sign in sign up
<<
Home , Drug delivery, Gel, Route of administration, Suspension (chemistry)

Review Article ISSN 2277-3657 Available online at www.ijpras.com

International Journal of Volume 2, issue 1 (2013),14-24 Pharmaceutical Research & Allied Sciences

Fast Dissolving Films: An Innovative Delivery System Kaur Mandeep*,A.C. Rana, Seth Nimrata Department of Pharmaceutics, Rayat Institute of , S.B.S.Nagar-144533(Punjab) India

*Email id: [email protected] Subject: Pharmaceutics

Abstract

In the recent years, many of the pharmaceutical groups are focusing their research on rapid dissolving technology. Amongst the plethora of avenues explored for rapid drug releasing product, Fast Dissolving Films technology is gaining much attention. Fast Dissolving Films evolved over the past few years from the confection and oral care markets in the form of breath strips and became a novel and widely accepted form by consumers for delivering vitamins and personal care products. These are dosage forms, which disintegrate or dissolve within 1 min when placed in the mouth without drinking water or chewing. This technology has been used for local action, rapid release products. The oral films are formulated using polymers, plasticizer, flavors, colors and sweeteners. This review describes about the formulation methodology, evaluation parameters and the future aspects of fast dissolving films.

Keywords: Fast Dissolving Films, casting technique, Rapid disintegrating, Patented technologies

Introduction

Oral is the most delivery markets [2,3]. Pharmaceutical convenient and preferred route of companies and consumers alike have embraced administration among the various other FDFs as a practical and accepted alternative to delivery system. More than 70% of are traditional OTC medicines, such as , available in the market in the form of oral drug tablets and capsules, because of the various delivery system due to pain avoidance and benefits of the films. FDFs offer fast, accurate versatility (to accommodate various types of dosing in a safe, efficacious format that is drug candidates) [1]. Dysphagia is commonly convenient and portable, without requiring the found among all age groups. Due to this use of water or a spoon. A variety of polymers problem, approximately 50% of population, are available for preparation of RDFs. The mainly pediatric and geriatric patients, tend to polymers can be used alone or in combination avoid taking oral solid dosage preparations due to obtain the desired film properties. The films to fear of choking. To overcome various obtained should be tough enough so that they problems related to swallowing, Fast are not damaged while handling or during dissolving Tablets (FDTs) were designed in transportation. On the other hand, Mouth early 19 th century, which slowly led to their dissolving films should have the property to further advancement and thus Fast Dissolving dissolve within seconds when placed in mouth Films (FDFs) were developed. Fast dissolving and deliver the drug to the oral cavity has become increasingly instantaneously. The employed in important because of their unique properties. FDFs are preferably hydrophilic in nature They quickly disintegrate and dissolve, and whereas drug may be either hydrophilic or can be administered without water, making hydrophobic. As the film forming polymer them particularly suitable for pediatrics and (which forms the platform for the RDFs) and geriatric patients. Fast dissolving films (FDFs), plasticizer are the most essential and major have gained popularity not only in breath strips component of the FDFs, at least 40-50 % w/w but also in personal care, food and drug of polymer and upto 20% (total weight of

14

Available online at www.ijpras.com polymer) of plasticizer should generally be • The drug to be incorporated should have present based on the total weight of dry RDFs. low upto 40 mg. Technology Catalysts forecasts the market for • The drugs with smaller and moderate drug products in oral thin film formulations molecular weight are preferable. was valued of $500 million in 2007 and could • Good in water as well as in reach $2billion in 2012. Based on upward saliva and also good stability. global growth trends of the past decade, the Classification of Oral Films [6] fast dissolving dosage market could produce There are three different subtypes of oral revenues of $13billion by 2015[4]. The FDFs films: technology continues to be viewed as an i. Flash release alternative for FDT products that would afford ii. Mucoadhesive melt-away wafer a superior barrier to generic entry and product iii. Mucoadhesive sustained-release wafers differentiation to over ‐the ‐counter brands. Types of oral films and their properties From the marketing perspective, a patented are described in Table 1 ODF technology would be beneficial. The grant of marketing exclusivity to the new dosage form would help to gain more revenue. Classification of Fast Dissolving The various synonyms used for FDFs include Technology mouth dissolving films (MDFs), orally For ease of description, fast-dissolve disintegrating films (ODFs), melt in-mouth films, technologies can be divided into three oro-dispersible, quick dissolving and rapid broad groups: disintegrating films.[4,5] i. Lyophilized systems: The technology Advantages of Fast Dissolving Films [6] around these systems involves taking a • No risk of choking and obstruction. or of drug with other • No need of water has led to better structural excipients, through the use of a acceptability amongst the dysphagic mould or blister pack, forming - patients shaped units. The units or tablets are then • Improved oral of drugs frozen and lyophilized in the pack or • Taste masking mould. The resulting units have a very high porosity, which allows rapid water • Enhanced stability or saliva penetration and very rapid • Improved patient compliance disintegration. • Oral films are flexible and they are not as ii. Compressed tablet-based systems: This fragile as most of the ODTs system is produced using standard tablet • Reduction in first pass may technology by direct compression of lead to reduction in the dose excipients. Depending on the method of • The oral or buccal mucosa is highly manufacture, the tablet technologies have vascularized, hence drugs can be different levels of hardness and friability. absorbed directly and can enter the The speed of disintegration for fast- systemic circulation without undergoing dissolve tablets compared with a standard first-pass hepatic metabolism tablet is achieved by formulating using Ideal Properties of Fast Dissolving either water soluble excipients, super- Films disintegrant or effervescent components, • It should have an acceptable taste. to allow rapid penetration of water into • It should give a pleasing mouth feel. the core of the tablet. • It should be less friable and have good iii. Thin film strips: Oral films, also called mechanical strength to withstand the post oral wafers, evolved over the past few manufacturing handling. years from the confection and oral care • It should be stable in environmental markets in the form of breath strips and conditions. became a novel and widely accepted form • Subsequent to , it by consumers for delivering vitamins and should leave least or no residue in mouth. personal care products. Today, FDFs are a • It should quickly dissolve to release drug proven and accepted technology for the instantaneously in mouth. systemic delivery of APIs for over-the- counter (OTC) and are in the • It should be compatible with the other early- to mid development stages for ingredients. prescription drugs. This has been Drug Selection Criteria for Fast attributed to the success of the breath Dissolving Films[7] freshener products by consumers such as • The drug should have pleasant taste. Listerine Pocket Paks in the US consumer

15

Available online at www.ijpras.com

market. Such systems use a variety of iii. Plasticizers: Plasticizer is a vital ingredient hydrophilic polymers to produce a 50- of the oral films. The selection of plasticizer 200 mm film. The film is manufactured depends upon its compatibility with the as a large sheet and then cut into polymer and also the type of solvent employed individual dosage units for packaging in a in the casting of film. It helps to improve the range of pharmaceutically acceptable flexibility of the film and reduces the formats. brittleness of the film . Plasticizer significantly improves the strip properties by reducing the Formulation Aspects for Fast Dissolving transition temperature of the polymer. Films [7] Typically the plasticizers are used in the 1) Drug Category of 1 - 20%w/w of dry polymer 2) Film Forming Polymers weight. Examples include: Glycerol, Propylene 3) Plasticizers glycol, Low molecular weight polyethylene 4) Sweetening Agents glycols, Citrate derivatives like triacetin, acetyl 5) Saliva Stimulating Agents citrate, Phthalate derivatives like dimethyl, 6) Cooling Agent diethyl, dibutyl derivatives, Castor etc. 7) Flavoring Agent iv. Sweetening agents: Sweeteners have 8) Coloring Agent become the important part of the food products 9) Surfactants as well as pharmaceutical products intended to 10) Stabilizing and thickening agents be disintegrated or dissolved in the oral cavity. Formulation of FDFs involves the intricate The sweet taste in formulation is more application of aesthetic and performance important in case of pediatric population. characteristics such as taste masking, fast Natural sweeteners as well as artificial dissolution, physical appearance, mouth feel sweeteners are used to improve the palatability etc. From the regulatory perspectives, all of the mouth dissolving formulations. excipients used in the formulation of OS Suitable sweeteners include: should be Generally Regarded as Safe (i.e. (a) Water soluble natural sweetener: xylose, GRAS-listed) and should be approved for use ribose, glucose, sucrose, maltose, stevioside in oral pharmaceutical dosage forms. A typical etc. composition includes various ingredients (b) Water soluble artificial sweetener: sodium which are described in the Table 2. or calcium saccharin salts, cyclamate salts, i. Drug Category: This technology has the acesulfame-k etc. potential for delivery of variety of APIs. (c) based sweetener: aspartame However since the size of the dosage form has v. Saliva stimulating agent: The purpose of limitation, high dose drugs are difficult to be using saliva stimulating agents is to increase incorporated in films. Several classes of drugs the rate of production of saliva that would aid can be formulated as fast dissolving films in the faster dissolution of the film including antiulcer, antiasthamatics, formulations. Generally acids which are used antitussives, expectorants, antihistaminics, in the preparation of food can be utilized as NSAID’S etc. salivary stimulants. Citric acid, malic acid, ii. Film Forming Polymers: Water-soluble lactic acid, ascorbic acid and tartaric acid are polymers are used as film formers as they the few examples of salivary stimulants, citric provide rapid disintegration, good mouthfeel, acid being the most preferred amongst them. and mechanical strength to the films. The vi. Cooling agents: Cooling agents like robustness of the strip depends on the type of monomethyl succinate can be added to polymer and its amount in the formulations. improve the flavor strength and to enhance the Water-soluble polymers film, adheres to the mouth-feel effect of the product. Other cooling bucosal mucosa and rapidly delivers agents like WS3, WS23 and Utracoll II can into the systemic circulation. A also be used in conjunction with flavors [31]. variety of polymers are available for vii. Flavoring agents: Perception for the preparation of films of which pullulan, flavour changes from individual to individual and hypromellose are most commonly used. At depending on the ethinicity and liking. It was least 45%w/w of polymer should generally be observed that age plays a significant role in the present based on the total weight of dry film taste fondness. Flavoring agents can be [18]. Examples of water-soluble polymers selected from synthetic flavor , oleo resins, include: Pullulan, Gelatin, guargum, Xanthum extract derived from various parts of the plants gum, Hydroxyl propyl , like leaves, fruits and flowers. Modified starches, Hydroxyl ethyl cellulose Peppermint oil, cinnamon oil, oil of nutmeg etc. are examples of flavor oils while vanilla, cocoa, coffee, chocolate and citrus are fruity

16

Available online at www.ijpras.com flavors. Apple, raspberry, cherry, are preparation of solution or suspension should few examples of fruit essence type. The ideally be selected from ICH Class 3 solvent amount of flavor needed to mask the taste list [2]. Specific types of equipment such as depends on the flavor type and its strength. rollers are required for pouring the solution on viii. Coloring agents: Pigments such as an inert base. The between the roller titanium dioxide or FD&C approved coloring and the substrate determines the required agents are incorporated (not exceeding thickness of the film. The final step, drying the concentration levels of 1%w/w) in OS when film, removes the solvent and helps to obtain some of the formulation ingredients or drugs the finished product. Usually, glass, plastic, or are present in insoluble or suspension form. teflon plates are used as an inert base for film ix. Surfactants: Surfactants are used as casting. When the manufacturing technology is solubilizing or wetting or dispersing agents so transferred from laboratory scale to production that the film gets dissolved within seconds and scale, several problems can be encountered. release active agent immediately. Surfactants These problems can include the casting of the also improve the solubility of poorly soluble film, obtaining uniform thickness of the film, drugs in fast dissolving buccal films. Some of and proper drying of the sample. The selection the commonly used are polaxamer 407, sodium of the proper type of dryer is needed in the lauryl , benzalkonium chloride, final step of drying. benzthonium chloride, tweens and spans etc. Once the films are dried, cutting, stripping, and x. Stabilizing and thickening agents: The packaging is done. Suitable size and shapes of stabilizing and thickening agents are employed films can be cut. The commonly available to improve the and consistency of sizes of films are 3 x 2 cm2 and 2 x 2 cm2. or solution of the strip preparation Flowchart showing the solvent casting method solution or suspension before casting. Natural is described in figure.1. like xanthan gum, locust bean gum, carragenan and cellulosic derivatives can be 2) Semisolid casting used in the concentration up to 5%w/w as In semisolid casting method, firstly a solution thickening agents and stabilizing agents. of water soluble film forming polymer is prepared. The resulting solution is added to a Methods of Manufacturing Fast solution of acid insoluble polymer (e.g. Dissolving Films [8] cellulose acetate phthalate, cellulose acetate Following are the methods of manufacturing butyrate), which can be prepared in ammonium for fast dissolving films. One or combination or sodium hydroxide. Then appropriate amount of the following process can be used to of plasticizer is added so that a mass is manufacture the fast dissolving films – obtained. Finally the gel mass is casted in to i. Solvent casting method the films or ribbons using heat controlled ii. Semisolid casting method drums. The thickness of the film is about iii. Hot melt extrusion 0.015-0.05 inches. The ratio of the acid iv. Solid dispersion extrusion insoluble polymer to film forming polymer v. Rolling method should be 1:4. Generally the solvent casting method is employed for manufacture of strips. 3) Hot melt extrusion Hot melt extrusion is commonly used to 1) Solvent Casting Technique prepare granules, sustained-release tablets, and Fast dissolving films are preferably formulated and transmucosal drug-delivery using the solvent casting method, whereby the systems. In hot melt extrusion method firstly water soluble ingredients are dissolved to form the drug is mixed with carriers in solid form. a clear viscous solution and the drug along Then the extruder having heaters melts the with other excipients is dissolved in suitable . Finally the melt is shaped in to films solvent then both the are mixed and by the dies. Usually, when designing RDFs, finally casted in to the Petri plate and dried, polymers with low molecular weight or which is then cut into pieces of the desired viscosity, such as HPMC E5 or pullulan PI.20, size. The properties of the API play a critical are preferred. A combination of various grades role in the selection of a suitable solvent. of polymers may also be used to achieve Water-soluble hydrocolloids used to prepare desired physical properties. Mixing polymers RDFs include: hydroxyl propyl methyl of high and low viscosity produces a film with cellulose (HPMC), hydroxyl propyl cellulose good mechanical strength and high drug (HPC), pullulan, sodium alginate, pectin, solubility in the film. The manufacturing carboxy methyl cellulose (CMC), polyvinyl process for the wafers in the pharmaceutical alcohol (PVA). used for the industry is divided into different steps.

17

Available online at www.ijpras.com

Generally, the mass is prepared first under the Patented Technologies [13] control of temperature and steering speed. Afterwards, the wafers are coated and dried in 1) XGel: XGel is at the heart of Meldex a drying tunnel, once again the temperature, air international’s intellectual properties used in circulation and line speed are controlled. Then all its film system and its ingestible delivery follows a slitting and in the last step the wafers technologies. XGel film Technology are punched, pouched and sealed. Other ways developed by BioProgress is bringing a of revolution in the product offerings and manufacturing oral wafers are spraying process manufacturing methods now available to the or extrusion, in particular hot-melt extrusion pharmaceutical industry. X Gel film, There are certain benefits of hot melt potentially enhance the product stability. It has extrusion. also been developed for non-ingestible • Fewer operation units applications such as cosmetic, ostomy • Better content uniformity pouches, sanitary and healthcare devices. The • An anhydrous process development and manufacture of XGel films Disadvantages: uses a means called “solution casting”. • Thermal process so drug/polymer stability problem 2) Soluleaves: In this technology, the film is • Flow properties of the polymer are produced in order to release the active essential to processing ingredients on coming in contact with saliva. • Limited number of available This is applied to flavour-release products such polymers as mouth fresheners, confectionery and Comparison of solvent-casting and HME for vitamin products. SOLULEAVES technology the manufacturing of ODFs is described in the can be used to deliver active ingredients to oral Table 3. cavity efficiently and in a pleasant and easily portable form. The delivery system can be 5) Solid dispersion extrusion used for the cough/cold, gastrointestinal and The term solid dispersion refers to the pain therapeutic areas as well as nutritional dispersion of one or more APIs in an inert products. SOLULEAVES films can also be carrier in a solid state in the presence of designed to adhere to mucous membranes and amorphous hydrophilic polymers using to release the active ingredients slowly over 15 methods such as HME. In this method, minutes. immiscible components are extruded with drug and then solid dispersions are prepared. Finally 3) Wafertab: WAFERTAB is a the solid dispersions are shaped in to films by system that incorporates pharmaceutical means of dies. actives into ingestible films. It is a patented delivery system that uses a unique process to 6) Rolling Method prepare drug-loaded thin films which can be In rolling method a solution or suspension used in topical or oral application. Active containing drug is rolled on a carrier. The ingredients are incorporated into the film after solvent is mainly water or a mixture of water casting. WAFERTAB system lends itself to and alcohol. The film is dried on the rollers many possibilities for innovative , and cutted into desired shapes and sizes. Three enabling multiple films with different actives roll coating unit Diagram is shown in fig 2. to be bonded together.

Objective of Formulation of Fdfs 4) Foamburst: FOAMBURST is a patent The aim of the present research work is granted in September 2004 which is for development and characterization of mouth capsules made of foamed film. is blown dissolving oral films of a suitable drug into the film during production, resulting in a candidate so as to achieve following film with a honeycombed structure. The voids objectives: in the film may be gas-filled, empty or filled i. To improve patient compliance. with other materials to produce specific taste- ii. To provide a rapid . burst characteristics or to deliver active drugs. iii. To reduce the extent of hepatic first pass The light honeycombed structure results in metabolism. capsules that dissolve rapidly, causing a melt- iv. To reduce the dose administered and thus in-the mouth sensation. FOAMBURST has the side effects associated with it. attracted from and confectionary manufactures v. To enhance the oral bioavailability of as a mean of carrying and releasing flavours. molecules. 5) Micap: Micap signed an option agreement in 2004 to combine its expertise in micro

18

Available online at www.ijpras.com encapsulation technology with the Bio Progress water-soluble films. The Dryness test/tack test developments aimed at providing new delivery Tack is the tenacity with which the strip mechanisms for the $1.4bn global market for adheres to an accessory (a piece of paper) that cessation products (SCPs). has been pressed into contact with the strip.

Pharmacopoeial Status of Oral Films Tensile Strength Monographs of common dosage forms are Tensile strength is the maximum stress applied provided by the pharmacopoeias (e.g. Ph. Eur., to a point at which the strip specimen breaks. It USP). Even though dosage forms for is calculated by the applied load at rupture application in the oral cavity such as divided by the cross-sectional area of the strip Medicated chewing gums, Oromucosal as given in the equation below: preparations, Orodispersible tablets or oral Lyophilisates are included, monographs and Tensile strength = Load at failure × 100 specifications for oral films of diverse Strip thickness × Strip width dissolution kinetics has not yet been established. There are inadequate Percent Elongation pharmaceutical technical procedures for When stress is applied, a strip sample stretches analysis in development and quality control of and this is referred to as strain. Strain is oral films as well. For instance, disintegration basically the deformation of strip divided by and dissolution testing procedures may be original dimension of the sample. Generally provided, but the recommended conditions elongation of strip increases as the plasticizer such as volumes of media do not reflect the content increases. natural conditions in the oral cavity. % Elongation =Increase in length of strip×100 Evaluation of Fast Dissolving Films 1) Organoleptic evaluation Initial length of strip 2) Mechanical properties a) Thickness Tear Resistance b) Dry test/tack test Tear resistance of plastic film or sheeting is a c) Tensile Strength complex function of its ultimate resistance to d) Percent Elongation rupture. Basically very low rate of loading 51 e) Tear Resistance mm (2 in)/min is employed to measure the f) Young’s modulus force to initiate tearing. The maximum stress g) Folding endurance or force (that is generally found near the onset 3) Swelling properties of tearing) required to tear the specimen is 4) Transperency recorded as the tear resistance value in 5) Contact angle Newtons (or pounds-force). 6) Assay/Content uniformity 7) Disintegration time Young's Modulus 8) In-vitro Dissolution test Young's modulus or elastic modulus is the measure of stiffness of strip. It is represented 1) Organoleptic evaluation: For evaluation of as the ratio of applied stress over strain in the the product, special controlled human taste region of elastic deformation as follows: panels are used. Invitro methods of utilizing taste , are being used for this purpose. Young’s modulus= Slope × 100 These invitro taste assessment apparatus and Strip thickness ×cross-head speed methodologies are well suited for high ‐throughout taste screening of oral films. Folding Endurance Folding endurance is determined by repeated 2) Mechanical properties: folding of the strip at the same place till the strip breaks. The number of times the film is Thickness folded without breaking is computed as the The thickness of strip can be measured by folding endurance value. micrometer screw gauge at different strategic locations. This is essential to ascertain 3) Swelling property: Film swelling study is uniformity in the thickness of the film as this is conducted using simulated saliva solution. directly related to the accuracy of dose in the Each film sample is weighed and placed in a strip. preweighed stainless steel wire mesh. The mesh containing film sample is submerged into

19

Available online at www.ijpras.com

15ml medium in a plastic container. Increase this study. Typical disintegration time for in the weight of the film is determined at preset strips is 5–30 s. time interval until a constant weight is observed. The degree of swelling is calculated 8) In-vitro Dissolution Test: Dissolution using formula- testing can be performed using the standard α = (wt – wo)/wo basket or paddle apparatus described in any of wt is weight of film at time the pharmacopoeia. The dissolution medium t, and wo is weight of film at time zero. will essentially be selected as per the sink conditions and highest dose of the API. Many 4) Transparency: The transparency of the times dissolution test can be difficult due to films can be determined using a simple UV tendency of the strips to float on the spectrophotometer. Cut the film samples into dissolution medium where paddle system is rectangles and placed on the internal side of used. the spectrophotometer cell. Determine the transmittance of films at 600 nm. The Storage and Packaging of Films transparency of the films can be calculated as A variety of storage and packaging options are follows: available for fast dissolving films. The Transparency = (logT600)/b = - €c packaging stage provides product flexibility to Where T600 is the transmittance at 600 nm, b the drug manufactures. Single packaging is is the film thickness (mm) and c is mandatory for films, which are pharmaceutical concentration products; an aluminum pouch is the most commonly used packaging format. APR- 5) Contact Angle: Contact angle Labtec has developed the Rapid card, a measurements are performed at the room proprietary and patented packaging system, temperature with a goniometry. A drop of which is specially designed for the Rapid double distilled water was placed on the films. The rapid card has same size as a credit surface of the dry film. Images of the water card and holds three raid films on each side. droplet were recorded by means of digital Every dose can be taken out individually. camera, digital images are analyzed by the image 1.28v software for angle determination. Conclusion Fast Dissolving Films have several advantages 6) Assay/ Content uniformity: This is over the conventional dosage forms. They are determined by any standard assay method considered as a most important drug delivery described for the particular API in any of the system today because of their rapid standard pharmacopoeia. Content uniformity is disintegration, improved dissolution. They determined by estimating the API content in combine the greater stability of a solid dosage individual strip. Limit of content uniformity is form and good applicability of the and 85–115 percent. thus bridge the gap between the two ideas, incorporating positive elements from both 7) Disintegration Time: The disintegration solid and liquid dosage forms into an elegant, time limit of 30 s or less for orally stable and effective delivery vehicle. So they disintegrating tablets described in CDER are of great importance during the emergency guidance can be applied to fast dissolving oral cases such as allergic reactions and asthamatic strips [44]. Although, no official guidance is attacks whenever immediate onset of action is available for oral fast disintegrating desired. So this technology is growing in fast films/strips, this may be used as a qualitative pace challenging most of the pharmaceutical guideline for quality control test or at companies to develop oral films for a wide development stage. Pharmacopoeial range of active pharmaceutical ingredients disintegrating test apparatus may be used for .

20

Available online at www.ijpras.com

Table 1: Types of Oral Films and their Properties

Property/Sub FlashRelease Water Mucoadhesive Mucoadhesive Type Melt-Away Wafer Sustained Release Wafer Area (cm 2) 2-8 2-7 2-4 Thickness (µm) 20-70 50-500 50-250 Structure Film: single layer Single or multilayer Multi layer system System Excipients Soluble, highly Soluble, hydrophilic Low/Non-soluble hydrophilic polymers Polymers Polymers Drug phase Solid solution or Suspension and/or solid suspended Solution drug Application (upper palate) Gingival or buccal Gingival, (other region Region in the oral cavity Dissolution Maximum 60 Disintegration in a few Maximum 8-10 hours seconds minutes, forming gel

Table 2: A typical composition contains the following ingredients:

AGENTS CONCENTRATION DRUG 1-25%

WATER SOLUBLE POLYMER 40-50% PLASTICIZERS 0-20% FILLERS,COLOURS,FLAVOURS ETC. 0-40%

Table 3: Compares solvent-casting and HME for the manufacturing of FDFs.

PROCESS PARAMETERS SOLVENT CASTING HOT MELT EXTRUSION API selected Thermoliable, thermostable Thermostable Solvent required Yes No Process Hydrous Anhydrous Equipment required Rollers, coaters Hot-melt extruder Scale-up May create problems May not be difficult Chance of air entrapment High chance Low chance

Table 4: List of marketed products of films

Product Category Ingredients Applications

Appetite suppressant fucusvesiculosus and guarana These are top selling extract, garciniacambogia natural ingredients associated with weight loss. Cambogia helps to reduce the food intake by suppressing appetite

21

Available online at www.ijpras.com

Breath freshener strip, Contain mint flavor and It is used as mouth (Antibacterial strip) antibacterial agent, freshener and to stop bad breath

Donezepil Rapid film® Donepezil Hydrochloride 5 mg Treatment of mild to and 10 mg. moderately severe dementia of the Alzheimer's type

Suppress™ Cough Artificial flavors, ascorbic acid, Temporarily suppresses strips with menthol aspartame, asulfame potassium, coughs due to minor , diglycerides, fatty throat and bronchial acid ester etc. irritation.

Saliva promoting strips Fruit acid extracts, range of It is used in the dry flavors mouth as a side effect of the other medications Energy boosters Caffeine, green tea extract and The product maintains the guarana energy levels.

Smoking cessation To reduce the smoking habit Vitamins and food Various vitamins, minerals and It is useful for the people supplements supplements who do not like to pop up the tablets or soluble supplements Labtec GmbH Ondansetron 4 mg and 8 mg. It is used in the OndansetronRapidfilm® prevention of and radiation- induced nausea and vomiting and prevention of postoperative nausea and vomiting InnozenInc Benzocaine 3 mg, BHT, corn Occasional minor Chloraseptic® starch, erythritol, FD&C Red irritation, pain, sore Relief Strips™ 40, hydroxypropyl throat and sore mouth methylcellulose, malic acid, menthol, monoammonium glycyrrhizinate, cherry flavors, polyethylene oxide, sucralose Chloraseptic® Kids Benzocaine 2 mg and menthol, Occasional minor Sore Throat Relief strips grape flavor, BHT, corn starch, irritation, pain, sore erythritol, FD&C Blue 1, FD&C throat and sore mouth Red 40, hydroxypropyl methylcellulose, malic acid, menthol, monoammoniumglycyrrhizinate, polyethylene oxide, sucralose

22

Available online at www.ijpras.com

Fig 1: Flow chart of solvent casting method for the preparation of fast dissolving films

Fig 2: Three roll coating unit

Cite this article”

K. Mandeep, A.Rana, S. Nimrata “Fast Dissolving Films: An Innovative Drug Delivery System” Int. J. of Pharm. Res. & All. Sci.2013; Volume 2, Issue 1, 14-24

23

Available online at www.ijpras.com

References

[1] Dixit, RP, Puthli, SP., Oral strip [15] Mishra, R, Amin, A., Quick API delivery, technology: overview and future potential, J Pharm Technol Europe, 1-5. Control Release 2009, 139, 94-107 [16] Sau-hung, S, Robert, S, Lori D., “Fast [2] Patel, R, Prajapati, S, Raval, A., Fast dissolving orally consumable films”, U.S. dissolving films (FDFs) as a newer venture in Patent, July 22, 2003, 6, 298-596. fast dissolving dosage forms, Int J Drug Dev& [17] Israel, K, Leo, M. “Salivary stimulant”, Res 2010, 2(2), 232-236. U.S. Patent 4820506, April 11, 1989. [3] Rathi, V, Senthil, V, Kammili, L, Hans, R., [18] Kennedy, SW, Triethyl citrate, in, Rowe, a brief review on oral film technology, Int J RC, Sheskey, PJ, Owen, SC (Eds.)., Handbook Res Ayurvedic & Pharmacy 2011, 2(4), 1138- of pharmaceutical excipients. Pharmaceutical 1147. press, London, 2006, 796–97. [4] Jeong, S.H., Y. Takaishi, Y., Fu and K. Park, [19] Brown, D., Orally disintegrating tablets – 2008, Material properties for making fast taste over speed.,Drug Del Technol, 2003, dissolving tablets by a compression method, 3(6). Journal of Materials , 18, 3527-3535. [20] Kennedy, SW, Dibutylsebacate, in:Rowe [5] Banker, G.S, Film coating theory and RC, Sheskey, PJ, Owen, SC(Eds.)., Handbook practice, J. Pharm. Sci,. 1966 ; 55: 81 ‐ 89. of pharmaceutical excipients, Pharmaceutical [6] Aggarwal, J, Singh, Gurpreet, Saini, press: London, 2006, 236–37. Seema, Rana, A.C., Int Res J Pharmacy 2011, [21] International Conference on 2(12), 69-74. Harmonization, ICH topic Q3C(R3) [7] Bhyan B, Jangra, S, Kaur M, Singh H., Impurities, residual solvents. Note for Orally fast dissolving films: innovations in guidance on Impurities, residual solvents. formulations and technolog, Int J Pharm sci (CPMP/ICH/283/95), Rev &Res 2011, 9(2), 50-57. (www.emea.europa.eu/pdfs/human/ich/028395 [8] Arya, A, Chandra, A, Sharma, V, Pathak, en.pdf ). K., Fast dissolving films: an innovative drug [22] Felton, L, Donnell, PO’, McGinity, J., delivery system and dosage form, Int J Mechanical properties of polymeric films ChemTech 2010, 576-83. prepared from aqueous dispersions, in: [9] Frey, P., Film strips and pharmaceuticals, Aqueous polymeric coatings for pharma. mfg. & package, Sourcer, winter, pharmaceutical dosage forms, 3rd edition, 2006, 92-93. McGinity, J, Felton, L(Eds)., Drug Pharm Sci [10] Gavaskar, B, Kumar, SV, Sharan, G, Rao, vol.176, 108. Y.M, .overview on fast dissolving films, Int J [23] Fulzele, SV, Sattuwar, SV, Dorle, AK., Pharmacy &Pharm Sci, 2010, 2(3), 29-33. Polymerized rosin: novel film forming [11] Zhang, H, Zhang, J, Streisand, JB., Oral polymer for drug delivery, Int J Pharm 2002, mucosal drug delivery: clinical 249, 175–84. and therapeutic applications, [24] American standard of testing and ClinPharmacokinet, 2002, 41(9), 661-80 . materials, ASTM D1004 – 08 Standard test [12] Choudhary, D., Patel, V., Patel, H., method for tear resistance (Graves Tear) of Kundawala. A., Film former properties of film plastic film and sheeting. former used in the formulation of Rapid [25] Shinde, AJ, Garala, KC, More, HN., dissolving films, Int J ChemTech Res, 2011, Development and characterization of 3(2), 531-533. transdermal therapeutics system of tramadol [13] Vondrak, B, Barnhart, Scott., Dissolvable hydrochloride, Asian J Pharm 2008, 2(4), films: Dissolvable films for flex product 265–69. format in drug delivery, Pharm technol, 2008, [26] Wale, A, Weller, PJ., Handbook of 1-5. pharmaceutical excipients, 1994, [14] Siddiqui, Nehal, M.D., Garg, G., Sharma, 24,27,352,448. http://www.watson- K.., A short review on: Noval Approach in inc.com/film_edible.php Oral Fast Dissolving Drug Delivery system and their Patents, 2011, 5(6), 291-303.

24