FAST DISSOLVING ORAL FILMS FOR IMMEDIATE DRUG RELEASE: …

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Poladi et al. World Journal of Pharmaceutical Research

FAST DISSOLVING ORAL FILMS FOR IMMEDIATE DRUG

RELEASE: A REVIEW

Dr. Anna Balaji, Kranthi Kumar Poladi*, Achuth Reddy Vookanti

Trinity College of Pharmaceutical Sciences, Peddapalli, Karimnagar, 505172

Andhra Pradesh, India.

ABSTRACT

Fast dissolving oral films are the most advanced form of oral solid

dosage forms due to more flexibility and comfort. It improves the

efficacy of APIs by dissolving within minute in oral cavity with saliva

without chewing and water for administration. It gives quick

absorption and instant bioavailability of drugs due to high blood flow

and permeability of oral mucosa which is 4-1000 times greater than

that of skin. Fast dissolving oral films are useful for all types of health

conditions. The FDOFs plays as an alternative over conventional

tablets or capsules. Fast dissolving film combines all the advantages of

tablets with those of liquid dosage forms. It has reduced hepatic first

pass effect, minimal side effects, dose accuracy and site specific

action. The disadvantage of OTF is that high dose of drug cannot be incorporated into strip.

FDOFs can be prepared using drug 5-20% w/w, water soluble polymer 45%w/w, plasticizers

0-20%, sweetening agents 3-6%, saliva stimulating agents 2-6%, surfactants, fillers, colours

and flavours. The manufacturing methods for oral films are solvent casting, semisolid

casting, hot melt extrusion, solid dispersion extrusion and rolling. The oral films can be

evaluated by using tack test, tensile strength, tear resistance, swelling index, contact angle

measurement, disintegration time and dissolution test. The fast dissolving oral films are most

acceptable and accurate oral dosage form which bypass the hepatic system and show more

therapeutic response. Oral films can replace the over the counter drugs (OTC).

Keywords: Fast dissolving oral films, Solvent casting, OTF, Extrusion.

INTRODUCTION

Oral route is the most preferred route for the delivery of the drugs than other routes.But oral

World Journal of Pharmaceutical ReseaRch

Volume 3, Issue 2, 3751-3775. Review Article ISSN 2277 – 7105

Article Received on 01 February 2014, Revised on 26 February 2014 Accepted on 21 March 2014

*Correspondence for

Author

Kranthi Kumar Poladi

Trinity College of

Pharmaceutical Sciences,

Peddapalli, Karimnagar,

Andhra Pradesh, India.


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drug delivery systems still needs some advancements because of their some drawbacks

related to particular patients which includes geriatric, pediatric and dysphasic patients

associated with many medical conditions as they have difficulty in swallowing or chewing

solid dosage forms. Many pediatric and geriatric patients have difficulty to take solid

preparations due to fear of choking. Even with fast dissolving tablets there is a fear of

choking due to its appearance. One study showed that about 26% of 1576 patients

experienced difficulty in swallowing tablets. The most common complaint was tablet size,

appearance and taste. The problem of swallowing tablets was more difficult to geriatric and

pediatric patients, as well as travelling patients who may not have ready access to water1-4.

So, fast-dissolving drug-delivery systems came into existence in the late 1970’s as an

alternative to tablets, capsules and syrups for pediatric and geriatric patients. These systems

consist of the solid dosage forms that disintegrate and dissolve quickly in the oral cavity

without the administration of water. Research and development in the oral drug delivery from

simple conventional tablets or capsules to modified release tablets or capsules to oral

disintegrating tablet (ODT) to wafer to the recent development of oral fast dissolving films

(OFDFs). Amongst the rapid drug releasing products, oral strip technology is gaining much

attention5,6.

Orally fast-dissolving film is new drug delivery system for the oral drug delivery and

developed on the basis of technology of the transdermal patch. The delivery system consists

of a very thin oral strip, which is simply placed on the tongue or any oral mucosal tissue, due

to saliva it instantly wet, rapidly hydrates and adheres onto the site of application. It then

rapidly disintegrates and dissolves to release the medication for oromucosal absorption.

Technology Catalysts forecasts the market for drug products in oral thin film formulations

was valued of $500 million in 2007 and could reach $2 billion in 2012. Based on upward

global growth trends of the past decade, the fast dissolving dosage market could produce

revenues of $13 billion by 20157,8.

Current technologies of Oral Fast-Dispersing Dosage Form

Out of several technologies, few have reached commercial marketed products. Several

methods are available in the preparation of oral fast-dispersing tablets, such as modified

tableting systems, floss, or Shearform™ formation by application of centrifugal force,

controlled temperature and freeze drying14,15.


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Classification Of Fast Dissolve Technology

Fast-dissolve technologies can be divided in to three broad groups:

1. Lyophilized systems,

2. Compressed tablet-based systems,

3. Thin film strips.

1. Lyophilized systems

The technology involves taking a suspension or solution of drug with other structural

excipients and through the use of a mould forms tablet-shaped units. The tablets are then

frozen and lyophilized in the mould. The resulting tablets have a very high porosity, which

allows rapid water or saliva penetration and very rapid disintegration44.

Dose-handling capability for these systems differs depending on whether the active

ingredients are soluble or insoluble drugs. The dose capability being slightly lower for some

tablet based systems. The units require a range of taste-masked materials and have more rapid

disintegration than other tablet-based systems45.

2. Compressed tablet-based systems

This system is completely based on standard tablet technology by direct compression of

excipients.Depending on the method of manufacture, the tablet technologies have different

levels of hardness and friability. These results in varying disintegration and packaging, which

can range from standard HDPE bottles to more specialist pack designs for product

protection– for example- CIMA Labs’, PackSolv46. The speed of disintegration for fast-

dissolve tablets compared with a standard tablet is achieved by using water soluble

excipients, super-disintegrant or effervescent components, to allow rapid penetration of water

into the core of the tablet. The one exception to this approach is BiovailsFuisz technology. It

uses theShearform system to produce drug-loaded candy floss, which is then used for

tableting with other excipients. These systems can accommodate relatively high doses of drug

material, including taste-masked coated particles. The potential disadvantage is that they take

longer time to disintegrate than the thin-film or lyophilized dosage forms. The loose

compression tablet approach has increasingly been used by some technology, branded

companies and generic pharmaceutical companies, for development of fast-dissolve dosage

forms47.


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3. Oral Thin Films (OTF)

Oral films, also called oral wafers, which are administered into the oral cavity. Although oral

film systems, the third class, have been in existence for a number of years, they have recently

become advanced in fast-dissolve pharmaceutical drug delivery.

Dissolvable oral thin films (OTFs) or oral strip (OS) evolved over the past few years and in

the oral care markets in the form of breathe strips and became a novel and accepted form by

consumers for delivery of vitamins and personal care products. Companies with experience in

the formulation of polymer coatings containing active pharmaceutical ingredients (APIs) for

Transdermal drug delivery capitalized this technology to OTF formats. Today, OTFs are a

accepted technology for the systemic delivery of APIs for over-the-counter (OTC)

medications and are in the early- to middevelopment stages for prescription drugs48.

This is largely the success of the consumer breath freshener products such as Listerine

PocketPacks in the US consumer market. Such systems use a variety of hydrophilic polymers

to produce a 50-200 mm film. This film can incorporate soluble, insoluble or taste-masked

drug substances. The film is manufactured as a large sheet and then cut into dosage units for

packaging in pharmaceutically acceptable formats49.

Table 1: Types of wafers and their properties

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) Site of action Systemic or local Systemic or local Systemic or local

Dissolution Maximum 60 seconds

Disintegration in a few minutes, forming gel Maximum 8-10 hours


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Classification of Oral Film

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 following table 1.

Advantages of Oral Thin Film

1. This dosage form has some advantages over other oral formulations such as-

2. Availability of large surface area that leads to the rapid disintegration and dissolution in

oral cavity.

3. The disadvantage of most ODT is that they are fragile and brittle which needs special

package for protection during storage and transportation. Since the films are flexible there

is ease of transportation, consumer handling and storage.

4. As compared to drops or syrup formulations, precision in the administered dose is

ensured for each of the strips.

5. Pharmaceutical companies and consumers preferred OTFs as accepted alternative to

traditional medicine forms such as liquids, tablets, and capsules. OTFs offer fast, accurate

dosing in a safe, efficacious format that is convenient and portable, without the need of

water.

6. The oral or buccal mucosa being highly vascularized, drugs can be absorbed directly and

can enter the systemic circulation without undergoing first-pass metabolism. This

advantage can be exploited in preparing products with improved oral bioavailability.

7. Since the first pass effect can be avoided, there can be reduction in the dose which can

lead to reduction in side effects.

8. Patients suffering from dysphagia, repeated emesis, motion sickness, and mental

disorders prefer this dosage form as they are unable to swallow large quantity of water.

9. OTFs disintegrate on a patients tongue in a few seconds for the rapid release of one or

more APIs. The formulation of dissolvable films is facilitated through aqueous polymer

matrices with high molecular weight (MW), and provides flexibility to achieve certain

physical properties.

10. Beneficial in cases such as motion sickness, acute pain, suede episodes of allergic attack

or coughing, where an ultra rapid onset of action required60.


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11. Stability for longer duration of time, since the drug remains in solid dosage form till it is

consumed. So, it combines advantage of solid dosage form in terms of stability and liquid

dosage form in terms of bioavailability.

12. The sublingual and buccal delivery of a drug via thin film has the potential to improve the

onset of action, lower the dosing, and enhance the efficacy and safety profile of the

medicament.

13. Provide new business opportunity like product differentiation, product promotion, patent

extension50.

Disadvantage of Oral Strip

The disadvantage of Oral Strip is that high dose cannot be incorporated into the strip.

However, research has proven that the concentration level of active ingredient can be

improved up to 50% per dose weight51. Novartis Consumer Health's Gas-X® thin strip has a

loading of 62.5 mg of simethicone per strip61. There are number of technical limitations with

the use of film strips. The volume of the dosage unit is clearly proportional to the size of the

dose, which means these are best suited to lower-dose products. For example, Labtec claim

that the Rapid Film technology can incorporate dose of up to 30 mg. The other challenge with

these dosage forms is achieving Dose Uniformity61.

Special features of mouth dissolving films

Thin elegant film

Available in various size and shapes

Unobstructive

Excellent mucoadhesion

Fast disintegration

Rapid release9

The ideal characteristics of a drug to be selected

The drug should have pleasant taste.

The drug should have low dose upto 40 mg.

The drugs with smaller and moderate molecular weight are preferable.

The drug with good stability and solubility in water and in saliva.

It should be partially unionized at the pH of oral cavity.

It should have the ability to permeate oral mucosal tissue10.


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Table 2: Comparison between orally fast dissolving films and oral disintegrating

tablets11.

Orally Dissolving Films Oral Disintegrating Tablets It is a film It is a tablet Greater dissolution due to larger surface area

Lesser dissolution due to less surface area

Better durable than oral disintegrating tablets

Less durable as compared with oral films

More patient compliance Less patient compliance than films

Low dose can only be incorporated

High dose can be incorporated

No risk of chocking It has a fear of chocking STRUCTURAL FEATURES OF ORAL MUCOSA

Structure

The outermost layer of the oral mucosa is the stratified squamous epithelium. Beneath this

lies a basement membrane, which is a lamina propria followed by the sub mucosa as the

innermost layer. The epithelium layer is similar to that of stratified squamous epithelia found

in the rest of the body in that it has a mitotically active basal cell layer, advancing through a

number of differentiating intermediate layers to the superficial layers, where cells are shed

from the surface of the epithelium16. The turnover time for the buccal epithelium has been

estimated for about 5-6 days and this is representative of the oral mucosa as a whole. The

thickness of oral mucosa varies depending up on the site: such as the buccal mucosa

measures about 500-800 µm, whereas the mucosal thickness of the hard and soft palates, the

floor of the mouth, the ventral tongue and the gingivae measures about 100-200 µm. The

epithelium composition also varies depending upon the site in the oral cavity. The mucosa of

the gingivae and hard palate are keratinized which are similar to the epidermis which contains

ceramides and acylceramides (that are neutral lipids) which have been found to be associated

with the barrier function. The mucosal layer of the soft palate, the sublingual and the buccal

regions, however, are not keratinized and relatively impermeable to water and have only

small amounts of ceramides17-19. They also contain small amounts of neutral but polar lipids,

mainly cholesterol sulphate and glucosylceramides. The non-keratinized epithelial layer have

been found to be more permeable to water than keratinized epithelia17-20.


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Fig 1: Different layers of oral mucosa

Permeability

The above figure represents the layers of oral mucosa from outside to innermost. In general in

terms of permeability the oral mucosa is intermediate between that of the epidermis and

intestinal mucosa. It is estimated that the permeability of the buccal mucosa is about 4-4000

times greater than that of the skin21. It has been assumed that there are considerable

differences in permeability between different regions of the oral cavity because of the diverse

structures and functions of the different oral mucosa17.

The permeation enhancer plays an important role in oral region or the better absorption of

APIs. So there is need of permeation enhancer in case of drugs that are absorbed orally where

the drug is released from the formulation. Some of the examples of permeation enhancers are:

Aprotinin22

23-lauryl ether23

Azone24-26

Benzalkonium chloride27

Cetylpyridinium chloride 28-31

Cyclodextrin32

Dextran sulphate33

Menthol 23

Sodium glycodeoxycholate34-39

Sodium taurodeoxycholate40


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Composition of oromucosal region

The oromucosal cells are mainly made up of proteins and carbohydrates. It acts as a lubricant

and adhesive in nature, allowing cells to move freely relative to one another with less

friction41. The mucus present is also believed to play an important role in bio adhesion of

mucoadhesive drug delivery systems42. In the oral mucosa, mucus is secreted by the major

and minor salivary glands as part of saliva whereas in other parts of body mucus is

synthesized and secreted by the goblet cells. The 70% of the total mucin found in saliva is

contributed by the minor salivary glands41-43.

Another important feature of the oral cavity is the presence of saliva (contributes to digestive

secretion) produced mainly by the three pairs of salivary glands such as (parotid,

submandibular and sublingual glands). Saliva is mostly water contributing of 1% organic and

inorganic materials. The digestive enzyme which is present in saliva is the salivary amylase,

which helps in breaking down starch molecules to shorter chains of glucose molecules. The

Saliva contains many of the chemicals that are found in plasma as the saliva is made from

blood plasma.

The flow rate is the major determinant of the salivary composition which in turn mainly

depends upon three factors: that is the time of day, the type of stimulus and the degree of

stimulation41-43. The pH of saliva ranges from 5.5 to 7. The daily production of salivary

volume ranges between 0.5 to 2 litres and it is this amount of fluid that is available to hydrate

oral mucosal dosage forms. The main reason behind the selection of hydrophilic polymeric

matrices as vehicles for oral transmucosal drug delivery systems is this water rich

environment of the oral cavity.

FORMULATION CONSIDERATION12

Active pharmaceutical ingredient

Film forming polymers

Plasticizer

Surfactants

Sweetening agent

Saliva stimulating agent

Flavoring agent

Coloring agent


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Active pharmaceutical ingredient

A typical composition of the film contains 1-25% w/w of the drug and variety of APIs can be

delivered through fast dissolving films. Small dose molecules are to be incorporated in

OFDFs. Multivitamins upto 10% w/w of dry film weight was incorporated in the films with

dissolution time of less than 60 seconds. It is useful to have micronized API which will

improve the texture of the film and gives better dissolution and uniformity in the OFDFs.

Many APIs,are bitter in taste which are potential candidates for this technology80. This makes

the formulation unpalatable especially for pediatric preparations, so the API should be taste

masked with sweeteners. Various methods can be used to improve the palatability. Among

those, the simplest one involves the mixing and co-processing of API with excipients with

pleasurable taste and termed as obscuration technique13.

Table 3: The drugs which have incorporated via orally fast dissolving films are

mentioned below

Drug Action Dose (mg)

Salbutamol Anti asthmatic 4 Levocetrizine Antihistaminic 75

Chlorohexidine Antiseptic 12 Ondensteron Anti emetic 2.5

Film forming polymer

The final thin film that is used must necessarily be water soluble as it should be disintegrated

in saliva. To prepare a thin film formulation that is water-soluble, excipients or polymer must

be water soluble with low molecular weight and excellent film forming capacity. The

polymer employed should be non-toxic, non-irritant and devoid of leachable impurities. It

should have good wetting and spread ability property53.

The polymer should exhibit sufficient peel, shear and tensile strengths. It should be readily

available and should not be very expensive. The polymers can be used alone or in

combination to improve hydrophilicity, flexibility, mouthfeel and solubility characteristics of

fast dissolving films81.

The stiffness of the strip depends on the type of polymer and the amount of polymer in the

formulation. Polyvinyl pyrrolidone films are brittle in nature and so co-povidone is mixed

with poly vinyl pyrrolidone for preparation of flexible fast disintegrating films.Combination

of microcrystalline cellulose and maltodextrincan be used to formulate fast dissolving films


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of piroxicam by hot melt extrusion technique. In this case, microcrystalline cellulose is used

to achieve the film non-sticky, smooth and also used to decrease the disintegration time,

improve the dissolution of drug from the films. Water soluble polymer include natural gums

such as those derived from guar, xanthun, acacia, Arabic or tragacanth, other available

polymers are, polyethylene oxide, acrylic based polymer and several types of sodium

carboxymethyl cellulose (CMC), several types of hydroxypropyl methyl cellulose (HPMC), a

synthetic copolymer of polyethylene glycol–polyvinyl alcohol (Kollicoat IR) and sodium

alginate. Cellulose ethers are widely available. Pullulan, an a-1,6-linked maltotriose produced

from the fungus Aureobasidiumpullulans, has also been used. Five starches and maltodextrin

have investigated as alternative film formers. The physicochemical characteristic of the

polymers selected for film formulation play a vital role in determining the disintegration time

of thin film oral dosage form65.

Plasticizer

Plasticizer is a vital ingredient of the fast dissolving films which help to improve the

flexibility of the strip and reduces the brittleness of the films. It improves the film forming

properties by reducing the glass transition temperature of the polymer. The selection of

plasticizer will depend upon its compatibility with the polymer and also the type of solvent in

the casting of film. The flow of polymer will get better with the use of plasticizer and

enhances the strength of the polymer. Glycerol, Propylene glycol, low molecular weight

polyethylene glycols, phthalate derivatives like dimethyl, diethyl and dibutyl phthalate,

citrate derivatives such as tributyl, triethyl, acetyl citrate, triacetin and castor oil are some of

the commonly used plasticizer82.

Typically the plasticizers are used in the concentration of 0–20 percent; w/w of dry polymer

weight. Inappropriate use of plasticizer may lead to film cracking, splitting and peeling of the

strip. The use of certain plasticizers may also affect the absorption rate of the drug64.

Surfactants

Surfactants act as solubilizing or wetting or dispersing agent in formulation so that the film

gets dissolved within seconds and release active agent quickly. Some of the commonly used

surfactants are sodium lauryl sulphate, benzalkonium chloride, tweens etc. One of the most

important surfactant is polaxamer 407 that is used as solubilizing, wetting and dispersing

agent83.


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Sweetening agents

Sweeteners are important part of the formulation intended to be disintegrated or dissolved in

the oral cavity. Sweeteners are used in the concentration of 3 to 6 %w/w either alone or in

combination. Both natural sweeteners as well as artificial sweeteners are used in fast

dissolving films. Polyhydric alcohols such as sorbitol, mannitol, and isomalt can be used in

combination as they provide good mouth‐feel and cooling sensation. However the use of

natural sugars in such preparation needs to be restricted for diabetic patients. Due to this

reason, the artificial sweeteners have gained more popularity in food and pharmaceutical

preparations. Saccharin, cyclamate and aspartame are the first generation of the artificial

sweeteners followed by acesulfame-K, sucralose, alitame and neotame which fall under the

second generation artificial sweeteners84.

Acesulfame-K and sucralose have more than 200 and 600 time sweetness. Neotame and

alitame have more than 2000 and 8000 time sweetening power as compared to sucrose.

Aspartame was used for the preparation of oral strips of valdecoxib. Sucralose and

neotameare used in the suppression of the bitter taste of fast dissolving films of diclofenac

and ondansetronrespectively.

Saliva stimulating agent

The saliva stimulating agents is used to increase the rate of production of saliva that would

aid in the faster disintegration of the formulations. Generally acids which are used in the

preparation of food can be utilized as salivary stimulants. Eg.Citric acid, malic acid, lactic

acid, ascorbic acid and tartaric acid. These agents are used alone or in combination between 2

to 6%w/w of weight of the strip85.

Flavoring agents

Preferably up to 10%w/w flavors are added in the OFDF formulations The acceptance of the

oral dissolving formulation is largely depends on the initial flavor quality which is observed

in first few seconds after the product has been consumed and the after taste of the formulation

which lasts for at least about 10 min. The selection of flavor is dependent on the type of drug

to be used in the formulation. Age plays a significant role in the taste fondness86. The

geriatric like mint or orange flavors while younger generation like flavors like fruit punch,

raspberry etc. Flavoring agents can be selected from synthetic flavor oils, oleo resins, extract

derived from various parts of the plants like leaves, fruits and flowers and can be used alone


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or in the combination87. Peppermint oil, cinnamon oil, spearmint oil, oil of nutmeg are

examples of flavor oils while vanilla, cocoa, coffee, chocolate and citrus are fruity flavors.

Apple, raspberry, cherry, pineapple are few examples of fruit essence type88.

Coloring agents

FD & C approved coloring agents are used (not exceeding concentration levels of 1 percent;

w/w) in themanufacturing of orally fast dissolving films. Eg.Titaniumdioxide89.

METHOD OF PREPARATION

One or more of the following process can be used combinely to manufacture the mouth

dissolving films.

1. Solvent casting

2. Semisolid casting

3. Hot melt extrusion

4. Solid dispersion extrusion

5. Rolling52

1. Solvent casting method

In solvent casting method excipients are dissolved in water. Then water soluble polymers are

added and dissolved. At last drug is added and stirred to form homogeneous solution. Finally

solution is casted in to the Petri plate and dried54.

Water / suitable solvent + Excipients

Heated upto 600c Stirred at 1000rpm

Solution + Add Polymers

Cooled to room temp Stirred at 1000rpm

Add Drug

Stirred until to form homogeneous solution

Dried on petry dish

Film is formed

Figure 2: Flow chart of solvent casting method for the preparation of fast dissolving

films


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Advantages

Better uniformity of thickness and better clarity than extrusion.

Film has fine gloss and freedom from defects such asdie lines.

Film has more flexibility and better physical properties. The preferred finished film

thickness is typically 12-100 µm, although various thicknesses are possible to meet API

loading and dissolution needs55.

Disadvantages

The polymer must be soluble in a volatile solvent or water.

A stable solution with a reasonable minimum solid content and viscosity should be

formed.

Formation of a homogeneous film and release from the casting support must be

possible56.

2. Semisolid casting

This method is adopted when acid insoluble polymers are to be used. Add solution of film

forming to a solution of acid insoluble polymer in ammonium or sodium hydroxide gel mass

is obtained. Acid-insoluble polymers used to prepare films include: cellulose acetate

phthalate, cellulose acetate butyrate. Acid insoluble polymer and film forming polymer

should be used in the ratio of 1:457.

3. Hot melt extrusion

In hot melt extrusion method the drug is mixed with carriers in solid form. Then dried

granular material is introduced into the extruder and screw speed should set at 15 rpm to

process the granules inside extruder for approximately 3–4 min. The processing temperatures

should be 800C (zone 1), 1150C (zone 2), 1000C (zone 3) and 650C (zone 4). The extrudate (T

= 650C) then pressed into a cylindrical to obtain a film58.

Advantages

Without use of any solvent or water.

Fewer processing steps.

Compressibility properties of the API may not be of importance.

Better alternative for poorly soluble drugs.

More uniform dispersion because of intense mixing and agitation.

Less energy compared with high shear methods59.


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Disadvantages

Thermal degradation due to use of high temperature

Flow properties of the polymer are essential to processing

Limited number of available polymers

All excipients must be devoid of water or any other volatile solvent63

Solid dispersion extrusion

In this method immiscible components are extrude with drug and then solid dispersions are

prepared. Finally the solid dispersions are shaped in to films by means of dies66-69.

Rolling Method

In rolling method a solution or suspension of drug with film forming polymer is prepared and

subjected to the roller. The solution or suspension should have specific rheological

consideration. The solvent is mainly water and mixture of water and alcohol. The film is

dried on the rollers and cuttedin to desired shapes and sizes70.

EVALUATION

Mechanical properties

Thickness

Dryness/tack test

Tensile strength

Percent elongation

Young’s modulus

Tear resistance

Folding endurance

Organoleptic test

Swelling test

Surface pH test

Contact angle

Transparency

Assay/Content Uniformity

Disintegration test

In-vitro Dissolution test


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Mechanical properties

Thickness: As the thickness of film is directly proportional with drug content uniformity so it

is necessary to maintain uniformity in the thickness of the film. It can be measured by screw

gauge or calibrated digital Vernier Calipers at different strategic locations71.

Dryness test/tack tests :About eight stages of film drying process have been identified and

they are set‐to‐touch, dust‐free, tack‐free (surface dry), Dry‐to touch, dry‐hard, dry‐through

(dry‐to‐handle), dry‐to‐recoat and dry print‐free. Although these tests are primarily used for

paint films most of the studies can be adapted to evaluate pharmaceutical OFDF. Tack is the

tenacity with which the strip adheres to an accessory (a piece of paper) that has been pressed

into contact with the strip. Instruments are also available for this study62.

Tensile strength :Tensile strength is the maximum stress applied to a point at which the strip

breaks. It is calculated by the applied load at rupture divided by the cross‐sectional area of the

strip as given in the equation below72.

Percent elongation :When stress is applied, a film sample stretches and this is referred to as

strain. Strain is basically the deformation of film divided by original dimension of the sample.

Generally elongation of film increases as the plasticizer content increases73.

L = Increase in length of film

L0 = Initial length of film

Young's modulus: Young's modulus or elastic modulus is the measure of stiffness of strip. It

is represented as the ratio of applied stress over strain in the region of elastic deformation as

follows:


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Hard and brittle strips demonstrate a high tensile strength and Young's modulus with small

elongation74.

Tear resistance: Tear resistance of plastic film or sheeting is a complex function of its

resistance to rupture. Basically very low rate of loading 51 mm (2 in)/min is employed and is

to measure the force to initiate tearing. The maximum stress or force (that is generally found

near the onset of tearing) required to tear the strip is recorded as the tear resistance value in

Newtons (or pounds‐force)75.

Folding endurance :Folding endurance is determined by repeated folding of the strip at the

same place till the strip breaks. The number of times the film is folded without breaking is

said as the folding endurance value76.

Organoleptic evaluation :For evaluation of psychophysical evaluation of the product,

special controlled human taste panels are used. In-vitro methods of utilizing taste sensors,

specially designed apparatus and drug release by modified pharmacopoeial methods are being

used for this purpose. These in-vitro taste assessment apparatus and methodologies are well

suited for high‐throughput taste screening of oral pharmaceutical formulations77.

Surface pH of film :Surface pH of the films was determined by placing the film on the

surface of 1.5% w/v agar gel followed by placing pH paper (pH range 1-11) on films. The

change in the colour of pH paper was observed and reported78.

Swelling index :It is useful in case of film formulation having gelling property and measured

by 2methods.

1. Linear expansion coefficient in water

Film is immersed in water. Specimen is taken 2,4,6,8,10,15,30 and 60 seconds and the size of

side length is measured. It is calculated as:

Where:

L1 = Side length after immersion

L0 = Side length before immersion


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2. Amount absorbed in purified water

The film is weighed (W1) and put into the stainless steel mesh basket. The weight after

immersion in water is measured (W2).Similarly weight after immersion of basket without

film(W3).The amount absorbed(W) is determined by following equation

Transparency: The transparency of the films can be determined using a simple UV

spectrophotometer. Cut the film samples into rectangles and placed on the internal side of the

spectrophotometer cell. The determine transmittance of films at 600 nm. The transparency of

the films was calculated as follows

Transparency = (logT600)/b = - €c

Where T600 is the transmittance at 600 nm and b is the film thickness (mm) and c is

concentration79.

Assay/ Content uniformity: This is determined by any standard assay method described for

the particular API in any of the standard pharmacopoeia. Content uniformity is determined by

estimating the API content in individual strip. Limit of content uniformity is 85–115

percent73.

Disintegration time : Disintegration of orally fast dissolving films requires USP

disintegration apparatus. The disintegration time limit of 30 seconds or less. Disintegration

time will vary depending on the formulation but typically the disintegration range from 5 to

30 seconds. Although, no official guidance is available for oral fast disintegrating films strips.

Dissolution test: Dissolution testing can be performed using the standard basket or paddle

apparatus. 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 employed75.

Contact angle measurement :Time dependent contact angle is measured by an optical

contact angle meter. The Contact angle is measured by different methods like the two

tangential methods, a height width ratio, the circle fitting and sessile drop fitting76.


3769


Table 4: Commercial Thin Film oral Dosage Form Products

Product Manufacturer Active Pharmaceutical Agent Strength (mg)

Triaminic Novartis Dextromethorphan HBr 7.5

Triaminic Novartis Diphenhydramine HCl 12.5

Theraflu Novartis Dextromethorphan HBr 15

Gas-X Novartis Simethicone 62.5

Sudafed Pfizer Phenylephrine HCl 10

Benadryl Pfizer Diphenhydramine HCl 12.5

Chloraseptic Prestige Benzocaine Menthol 3/3

Suppress InnoZen Menthol 2.5

Orajel Del Menthol/Pectin 2/30

Listerine Pfizer Cool mint –

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