3. Using the data in Table 1 (at the direction of the head of the course work), make a working prescription for production of medicines for parenteral use (Values of consumption ratios conventionally considered the same for all components of the prescription). Make a flow chart of manufacture of the drug in accordance with the requirements of GMP, give a description and specify the technology used equipment. Tabl. № 1 № Drug name Quantit Cons. Cons. Cons. Cons. Cons. y Factor Factor Factor at Factor Factor (packin at the at the the stage of at the at the g) stage stage at the stage stage of stage of of of of filling steriliza labeling prepa prepar and sealing tion packagi ration ation ng of raw of the materi solutio als, n 1 2 3 4 5 6 7 8 1 Sol. camphor oil 20% amp. 1500 1,009 1,007 1,011 1,007 1,003 2 ml 2 Sol. dezoksikortikosteron- 1200 1,010 1,009 1,012 1,009 1,004 acetate in oil 0.5% amp. 1 ml 3 Sol. Sinestrol in oil 2% 1000 1,009 1,008 1,011 1,007 1,003 amp. to 1ml 4 Methylprednisolone 2500 1,002 1,007 1,009 1,008 1,002 (powder) amp. 0,002 5 Methylprednisolone 2300 1,002 1,006 1,010 1,007 1,003 (powder) amp. 0.04 6 Lidaza (powder) - fl. 64 ED 2000 1,003 1,005 1,009 1,010 1,002 7 Fibrinolysin (powder) - fl. 800 1,004 1,004 1,011 1,011 1,003 at 20000 ED. 8 Fibrinolysin (powder) - fl. 700 1,005 1,005 1,010 1,012 1,004 at 300 ED. 9 Elastolipin (powder) - fl. 450 1,004 1,005 1,009 1,009 1,003 0,020 ED 10 Dezoksiribrnukleaza 500 1,003 1,006 1,009 1,010 1,004 (powder) fl. 0,010 ED

3. Conclusion. Perspectives of technology development of drug for parenteral use in Ukraine.

37

Topic № 21 Structural - mechanical (rheological) properties of soft dosage drugs. Introduction. Assortment of the medicinal systems with plastic resiliently - by a viscid environment at the pharmaceutical market of Ukraine 1. Review of literature. 1.1. A value of rheological properties is in the production of ointments. 1.1.1. Concept of viscidity. 1.1.2. Properties of thixotropy. 1.1.3. Osmotic properties of ointments. 1.1.4. Determination of rheological properties is in soft medications. 1.2. Influence of different factors on rheological properties of ointments. 2. Experimental (calculation) part. 2.1. Objects and research methods. 2.2. Name the assortment of soft medications, produced on the leading pharmaceutical enterprises of Ukraine. 2.3. Following data of table 1 (at the direction of supervisor of course project), make the working sample of writing for the receipt of necessary amount of preparation. (Magnitude consumption ratios conventionally considered the same for all components of prescription). Make a flow chart of production, provide a description and specify the technology used equipment. Table № 1

№ Drug Required F at the F at the stage F at the amount, kg stage of of stage of bases introduction homogeniz preparatio of medicinal ation n substances in basis 1 2 3 4 5 6 1 Ointment of «Analgolan» 120 1,002 1,004 1,008 2 Ointment of «Gevkamen» 110 1,004 1,006 1,003 3 Ointment of woundwort Dr. 140 1,001 1,003 1,008 Theiss 4 Ointment from callosities 135 1,007 1,005 1,004 5 Ointment of prednisalon 0,5% 115 1,002 1,007 1,010 6 Ointment of turpentine 130 1,004 1,006 1,007 7 Ointment of streptocid 114 1,002 1,004 1,009 8 Metrogil denta gel 200 1,001 1,005 1,008 9 Mikogel KMP 180 1,003 1,009 1,014 10 Ointment of «Mikoseptin» 190 1,005 1,013 1,021 3. Conclusion (Conclusions). Prospects for the development of production technology in the domestic pharmaceutical ointments. 38

Topic № 22 Production of medicines in the form of gels Introduction. Main directions of gels in medical practice. 1. Review of the literature. 1.1. Hydrophobic gels. 1.2. Hydrophilic gels. 1.3. Gelling agents and other auxiliaries in the production of gels. 1.4. Technological process of gels. 1.5. Quality control of gels. 2 . Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of gels produced by the leading pharmaceutical companies in Ukraine. 2.3. Guided by the data in Table 1 (at the direction of supervisor of course project), make a recipe of working to get the required amount of gel. (Magnitude consumption ratios conventionally considered the same for all components of prescription). Make a flow chart of production in accordance with the requirements of GMP, please give a description and specify the technology used equipment. Table № 1 № Drug Required F at the F at the F at the amount, stage of stage of stage of kg bases introduction homogeniz preparatio of medicinal ation n substances in basis 1 2 3 4 5 6 1 Diclofenac sodium gel 1% 300 1,002 1,004 1,005 2 Diclocin-KMP 250 1,005 1,006 1,004 3 Ketoprofen gel 80 1,002 1,010 1,019 4 Gel «Aescin» 100 1,004 1,008 1,006 5 Gel «Bifonal» 1% 180 1,003 1,005 1,011 6 Geparin-gel 200 1,010 1,006 1,008 7 Dentol-gel 180 1,006 1,004 1,008 8 Divigel 140 1,003 1,004 1,010 9 Diclonac-gel 200 1,006 1,005 1,009 10 Diclofen-gel 250 1,002 1,001 1,004 3.Conclusion (Conclusions). Prospects for the development of technology in the domestic pharmaceutical gels.

39

Topic № 23 Pharmaceutical and biological aspects of ointments Introduction. Characteristics of soft drugs and basic directions of ointments in medical practice. 1. Review of the literature. 1.1. Types of possible interactions between the subsidiary and medicinal substances . 1.2. Biopharmaceutical aspects ointments. 1.2.1. Factors influencing the degree, completeness release and absorption of drug substances . 1.2.2. Effect of adjuvants (activators suction) on the release of drugs from ointment. 1.3. Main directions of improvement of technology and quality control ointments. 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of ointments produced by the leading pharmaceutical companies in Ukraine. 2.3. Guided by the data in Table 1 (at the direction of the head of the course work), make a recipe of working to get the required amount of the drug. Magnitude consumption ratios conventionally considered the same for all components of prescription). Make a flow chart of production in accordance with the requirements of GMP, please give a description and specify the technology used equipment. Table № 1

№ Drug Required F at the F at the stage F at the amount, kg stage of of stage of bases introduction homogeniza preparation of medicinal tion substances in basis 1 2 3 4 5 6 1 Ointment «Levomecol» 100 1,002 1,004 1,008 2 Ointment «Levocin» 200 1,004 1,005 1,009 3 Ointment of streptocid 140 1,001 1,006 1,013 4 Ointment «Cinkundan» 140 1,002 1,011 1,013 5 Ointment «Espol» 110 1,001 1,004 1,008 6 Ointment «Apizatron» 150 1,002 1,008 1,006 7 Ointment «Dr. Мом» 200 1,003 1,005 1,004 8 Dolobene gel 180 1,004 1,007 1,009 9 Ibuprofen cream 5% 200 1,003 1,007 1,005 10 Ointment «Iricar» 250 1,009 1,007 1,018 3. Conclusion (Conclusions). Prospects for the development of production technology in the domestic pharmaceutical ointments.

40 Topic № 24 Drugs in the form of suppositories Introduction. Suppositories in the pharmaceutical market of Ukraine. 1. Review of the literature. 1.1. General characteristics of the suppositories. 1.2. Physico-chemical properties of suppositories. 1.2.1. Viscosity. 1.2.2. Thixotropic properties. 1.2.3. Elasticity. 1.2.4. Plasticity. 1.2.5. Hardness. 1.3. The main factors affecting the rheological properties of suppositories bases (molecular weight, temperature, concentration of excipients, machining). 1.4. Equipment used to the production of suppositories 1.5. Advanced types of rectal suppositories. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Specify the assortment of suppositories produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of suppositories (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production of child medicinal form in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1 № Drug Required F at the F at the stage F at the amount stage of of introduction stage of packs bases of medicinal homogeniza (pcs.) preparation substances in tion basis 1 2 3 4 5 6 1 Ginotrozid suppositories 900 1,004 1,006 1,009 2 Dikloberl suppositories 1000 1,002 1,006 1,009 3 Kontratseptin Т suppositories 800 1,003 1,001 1,008 4 Osarbon suppositories 950 1,004 1,006 1,018 5 Gravagin suppositories 700 1,002 1,003 1,009 6 Suppositories with methyluracil 600 1,005 1,008 1,004 7 Suppositories with paracetamol 750 1,002 1,004 1,009 8 Suppositories with bisacodyl 820 1,001 1,006 1,008 9 Suppositories with seabuckthorn 950 1,003 1,005 1,010 fruit oil 10 Ultraproct suppositories 1000 1,004 1,003 1,008

41 3. Conclusion. Development prospects of suppositories technology in the national pharmacy.

Topic № 25 Suppository bases and excipients used in the manufacturing of suppositories. Introduction 1. Review of the literature. 1.1. The suppositories dosage form. 1.2. Suppository bases. 1.2.1. Lipophilic bases. 1.2.2. Hydrophilic base. 1.2.3. Amphiphilic basis. 1.3. Excipients used in the manufacturing of suppositories. 1.3.1. Solvents. 1.3.2. Surface-active compounds (surfactants). 1.3.3. Builders. 1.3.4. Antioxidants. 1.3.5. Preservatives. 1.3.6. Dyes. 1.4. Industrial production of suppositories 1.4.1. Pouring method 1.4.2. Pressing method 1.5. Assessment of quality of suppositories. Requirements for packaging and storage. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Specify the assortment of suppositories produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of suppositories (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production of child medicinal form in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1 42

№ Drug Required F at the F at the stage F at the amount stage of of introduction stage of packs bases of medicinal homogeniza (pcs.) preparation substances in tion basis 1 2 3 4 5 6 1 Anestezol suppositories 1,4 g 900 1,006 1,010 1,012 2 suppositories with ihtiola 0.2 g- 750 1,005 1,011 1,006 on the PEO-base, 1.4 g 3 Suppositories with ihtiola extract 650 1,003 1,010 1,009 0.2 g and 0,015 g of fat base, 1.4 g 4 The suppositories with extract 800 1,002 1,009 1,008 0,015 g fat base, 1.4 g 5 Anuzol suppositories, 1,4 g 1000 1,003 1,005 1,010 6 Аspirin suppositories,0.2 g 950 1,002 1,005 1,007 7 Atselizin suppositories 0,6 g 800 1,003 1,010 1,009 8 Betiol suppositories 2000 1,002 1,005 1,007 9 Sintomitsin vaginal 900 1,003 1,006 1,007 suppositories 0.25 g 10 Voltaren suppositories 50 mg 1000 1,001 1,004 1,014

3. Conclusion. Development prospects of suppositories technology in the national pharmacy.

Topic № 26 Current approaches to creation of aerosol systems in manufacturing of preparations under the pressure Introduction. The main goals and objectives of preparation development under pressure. 1. Review of literature. 1.1. Manufacture of pharmaceutical aerosols in domestic pharmacy. The main types of aerosol systems. 1.1.1. Classification of aerosol systems according to the physico -chemical properties. 1.1.2. Characteristics of a two-phase system. Solvents. (Bring the formulation examples of dosage forms in the form of aerosols, solutions). 1.1.3. Three-phase aerosol systems and its characteristics. 1.2. Technology of preparation of aerosol systems. 1.2.1. Technological aspects of preparation aerosols-solutions. (Give examples). 1.2.2. Factors affecting the preparation of solutions, aerosols. 1.3. Characterization of aerosols-suspensions. Advantages and disadvantages dosage forms in the form of aerosols-suspensions. Technology of suspensions aerosols production. 43 1.3.1. Effect of various factors contributing to the quality of preparations in the form of aerosols. 1.4. Foam. 1.4.1. Classification of foams. Their advantages and disadvantages. 1.4.2. Rationale for selection of excipients to aerosol foam preparation. 1.4.3. Technology features of foam formulations. (give an example of the preparation technology of foam). 2. Experimental (calculated) part. 2.1. Objects and methods. 2.2. Name the range of drugs under the pressure produced by the leading Ukrainian pharmaceutical companies. 2.3. Using the data in Table 1 (at the direction of the head of the course work), make a recipe of working for the production of aerosols. (Values consumption ratios conventionally considered the same for all components of the recipe). Make a flow chart of production of drugs under pressure in accordance with the requirements of GMP, please give a description and specify the technology used equipment. Table 1 № Name of drug Required Consumpti Consumption Consump amount of on index index tion index packaging, at the stage at the stage at the pcs of of stage of preparatio preparations packing n of raw materials 1 2 3 4 5 6 1 Aldecin 0,05 g 200 doses 4700 1,003 1,003 1,004 2 Spray Anginal with Calendula 2300 1,0020 1,0020 1,006 (Marigold) 3 Beclazone Eco 100 mcg 200 doses 6800 1,009 1,009 1,010 4 Allergodil, spray 2000 1,008 1,008 1,0087 5 Buserin spray 150 mcg, 17.5 ml 18000 1,009 1,009 1,0089 6 Delufen nasal spray 20ml 7800 1,002 1,002 1,0043 7 Deep freeze outdoor use, 200 ml 790 1,0094 1,0094 1,0089 8 Imidin N nasal spray 5400 1,0058 1,0058 1,0098 9 Desmopressin nasal spray, 5 ml of 1600 1,008 1,008 1,0066 50 doses 10 Ipravent 250 g № 1 3700 1,0092 1,0092 1,011

3. Conclusions. Prospects for the development of technology in the production of aerosol systems products under pressure in the domestic pharmacy.

Topic №27 Modern approaches to obtaining of child medicinal forms 44 Introduction. Topicality of the development of child medicinal forms in modern conditions of production. 1. Review of the literature. 1.1. Current state and problems of creating of child medicinal forms. 1.2. Features a child's body. 1.3. Requirements for medicinal forms for children. 1.3.1. Creation of medicines for children up to 1 year. 1.4. Medicinal forms for children: their advantages and disadvantages, technology of production and quality control. 1.4.1. Liquid dosage forms: solutions, syrups, suspensions, drops, etc. 1.4.2. Solid dosage forms: tablets, suppositories, granules, caramels, lozenges, lollipops, etc. 1.4.3. Soft dosage forms: ointments, gels, creams, pastes. 1.4.4. Aerosoldispersed systems: aerosols, sprays. 1.5. Excipients used in the technology of child medicinal forms (stabilizers- thickeners, emulsifiers, solubilizers, preservatives, solvents, etc.). Their characteristics, classification, function and using. 1.6. The role and functions of corrective substances in the technology of child medicinal forms. Corrigents of taste, smell and color. Their characteristics and application. Methodology for assessing the taste of medicinal substances. 1.7. Rules of dosing of medicines for children. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Specify the assortment of child medicinal forms, produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of child medicinal form (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production of child medicinal form in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1 № Name of the drug Required F at the F at the F at the stage amount stage of stage of the of filling and packs raw technology packing (pcs.) material preparatio n 1 2 3 4 5 6 45

1 Herbal cough lozenges «Doctor 300 1,008 1,002 1,006 MOM with pineapple flavor», №24 2 Cough lollipops «Travisil with 870 1,006 1,009 1,010 orange flavor», №16 3 Cough syrup "Lasolvan", vial 3670 1,015 1,008 1,007 100 ml 4 Oral suspension "Nurofen", vial 3560 1,016 1,009 1,005 100 ml 5 Drops for oral administration 2700 1,020 1,002 1,004 "Sinekod", dropper bottle 20 ml 6 Тablets «Anaferon», №20 1870 1,030 1,009 1,008 7 Suppositories «Аnalgin» for 900 1,025 1,005 1,009 children, №10 8 Аerosol «Bioparox», aerosol 650 1,092 1,008 1,006 bottle 10 мл 9 Oxolinic ointment 0.25%, tuba 700 1,094 1,008 1,098 10 g 10 Gel «Fenistil», tuba 20g 3400 1,086 1,008 1,006 3. Conclusions. New directions and development prospects of the technology of child medicinal forms in the domestic pharmacy.

Topic №28 The role of auxiliary substances in the stability of drugs Introduction. Stability, as the determining factor of industrial production of drugs. 1. Review of the literature. 1.1. Stabilizers used in the pharmaceutical industry and their classification. 1.2. Prevention of drugs’ hydrolysis with the help of chemical stabilization. 1.3. Antioxidants used in the manufacture of drugs, the requirements to them. 1.3.1. Classification of antioxidants by type of action. 1.3.2. Ways of preventing autooxidation processes. 1.3.3. Basic inhibitors of oxidation processes used in the world pharmaceutical practice in the manufacture of drugs. 1.4. Preservatives used in the manufacture of various pharmaceutical medicinal forms. 1.4.1. Classification and the characteristic of preservatives for sterile medicines. 1.4.2. Classification and the characteristic of preservatives for unsterile medicines. 1.4.3. Factors affecting the effectiveness of preservatives. 1.5. The control of the chemical stabilizers content in the drugs. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Specify the assortment of stabilizers, which are used in the drug. 46 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of the required amount of drug (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1 № F at the F at the stage F at the Name of the drug, the form, the Amount stage of raw of stage of firm-manufacturer (pcs.) material semiproducts packing of preparation preparation the product 1 4 5 6 2 3 1. Аltemix, syrup vial 100 ml 1000 1,012 1,004 1,002 («Zdorovye») 2. Аtrifrin-Zdorovye, sol. for inj. amp. 2000 1,017 1,005 1,001 1,7 ml № 10 («Zdorovye») 3. Bifonal-Zdorovye, gel 1%, tuba 500 1,012 1,003 1,001 15 g («Zdorovye») 4. Geparil-КМP, gel 1000 U/g, tuba 500 1,010 1,004 1,002 30 g (Аrterium) 5. Glucose, sol. inf. 5%, bottle glass. 1800 1,011 1,006 1,003 400 ml (Indar) 6. Dexamethasone, sol. for inj. 0,4%, 2000 1,015 1,008 1,002 amp. 2 ml 5% (OZ GNCLS) 7. Ketolong-Darnytsia, sol. for inj. 2500 1,013 1,00 1,002 3% аmp. 1 ml №10 (Darnytsia) 8. Kronofarm, eye drops 2% vial 1500 1,014 1,009 1,003 polymer. 5 ml (Farmak) 9. Soluseptol, syrup vial 100 ml 800 1,09 1,006 1,002 (Yuri-farm) 10. Timolol maleate, eye drops 0,25% 1450 1,010 1,004 1,001 vial 5 ml (Farmak) 3. Conclusions. Ways of improving the stability of drugs.

Topic №29 Nasal drugs Introduction. Current state of manufacturing of nasal drugs in Ukraine. 1. Review of the literature. 1.1. Anatomical and physiological features of the nasal cavity and their effects on the properties of the dosage form. 1.2. General characteristics of nasal drugs. Requirements for their quality. 1.3. Nasal drops as a dosage form, its advantages and disadvantages. 1.4. Features of the technology of nasal drops in the form of different dispersed systems. 47 1.4.1. Technology and equipment for the production of solutions. 1.4.2. Technology and equipment for the production of suspensions. 1.4.3. Technology and equipment for the production of emulsions. 1.5. Quality control of nasal drops. 1.6. Nasal aerosols (sprays) as a dosage form, its advantages and disadvantages. 1.7. Physical-chemical and technological properties of the compositions used in the form of a nasal spray. 1.8. Containers and packaging of nasal sprays. 1.8.1. Containers for sprays, requirements to the materials. 1.8.2. Types of dispersal devices, principle of their work. 1.9. Features of the quality control of drugs in the form of nasal sprays. 1.10. Requirements of GMP to the conditions of manufacture of nasal drugs. 1.11. Features of manufacture of soft and solid dosage forms for nasal application. 1.12. Excipients in the manufacture of nasal drugs (ointment bases, preservatives, buffers, prolongators, isotonizing substances). 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Specify the assortment of nasal drugs, produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of the required amount of drug (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1 № F at the F at the stage F at the Name of drugs Amount stage of raw of solution stage of (pcs.) material preparation filling and preparation packing 1 4 5 6 2 3 1. Kromofarm, nasal spray 2% vial 1000 1,009 1,006 1,002 polymer. with metering pump 15 ml (Farmak) 2. Кsilometazolin, nasal drops 0,1% 2500 1,007 1,004 1,001 glass vial 10 ml (Phytopharm) 3. Rinosept, nasal drops 0,025% vial 700 1,012 1,005 1,001 5 ml, №1 (OZ GNCLS) 4. Rinosal, nasal drops 0,05% 700 1,010 1,007 1,002 48

dropper bottle 10 ml (Darnytsia) 5. Rinasolin, nasal drops 0,01% vial 800 1,013 1,006 1,003 10 ml (Farmak) 6. Rinasolin, nasal drops 0,05% vial 2000 1,015 1,005 1,002 15 ml № 1 (Farmak) 7. Nokspray, nasal spray 0,05% vial 1500 1,010 1,007 1,002 polymer. 20 ml (Sperko Ukraine) 8. Farmazoline N, nasal spray 0,1% 1500 1,008 1,006 1,003 vial 15 ml (Farmak) 9. No-sol, nasal drops 0,65% vial 10 1000 1,009 1,006 1,002 ml (Farmak) 10. Mentovazol, nasal drops vial 1200 1,011 1,004 1,001 20 ml (Phytopharm) 3. Conclusion (Conclusions). Prospects of the use of intranasal administration route for drugs of resorptive action. 49

Topic № 30 Manufacture of medicinal gatherings (phytoteas) Introduction. Medicinal plant gatherings as a means of prevention and treatment of many diseases. 1. Review of the literature. 1.1. Current state of manufacturing of medicinal gatherings (phytoteas) in Ukraine. 1.2. Characteristic of gathering (phytotea) as a dosage form. Their classification. 1.3. Nomenclature of medicinal gatherings and phytoteas. 1.4. Rules of collecting and drying characteristics of medicinal plants in the production of gatherings (phytoteas). Used equipment. 1.5. The technology of obtaining of gatherings (phytoteas). Used equipment. 1.6. Filling and packing of gatherings (phytoteas). 1.7. Standardization of medicinal gatherings (phytoteas). 1.8. Storage of gatherings (phytoteas) as a dosage form. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 2.2. Specify the assortment of medicinal gatherings (phytoteas), produced by leading pharmaceutical companies in Ukraine. 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of the required amount of medicinal gathering (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production of medicinal gathering in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1

50

№ F at the F at the F at the p/p Name of drugs Amount stage of stage of stage of (packs) medicinal mixing of filling plant medicinal and material plant packing preparation material 1 2 3 4 5 6 1 Phytotea « Children calming » 800 1,004 1,011 1,005 1,5 g in filter-packet №20 2 Gathering "Nefrophyt" 1550 1,001 1,010 1,010 1,5 g in filter-packet №20 3 Gathering "Gepatophyt" 2000 1,005 1,011 1,007 1,5 g in filter-packet №20 4 Gathering "Bronchophyt" 1650 1,007 1,009 1,009 1,5 g in filter-packet №20 5 Gathering "Gastrophyt" 600 1,006 1,009 1,006 1,5 g in filter-packet №20 6 Gathering "Detoxiphyt" 1200 1,010 1,010 1,015 1,5 g in filter-packet №20 7 Gathering "Immunophyt" 1800 1,003 1,011 1,012 1,5 g in filter-packet №20 8 Gastric gathering №3 1250 1,011 1,010 1,011 1,5 g in filter-packet №20 9 Thoracic gathering №1 1500 1,009 1,003 1,008 1,5 g in filter-packet №20 10 Cholagogic gathering №2 1600 1,002 1,004 1,013 1,5 g in filter-packet №20 3. Conclusions. Development prospects of the technology of drugs in the form of medicinal plant gatherings (phytoteas) in the domestic pharmacy.

Subject № 31 The role of biotechnology in creating drugs

Introduction. Modern trends in technology production of pharmaceuticals, biologically active substances derived from biotechnology. 1. Literature review (at the direction of the head of the coursework choose the direction and object of research). 1.1. Microbiological synthesis of fermentation products, organic acids, antimicrobial substances, amino acids, vitamins, enzymes. 1.2. Culturing the cells of plants, animals, using genetic engineering methods. 1.3. Preparation of biologically active substances which stimulate the immune system: immunoglobulins, interferons, vaccines. 2. Experimental (calculated) part. 2.1. Objects and methods of research. 51 2.2. Name the range of drugs, biologically active substances derived from biotechnology. 2.3. Using the data in Table 1 make the technological scheme of production pills or capsules which include drugs derived from biosynthesis (does consumption ratios equal for all components prescriptions). Make the technological scheme of production preparation in accordance with the GMP requirements and equipment used. Table 1 № Drug name Numbe Coefficient Coefficient Coefficient r of expendable expendable masses expendable on packag masses in in preparation for stage tableting es preparation tableting (capsulating)) for (capsulating) encapsulation 1 Tablets 500 1,004 1,005 1,002 «Pancreasim», 500 № 50 2 Capsules 1000 1,006 1,033 1,001 «tablets», № 20 3 Tablets 600 1,002 1,045 1,012 «Mesim forte», № 10 4 Tablets 700 1,001 1,005 1,011 «Pansim forte», № 10 5 Effervescent tablets 1500 1,002 1,007 1,013 «Supradyn», № 30 6 Tablets 1000 1,003 1,006 1,014 «Supradyn», № 30 7 Capsules 1000 1,004 1,057 1,017 Vitamins for memory. Activ lecithin complex, № 30 (Doppelherz) 8 chewable tablets 1000 1,011 1,025 1,008 Vitamin C 500 mg, № 50 9 capsules 500 1,012 1,035 1,009 "Linex" number 16 10 Capsules "Bifiform" 1500 1,013 1,037 1,007 number 30 3. Conclusions. Prospects for the development of drugs based on biosynthesis.

Topic № 32 The application of nanotechnology in the development of technologies drugs Introduction. The role and place of nanodrugs in modern medicine. 52 1. Modern aspects in the creation of medicines 1.1. History of creation of nanodrugs. 1.2. Range of application nanodrugs. 1.3. Requirements to nanodrugs. 1.4. Advantages and disadvantages. 1.5. Classification of nanomaterials. 1.6. Definition of the nanodelivery system and types its. 1.7. Technology for producing nanodrugs. 1.8. Equipment used in the manufacture of nanodrugs. 1.9. Quality control. 2. Experimental part. 2.1. Objects and methods of research. 2.2. Assortment of nanodrugs. 2.3. Using the data of the Table 1 (at the direction of the yearly project’s advisor), make the working formula for manufacturing of soft medicinal forms with nanosilver (values of consumption factors conventionally considered the same for all components of the recipe). Make the technological flowchart of the production of child medicinal form in accordance with the requirements of GMP, specify a description of the technology and used equipment. Table 1 № Drug Required F at the F at the stage F at the amount stage of of bases stage of packs preparation preparation homogeniza (pcs.) of raw tion materials

1 2 3 4 5 6 1 Septic Prokto gel 30 1,002 1,023 1,056 2 Septic psoriasis gel with 750 1,005 1,011 1,006 nanosilver 3 Nanorower gel 650 1,003 1,010 1,009 4 Microsilver Plus-gel 800 1,002 1,009 1,008 5 Septic gerpe gel 1000 1,003 1,005 1,010 3. Conclusion. Development prospects of nanodrugs.

Topic № 33 Manufacture of essential oils and their use in pharmacy 1. Literature review. 1.1. Determination of essential oils 1.1.2 Characteristics of essential oils 1.1.3 Properties and applications of essential oils 1. 2. Raw materials for essential oils 1.2.1 Characteristics of Essential raw materials 1.2.2 Composition of essential oils 53 1.2.3 Classification of Essential raw materials 1.2.4 Localisation of essential oils, resins and waxes 1.3. Technology of producing of essential oils 1.3.1 Characteristics of methods for obtaining essential oils 1.3.2 Mechanical methods 1.3.3 Steam distillation 1.3.4 Extraction of volatile solvents 1.3.5 Extraction of the non-volatile solvent 1.3.6 Sorption method of extracting of essential oils 1.3.7 Improving of the technology of essential oils 1.4. Administration of essential oils 1.4.1 Application area of essential oils 1.4.2 The use of essential oils in the manufacture of drugs 2. Experimental (calculated) part 2.1. Objects and methods 2.2. Name the range of essential oils produced by pharmaceutical companies in Ukraine. 2.3. Using the data table, make a recipe of working for the essential oil. Make a flow chart of the production of the drug in accordance with the requirements of GMP, please give a description and specify the technology used equipment. Table 1

№ Name of Number Amount of Красх на Красх на стадии Красх на substance of vials oil in the стадии получения стадии (pieces) vial (ml) подготовки извлечения очистки сырья продукта

1 2 3 3 4 5 6 1 Orange 100,0 10,0 1,002 1,150 1,005 essential oil 2 Lemon 100,0 10,0 1,003 1,050 1,008 essential oil 3 Mint essential 50,0 5,0 1,002 1,080 1,004 oil 4 Clove essential 50,0 5,0 1,003 1,020 1,006 oil 5 Eucalyptus 100,0 10,0 1,001 1,090 1,005 essential oil 6 Lavender 50,0 5,0 1,002 1,100 1,008 essential oil 7 Essential oil of 100,0 10,0 1,003 1,090 1,004 lemongrass 8 Essential oil of 50,0 5,0 1,005 1,120 1,006 rose 9 Jasmine 100,0 10,0 1,003 1,200 1,005 essential oil 54

10 Essential oil of 100,0 10,0 1,002 1,100 1,003 anise

3. Conclusions. Advances in the development of new technologies essential oils.