Fast Dissolving Oral Films: A Review  

Hasanen Pinjari*, Rehan Deshmukh, Khan Faizan, Dr. Gulam Javed.

J.I.I.U’S Ali-Allana College of Pharmacy Akkalkuwa, Dist- Nandurbar (425415) Maharashtra, India.

*Correspondence: hasanainpinjari69@gmail.com

INTRODUCTION

Fast medication delivery systems are attracting more and more interest from the pharmaceutical industry. These systems usually dissolve or disintegrate in less than a minute without the need for chewing or water. With its potential for oromucosal absorption, these methods provide better clinical profiles and raise the drug bioavailability in terms of oral consumption orally. Thin films may melt or dissolve rapidly in the oral canal, according to recent theories. These contain pharma excipients or an active ingredient and are incredibly thin, like a postage stamp. The tongue or any other mucosal tissue is covered with these dose forms. Saliva quickly hydrates the films and causes them to stick to the application location [4]. With a little modification, For speedy medication release, it can be quickly dissolved, whether for mucosal or oral absorption.

Among the main advantages of these dosage forms are exact dosing in comparison to liquid dosage forms, no need for water, and no risk of choking in contrast to tablets and capsules. Pre-gastric absorption from the mouth, pharynx, and esophagus as the saliva travels down into the stomach after the drug disintegrates in the mouth improved the clinical efficacy of the medication. In these situations, the drug's bioavailability is far more than what is seen with a typical tablet dosage form [6]. Fast-dissolving buccal film drug delivery systems have become widely recognized as a significant new method of medication administration in recent times. They typically relate to pharmaceutical and nutraceutical goods. It is the most recent advancement in drug delivery technology and a highly convenient way to take vitamins and prescription drugs. If a localized effect is preferred in the mouth, these fast-dissolving films can also be used as a local anesthetic for pain in the teeth, mouth ulcers, cold sores, or teething [7].

For a systemic effect, the oral mode of administration is the most recommended. Solid dosage forms account for about 60% of all formulations because they are simple to manufacture, transport, and increase patient compliance [8]. Typically, people who are pediatric, elderly, or prohibited have trouble swallowing the regular tablet. A fresh formulation was devised to solve this difficulty. that is, quickly dissolving films.

FDF is made using hydrophilic polymers, which dissolve quickly in the buccal cavity and transport the drug through the oral mucosa to the systemic circulation [8]. Drug delivery methods that rapidly disintegrate are designed to enhance the bioavailability of medications that have small doses and significant first-pass metabolism.

Perfect qualities for a potential drug candidate: [5]

§  The drugs need to have a pleasant taste.

§  The amount of a drug to be added should be limited to no more than 40 mg.

§  Utilizing medications with moderate and smaller molecular weights is advised.

§  The medications have to be soluble in saliva and well-stable in water.

It needs to be able to cross oral mucosal tissue and partially ionize at the pH of the oral cavity

The advantages of oral film:[9,10]

§  The drug is delivered by a film that is applied sublingually and which has the potential to improve the drug's safety profile, effectiveness, and beginning of action while lowering the dosage.

§  Soft gels, liquid formulations, and single-unit dose forms all enter the bloodstream primarily through the gastrointestinal tract, where they are broken down by bile, digestive enzymes, gastric acid, and other first-pass effects Consequently, the effects of these formulations usually take longer to appear and require larger doses. But by making use of modern oral film drug delivery technologies, which result in a rapid beginning of effect at lower doses, these issues can be avoided.

§  Compared to other conventional methods, oral film is better, more reliable, and disintegrates more quickly. Compared to liquid formulations, the oral film allows for more accurate dosing because each oral film strip is made to precisely contain the prescribed dosage.

§  The oral film offers more precise medication administration. Because oral film is so easy to administer and has an understandable dosing form, it can increase compliance.

§  Patients with pediatric, geriatric, and neurological diseases, for whom accurate and comprehensive dosage might be challenging, can particularly benefit from these qualities.

§  The ability of oral films to dissolve quickly without the water gives patients who experience nausea or dysphasia—such as those undergoing chemotherapy an alternative.

Disadvantages:[9,10]

§  High dose can’t be introduced in the strip

§  Unstable drugs at buccal pH can’t be used.

§  Taste masking needs to be done as most drugs are bitter in nature.

§  Gaining dose uniformity is a challenge.

§  The range of compatible drugs is limited.

Composition of the ODF: [11]

A thin film containing an API that has an area of 2-8 cm2 is called a fast-dissolving film. A special matrix is used to achieve quick dissolution in water or saliva [11]. polymers soluble in water drugs can be taken in single doses of up to 30 mg. It has been observed that formulation plays a major influence in defining the films' mechanical characteristics. The excipients used in the formulation of orally dissolving films are also covered in detail. From a regulatory perspective, every excipient used in the formulation should be accepted for use in oral pharmaceutical dosage forms and widely acknowledged as safe.

 Any class of pharmaceutically active ingredients that can be administered orally or through the buccal mucosa is referred to as an API. comparable to drugs that are antiepileptic, antitussive, antihistaminic, expectorant, aniasthmatic, and antianginal, among other medications. For the best formulation, the dosage of the medication should be in milligrams (less than 20 mg/day). [12]

Oral Film Formulations: [13]

The following components were used in the preparation:

1. API (1%–30%)

2. Polymers (40–50%)

3. Plasticizer (0%–20%)

4. Surfactant   Q.S.

5. Sweetening Agents (0%–10%)

6. Q.S. saliva stimulants (2–6%)

7. Flavouring Agent:

1.      Active Pharmaceutical Ingredients (APIs): [7,14]

For oral thin film, stronger, less bitter, and highly lipophilic medications should be used. Mouth-dissolving films can be made from a variety of pharmacological classes, such as NSAIDs (Valdecoxib, Meloxicam), expectorants, antitussives, anti-ulcers (Omeprazole), and antiasthmatic (Salbutamol sulfate). To make a film, roughly 5% to 30% w/w of the API can be used [19]. The introduction of high-dose medications is restricted by the size of the dosage form.

2.      Film Forming Polymers: [14]

Quick-dissolving films can be made with a variety of polymers. Polymers can be used alone or together to provide the necessary tape characteristics. The completed film needs to be sturdy enough to not shatter when handled or transported. The type and amount of polymer determine how sturdy the strip is. However, to deliver medication to the buccal cavity quickly, a fast-dissolving strip dosage form needs to be able to dissolve in the mouth in a couple of seconds [15]. The most significant component of the fast-dissolving film, the streak-forming polymer, should normally make up at least 45% of the polymer by weight, based on the total dry weight. Polymers like gelatin and pullulan are frequently used.

3.      Plasticizers: [16]

Plasticizers are used to make the strip less brittle and more flexible. It is a crucial sequence in the movie. To enhance the film's qualities, it decreases the polymer's glass transition temperature. The strength of the film is determined by how well the plasticizer works with the chosen polymer and casting solvents. The strength and flow of the polymer are enhanced by plasticizer. Glycerol, propylene glycol, low molecular weight polyethylene glycols, phthalate, and derivatives of citrate are among the plasticizers utilized in the creation of films. Incorrectly given plasticizers have the potential to split, crack, and pill. The degree to which a plasticizer peel is determined by how volatile it is and how well it interacts with polymers. The glass transition temperature of a polymer can be lowered with plasticizers to less than 75 °C in aqueous systems and non-aqueous solvent systems between 40 and 60 °C. Plasticizers were supposed to function well with the API and selected excipients. That is to say, ethylene glycol can be utilized for PVA and HPMC film, whereas glycerol works better as a plasticizer for PVA [17].

4.        Surfactants: [2,17]

Surfactants can function as agents that solubilize, hydrate, or disperse materials. The film dissolves in a matter of seconds during formation, releasing an active agent swiftly. Benzalkonium chloride, tweens, polyethylene glycol, sodium lauryl sulfate, and others are examples of surfactants that are frequently utilized [18]. One of the most significant surfactants for solubilizing, wetting, and dispersing materials is poloxamer 407.

5.    Sweeteners: [17]

These days, sweeteners are an integral ingredient of both nutraceutical and pharmaceutical products. Sweeteners liquefy in the tongue. The following are some sources of sweeteners: glucose, fructose, liquid glucose, maltose, and dextrose. Fructose is commonly used as a sweetener since it is sweeter than sorbitol and mannitol [18]. They also have a cooling effect and a pleasant tongue sensation. It is possible to mix polyhydric alcohols like sorbitol, mannitol, and malt. Two major benefits of polyhydric alcohols are that they are less carcinogenic and have no aftertaste, which is important when creating oral therapies.

6.    Saliva Stimulating Agent: [19]

The fast-dissolving film formulations disintegrate more quickly when more saliva is produced. As a result, the formulations might contain acids that stimulate saliva production as food is being prepared. Salivary stimulants include tartaric acid, ascorbic acid, lactic acid, malic acid, and citric acid. In this category, people most commonly prefer citric acid [20].

7.    Flavouring Agent:[20]

You can add any flavour to the recipe that has been approved by the US FDA. E.g., strong mints, sour fruit flavours, or sugary candy flavours. Depending on the kind and strength of the flavour, the amount of agent required to cover it. The primary goal of adding colouring additives to pharmaceutical dosage forms is to give them a distinctive look. Natural colours like chlorophylls and curcumin, as well as EU and FD colours, make up the entire colour spectrum. [6,20]

Manufacturing Methods:

 One of the following methods can be used to prepare fast-dissolving oral film.

Solvent casting Method: [7,21]

Films were developed using solvent casting. After carefully weighing the polymer and dissolving it in water, glycerine was added to the mixture (solution I). With the aid of a magnetic stirrer, Mix the drug and additional substances with water in a separate beaker to make a solution. The colour and flavour are added to the mixture and continuously whirled for 15 minutes to liberate all trapped air bubbles. After that, the mixture was put in a Petri dish and allowed to dry for a full day at room temperature. These films were removed from the petri dish when they were dried and cut into predefined shapes and sizes. Films are placed in desiccators and wrapped in aluminium foil for further analysis [22].

Semi-solid Casting Method: [22]

The first step in the semisolid casting process is a polymer solution that forms films in water. The resulting mixture is combined with a sodium-based polymer solution.to dissolve an acid-insoluble polymer (such as cellulose acetate butyrate or phthalate), use sodium hydroxide or ammonium hydroxide. The right quantity of plasticizer is then added, which results in the development of a gel mass. In the end, heat-controlled drums are used for casting. The gel substance is contained in the films or strips. The film has a thickness that varies between 0.015 and 0.05 inches. For the acid-insoluble and film-forming polymers, a ratio of 1:4 [22].

Solid dispersion Method: [23]

This method produces solid dispersions by extruding the medication with immiscible ingredients. Finally, dies are used to form the solid dispersions into films.

Hot Melt Extrusion: [23]

The current method prepares the mass first and then regulates temperature and steering speed. Following coating, the film is dried in a drying tunnel where airflow, temperature, and line speed are all again regulated. Punching and sealing the films is the final step, after which they are slit. Hot melt extrusion is first used to combine the drug and carriers in a solid state. After that, the mixture is melted using a heated extruder. After that, dies are used to mold the melt into films. Using the rolling method, a drug-containing suspension or solution is rolled on a carrier. Water and a mixture of alcohol and water make up the solvent's major constituents. The film is cut into the proper sizes and shapes after it has dried on the rollers. Using a high-shear processor, additional components, such as active substances, were dissolved in a small amount of an aqueous solvent. Water is used to dissolve soluble substances to produce a homogenous, viscous solution [24, 25].

EVALUATION PARAMETERS: 

The following parameters are assessed for FDOFs.

Weight of the Films: [25]

By weighing mouth-dispersing oral films with an analytical balance, the average weight of each film could be ascertained. A nearly constant weight for the films is desirable. It's crucial to make sure a film contains the appropriate quantity of API and excipients.

Film Thickness: [25]

Five distinct locations were used to measure the film's thickness using a micrometre screw gauge, and an average of three values was determined. This is necessary to ensure consistency in the film's thickness This has a direct bearing on how accurately the dose is shown in the movie.

Folding Endurance: [26]

To measure folding endurance, a film strip is cut and folded several times at the same location where it broke. The folding endurance rating is based on how many times a film can be folded in the same way without breaking. Film typically has a folding endurance of 100 to 150.

Tensile Strength: [27]

Tensile strength is the maximum stress applied to the point at which the strip specimen splits. A formula can be utilized to determine it.

Percentage Elongation: [28]

Strain is the term used to describe how much a material extends when subjected to stress. In essence, strain is the film's distortion divided by the substrate's initial dimension. In general,

The longer the film, the more plasticizer there is in it.

The formula used to calculate it is

% Elongation       =    strip's length increase  100 ÷    initial length of strip

Surface pH: [28]

After adding 0.5 ml of distilled water to a Petri dish containing the film to be tested, the dish was left for 30 seconds. Following one minute of equilibration and contact between the pH meter's electrode and the formulation's surface, the pH was measured. Three determinations on average were made for every formulation.

In vitro Disintegration Test: [11,21,28]

 The moment an oral film begins to break when it comes into contact with saliva or water is known as the disintegration time. A fast-dissolving film should dissolve in 5 to 30 seconds at most. The United States Pharmacopoeia (USP) disintegration equipment can be used to study disintegration time. Using a different technique, the film can be dipped in 25 ml of water in a beaker to visually measure the disintegration time. Gently shake the beaker, and record the moment the film begins to shatter or disintegrate.

Organoleptic Evaluation:

The film should exhibit appropriate organoleptic properties, such as colour, flavour, and taste, as it breaks down in the oral cavity.

Property of swelling: [29]

The investigation of film swelling employs a saliva solution that is mimicked. Weighing every film sample and putting it in a stainless steel wire mesh that has been previously weighed 15 millilitres of medium are poured over the mesh containing the film sample in a plastic container. The weight of the film was gradually increased until a constant weight was observed.

The formula for estimating the degree of swelling was

 α = wt - wo/wo

where,

Wt. is the weight of the film at times,

 And Wo is the weight of film at time zero

Transparency: [27]

The transparency of the films can be measured using a basic UV spectrophotometer. Cut the film into a rectangle then insert it into the spectrophotometer cell. Ascertain the film's transparency at 600 nm.

Transparency = (log T600)/b =  єC

Where,

 b = film thickness (mm)

 T600 = transmittance at 600 nm

 C = concentration.

Drug Content Uniformity: [30]

Any standard test procedure specified for the specific API is used to determine this. Not your typical pharmacopoeia. Sampling the material from the API to assess content homogeneity.85–115% is the limit of content consistency for an individual strip.

CONCLUSION:

These days, tongue-dissolving films are becoming more and more successful in the worldwide market; all that's needed to successfully conceal a flavour is the dissolving film, which is a pharmaceutical formulation that is taken "without water," and has many benefits over traditional oral disintegrating tablets. The reason so many pharmaceutical firms have launched this technology and film is because it is crucial in emergency circumstances such as infection, hypertension, etc., and because it has high patient compliance and requires simple equipment and methods to create. This mouth-displacing film offers economically viable developmental potential for the future.

ACKNOWLEDGEMENT:

We are thankful to Principal and Management of Ali Alllana College of Pharmacy, Akkalkuwa for providing all necessary facilities during this study.

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