INTRODUCTION:

Fast dissolving dosage forms (FDDS)

Oral route of drug administration has been one of the most convenient and accepted route of drug delivery and amongst it the intraoral route is the most preferred due to its convenience and rapid onset of action.

Intraoral dosage forms have evolved as an alternative to conventional tablets, capsules and liquid preparations of the intraoral dosage forms, fast dissolving dosage forms have gained much attention due to improved patient compliance and ease of administration[1].

Fast dissolving drug delivery system (FDDS) is gaining popularity in pharmaceutical companies as theyare new drug delivery technique in order to provide the patient with medicine without obstacles in swallowing[2]

FDDS include tablets, films. Fast dissolving tablets are designed in such a way that they disintegrate and then swallowed without the need of water as compared to other conventional dosage form[3] Films are the small polymeric strips which when placed on the mucosal surface rapidly dissolve within a fraction of seconds in order to release the active ingredients without the consumption of water[4,5]

FDDDS are useful in patients such as paediatrics, geriatrics, bedridden, emetic patients, diarrhoea, sudden episodes of allergic attacks, or coughing.

Ideal characteristics of fast dissolving drug delivery system [5,6]:

· Require no water for administration

· Cost effective production methods

· Leave minimal or no residue in mouth

· Dissolve within a fraction of seconds

· Have a pleasant mouth feel

Advantages of FDDS [6]:

· Ease of administration

· Water consumption is not required

· Rapid dissolution and absorption of drug

· Bioavailability is increased

Fast dissolving tablets[7]:

Orally disintegrating dosage forms has to be placed in mouth and then get dispersed in saliva without the need of water. Orally disintegrating tablets are also called as oral disperse, mouth dissolving, rapidly disintegrating, fast melt, and quick dissolve system

Approaches for preparation of fast disintegrating tablets:[8]:

The performance of ODT depends on the technology used in their manufacture. The orally disintegrating property of the tablet is attributable to a quick ingress of water into the tablet matrix, which creates porous structure and results in rapid disintegration

Following technologies have been used by various researchers to prepare FDTS

· Freeze-Drying or Lyophilization

· Tablet Molding

· Spray Drying

· Sublimation

· Direct Compression

· Cotton Candy Process

· Mass-Extrusion

· Nanonization

Freeze-Drying or Lyophilization:

Freeze drying is the process in which solvent is sublimed from a frozen drug solution or suspension containing structure forming excipients. This technique creates an amorphous highly porous structure that allows rapid dissolution or disintegration.. A typical procedure involved in the manufacturing of ODT using this technique is mentioned here. The active drug is dissolved or dispersed in an aqueous solution of a carrier/polymer. The mixture is dosed by weight and poured in the pockets of the preformed blister packs. The trays holding the blister packs are passed through liquid nitrogen freezing tunnel to freeze the drug solution or dispersion. Then the frozen blister packs are placed in refrigerated cabinets to continue the freeze-drying. After freeze-drying the aluminium foil backing is applied on a blister-sealing machine. Finally the blisters are packaged and shipped.

The Zydis® technology is the most well known example of the freeze drying. In the Zydis® formulation, the drug is physically trapped in a matrix compound of two components, a saccharide (e.g; Mannitol) and a polymer. Other standard excipients can be incorporated to adjust pH or add flavor, color and modify texture. When working with coated drug particles, excipients such as xanthan gum can be added to the liquid admixture because it improves the ability of the liquid composition to suspend relatively large particles during the manufacturing process. Products manufactured using Zydis® technology and marketed in USA are presented in Table 1.

Quicksolv® (Janssen Pharmaceutical) and Lyoc® (Farmalyoc Laboratories) are also produced by freeze drying method.

In the Quicksolv® formulation, the matrix compositions are dissolved in the first solvent (usually water), and then the solution is frozen. Components of the matrix generally include a water soluble hydratable gel or foam forming material (such as gelatin), a rigidifying agent (such as mannitol or other saccharide), and one or more amino acids. At the temperature at which the first solvent will remain in the solid form, the frozen solution contact the second solvent, which is substantially miscible with the first solvent. For example, ethanol, methanol or acetone is used as the second solvent with water as the first solvent. The matrix composition should be immiscible to the second solvent. Thus, the first solvent is substantially removed after a few hours of contacting the second solvent to result in a usable matrix. The final product disintegrates almost instantly. This method is claimed to prevent or reduce incidence of cracking during the final preparation, having uniform porosity and adequate strength for handling.

Products manufactured using Quicksolv™ technology and marketed in USA are presented in Table 2.

In the Lyoc® formulation, the porous solid is obtained by freeze drying an aqueous solution, suspension, or oil in water emulsion of the active principle and ingredients, filling into preformed blister, and freeze drying the product. In order to prevent inhomogeneity by sedimentation during freeze drying this formulation requires a large proportion of undissolved inert filler to increase the viscosity of the suspension. The high portion of filler reduces the porosity of the tablet, and as a result, the disintegration is slower. Products manufactured using Lyoc® technology and marketed in USA are presented in Table 3

Table 3

Brand	Active Ingredient	Indication	Innovator/ Partner
Spasfon®	Phloroglucinol	Spasmodic Pain	Cephalon
Sermion®	Nicergoline	Cerebral metabolic Vascular disorder	Cephalon
Vogalene®	metopimazine	Emesis	Cephalon
Proxalyoc®	Piroxicam	Pain Inflammation	Cephalon
Paralyoc®	Acetaminophen	Pain Fever	Cephalon
Seglor®	dihydroergotamine	Headache, migraine	Cephalon
Loperamide Lyoc®	Loperamide	Diarrhoea	Cephalon

NanoCystal™ technology (Elan Drug Delivery Inc) uses nanoparticles into a highly porous, microfine tablet matrix. The nanoparticles are less than two microns and are produced by a proprietary milling technique. Direct compression and standard tabletting are then used to produce the finished orally disintegrating tablets. In addition, an alternative approach to manufacturing Nanocrystal ODT dosage forms has been developed to facilitate the preparation of small scale clinical supplies. Nanocrystal colloidal dispersions of drug substance are combined with water soluble GRAS ingredients, filled into blisters, and lyophilized. The resultant wafers are remarkably robust, yet dissolve in small quantities of water in seconds. This approach is ideal when working with highly potent or hazardous materials because it avoids manufacturing operations (for example: granulation, blending and tableting) that generate large quantities of aerosolized powder. The freeze drying approach also enables small quantities of drug to be converted into ODT dosage forms because manufacturing losses are negligible.

The major disadvantages of lyophillization technique are that it is expensive and time consuming; fragility makes conventional packaging unsuitable for these products and poor stability under stressed conditions.

Tablet Molding:

The preparation of ODT using molding technology employs water-soluble ingredients so that the tablet dissolves completely and rapidly. The active ingredients in most cases are absorbed through the mucosal lining of the mouth..

Molding process is of two types i.e. solvent method and heat method. Solvent method involves moistening the powder blend with a hydroalcoholic solvent followed by compression at low pressures in molded plates to form a wetted mass (compression molding). The solvent is then removed by air drying. The tablets manufactured in this manner are less compact than compressed tablets and possess a porous structure that hastens dissolution.

The heat molding process involves preparation of a suspension that contains a drug, agar and sugar (e.g. mannitol or lactose) and pouring the suspension in the blister packaging wells, solidifying the agar at the room temperature to form a jelly and drying at 30˚ under vacuum. The mechanical strength of molded tablets is a matter of great concern. Binding agents, which increase the mechanical strength of the tablets, need to be incorporated. Compared to the lyophillization technique, tablets produced by the molding technique are easier to scale up for industrial manufacture[9]Masaki uses an agar solution as a binding agent and a blister packaging as well as a mold to prepare an intrabuccally fast disintegrating tablet[10].

Spray Drying:

Spray drying is used in pharmaceutical industries to produce highly porous powders. The processing solvent is evaporated rapidly by spray drying, which renders the product highly porous and thus can be used in manufacturing ODT. In this technique, gelatin can be used as a supporting agent and as a matrix, mannitol as a bulking agent and sodium starch glycolate or cross carmellose or crospovidone are used as superdisintegrants. Tablets manufactured from the spray-dried powder have been reported to disintegrate in less than 20 seconds in aqueous medium[11].

Allen and Wang[12-15]have reported this technique for preparing fast dissolving tablets. The formulation contained bulking agent like mannitol and lactose, a superdisintegrant like sodium starch glycolate and crosscarmellose sodium and acidic ingredient (citric acid) and/or alkaline ingredients (e.g. sodium bicarbonate). This spray-dried powder, which compressed into tablets showed rapid disintegration and enhanced dissolution.

Sublimation:

The key to rapid disintegration of ODT is preparation of a porous structure in the tablet matrix[16-21]. To generate such a porous matrix, volatile ingredients are incorporated in the formulation that is later subjected to a process of sublimation. Highly volatile ingredients like ammonium bicarbonate, ammonium carbonate, benzoic acid, camphor, naphthalene, urea, urethane, hexamethylene tetramine and phthalic anhydride may be compressed along with other excipients into a tablet. This volatile material is then removed by sublimation leaving behind a highly porous matrix. Tablets manufactured by this technique have reported to usually disintegrate in 10-20 sec.

Vacuum drying technique has been very often used by researchers to sublime the volatile ingredients and thus maximize the porous structure in the tablet matrix[16-21]. It is likely that a porous hydrophilic matrix will easily pick up the disintegrating medium and disintegrate rapidly.

Direct Compression:

Direct compression represents the simplest and most cost effective tablet manufacturing technique. This technique can now be applied to preparation of ODT because of the availability of improved excipients especially superdisintegrants and sugar based excipients.

(a) Superdisintegrants:

In many orally disintegrating tablet technologies based on direct compression, the addition of superdisintegrants principally affects the rate of disintegration and hence the dissolution. The presence of other formulation ingredients such as water-soluble excipients and effervescent agents further hastens the process of disintegration.

Ethylpharm (France) has introduced a Flash- dose technology, which contains coated crystals and micro granules along with the disintegrants. In this technology, two types of granules are used; a disintegrating agent (e.g. modified cellulose- cross carmellose) which has a high swelling force, and a swelling agent (e.g. starch) which has a low swelling force.

Orasolv®, Durasolve® and Oravescent® technology:

Orasolv® technology developed by Cima Lab produces tablets by low compression force. It uses an effervescent disintegration agents that releases gas upon contact with water or saliva. The carbon dioxide evolved provide some fizzing which provide good sensation in the mouth. As low compression force produced soft and friable tablets, so special packaging system PakSolv ®was developed by Cima to handle the tablets during shipment and consumer usage

Durasolv ®technology:

Second-generation technology developed by Cima Labs produces robust and durable oral dosage form with an orally disintegrating technology. DuraSolv product may be packaged in conventional packaging, such as foil pouches or bottles, mouth dissolving tablets.

OraVescent®,

(b) Sugar Based Excipients

This is another approach to manufacture ODT by direct compression. The use of sugar based excipients especially bulking agents like dextrose, fructose, isomalt, lactilol, maltilol, maltose, mannitol, sorbitol, starch hydrolysate, polydextrose and xylitol, which display high aqueous solubility and sweetness, and hence impart taste masking property and a pleasing mouthfeel.

WOWTAB® Technology:

Yamanouchi’s WOWTAB® (WithOut Water) technology employs a combination of saccharides to produce fast dissolving tablets using conventional granulation, blending, drying and direct compression of tablets.

Taste masking is provided by the combination of one or more sugar-like excipients or microencapsulation of the active ingredients. These tablets exhibit significant hardness allowing packaging in conventional bottles or blisters.

Products manufactured using WOWTAB® technology and marketed in USA are presented in Table 4

Table 4

Product	Marketer
Benadryl® Allergy and Sinus Fastmelt® (OTC)	Pfizer Consumer
Children’s Benadryl® Allergy and Cold Fastmelt® (OTC)	Pfizer Consumer
Gaster-OD® (famotidine)	Yamanouchi
Nasea® (ramosetron)	Yamanouchi
Terbomin D (atenolol)	Yamanouchi
Helparol (haloperidol)	Yamanouchi
Yamaolol (procaterol)	Yamanouchi
Aramol (alacepril)	Yamanouchi
Noctan D (ambroxol HCl)	Yamanouchi

Cotton Candy Process:

The cotton candy process is also known as the “candy floss” process and forms the basis of the technologies such as Flash Dose (Fuisz Technology).[22-24].

Flash dose rapidly dissolving tablets are based on Shearform technology developed by Biovail. Flash Dose dosage forms are produced using a special process whereby a unique blend ofsugars or similar ingredients are placed in a fast-spinning centrifuge and subjected to flash heat. A specially designed machine head produces long, cotton candy-like fibers (referred to as "floss"). Shear form matrices are of two types. Single floss or Unifloss, consisting of a carrier, and two or more sugar alcohols, of which one is xylitol.

Dual floss consists of a first shear form carrier material (termed “base floss”, contains a carrier and at least one sugar alcohol generally sorbitol), and a second shear form binder matrix (“binder floss”, contains a carrier and xylitol).The candyfloss can then be milled and blended with active ingredients and other excipients and subsequently compressed into ODT. However the high processing temperature limits the use of this technology to thermostable compounds FlashDose tablets can accommodate up to 600 mg of active ingredient, and typically dissolve in the oral cavity within 5-15 seconds. Products developed by Biovail (now Valeant) using Flash dose technology are presented in Table 5.

Table 5.

Product	Indication	Indication	Innovator/ Partner
Nurofen® Meltlets Ibuprofen	pain, inflammation	FlashDose®	Biovail (Now Valeant)
Fluoxetine	Depression	FlashDose®	Biovail (Now Valeant)
Paroxetin	Depression	FlashDose®	Biovail (Now Valeant)
Ralivia FlashDose (tramadol)	Pain Management	FlashDose®	Biovail (Now Valeant)
Zolpidem	Insomnia	FlashDose®	Biovail (Now Valeant)

Mass-Extrusion:

This technology involves softening the active blend using the solvent mixture of water-soluble polyethylene glycol and methanol and subsequent expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets[25]. Other Technologies that can be used for manufacturing of new Oral disintegrating dosage forms (tablets/Films) are as follows:

Supercritical Fluid technology:

Ferro Corporation has developed a portfolio of novel supercritical fluid (SCF)[26]processes. The preferred process medium is carbon dioxide. It is supplied to the reactor in a supercritical state or is heated and pressurized in the reactor to attain a supercritical state.

Supercritical fluid processes can be used to obtain stable aqueous suspensions of water-insoluble drugs, low bulk density porous particles for inhalation and composite particles comprised of porous particles of polymer that are infused with the biologically active ingredient. The particles have sizes ranging from 10 nm to several microns. The finely divided particles produced using Ferro’s supercritical fluid processes can be incorporated into ingestable formulations, such as tablets or capsules. Ferro's uses the following:

SCF extraction of emulsions (SFEE):

Pure drug or pure drug plus a polymer is dissolved in an organic solvent and dispersed in water using surfactants to form an emulsion.

The organic solvent is then extracted using super critical fluid (SCF). This process can be used with small actives, lipids, polymers, and some biologics. The advantages of the SFEE process include a processing time of only a few minutes, low residual solvent in the final product, low cost, and narrow particle size distribution.

Spray-freeze drying with CO2:

Active ingredient is dissolved in water to form a solution that is then saturated with CO2. The solution is then sprayed using a nozzle to form fine frozen droplets. Porous or hollow particles are then formed by removing the water by freeze drying. This process can be used to formulate proteins. Advantages of the spray-freeze drying method are that it is suitable for sugar stabilization and is more efficient than other lyophilization techniques

Expansion of SCF saturated solutions:

Polymer plus drug mixture is saturated with SCF creating a liquefied solution, which is then sprayed to form particles via cooling and SCF diffusion from the melt. This process allows for coating at mild temperatures.

SCF anti solvent with enhanced mixing:

Material is dissolved in an organic solvent to form a solution that is injected intosupercriticalCO2. This results in precipitation of the material as particles. This process is can be used with poorly water soluble drugs and small actives.

Evaluation of tablets: 27-29

General Appearance:

The general appearances of a tablet include size, shape, colour, taste, odour, surface texture. Size, Shape, Thickness and diameter:

The size and shape of the tablet can be dimensionally described, monitored and controlled. Thickness of tablets is an important characteristic for appearance and also in counting by using filling equipment. Some filling equipment utilizes the uniform thickness of the tablets as accounting mechanism. Ten tablets were taken and their thickness measured by vernier caliper.

Uniformity of weight:

In Indian Pharmacopoeia procedure for uniformity of weight was followed, ten or twenty tablets were taken and their weight was determined individually and collectively on a digital weighing balance. The average weight of one tablet was determined from the collective weight. The weight variation test would be a satisfactory method of determining the drug content uniformity.

Hardness of Tablets:

Hardness of tablet is defined as the force applied across the diameter of the tablet in the order to break the tablet. The resistance of the tablet to chipping, abrasion or breakage under condition of storage transformation and handling before usage depends on its hardness. Hardness of the tablet of each formulation was determined using Monsato Hardness tester.

Friability of tablets:

Fribrater consist of a plastic-chamber that revolves at 25 rpm, dropping those tablets at a distance of 6 inches with each revolution. The tablets were rotated in the fribrater for at least 4 minutes. At the end of test tablets were dusied and reweighed, the loss in the weight of tablet is the measure of friability and is expressed in percentage

Wetting time:

In this method measure tablet wetting time. Simple tissue paper (12 cm X 10.75cm) folded twice was placed in a small petridish (ID = 6.5 cm) containing 6 ml of Sorenson’s buffer pH 6.8. A tablet was put on the paper, and the time for complete wetting was measured. Three trials for each batch and the standard deviation were also determined.

Solution volume:

In this test take one tablet in a Petri –dish with suitable solvent. One or two drop of solvent used until the tablet shows soluble property that is called soluble or solution volume. V = Final volume of blend in cm 3

In Vitro Disintegration test: [30-31]

In Vitro disintegration time was measured by dropping a tablet in a beaker containing 50 ml of Sorenson’s buffer pH 6.8. Three tablets from each formulation were randomly selected and In Vitro dispersion time was performed.

In Vivo Disintegration test: [31]

The test was carried out on 2 or 3 tablets using in the mouth and the time in second taken for complete disintegration of the tablet was measured in few seconds.

In Vitro Dissolution Test [30-32]

In-vitro dissolution study was performed by using USP Type II Apparatus (Paddle type) [Electro lab (ETC-11L) Tablet Dissolution Tester] at 50 rpm. Phosphate buffer pH 6.8, 900 ml was used as dissolution medium which maintained at 37±0.5°C. Aliquot of dissolution medium (10 ml) was withdrawn at specific time intervals (2 min) and was filtered. The amount of drug dissolved was determined by UV spectrophotometer (Shimadzu, Japan) by measuring the absorbance of the sample at 248.0 nm. Three trials for each batch were performed and average percentage drug release with standard deviation was calculated and recorded.

Stability Study (Temperature Dependent) [30-32]

The fast dissolving tablets are packed in suitable packaging and stored under the following conditions for a period as prescribed by ICH guidelines for accelerated studies.

(i) 40 ± 1 °C

(ii) 50 ± 1°c

(iii) 37 ±1 ° C and RH 75% ± 5%

The tablets were withdrawn after a period of 15 days and analyzed for physical characterization (Visual defects, Hardness, Friability, Disintegrations, and Dissolution etc.) and drug content. The data obtained is fitted into first order equations to determine the kinetics of degradation. Accelerated stability data are plotting according Arrhenius equation to determine the shelf life at 25 ° C.

Fast dissolving films:[33]:

Oral films, also called oral wafers or oral strips. It is a new type of formulation in FDDDS that provides a very convenient means of taking medications. In this technique, a solution is prepared containing water soluble film forming polymer (pullulan, hydroxypropyl methylcellulose, carboxy methylcellulose, hydroxyl ethylcellulose, hydroxyl propylcellulose, polyvinyl pyrrolidone, polyvinyl alcohol or sodium alginate, etc.), drug and other taste masking ingredients, which was then allowed to form a film after evaporation of solvent. This film, when placed in mouth, melts or dissolves rapidly, releasing the active drug in mouth.

Classification of Oral Film:[34]:

There are three different subtypes

(1) Flash release,

(2) Mucoadhesive melt-away wafer,

(3) Mucoadhesive sustained-release wafers.

These three types of oral films are differentiated from each other in Table 6.

Manufacturing methods for producing fdf[35-36]:

There are five methods for manufacturing purpose i.e.

· Solvent casting

· Hot melt extrusion

· Semisolid casting

· Solid dispersion extrusion

· Rolling

Solvent casting method:

In this method the water-soluble ingredients are dissolved to form a clear viscous solution. The API and other agents are dissolved in smaller amounts of the solution and combined with the bulk. This mixture is then added to the aqueous viscous solution. The entrapped air is removed by vacuum. The resulting solution is cast as a film and allowed to dry, which is then cut into pieces of the desired size.

Hot Melt Extrusion:

In present method the mass is prepared first under the control of temperature and steering speed. Afterwards, the film is coated and dried in a drying tunnel, once again the temperature, air circulation and line speed are controlled. Then follows a slitting and in the last step the films are punched, pouched and sealed.

Semisolid Casting:

In this method solution of water soluble film forming polymer are mixed to solution of acid insoluble polymer to form homogenous viscous solution (e.g. cellulose acetate phthalate, cellulose acetate butyrate).After sonication it is coated on non-treated casting film. On drying the thickness of the film is about 0.381-1.27 cm. The ratio of the acid insoluble polymer to film forming polymer should be 1:4.

Solid Dispersion Extrusion:

Solid dispersions are prepared by immiscible components and drug. Finally the solid dispersions are shaped in to films by means of dies.

Rolling Method:

In this method a solution or suspension containing drug is rolled on a carrier. The solvent is mainly water and mixture of water and alcohol.The film is dried on the rollers and gives desired shape and size [37].

Evaluating parameters For fast dissolving films[38]:

Morphology study: The morphology of the films is studies using electron microscopic (SEM), at definite magnification.

Weight Variations:

Weight variation is studies by individually weighing 10 randomly selected films and calculating the average weight. The average weight should not deviate significantly from average weight.

Thickness:

The thickness of film is determined by screw gauge or micrometer at different points of the films.

Drug content:

A film of size 2 cm2 was cut and put 10 ml of volumetric flask which containing solvent. This was then shaken in a mechanical shaker for 2 hrs to get a homogeneous solution and filtered.

The drug was determined spectroscopically by appropriate dilution.

Tensile strength:

Tensile strength of films was determined using an apparatus fabricated in laboratory.

A small film strip (2 cm2) was cut and fixed to assembly. The weight required to break the film was noted and simultaneously film elongation was measured with the help of pointer mounted on the assembly.

Tensile strength =break force /ab (1+ ΔL/L)

a, b and L are width, thickness, and length of the strip, and ΔL is the elongation at break.

Percentage elongation:

Determined by noting the distance travelled by pointer before break of the film on the graph paper.

% Elongation = Increase in length/original length X 100.

Folding endurance:

Folding endurance is evaluation of films involves determining the folding capacity of the films when subjected to frequent extreme condition of folding. It was determined by repeatedly folding the film at same place until it broke. The number of times the film could be folded at the same place without breaking/cracking gave value of folding endurance

Disintegration test:

Determined manually by dipping the film in 10 ml of water in beaker with gently shaking when film was dissolved, time was noted.

In vitro drug release:

Dissolution testing can be performed using the standard basket or paddle apparatus described in any of the pharmacopoeia. The dissolution medium will essentially be selected as per the sink conditions and highest dose of the API. Many times the dissolution test can be difficult due to tendency of the strip to float onto the dissolution medium when the paddle apparatus is employed

Stability studies:

Stability study was carried out for all the batches at accelerated condition 65% relative humidity and 35 ºC (temperature) in the humidity chamber for the three months. After 3 months the films were evaluated for the drug content, disintegration time and physical appearance observation.

CONCLUSION:

The FDDDS have potential advantages over conventional oral dosage forms with their improved patient compliance; convenience, bioavailability and rapid onset of action which drawn the attention of many manufactures over a decade. The formulations obtained by some of these technologies have sufficient mechanical strength, quick disintegration/dissolution in the mouth. Many drugs can be incorporated especially unpalatable drugs. Today, fast Dissolving drug delivery systems are more widely available as over-the-counter products for the treatment of allergies, cold and flu symptoms. The target population has expanded to those who want convenient dosing anywhere, anytime, without water.

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36. Orally fast dissolving films as dominant dosage form for quick release by Dipika Parmar ,Dr. Upender Patel, Bhavin Bhimani, Aditi Tripathi, Dhiren Daslaniya , Ghanshyam Patel

Received on 12.11.2012 Modified on 23.11.2012

Research J. Pharm. and Tech. 6(1): Jan. 2013; Page 04-11

Brand Active	Active Ingredient	Indication	Innovator/Partner
Claritin® /Reditabs®	Loratadine	Allegies	Cardinal/Schering
Maxalt MLT®	Rizatriptan	Migraine	Cardinal/Merck
Zyprexa®	Olanzapine	Schizophrenia	Cardinal/Eli Lilly
Zofran ODT®	Ondansetron	Emesis	Cardinal/GSK
Imodium®	Loperamide	Diarrhea	Cardinal/JandJ
Zelapar®	Selegiline	Parkinson’s	Cardinal/Elan
Pepcidine Rapitab	Famotidine	Heartburn/Indigestion	Cardinal/Merck
Seresta Expidet®	Oxazepam	Anxiety disorder	Wyeth

Property/Sub Type	Flash release water	Mucoadhesive melt-away wafer	Mucoadhesive sustained release wafer
Area (cm2)	2-8	2-7	2-4
Thickness(µm)	20-70	50-500	50-250
Structure	Film: single layer	Single or multilayer System	Multi layer system
Excipients	Soluble, highly hydrophilic polymers	Soluble, hydrophilic Polymers	Low/Non-soluble Polymers
Drug phase	Solid solution	Solid solution or suspended drug particles	Suspension and/or solid Solution
Application	Tongue(upper palate)	Gingival or buccal Region	Gingival, (other region in the oral cavity)
Dissolution	Maximum 60 seconds	Disintegration in a few minutes, forming gel	Maximum 8-10 hours
Site of action	Systemic or local	Systemic or local	Systemic or local

formulations	Brand name	Types	Manufacturer	Country
Fast dissolving oral film	Zolmitriptan Rapidfilm®	prescription product	Labtec's production site in Hamburg, Germany	Europe
Ondansetron ODF	Setofilm®	prescription product	BioAlliance Pharma	Europe
Ondansetron ODF	Zuplenz(R)	prescription product	MonoSol Rx Marketed by Strativa Pharmaceuticals	United States
Oral films of Methylcobalamin	-	OTC	Hughes Medical Corp.	-
Loratidine	-	OTC	Hughes Medical Corp.	-