DOCSLIB.ORG

R.Somma, Thesis: "Hardness Effects Due to Aging and Dwell Time

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
R.Somma, Thesis: HARDNESS EFFECTS DUE TO AGING AND DWELL TIME DURING COMPRESSION OF FATTY ALCOHOL COMPACTS AND THEIR EXCIPIENTS By RUSSELL F. SOMMA A dissertation submitted to the Graduate School , New Brunswick Rutgers , The State University of New Jersey in partial fulfillment of the requirements for the degree of Doctor of Philosophy Graduate Program in Pharmaceutical Science Written under the direction of Professor Nicholas G. Lordi and approved by New Brunswick , New Jersey May 1987 ABSTRACT OF THE DISSERTATION HARDNESS EFFECTS DUE TO AGING AND DWELL TIME DURING COMPRESSION OF FATTY ALCOHOL COMPACTS AND THEIR EXCIPIENTS By RUSSELL F. SOMMA Dissertation Director: Professor Nicholas G. Lordi This study was initiated based on observations made during process optimization trials for a sustained release potassium chloride supplement . It was noted during compression that compact "hardness" varied with time as a function of the rotational speed of the com- pression equipment. These changes in compact strength and the subsequent unpredict- able effects on the behavior of the sustained release dosage form sug- gested a need for detailed analysis of the components and their pro- cessing. The sustained release system which was studied was of the erosion or matrix type. Changes in tablet hardness with time are not unique; however, the compacts which have been characterized in this research vary sub- stantially from the more standard tablet formulations. The fatty alcohols used in sustained release dosage forms possess unusual com- pressional and physicochemical properties which set off the erosion/ matrix compact as unique. The matrix formers (fatty alcohols) were characterized using differential scanning calorimetry, microscopy, as well as being formed into compacts for tensile strength measurements. The potassium chloride was evaluated with respect to moisture content, particle size, compressibility, and tensile strength of resulting compacts. Com- pression was carried out for all samples and sample mixtures using a universal testing machine , as well as an instrumented single station press. It was found that the fatty alcohols used in compact formation must have a minimal amount of solid-solid transition as measured by the heat of freezing. Samples with a high solidification energy pro- duce superior tablets. Potassium chloride, which possesses a fine particle size with an irregular configuration, produces strong compacts. The amount of surface moisture was found to be critical with a high level producing compacts with low tensile strength. Some degree of intracrystalline moisture promotes better compaction properties but also increases aging effects as measured by changes in tensile strength. Potassium chlor- ide with the aforementioned properties was found to be most sensitive to the length of dwell time employed during compression. Fatty alcohol compacts did not exhibit sensitivity to dwell time and reduced the aging properties of potassium chloride when used in mixtures with this material. Dedicated to my best friend and wife Mary Louise Somma iv Acknowledgements This work was supported solely by CIBA-GEIGY Corporation , Pharma- ceuticals Division. The author would like to thank Dr. LuAnn Ball, Dr. James Clevenger, and Mr. Louis Zagst for their technical assis- tance, Dr. Nicholas G. Lordi for his advise and technical direction, and Mrs. Jeanne Castaldo for her meticulous typing and preparation of the manuscript. v Contents Abstract ii Dedication iv Acknowledgements v Contents vi List of Tables x List of Figures xii I. Introduction 1 II. Background and Literature Survey 5 A. Raw Materials 6 A.1 Matrix Forming Components, Processing 6 and Synthesis A.2 Matrix Forming Components, Physico- 10 chemical Properties A.3 Potassium Chloride Processing and 18 Refining A.4 Potassium Chloride and Related 21 Excipients: Physicochemical Properties During Compaction B. Compaction Physics and Related Physical 26 Manifestations B.1 Theories of Bond Formation in Compacts 26 B.2 Characterization of Bonding Mechanism 32 B.3 Die Wall Effects on Compacted Systems 43 B.4 Aspects of Compact Strength 46 III. Experimental 49 A. Materials 49 vi B. Physical Characterization of Potassium 51 Chloride B.1 Moisture Content 52 B.2 Density 53 B.3 Particle Size 54 B.4 Microscopy 55 C. Thermal Analysis 57 C.1 Instrumentation 57 C.2 Sample Treatment 58 C.3 Calibration 60 C.4 Procedure 65 C.5 Data Analysis 65 D. Sample Preparation and Processing 66 E. Assessment of Compressibility 68 E.1 Instron Process 68 E.2 Instrumentation Description 68 E.3 Calibration: Instron 70 E.4 Procedure: Instron 70 E.5 Data Analysis, Tensile Strength 73 E.6 Data Analysis, Heckel Plots 73 E.7.a Instrumented Tablet Press Process 75 E.7.b Instrumentation 75 E.7.c Calibration: Instrumented F-Press 80 E.7.d Procedure: Instrumented F-Press 84 E.7.e Data Analysis 85 F. Compact Strength Measurement 85 F.1 Instrumentation 85 Vii F.2 Calibration 86 F.3 Data Analysis 88 IV. Results and Discussion 90 A. Matrix Forming Components, Fatty Alcohol 90 Behavior A.1 Cetostearyl Alcohol 90 A.2 Tetradecanol (C14) 94 A.3 Hexadecanol (C16) 97 A.4 Octadecanol (C18) 100 A.5 Octadecanol/Hexadecanol Mixtures 102 A.6 Energy Measurements of Fatty Alcohols 106 A.7 Process Evaluation: Compaction of 108 Fatty Alcohols A.8 Aging Effects on Fatty Alcohol 114 Compacts B. Active Ingredient Component, Potassium 115 Chloride B.1 Moisture Content 116 B.2 Particle Size 117 B.3 Assessment of Compressibility and 119 Compact Strength B.4 Surface Moisture Effects 125 B.5 Aging Effects of Potassium Chloride 127 Compacts B.6 Assessment of Densification and Bond 131 Formation: Heckel Plots C. Mixtures of Matrix Formers and Potassium 135 Chloride C.1 Mixtures of Cetostearyl Alcohol and 136 Potassium Chloride viii C.2 Hexadecanol/Octadecanol and Potassium 141 Chloride C.3 Thermal Properties of Cetostearyl 143 Alcohol and Potassium Chloride Mixtures D. Evaluation of Components Using an Instrumented 145 Tablet Press D.1 Potassium Chloride 145 D.1.a Potassium Chloride, Lot L7490 145 D.1.b Cycle Plot Evaluation of 149 Potassium Chloride, Lot L7490 D.1.c Potassium Chloride, Lot 10195 150 D.1.d Cycle Plot Evaluation of 153 Potassium Chloride, Lot 10195 D.2 Potassium Chloride and Fatty Alcohol 155 Mixtures D.2.a Cetostearyl Alcohol, Lot K4991, 156 and Potassium Chloride, Lot L7490 D.2.b Cetostearyl Alcohol, Lot K4991, 158 and Potassium Chloride, Lot 10195 D.2.c Cycle Plot Evluation of Mixtures 159 of Potassium Chloride and Cetostearyl Alcohol V. Summary and Conclusions 162 A. Matrix Forming Components 162 B. Potassium Chloride 163 C. Mixtures 165 VI. Tables and Figures 167 VII. References 269 Vita 277 ix Tables Reference Table Title Page I Physical Properties of Pure Alcohols 11 II Physical Properties of Potassium Chloride and 21 Magnesium Stearate III Fatty Alcohol Samples and Origins of Supply 49 IV Potassium Chloride Samples and Origin of Supply 50 V Transducer Calibration Data Using the Instron 82 VI Die Wall Transducer Calibration Data Using the 83 Instron VII Hardness Tester Calibration Data 87 VIII Cetostearyl Alcohol Composition 90 IX Heat of Fusion, High Purity Fatty Alcohol 107 Samples X Energy of Freezing as a Function of C16 108 Concentration XI Compact Strength of Fatty Alcohols Recorded as 108 Tensile Strength XII Effects of C14 on Energy of Freezing for 112 Cetostearyl Alcohol, Lot L4593, and Resulting Increase in Tensile Strength XIII Surface Moisture of Potassium Chloride 116 XIV Characterization of Size Fractions for Potassium 117 Chloride, Lot 10195 XV Characterization of Size Fractions for Potassium 117 Chloride, Lot L7490 XVI Particle Size Distribution, Milled Lot 10195 121 XVII Surface Moisture Effects on Tensile Strength of 125 Potassium Chloride Compacts x Reference Table Title Page XVIII Aging Effects on Tensile Strength of 128 Potassium Chloride, Lot 10195, Compacts XIX Aging Effects on Tensile Strength of 128 Potassium Chloride, Lot L7490, Compacts XX Heckel Plot, %AUC for 0.2 and 10.0 Second 132 Dwell Time XXI Compact Tensile Strength of Cetostearyl 137 Alcohol and Potassium Chloride Mixtures XXII Compact Tensile Strength of an Increased 139 Level of Cetostearyl Alcohol and Potassium Chloride Mixtures XXIII C16/C18 Fatty Alcohol Combinations and 141 Potassium Chloride Mixtures XXIV Compression Results, Potassium Chloride, 146 Lot L7490 XXV Compression Results, Potassium Chloride, 151 Lot 10195 XXVI Compression Results, Cetostearyl Alcohol and 156 Potassium Chloride Mixtures XXVII Compression Results, Increased Level of 157 Cetostearyl Alcohol and Potassium Chloride Mixture XXVIII Compression Results, Cetostearyl Alcohol and 158 Milled Potassium Chloride Mixture XXIX Compressions Results, Cetostearyl Alcohol and 159 Potassium Chloride Mixture xi Figures Reference Figure Title Page 1 Phase Diagram of C16 and C18 Fatty Alcohol, 17 Literature Reference 2 Typical Theoretical Heckel Plots 34 3 Cycle Plots, Theoretical Examples 38 4 Tablet Stress Components During Diametral 47 Compression 5 Typical Compact Fracture Patterns 48 6 Flow Diagram for Potassium Chloride Sizing 50 7 Schematic Representation of the DSC Cell 58 8 Matrix Granulation Fusion Procedure 66 9 Instron Punch Holding Fixture 69 10 Integrated Circuit Piezoelectric Transducer 76 11 F-Press Configuration Showing Instrumented 78 Components 12 Upper Punch Holder, Transducer Location 78 Drawing 13 Lower Punch Holder, Transducer Location 79 Drawing 14 Instrumented Die, Transducer Location 79 Drawing 15 Die Table Modifications 79 16 Upper Punch Transducer Calibration
Load more

Recommended publications
  • Catalyst in Basic Oleochemicals
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Diponegoro University Institutional Repository Bulletin of Chemical Reaction Engineering & Catalysis, 2(2-3), 2007, 22-31 Catalyst in Basic Oleochemicals Eva Suyenty, Herlina Sentosa, Mariani Agustine, Sandy Anwar, Abun Lie, and Erwin Sutanto * Research and Development Department, PT. Ecogreen Oleochemicals Jln. Pelabuhan Kav 1, Kabil, Batam 29435, Telp/Fax: (0778)711374 Presented at Symposium and Congress of MKICS 2007, 18-19 April 2007, Semarang, Indonesia Abstract Currently Indonesia is the world largest palm oil producer with production volume reaching 16 million tones per annum. The high crude oil and ethylene prices in the last 3 – 4 years contribute to the healthy demand growth for basic oleochemicals: fatty acids and fatty alcohols. Oleochemicals are starting to replace crude oil derived products in various applications. As widely practiced in petrochemical industry, catalyst plays a very important role in the production of basic oleochemicals. Catalytic reactions are abound in the production of oleochemicals: Nickel based catalysts are used in the hydrogenation of unsaturated fatty ac- ids; sodium methylate catalyst in the transesterification of triglycerides; sulfonic based polystyrene resin catalyst in esterification of fatty acids; and copper chromite/copper zinc catalyst in the high pressure hydro- genation of methyl esters or fatty acids to produce fatty alcohols. To maintain long catalyst life, it is crucial to ensure the absence of catalyst poisons and inhibitors in the feed. The preparation methods of nickel and copper chromite catalysts are as follows: precipitation, filtration, drying, and calcinations. Sodium methy- late is derived from direct reaction of sodium metal and methanol under inert gas.
    [Show full text]
  • Study of Fatty Acid and Fatty Alcohol Formation from Hydrolysis of Rice Bran Wax Kelly L
    1747 A publication of CHEMICAL ENGINEERING TRANSACTIONS The Italian Association VOL. 32, 2013 of Chemical Engineering Online at: www.aidic.it/cet Chief Editors: Sauro Pierucci, Jiří J. Klemeš Copyright © 2013, AIDIC Servizi S.r.l., ISBN 978-88-95608-23-5; ISSN 1974-9791 Study of Fatty Acid and Fatty Alcohol Formation from Hydrolysis of Rice Bran Wax Kelly L. Tronia, Simone M. Silvab, Antonio J.A. Meirellesb, Roberta Ceriani*a a Faculty of Chemical Engineering, University of Campinas (UNICAMP), Zip Code, 13083-852, Campinas, São Paulo, Brazil b Faculty of Food Engineering, University of Campinas (UNICAMP), Zip Code, 13083-862, Campinas, São Paulo, Brazil [email protected] Rice bran wax is waste material of dewaxing process in oil refining. Dewaxing is accomplished by cooling and filtrating for separating wax from the oil to avoid turbidity in the final product. The dewaxing residue may have 20 up to 80 wt% of oil, followed by a main fraction of waxes, free fatty alcohols, free fatty acids and hydrocarbons. The wax fraction of the residue is composed by long-chain fatty alcohols esterified with long-chain fatty acids. Considering that rice bran oil has 4 – 6 wt% of wax, a large amount of this natural source of fatty compounds is undervalued. Noweck and Rider (1987) describe a process based on hydrolysis of waxes with sodium hydroxide, followed by distillation of fatty alcohols and soap. According to best of our knowledge no work has been reported on the formation of fatty acids and alcohols from the hydrolysis of the dewaxing residue using supersaturated stripping steam under high temperatures and high vacuum.
    [Show full text]
  • ( 12 ) United States Patent ( 10 ) Patent No .: US 10,751,310 B2 Freeman Et Al
    US010751310B2 ( 12 ) United States Patent ( 10 ) Patent No .: US 10,751,310 B2 Freeman et al . ( 45 ) Date of Patent : Aug. 25 , 2020 ( 54 ) PREVENTION , TREATMENT AND ( 56 ) References Cited REVERSAL OF DISEASE USING THERAPEUTICALLY EFFECTIVE U.S. PATENT DOCUMENTS AMOUNTS OF DICARBOXYLIC ACID 3,527,789 A 9/1970 Payne COMPOUNDS 4,166,913 A 9/1979 Kesling , Jr. et al . 6,528,499 B1 * 3/2003 Kozikowski C07C 59/347 ( 71 ) Applicant: UNIVERSITY OF 514/574 8,324,277 B2 12/2012 Freeman PITTSBURGH — OF THE 8,735,449 B2 5/2014 Freeman COMMONWEALTH SYSTEM OF 9,066,902 B2 6/2015 Freeman et al . HIGHER EDUCATION , Pittsburgh , 9,186,408 B2 11/2015 Freeman et al . PA (US ) 9,700,534 B2 7/2017 Freeman et al . 9,750,725 B2 9/2017 Freeman et al . 10,213,417 B2 2/2019 Freeman et al . ( 72 ) Inventors : Bruce A. Freeman , Pittsburgh , PA 10,258,589 B2 4/2019 Freeman et al . ( US ) ; Francisco J. Schopfer , 2015/0018417 Al 1/2015 Freeman et al . Pittsburgh , PA ( US ) FOREIGN PATENT DOCUMENTS ( 73 ) Assignee : University of Pittsburgh — of the CN 103705499 4/2014 Commonwealth System of Higher DE 102011118462 5/2013 Education , Pittsburgh , PA ( US ) GB 1153464 5/1969 WO WO 2002/022627 3/2002 WO WO 2009/017802 2/2009 ( * ) Notice : Subject to any disclaimer , the term of this WO WO 2009/112455 9/2009 patent is extended or adjusted under 35 WO WO 2010/005521 1/2010 U.S.C. 154 ( b ) by 0 days . WO WO 2010/014889 2/2010 WO WO 2011/014261 2/2011 WO WO 2013/116753 8/2013 ( 21 ) Appl.
    [Show full text]
  • Predicting Distribution of Ethoxylation Homologues With
    1 PREDICTING THE DISTRIBUTION OF ETHOXYLATION HOMOLOGUES WITH A PROCESS SIMULATOR Nathan Massey, Chemstations, Inc. Introduction Ethoxylates are generally obtained by additions of ethylene oxide (EO) to compounds containing dissociated protons. Substrates used for ethoxylation are primarily linear and branched C12-C18 alcohols, alkyl phenols, nonyl (propylene trimer) or decyl (propylene tetramer) groups, fatty acids and fatty acid derivatives. The addition of EO to a substrate containing acidic hydrogen is catalyzed by bases or Lewis acids. Amphoteric catalysts, as well as heterogeneous catalysts are also used. The degree of ethoxylation ( the moles of EO added per mole of substrate ) varies over wide ranges, in general between 3 and 40, and is chosen according to the intended use. As an illustration of how this distribution might be predicted using a process simulator, Chemcad was used to simulate the ethoxylation of Nonylphenols. Description of the Ethoxylation Chemistry The reaction mechanisms of base catalyzed and acid catalyzed ethoxylation differ, which affects the composition of the reaction products. In base catalyzed ethoxylation an alcoholate anion, formed initially by reaction with the catalyst ( alkali metal, alkali metal oxide, carbonate, hydroxide, or alkoxide ) nucleophilically attacks EO. The resulting union of the EO addition product can undergo an equilibrium reaction with the alcohol starting material or ethoxylated product, or can react further with EO: Figure 1 O RO- + H2CCH2 - - RO CH2CH2O O ROH H2CCH2 - - RO RO CH2CH2OH RO RO CH2CH2O 2 As Figure 1 illustrates, in alkaline catalyzed ethoxylations several reactions proceed in parallel. The addition of EO to an anion with the formation of an ether bond is irreversible.
    [Show full text]
  • Unusual Aldehyde Reductase Activity for Production of Full-Length Fatty Alcohol by Cyanobacterial Aldehyde Deformylating Oxygenase
    Unusual Aldehyde Reductase Activity for Production of Full-length Fatty Alcohol by Cyanobacterial Aldehyde Deformylating Oxygenase Supacha Buttranon Vidyasirimedhi Institute of Science and Technology Pattarawan Intasian Vidyasirimedhi Institute of Science and Technology Nidar Treesukkasem Vidyasirimedhi Institute of Science and Technology Juthamas Jaroensuk Vidyasirimedhi Institute of Science and Technology Somchart Maenpuen Burapha university Jeerus Sucharitakul Chulalongkorn University Faculty Of Dentistry Narin Lawan Chiang Mai University Faculty of Science Pimchai Chaiyen Vidyasirimedhi Institute of Science and Technology Thanyaporn Wongnate ( [email protected] ) School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), 555 Wangchan Valley, Rayong 21210, Thailand https://orcid.org/0000-0001-5072-9738 Research Keywords: Non-heme diiron enzyme, Aldehyde-deformylating oxygenase, NADPH-dependent fatty aldehyde reductase, Fatty alcohol, Oxido-reductase Posted Date: November 5th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-100741/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/28 Abstract Background: Aldehyde-deformylating oxygenase (ADO) is a non-heme di-iron enzyme that catalyzes deformylation of aldehydes to generate alkanes/alkenes. In this study, we report for the rst time that under anaerobic or limited oxygen conditions, Prochlorococcus marinus (PmADO) can generate full- length fatty alcohols from fatty aldehydes without eliminating a carbon unit. Results: Unlike the native activity of ADO which requires electrons from the Fd/FNR electron transfer complex, the aldehyde reduction activity of ADO requires only NADPH. Our results demonstrated that yield of alcohol products can be affected by oxygen concentration and type of aldehyde.
    [Show full text]
  • C16-18 Fatty Alcohol
    Date: 06/09/2017 Environmental Fact Sheet (#13) C16‐18 Fatty Alcohol oleochemical precursor Substance Identification IUPAC Name Alcohols, C16‐18 CAS Number 67762‐27‐0 Other Names Cetearyl Alcohol Structural formula (example): Molecular Formula C16H34O / C18H380 Physical/Chemical Properties Molecular Weight 242.44 ‐ 270.49 g/mol Physical state Liquid Appearance No data available Odour No data available Density No data available Melting Points No data available Boiling point No data available Flash Point No data available Vapour Pressure No data available Water Solubility No data available Flammability No data available Explosive Properties No data available Surface Tension No data available Octanol/water Partition coefficient No data available (Kow) C16‐18 fatty alcohol is a surfactant precursor. C16‐18 fatty alcohol (oleo) is produced from natural sources which contain fatty acids in the form of triglycerides that can be hydrogenated after suitable pre‐treatment. For the production of C16–18 alcohols, preferably palm oil, and tallow are used. The production stages of C16‐18 fatty alcohol are [4]: 1) Contaminants such as phosphatides, sterols, or oxidation products and impurities such as seed Product and Process particles, dirt, and water are removed in a cleaning stage, which includes refining by treatment with Description phosphoric acid, centrifugation, and adsorption, e.g., on charcoal or bentonite. 2) Hydrolyzing of the refined triglycerides to yield fatty acids or trans‐esterified with lower alcohols to yield fatty acid esters. 3) The Refined fatty acid methyl esters are used for hydrogenation to generate fatty alcohol. Fatty alcohols possess good foaming properties and ready biodegradability, and are extensively used as base surfactants for laundry detergent products, shampoo, dishwashing liquids and cleaners.
    [Show full text]
  • SANCO/10387/2013-EN Rev. 1 ANNEX
    EUROPEAN COMMISSION Brussels, XXX SANCO/10387/2013 Rev. 1 ANNEX (POOL/E3/2013/10387/10387R1-EN ANNEX.doc) D030733/02 […](2014) XXX draft ANNEX 1 ANNEX to the COMMISSION REGULATION (EU) No …/.. granting derogation from certain provisions of Annex II to Regulation (EC)No 852/2004 as regards the transport of liquid oils and fats by sea EN EN ANNEX LIST OF ACCEPTABLE PREVIOUS CARGOES Substance (synonyms) CAS No Acetic acid (ethanoic acid; vinegar acid; methane carboxylic 64-19-7 acid) Acetic anhydride (ethanoic anhydride) 108-24-7 Acetone (dimethylketone; 2-propanone) 67-64-1 Acid oils and fatty acid distillates — from vegetable oils and --- fats and/or mixtures thereof and animal and marine fats and oils Ammonium hydroxide (ammonium hydrate; ammonia solution; 1336-21-6 aqua ammonia) Ammonium polyphosphate 68333-79-9 and 10124-31-9 Animal, marine and vegetable and hydrogenated oils and fats --- according to the MEPC.2/Circ. of the IMO. Benzyl alcohol (pharmaceutical and reagent grades only) 100-51-6 N-butyl acetate 123-86-4 Sec-butyl acetate 105-46-4 Tert-butyl acetate 540-88-5 Ammonium nitrate solution 6484-52-2 Calcium nitrate (CN-9) solution and their double salt 35054-52-5 NH4NO3.5Ca(NO3)2.10H2O, named "nitric acid, ammonium calcium salt" Calcium chloride solution 10043-52-4 Cyclohexane (hexamethylene; hexanaphthene; 110-82-7 hexahydrobenzene) Epoxidised soyabean oil (with a minimum 7 % - maximum 8 % 8013-07-8 oxirane oxygen content) Ethanol (ethyl alcohol) 64-17-5 Ethyl acetate (acetic ether; acetic ester; vinegar naphtha) 141-78-6 2-ethylhexanol
    [Show full text]
  • Functionality and Role of Different Fatty Alcohols in Topical O/W Cream Formulation
    University of Mississippi eGrove Electronic Theses and Dissertations Graduate School 2018 Functionality And Role Of Different Fatty Alcohols In Topical O/W Cream Formulation Supriya Bhide University of Mississippi Follow this and additional works at: https://egrove.olemiss.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Bhide, Supriya, "Functionality And Role Of Different Fatty Alcohols In Topical O/W Cream Formulation" (2018). Electronic Theses and Dissertations. 725. https://egrove.olemiss.edu/etd/725 This Thesis is brought to you for free and open access by the Graduate School at eGrove. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of eGrove. For more information, please contact [email protected]. FUNCTIONALITY AND ROLE OF DIFFERENT FATTY ALCOHOLS IN TOPICAL O/W CREAM FORMULATION A thesis presented in partial fulfillment of requirements for the degree of Master of Science in the Department of Pharmaceutics and Drug Delivery The University of Mississippi by SUPRIYA S.BHIDE May 2018 Copyright Supriya S. Bhide 2018 ALL RIGHTS RESERVED ABSTRACT Fatty alcohols are excipients that are abundantly used in various pharmaceutical formulations. The objective of the present study was to evaluate the impact of incorporating different fatty alcohols on microstructural and formulation characteristics of topical o/w clotrimazole cream formulation. The formulations containing different fatty alcohols as Kolliwax® CSA 50 (CSA 50), Kolliwax® CSA 70 (CSA 70), Kolliwax® MA (MA), Kolliwax® CA (CA), Kolliwax® SA (SA) were prepared by selecting suitable RPM and homogenization time. The M.P. of API and fatty alcohols were determined using DSC technique.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2002/0177609 A1 Swindell Et Al
    US 2002O177609A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0177609 A1 Swindell et al. (43) Pub. Date: Nov. 28, 2002 (54) FATTY ALCOHOL DRUG CONJUGATES Related U.S. Application Data (60) Provisional application No. 60/278,457, filed on Mar. (76) Inventors: Charles S. Swindell, Merion, PA (US); 23, 2001. Glenn J. Fegley, Eagleville, PA (US) Publication Classification Correspondence Address: (51) Int. Cl." ..................... A61K 31/4453; A61K 31/40; Edward R. Gates, Esq. A61K 31/15 Chantal Morgan D'Apuzzo (52) U.S. Cl. ......................... 514/329; 514/426; 514/640; Wolf, Greenfield & Sacks, P.C. 546/244; 548/558; 564/256 600 Atlantic Ave Boston, MA 02210 (US) (57) ABSTRACT The invention provides conjugates of fatty alcohols and (21)21) AppAppl. No.: 10/107,537/107, p harmaceutical agents9. useful in treating9. cancer, Viruses, psychiatric disorders. Compositions, pharmaceutical prepa rations, and methods of preparation of the fatty alcohols 22) Filled: Mar. 25, 2002 p harmaceutical agent9. coniugatesJug are pprovided. US 2002/0177609 A1 Nov. 28, 2002 FATTY ALCOHOL DRUG CONJUGATES was observed (for an adenosine receptor agonist), and it was postulated that the pendant lipid molecule interacted with RELATED APPLICATION the phospholipid membrane to act as a distal anchor for the 0001. This application claims priority under 35 U.S.C. S receptor ligand in the membrane micro environment of the 119 (e) from U.S. provisional patent application Serial No. receptor. This increase in potency, however, was not 60/278,457, filed on Mar. 23, 2001, entitled Fatty Alcohol observed when the same lipid derivatives of adenosine Drug Conjugates.
    [Show full text]
  • An Engineered Fatty Acid Synthase Combined with a Carboxylic Acid
    Henritzi et al. Biotechnol Biofuels (2018) 11:150 https://doi.org/10.1186/s13068-018-1149-1 Biotechnology for Biofuels RESEARCH Open Access An engineered fatty acid synthase combined with a carboxylic acid reductase enables de novo production of 1‑octanol in Saccharomyces cerevisiae Sandra Henritzi1, Manuel Fischer2, Martin Grininger2, Mislav Oreb1 and Eckhard Boles1* Abstract Background: The ideal biofuel should not only be a regenerative fuel from renewable feedstocks, but should also be compatible with the existing fuel distribution infrastructure and with normal car engines. As the so-called drop-in biofuel, the fatty alcohol 1-octanol has been described as a valuable substitute for diesel and jet fuels and has already been produced fermentatively from sugars in small amounts with engineered bacteria via reduction of thioesterase- mediated premature release of octanoic acid from fatty acid synthase or via a reversal of the β-oxidation pathway. Results: The previously engineered short-chain acyl-CoA producing yeast ­Fas1R1834K/Fas2 fatty acid synthase variant was expressed together with carboxylic acid reductase from Mycobacterium marinum and phosphopantetheinyl transferase Sfp from Bacillus subtilis in a Saccharomyces cerevisiae Δfas1 Δfas2 Δfaa2 mutant strain. With the involve- ment of endogenous thioesterases, alcohol dehydrogenases, and aldehyde reductases, the synthesized octanoyl- 1 CoA was converted to 1-octanol up to a titer of 26.0 mg L− in a 72-h fermentation. The additional accumulation of 1 90 mg L− octanoic acid in the medium indicated a bottleneck in 1-octanol production. When octanoic acid was sup- plied externally to the yeast cells, it could be efciently converted to 1-octanol indicating that re-uptake of octanoic acid across the plasma membrane is not limiting.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,326,514 B1 Klug Et Al
    USOO632651.4B1 (12) United States Patent (10) Patent No.: US 6,326,514 B1 Klug et al. (45) Date of Patent: Dec. 4, 2001 (54) PROCESS FOR THE PREPARATION OF 5,233,087 * 8/1993 Cripe. ETHER CARBOXYLIC ACIDS WITH LOW 5,420,315 * 5/1995 Uhrig et al. RESIDUAL ALCOHOL CONTENT 5,523,479 * 6/1996 Sanders et al. FOREIGN PATENT DOCUMENTS (75) Inventors: Peter Klug, Grossostheim; Rainer Kupfer, Hattersheim; Ignaz Wimmer, O 166958 1/1986 (EP). Winhöring; Ridiger Winter, Frankfurt, O 295-578 12/1988 (EP). all of (DE) OTHER PUBLICATIONS (73) Assignee: Clariant GmbH, Frankfurt (DE) EPO Search Report. Derwent Patent Family Abstract for EP 0 166958. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 * cited by examiner U.S.C. 154(b) by 0 days. Primary Examiner Johann Richter Assistant Examiner Sikarl A. Winterspoon (21) Appl. No.: 09/596,418 (74) Attorney, Agent, or Firm-Susan S. Jackson; Scott E. Hanf (22) Filed: Jun. 19, 2000 (57) ABSTRACT (30) Foreign Application Priority Data The invention provides a process for the preparation of ether Jun. 19, 1999 (DE) .............................................. 19928 128 carboxylic acids or alkali metal or ammonium Salts thereof (51) Int. Cl." ...................... C07C 59/125; CO7C 59/305; with low residual alcohol content, which comprises firstly CO7C 59/58 converting a mono- or polyhydric alcohol into the corre (52) U.S. Cl. ........................... 562/583; 562/588; 568/620 sponding alkoxide using a SubStoichiometric amount (58) Field of Search ..................................... 562/583,588; between 5 and 95 mol % of a basic compound, and then 554/124; 568/620 reacting the alkoxide with alkylene oxides, and, if necessary after distilling off the residual alcohol which remains, alky (56) References Cited lating the highly alkaline reaction mixture, which comprises more than 5 mol % of alkoxylated alkoxides, directly with U.S.
    [Show full text]
  • 1-Dodecanol Cas N°: 112-53-8
    OECD SIDS 1-DODECANOL FOREWORD INTRODUCTION 1-DODECANOL CAS N°: 112-53-8 UNEP PUBLICATIONS OECD SIDS 1-DODECANOL SIDS INITIAL ASSESSMENT PROFILE CAS No. 112-53-8 CHEMICAL NAME 1-Dodecanol STRUCTURAL FORMULA CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2(OH) CONCLUSIONS Only minor releases of Dodecanol are expected during production. The major use of this substance is as a chemical intermediate for the production of Dodecyl sulfates and ethoxylates. Consumers will be exposed directly due to presence in foods and cosmetics. Environment: Although Dodecanol exhibits non-polar narcotic toxicity to aquatic organisms of about 1 mg/l, the substance is readily degradable and releases during production, or through diffuse uses of the free alcohol do not give rise to environmental concerns. Human Health: No risks were identified as a result of animal testing or experience with human use. The substance is practically non-toxic, and is a permitted food additive (GRAS) in both the U.S. and the EU. RECOMMENDATIONS 1-Dodecanol is presently of low concern. 2 UNEP Publications OECD SIDS 1-DODECANOL SIDS Initial Assessment Report 1. Identity: 1-Dodecanol, Cas. no. 112-53-8, CH3(CH2)10CH2OH 2. Exposure 2.1 General Discussion The production of fatty alcohols of this type range between 1000 and 10,000 tons per year in Denmark. In 1993 the European production of Dodecanol was estimated as being max. 60,000 tons. In the U.S.A. output of plasticizer type alcohols including Dodecanol was estimated at 110,000 tons in 1975. Domestic consumption of detergent alcohols in the U.S. in 1992 included about 24,000 tons as free alcohols.
    [Show full text]