A Systematic Review on Oral Drug Delivery as a Fast Dissolving Film to Improve Therapeutic Effectiveness

 

Nilesh S. Kulkarni*, Puja S. Wakase, Pratiksha S. Indore, Shashikant N. Dhole

Department of Pharmaceutics, PES Modern College of Pharmacy (For Ladies), Moshi, Pune 412105, Maharashtra, India. Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India.

*Corresponding Author E-mail: nileshpcist@gmail.com

 

ABSTRACT:

Oral routes are mainly preferred route to administer and to deliver drug. Most common oral dosage forms are capsule and tablet. In some cases, the solid oral dosage form may become difficult in swallowing e.g. sudden episode of allergic reaction, motion sickness, coughing, unavailability of water, fear of choking and in different age group of patient and patients who suffer from dysphagia. The administration of pediatric and geriatric population is the advantages of oral film technology where the difficulty in swallowing and larger oral dosage forms is eliminated. It is an interchange platform for molecules that undergo first pass metabolism. To overcome these problems, drug delivery systems of fast dissolving has been developed. Fast dissolving oral delivery systems are solid dosage forms, which dissolve or disintegrate within 1 min when placed in the mouth without chewing or water. The drug are formulated by Oral dissolving films incorporating with selected oral cavity absorption enhancers oral dissolving film carriers are specially designed. Oral films are formulated by using polymers, plasticizers, saliva stimulating agents, colours, flavors and sweeteners. Different methods are reported in literature as solvent casting method, hot melt extrusion method, rolling method and solid dispersion method for the preparation of film. The objective is to target local, for rapid onset of action, to avoid first pass metabolism and to mask bitter taste of drugs. Overall it leads to patient compliance with improved therapeutic success.

 

KEYWORDS: Fast dissolving film, solvent casting, first pass metabolism.

 

 


INTRODUCTION:

The administration of therapeutic agents is perfect route for oral route because the ease of administration and low cost of therapy lead to high levels of patient compliance. Oral dosage forms are more popular than other dosage forms because of ease of administration, accurate dosage, self- medication, pain avoidance, patient compliance, etc. sterile conditions is not require for solid oral delivery systems, therefore, manufacture is less expensive. for oral delivery system has Several novel technologies recently become available to address the pharmacokinetic and physicochemical characteristics of drugs, while improving patient compliance.1

 

The most popular oral solid dosage forms are capsules and tablet. Tablets are widely accepted because of the convenience in terms of compactness, self-administration, and ease in manufacturing. Children, geriatric patients and many other persons including disabled patient often have trouble in swallowing tablet or capsules, furthermore, dosing is an issue, as most medications are available in doses that are significantly too large for the paediatric population and cannot easily and reproducibly be divided into smaller doses1-5.

 

Oral route is most preferred route by manufacturer and medical practitioners due to highest acceptability by patients. All dosage forms are available about 60% of oral solid dosage form long onset time, lower bioavailability, and dysphagia patients turned the manufacturer to the parenteral and liquid orals. The liquid orals (emulsion, syrup, suspension, etc.) has the problem of correct dosing mainly and parenteral are painful drug delivery, which may affect the patient noncompliance. Fast dissolving drug delivery systems were first invented in the late 1970s as to overcome swallowing difficulties associated with tablets and capsules for pediatric and geriatric patients. Buccal drug delivery is the important route of drug administration.

 

Oral fast dissolving film (OFDF) is one such new approach to enhance consumer receiving by virtue of fast dissolution, self-organization without chewing or water. The film is an ideal intraoral fast-dissolving drug delivery system, which satisfies the unmet needs of the market, is easy to handle and administer, maintains a simple and convenient packaging, alleviates unpleasant taste, and is straightforward to manufacture. The film is placed on the top or the floor of the tongue. It is retained at the site of application and fast releases the active agent for systemic and local absorption. The improvement of a fast-dissolving film also provides an opportunity for a line addition in the market place, a wide range of drugs (cardiovascular drugs (e.g Bisoprolol Fumarate6), antihistamines analgesics (e.g Meclizine7), neuroleptics (e.g Diazepam8), and drugs for erectile dysfunction (e.g, Tadalafil9) can be considered candidates for this dosage form. Mouth dissolving films formulation containing large number of drugs. Innovative products may increase the therapeutic possibilities in the Geriatrics-Antiepileptic (e.g. Midazolam10), Pediatric- e.g. Metoclopramide Hydrochloride11, Antitussives (e.g, Dextromethorphan hydrobromide12) CNS- Antiparkinsonism therapy (e.g. Selegiline13), Gastrointestinal diseases (e.g clarithromycin14), Pain (Migraine e.g Zolmitriptan15).

 

Research and increase in the oral drug delivery segment has led to change of dosage forms from simple conventional capsules or tablets to modified release tablets or capsules to oral disintegrating tablet (ODT) to wafer to the new development of oral fast dissolving films (OFDFs). Amongst the rapid drug releasing products, explored for plethora of avenues. The oral strip technology is gaining much attention. (ODFT) was previously popular between the people in the early 2000 year with the introduction and common use of Listerine pocket strips, a new launch in the mouthwash range16,17. Orally disintegrating films, when placed on tongue, immediately hydrates by soaking saliva following disintegration and dissolution releasing active pharmaceutical agent from the dosage form. Orally disintegrating films are kind of formulations which are usually prepared using hydrophilic polymers enabling rapid dissolution upon contact saliva. These systems were developed in late 1970 to serve as an unconventional to conventional dosage forms, for instance, fast disintegrating tablet and capsules having difficulty in swallowing conventional dosage forms for geriatrics and pediatric patients18,19.

 

SPECIAL FEATURES OF FAST DISSOLVING FILM:

·       Film should be elegant and thin.

·       Available in various size and shapes.

·       Rapid releases

·       Should processes fast disintegration without water.

·       Thin elegant film

·       Unobstructive

·       Excellent mucoadhesion

·       Fast disintegration

 

ADVANTAGES:20,21,22

·       Provide quicker onset of action at lower doses and avoid first pass metabolism. e.g, Nifedipine23

·       Large surface area provides rapid disintegration and dissolution in the oral cavity. e.g Loratadine

·       Improved patient compliance, especially patients suffering from dysphasia and pediatric and geriatric population. e.g Etophylline

·       Improved stability due to better packaging. e.g Atomoxetine HCl

·       Enhances bioavailability of drugs Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. e.g Aprepitant.

 

DISADVANTAGES:

·       High dose of drug cannot be incorporated into the film.

·       Drugs which causes irritation to the mucosa cannot be administered.

·       Drug which are unstable at buccal pH cannot be administered by this route.

·       Some drugs have bitter taste, and need to have taste masking.

·       Special packaging require for products safety and stability.

·       It is hygroscopic in nature so it must be kept in dry places.

 

CLASSIFICATION OF ORAL FILM:

There are three different subtypes

a) Flash release.

b) Mucoadhesive melt-away wafer.

c) Mucoadhesive sustained-release wafers.

 

Anatomy and physiology of oral mucosa:

The oral cavity is smooth by multilayered mucosa membrane and thick dense of greatly vascularised nature. Drug penetrating interested in covering passes throughout net of capillaries and arteries and reach the systemic circulation. The delivery system is simply placed on any oromucosal tissue or patient’s tongue. The presence of hydrophilic polymer and other excipients, Instantly wet by saliva. The film rapidly dissolves and hydrates to release the medication for oromucosal absorption.


Table I Difference types of films

Sub tupe

Flash release wafer

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

Single layer

Single or multilayer system

Multilayer system

Drug phase

Solid solution

Solid solution or suspended drug particles

Suspension and/or solid solution

Excipients

Soluble, highly hydrophilic polymers

Soluble, hydrophilic Polymers

Low/Non-soluble Polymers

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 few minutes, forming gel

Maximum 8-10 hrs

 


Drug delivery through the oral cavity can be subdivided as follows

Sublingual delivery:

This is systemic delivery of drugs through the mucosal membranes lining the floor of the mouth (sublingual mucosa). Sublingual region shows higher drug permeability than buccal region. Drugs which require rapid onset of action are administered by this route e.g. Nitro-glycerine.

 

Buccal delivery:

The drugs administration through mucosal membranes lining the checks and the area between gums, upper and lower lips to the systematic circulation.

 

Local delivery:

Which is drug delivery in the oral cavity for the treatment of conditions of the oral cavity principally aphthous ulcers, fungal conditions, and periodontal.

 

STRUCTURE OF ORAL CAVITY:

The vestibule along with oral cavity are entirely lined by mucous membranes contain numerous small glands that, along with the three pairs of salivary glands, the mouth in liquefied, keeping it wet and clear of other debris and food. Both the gums (gingivae), form Specialized membranes which surround and support the surface of the tongue, and the teeth on which the membrane is rougher in texture, containing many small papillae that hold the taste buds. The enzymes and the mouth’s moist environment within its secretions help to soften food, facilitating, swallowing and beginning the process of digestion.

 

The salivary glands secrete mucin as part of saliva. Saliva pH ranges from 6.8 to 7. The permeability of buccal mucosa is found to be 4000 times greater than skin. The drug administered via the oral mucosa gain access to the systemic circulation through a network of arteries and capillaries. New oral drug delivery system is Fast dissolving buccal film. oral delivery system consists of a very thin oral strip, which is simply placed on the patient’s tongue or any oral mucosal tissue (buccal/sublingual), instantly wet by saliva the film rapidly. fast dissolving action is primarily due to the film of large surface area, which wets quickly when exposed to the moist oral environment.

Composition of the formulation:

Formulation of oral dissolving film (ODF) involves the intricate application of aesthetic and shows characteristics such as taste masking, fast dissolving, physical appearance and mouth feel etc. The excipients used formulations of oral dissolving film are given below as per their categories.

 

Table II: A typical composition of fast dissolving oral film contains following;

Ingredients

Amount (w/w)%

Drug

1-30

Polymer

40-50

Plasticisers

0-20

Surfactants

As Required

Sweetening and Flavouring Agents

3-6

Saliva Stimulating Agents

2-6

Colorants

As Required

 

I. Drug or Active Pharmaceutical Ingredients (API):

The drug is the core ingredient of these polymeric films and generally comprises of 1-30% (w/w) of the films. Always use low dose active pharmaceutical ingredient used because high dose of drug are difficult to incorporate in fast dissolving film micronized API is useful become it enhance the texture of film and uniformity in the fast dissolving film and provide improved dissolution.

 

Ideal characteristic of a drug to be selected:

·       Drug should have pleasant taste. ( not bitter )

·       Low dose should have up to 40 mg.

·       Drugs with minor and moderate molecular weight are preferable.

·       Drug should have good solubility and stability in saliva as well as in water.

·       Drugs should have the ability to permeate oral mucosal tissue through prepared oral film. Examples: antiallergic, antiemetic, antimigrant etc

 

II. Film Forming Agents:

Biocompatible and water-soluble polymers are the backbone of the OTFs and carry the drug. Various natural and synthetic drugs are available for this purpose. Multiple polymers can also be combined to achieve desired properties. The polymers must be non-toxic, no-irritant and devoid of any impurities. Polymers are selected not only for the physical characteristics of the films but also for the rate at which they dissolve. The dissolution rate of the dissolving polymer inversely related to the molecular weight of the polymer. In formulation at least 45 % w/w of polymer should be present based on the total weight of the film.

 

Ideal properties of film forming polymer:

1.     Should be non-toxic and nonirritant.

2.     Must be hydrophilic.

3.     Should have excellent film forming capacity.

4.     Should have good spread and wetting ability property.

5.     Should be readily available and should not be very expensive.

6.     Should have low molecular weight.

7.     Should have sufficient shelf-life.

8.     Must be tasteless, colourless.

9.     Should not cause any secondary infection in oral mucosa.

10. Should exhibit adequate peel, shear and tensile strengths.

Examples: HPMC E3, E5 and E15; K-3 Methyl Cellulose; A-3, A-6 and A-15 Pullulan; pectin, gelatine, Chitosan, cellulose, starch

 

III. Plasticizers:

Plasticizers improve the strength and flexibility of the polymeric matrix. They decrease the brittleness. Plasticizers are chosen based on the polymers involved and the method used for formulation. It decrease the brittleness of the polymer film And also improves the flexibility of film. The selection of plasticizers depends upon the compatibility of polymer, nature of solvent, method of formulation. By lowering the glass transition temperature of the polymers more structurally pleasant, stronger and a flexible film can be prepared.

Examples: Glycerol, Dibutyl phthalate, Polyethylene glycol

 

IV. Surfactants:

Surfactants are the solubility enhancers that improve the wetting properties of the film to ensure drug release and rapid dissolution. There are many surfactants which are used-

Examples: Sodium Lauryl sulphate, Tween, Benzalkonium Chloride.

 

V. Sweetening and Flavouring Agents:

Sweetening and flavouring agents are necessary for taste and odour masking of the drug and to increase the appeal of the film. This is an important factor for paediatric patients. Natural and artificial sweeteners and flavours can be incorporated. Sweeteners have become the essential part of the food products as well as pharmaceutical products intended to be disintegrated to be disintegrated or dissolved in the oral cavity. artificial and natural sweeteners are used in the formulations and improves the palatability of the fast dissolving film.

Examples: Saccharin, Aspartame

 

VI. Saliva Stimulating Agents:

The OTFs disintegrate on coming in contact with the liquid in the oral cavity which is essentially saliva. Saliva Stimulating Agents produce saliva that helps in quick disintegration and dissolution of the films. The saliva stimulating agents promotes the saliva secretions. The increased saliva productions facilitate the faster disintegration and rapid dissolution rate. Saliva stimulating agents are used in concentration 2 to 6 % w/w of the film either used alone or in combination.

Examples: Citric acid, Lactic Acid, Ascorbic acid

 

VII. Colorants:

Colouring Agents are used to increase the appeal of the film. Pigments are used as colouring agents. In ODFs titanium dioxide is most widely used colorant and various other pharmaceutical preparations. A full range of colours are available including FD and C, custom pantone- matched and natural colours. In fast dissolving film colouring agent is not exceeding concentration a level of 1% w/w.

 

Method of prepration:

The following processes used to manufacture the oral fast dissolving films.

I.      Solvent casting

II.    Hot melt extrusion

III. Semisolid casting

IV. Rolling

V.   Solid dispersion extrusion

 

I. Solvent Casting Method:

The oral fast dissolving films are prepared by dissolving strip forming agents, plasticizer and saliva stimulating agent in the distilled water, then solution is continuous stirred on magnetic stirrer and remove all the air bubbles entrapped it kept for 1 hour. The separate container remaining water-soluble excipients i.e., disintegrating agent, saliva stimulating agent, sweetening agent, flavor and drug are dissolved with constant stirring. When the stirring is over both the solutions are mixed together with stirring for another 1 h on magnetic stirrer. Then keep the solution set for 1 hr to let the foams settle down. The resulting formulation is dried to form a film. The film is preferably dried or air-dried under oven then the film is carefully removed.

 

II. Hot-Melt Extrusion Method:

Drug and polymers are blended into a sigma blade mixer for 10 min, and then plasticizer is slowly added. The mixture is granulated in the presence of an anti-sticking agent. Granules are stored overnight at room temperature and then sieved through a 250μm sieve in order to remove the excess of powder and standardize the particle size. The dried granular material is fed into the extruder. The screw speed is set at 15 rpm in order to process the granules inside. The barrel of the extruder for approximately 3– 4 min. The processing temperatures are set at 800 C (zone 1), 1150 C (zone 2), 1000 C (zone 3) and 650 C (zone 4). The extrudate (T = 650 C) is then pressed into a cylindrical calendar in order to obtain a film with a thickness of about 200μm. At the end of the preparation processes, the films are cut according to the size required for testing, individually sealed in airtight packets and stored at 250C until use.

 

III. Semisolid Casting:

In semisolid casting method, firstly a water-soluble film forming polymer solution is prepared. The resulting solution is added to a acid insoluble polymer (e.g. cellulose acetate butyrate cellulose acetate phthalate) which was prepared in ammonium or sodium hydroxide. Then correct amount of plasticizer is added so that a gel mass is obtained. Finally the gel mass is casted in to the ribbons or films using heat controlled drums. The film thickness is about 0.015-0.05 inches. The ratio of film forming polymer to the acid insoluble polymer should be 4:1.

 

IV. Rolling Method:

In rolling method, the drug containing suspension or solution is rolled on a carrier. The solvent is mostly water and mixture of water and alcohol. The film is dried out on the rollers and cut in to required shapes and sizes Other ingredients with active agent are dissolved in small portion of aqueous solvent using high shear processor. Water soluble hydrocolloids dissolve in water to form homogenous viscous solution.

 

V. Solid dispersion:

The term solid dispersion refers to the dispersion of one or more active ingredients in an inert carrier in a solid state in the presence of amorphous hydrophilic polymers. In this method drugs dissolved in suitable solutions and solvents are incorporated into the dissolve of polyethylene glycol below 700 C. Then solid dispersions are shaped into the films.

 

EVALUATION TEST:

Weight Variation:

The weight variation test is determined by measuring the weight of the individual film of 3cm x2 cm area. digital analytical balance was used for the measurement of the weight. The weight of three films was determine and mean is taken.

Thickness:

The thickness of strip was measured by digital vernier caliper at different locations. This is necessary to establish uniformity in the thickness of the film as this is directly linked to the accuracy of dose in the strip.

 

Folding endurance:

Folding endurance is determined by repeat folding of the strip at the same place till the strip breaks. The number of film is folded without breaking is compute as the folding endurance value.

 

Tensile strength:

Tensile strength of films was determined using an apparatus fabricated in laboratory. A small film narrow piece (3 × 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. Measurements were done in triplicate for each batch. The mechanical properties tensile strength and % elongation were calculated for the fast dissolving film from the above measurements. Tensile strength is the ratio of maximum stress applied to a point at which the film specimen breaks and can be computed from the applied force at rupture to the cross-sectional area of the fractured film as a mean of three measurements and described in the equation-

               Load at breakage

Tensile strength = ––––––––––––––––––––––––

         Strip thickness × Strip width

 

Percent elongation:

When stress is applied, a sample strip stretches and this is referred as strain. Strain is mainly the deformation of strip divided by original dimension of the sample. Generally the plasticizer content increases elongation of strip increases.

 

Percent elongation= L*100/Lo

 

L = Increase in length of film

Lo = Initial length of film

 

Young's Modulus:

Young's modulus or elastic modulus is the measure of stiffness of film. It is expressed as the ratio of applied stress over straining the region of elastic deformation as follows:

 

                                  Force at corresponding strain               1

Young’s Modulus = ––––––––––––––––––––––––  X  –––––––––––––

                                        Cross sectional area         Corresponding strain

 

Brittle and Hard film demonstrates a high tensile strength and Young's modulus with small elongation.

 

pH Value:

The pH value can determine by one oral film is dissolving in 10ml distilled water and measuring the pH of the obtained solution. It is needed that film should have nearly uniform pH value.

 

Drug content:

Drug content determination of the film was carried out by dissolving the film of 2cm2 in 100ml of pH 6.8 phosphate buffer using magnetic stirrer for 1 hour. The drug concentration was evaluate spectrophotometrically at λmax. The determination was carried out in triplicate for all the formulations and average with standard deviation was recorded and reported.

 

Disintegration time:

The CDER guidance can be applied to oral film for describe orally disintegrating tablets. Although, for FDOF there is no official guidance is available, this may be used as a qualitative guideline for quality control test or at development stage. By taking the 25ml of distilled water in 50 ml beaker and individual film is dipped into that solution and disintegration time was recorded.

 

Swelling property:

Each film sample is placed and weighed in a pre-weighed stainless-steel wire mesh. Then the mesh containing film sample is submerge into 15ml medium (simulated saliva solution) in a plastic container. Increase in the weight of the film was determined at preset time interval until constant weight was observed.

 

Degree of swelling = Wt – Wo/ Wo

 

Where, Wt = weight of film on time t

Wo = weight of film on time zero

 

In Vitro Dissolution study:

Dissolution testing can be perform by using the standard paddle or basket apparatus describe in any of the pharmacopoeia. The dissolution medium mainly 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 in use.

 

Stability Studies:

Stability studies on the optimized oral fast dissolving film is carried out for determination of effect of temperatures and humidity on the stability of the drug. The film are stored in an aluminum foil and subjected to stability at room temperature. The sample can withdraw at 3 months and 6 months and subjected for cumulative % drug release and in vitro dissolution studies to determine disintegration time and disintegration test.

 

Storage and packaging:

The packaging and converting stage also provides product flexibility to drug manufacturers. The rolled film can be die-cut into any shape, size, slit into narrower rolls as essential for the application. For branding purposes and to meet up industry rules, converters may choose to print information directly onto the film unit doses before packaging. Criteria that may be taken into consideration include the need for unit-dose packaging, barcode labeling, and the content in instructions for use, child-resistant seals, and senior-friendly packaging.

 

Following table gives the highlights for the various studies carried out by various researchers for the development of fast dissolving oral films to improve therapeutic effectiveness (Table III).


 

Table III Current research in fast dissolving oral film

Drug

Excipient

Outcome

Films Developed Through Solvent Casting Technique

Aripiprazole

HPMC E5, maltodrxtrin, polyvinyl alcohol, aspartame, citric acid, Propylene glycol.

Aripiprazole is very fast andrapid dissolving film compare to marketed formulation24.

Dicyclomine

PVA, HPMC 5, 50, PEG 400, aspartame, citric acid, mannitol, Tween 80

Better therapeutic efficacy, increasing bioavilability and improving patient compliances25

Diazepam

HPMC E3, 5, 15, Hydroxyl propyl, β cyclodextrin, PEG 400, polyvinyl glycol, glycerine

All formulations showed good mechanical properties and in vitro drug release. The drug release is found to be 100 % within 15 mins26.

Aprepitant

Pullulan, PEG 400, citric acid, Tween 80, mannitol

The prepared optimized formulation showed minimum disintegration time (20s), highest dissolution rate (88.87%) and satisfactory physicochemical properties27

Etophylline

Polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC 15 cps and 50 cps), sucralose, PEG 400,

very quick onset of action, which is beneficial in managing severe situation of asthma aiding in the enhancement of bioavailability. suitable for clinical use in the treatment of asthma where a quicker onset of action for a dosage form is desirable along with the convenience of administration28

Montelukast Sodium (MDF)

HPMC, PEG-400, Tween 80, Crosscarmellose Sodium

The dissolution rate increased with increase in the concentration of SSG up to 8%29.

Zolpidem tartarate

HPMC E5, HPMC E15, PVA, Glycerol AR grade, PEG 400,

The oral film was prepared by using HPMC E15 in proportion of 1:1. Polymer was found to be compatible with glycerol as plasticizer. Disintegration time was found to be less than 60 seconds30.

Promethazine hydrochloride

Hydroxy propylmethyl cellulose E15, PEG400, SLS, MCC, Sucrose, strawberry, citric acid, Titanium dioxide,

The optimized formulation showed satisfactory pH, drug content (97.41±0.54%), effective in vitro drug release (96.03±0.68% in 16 min), disintegration time of 09 seconds and satisfactory stability31.

Atomoxetine hydrochloride

HPMC LV, sodium alginate, guar gum, PVA SSG, CCS, CP and KYRON 314.,

Atomoxetine HCl was successfully formulated as oral thin film. Drug excipient compatibility concluded that the drug and excipient were compatible with each other32.

Loratadine

HPMC E5, E15, PEG 400, glycerol, Propylene glycol, Glycerin, Tween 80, Saccharin sodium, citric acid, Dichloromethane, methanol

The film prepared with HPMC E5 and glycerol (F9) was selected as the best formulation based on various evaluation parameters, The ex vivo permeation study of the optimized formulation showed a permeation of 80.6% within 10 min which exhibit that it would provide an immediate relief from allergic reactions33.

Rofecoxib

HPMC-15cps, polyvinyl alcohol, aspartame, menthol, ethanol, Glycerin, poly-sorbate 80,

Tensile strength, percentage elongation and folding endurance of the films were increased with increase in the concentration of polymer due to increase in the elasticity nature of the polymer34. disintegration time of the films were increased with increase in the concentration of the polymer, as more fluid is required to wet the film in the mouth.

Bufotenin

HPMC E5, E15, K15, and Microcrystalline Cellulose (MCC), Polyvinyl Alcohol, glycerol,

The polymer HPMC E5 showed highest drug release rate than other polymers and F7 showed highest drug release rate. Hence, there is a lot of scope for future in vivo studies35.

Losartan potassium

Sodium carboxymethylcellulose, HPMC, Glycerol, SSG, Saccharin sodium, Na-CMC, Na–alginate, Gelatin, Menthol.

The present study confirms the enormous potential of MDFs for improving patient convenience and compliance, by hastening the onset of action and circumventing hepatic first-pass metabolism, especially in pediatric and geriatric patients36.

Amlodipine Besylate

HPMC, methylcellulose, PVPK30, SLS, Methanol, PEG400, Aspartame,

MDFs prepared with HPMC E3, E5, E15, and MC as film formers possessed good physicomechanical and dissolution properties. theF3(7.5%w/w HPMC E3 as film former and 0.04% w/w PVP K30) gave higher in vitro AMLO release (102.92 ± 1.15% at the end of 60sec) 37.

Ropinirole Hydrochloride

pullulan, PEG 400, HPMC, Sucralose, aspartame, sodium chloride,

Acceptable mechanical properties were obtained in the batch F4 with in vitro disintegration time of 20 sec. The optimized batch F4 was found to be stable for a period of 1 month at 25°C/40 %RH38.

Films Developed as Solid Dispersion And Converted As Film Through Solvent Casting Technique

Telmisartan

Maltodextrins, HPMC-K4M, PVP, Citric acid, Propylene glycol,

Among all the formulations telmisartan oral fast dissolving films containing combination of HPMC and Malt dextrin as hydrophilic polymers shows high percentage of drug release within 10 minutes compared to that of films containing HPMC alone as a polymer39.

Ebastine

pullulan, HPMC, PVP, Propylene glycol, aspartame,

formulation of film with pullulan has shown better invitro dissolution profile (97.2 ± 0.06%) in 60 min compared to other formulation40.

Amlodipine Besylate

PEG6000, PVP, sodium carboxy methyl cellulose, HPMC, lactose, Tween 80, glycerine,

The release rate from solid dispersion increased with increasing the ratio of drug to polymer (PEG6000 or PVP). As the concentration of SCMC increased in the film the release rate decreased significantly41.

 

Isradipine

PEG4000, PVP k30, Lycoat RS720, glycerine, tartaric acid, Sorbitol, Polaxamer 407,

99.89% of drug was released from F6 film within 7 minutes which was desirable for fast absorption42.

Films Developed as through Hot Melt Extrusion Technique

chlorpheniramine maleate

modified starch, Citric acid, glycerol, Sucralose, Lycoat® RS 780, Magnasweet®,

The films showed immediate disintegration and dissolution, which were attributed to the thinness and presence of hydrophilic excipients in the formulations43.

Films Developed as Mucoadhesive Oral Films

Atenolol

HPMC E15, HPMCE5, HPMC E6, pullulan, PEG-400, glycerine, crosspovidone, Aspertame, Ascorbic acid, Menthol,

Formulation of film with HPMC E6 400 mg has shown better in vitro dissolution profile (98.83%) in 150 seconds, compared with other formulations44.

Esomeprazole Magnesium Trihydrate

HPMC-K4M, Polyethylene glycol, HPMC (15cps), Methanol,

In vitro drug release and ex vivo permeation results were super impossible for films of HPMC K4M (3%). 3% HPMC K4M and 30% w/v plasticizer was required for better physico-chemicaland mechanical property45.

Glibenclamide

HPMCK15M, HPMCK100M and HPMC3000 cps, Propylene glycol,

HPMC3000 at low concentrations can be useful for buccal delivery. It is a good potential of erodible mucoadhesive buccal HPMC films46.

Ranitidine

HPMC (15cps), Ethanol, Propylene glycol, Dichloromethane

Formulations of bioadhesive buccal film promising one as the controlled drug delivery, improve bioavailability and the dose of ranitidine could be minimized and hence prevent the colonic degradation of ranitidine by colonic bacteria47.

 


CONCLUSION:

Fast dissolving oral film has many advantages related to bioavailability, disintegration and dissolution. It is rapidly disintegrates and dissolves to release the medicament. Fast dissolving films have already gained popularity in the form of breath freshener products. There are problem of tablets and painful parenteral dosage forms. Patient compliance is high in all age groups patients especially paediatrics and geriatrics. Fast dissolving drug delivery systems have better patient compliance and may offer improved biopharmaceutical properties, efficacy and better safety compared with conventional oral dosage forms The properties of FDOFs such as easy administration, quickly disintegration, consumer preference, rapid action, Fast dissolving buccal films can be a better option to optimize therapeutic efficacy of various active pharmaceutical ingredients which have extensive first pass metabolism. This technology is also a good tool to pharmaceutical company for product life cycle management for increasing the patent life of existing products. The FDOFs bridges the gap between consumer preferences and manufacturer.

 

REFERENCES:

1.      Bhattarai M., Gupta A. Fast Dissolving Oral Films: A Novel Trend to Oral Drug Delivery System. Sunsari Technical College Journal. 2015; 2 (1): 58-68

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Received on 21.01.2020             Modified on 26.03.2020

Accepted on 17.04.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(3):1771-1778.

DOI: 10.5958/0974-360X.2021.00315.2