A Review on Mouth Dissolving Film

Composition Of The System:

A thin film having an area of 2–8 cm2 that contains an active ingredient is called a mouth dissolving film. Water-soluble polymers form a unique matrix that allows for instant disintegration in water or saliva. Up to 30 mg of the medication can be added in a single dose.

The following are ingredients of mouth dissolving film:

Active Pharmaceutical agents:

Any class of pharmaceutically active chemicals that can be taken orally or through the buccal mucosa can contain an active pharmacological ingredient. It contains expectorants, antianginals, antiulcers, antiasthmatics, antitussive, antihistaminic, and antiepileptic medications.
The dosage of the medication should be in milligrams (mg) for an effective formulation (less than 20 mg/day). Several types of medications, including those for erectile dysfunction, antialzheimers, expectorants, antiepileptics, hypnotics, analgesics, anxiolytics, diuretics, antiemetic, neuroleptics, cardiovascular agents, antiallergic, sedatives, antiepileptic, anti-bacterial, and anti-parkinsonian.^(21-22)

Water soluble polymers:

The water-soluble polymers give the films their mechanical qualities, pleasant mouthfeel, and quick disintegration. The molecular weight of polymer film bases is increased to reduce the rate of polymer disintegration. Several water-soluble polymers, such as HPMC E-3 and K-3, methylcellulose A-3, A-6, and A-15, Pullulan, carboxymethylcellulosecekol 30, polyvinylpyrollidone PVP K-90, pectin, gelatin, sodium alginate, hydroxypropylcellulose, polyvinyl alcohol, maltodextrins, and eudragit-RD10, are employed as film formers.
One innovative film-forming polymer is polymerized rosin.^(23-24)

Plasticizers:

formulation plasticizer) variables (their application has been noted as a significant determinant of the mechanical characteristics of films. The inclusion of plasticizers has also enhanced the films' mechanical qualities, including tensile strength and elongation.
These characteristics could be impacted by changes in their concentration. Among the most widely used plasticizers are polyethylene glycols, glycerol, and di-butylphthallate.

Saliva Stimulating Agent:

Increased salivation facilitates the quick breakdown of fast-dissolving film compositions. Therefore, the formulations ought to include acids that are used as salivary stimulants in food preparation. A few examples of salivary stimulants are citric acid, malic acid, lactic acid, ascorbic acid, and tartaric acid; citric acid being the most favored of these.⁽²⁵⁾

Flavoring agents:

You can choose from a variety of flavoring agents, including synthetic flavor oils, oleo resins, and extracts made from plant components including leaves, fruits, and flowers. It is possible to utilize flavors separately or in combination. Any flavor can be added, including peppermint, sweet mint, spearmint, wintergreen, cinnamon, clove, sour fruit flavors like lemon or orange, sweet confectionary flavors like vanillin or chocolate, or fruit essences like apple, raspberry, cherry, and pineapple. Essential oils or water-soluble extracts of menthol are also acceptable. The type and strength of the flavor determine how much flavor is required to cover the taste. ⁽²⁶⁾

Sweetening agents:

Pharmaceutical goods meant to dissolve or disintegrate in the oral cavity now use sweeteners as a crucial component. Sucrose, dextrose, fructose, glucose, liquid glucose, and isomaltose are the traditional sources of sweeteners. In medicinal preparations, artificial sweeteners have grown in favor. First generation artificial sweeteners include saccharin, cyclamate, and aspartame; second generation artificial sweeteners include acesulfame-K, sucralose, alitame, and neotame. ^(27-28)

Coloring agents:

Titanium dioxide and other FD & C-approved coloring ants are utilized in the production of oral fast-dissolving films at concentrations no more than 1% w/w. ⁽²⁹⁾

Surfactants:

In formulation, surfactants serve as solubilizing, wetting, or dispersing agents, allowing the film to dissolve in a matter of seconds and release the active ingredient rapidly. Tweens, sodium lauryl sulfate, and benzoalkonium chloride are a few of the frequently utilized surfactants. Poloxamer 407 is a crucial surfactant that serves as a solubilizing, wetting, and dispersing agent. ⁽³⁰⁾

Methods Of Preparation Of Mouth Dissolving Film:

The Mouth dissolving film can be produced using one or a combination of the following methods:

1. Solvent casting

2. Semisolid casting

3. Solid dispersion extrusion

 4. Hot-melt extrusion

 5. Rolling Method

1. Solvent Casting Method:

After the excipients have been dissolved in water and the mixture has been stirred to produce a uniform solution, the medication is added in the solvent casting process. Water-soluble polymers are then introduced. Finally, the solution is poured into the petri dish and allowed to dry.⁽³¹⁾

2. Semisolid Casting:

This approach creates a uniform viscous solution by mixing a solution of an acid insoluble polymer (such as cellulose acetate butyrate and cellulose acetate phthalate) with a solution of a water soluble film producing polymer.
It is applied on untreated casting film after sonication. The film should have a thickness of 0.015 to 0.05 inches after drying. The acid-insoluble polymer to film-forming polymer ratio need to be 1:4. ^(32-33)

3. Solid dispersion extrusion method:

Immiscible components are first extruded with the medicine to create a solid dispersion, which is subsequently formed into films using dies.⁽³⁴⁾

4. Hot-melt extrusion:

Granular material is created by mixing the carpeting with a solid carrier. Following drying, these granules are added to the extruder. For the granules to stay inside the extruder for three to four minutes, the screw speed should be roughly 15 rpm. The ideal processing temperature is 100?C. To create a film, the extrudate is subsequently squeezed into a cylindrical calendar. ^(35-36-37)

5. Rolling Method :

Water and alcohol-water mixtures are the main solvents used in the rolling process, which involves creating a medication suspension or solution with a film-forming polymer and applying it to the roller. The film is then dried on the rollers and separated into the proper sizes and shapes, with special attention paid to the suspension's or solution's rheology. ⁽³⁸⁾

Evaluation Parameters:

1.Physical Parameters:

a. Appearance:

 All of the produced films can be checked to see if they seem clear or opaque. Although surface characteristics are often assessed visually, instruments like as microscopes can also be used.

b. Thickness:

The thickness of the resulting coating can be measured using micrometer screw gauges at several strategic locations. To determine the mean thickness, measurements should be taken at five different locations on the film: the center and each of the four corners. Maintaining uniformity in the film's thickness is essential because it directly affects the strip's dosage accuracy.

c. Weight variation:

 Weighing each movie separately and calculating the average weights is required. The next step is to deduct the average weight of the films from each one separately. An inefficient mode of administration and pharmaceutical content are suggested by a notable weight variation.

d. Contact angle:

The contact angle can be measured at room temperature using the Goniometer (AB Lorentz and Wetter, Germny). This can be done by applying a droplet of distilled water to the surface of a dry film. Ten seconds after the water droplets are deposited, images of them are taken with a digital camera. The contact angle can be measured on both sides of the descent, and an average is calculated.

e. Transparency:

A simple UV spectrophotometer can be used to evaluate the films' transparency. Place the film into the spectrophotometer cell after cutting it into a rectangle. Determine the transparency of the film at 600 nm. The following formula can be used to determine the transparency of the film:

Transparency= (log T600)/b = ??C 

Where,

 T600= transmittance at 600nm

 b= film thickness (mm)

C= concentration

f. Moisture content:

The degree of moisture affects a film's brittleness and friability. Essentially, the components of the product regulate how much moisture is present in a certain film. In general, the amount of moisture in the film can be ascertained using the weighing method, moisture content measurement apparatus, or Karl Fisher titration method. The amount of moisture in a pre-weighed film of a certain size is shown by the weight difference that results from heating the film to a constant weight, usually between 100 and 120 °C. Use the following formula to determine the moisture content:

% Moisture content= [(Initial weight – Final weight) ×100/Initial weight].  

 The moisture content in an ideal film should be <5%.

2. Chemical Parameters:

a. Surface pH test:

 By placing the film on 1.5% w/v agar gel and then putting pH paper (pH range 1–11) to the film, one can determine the surface pH of the film. The pH paper's hue is tracked and recorded.

b. Disintegration time:

A film's dissolution and disintegration characteristics can be inferred from its disintegration time. Film of the required size (2 × 2 cm2) is placed inside a stainless steel wire mesh that holds 25 ml of simulated salivary fluid with a pH of 6.8. The in-vitro disintegration period is the amount of time needed for a film to break and dissolve.

c. In vitro dissolution test:

A dissolving test can be performed using any of the conventional basket or paddle equipment listed in the pharmacopoeia. The choice of dissolving medium will mostly depend on the API's maximum dosage and the sink's circumstances. The dissolution test can often be difficult since the strip tends to float onto the dissolving medium when paddle equipment is employed.

d. Thermal analysis:

The thermograms of the samples can be recorded using a differential scanning calorimeter, which provides details on the condition of the drug molecules within the film. The drug molecule trapped in the film may be going through a phase transition, recrystallization, or molecular interaction if there is a shift in the endothermic or exothermic peak and an extension of the peak area. The sample will be heated from room temperature to a high temperature (~500°C) in an aluminum pan at a predetermined rate (~10°C/min) for the test.

e. Crystallinity:

It is possible to quickly ascertain if the drug molecule is crystalline or amorphous within the film by using an X-ray diffractometer for X-ray crystallographic analyses. Using a certain X-ray source with a start-to-finish diffraction angle, scan range, and scan speed, the films may be put in the sample holder and XRD transmission diffractograms can be produced.

f. Assay / Content uniformity:

To ascertain this, any standard pharmacopoeia outlining the assay procedure for each unique API will be used. We can assess content consistency by estimating the API content in each strip. The range for content homogeneity is 85–115%.

3. Mechanical Parameters:

a. Dryness / Tack test:

Dryness is the characteristic that is utilized to ascertain the solvent or water content of the film, whereas tenacity is the extent to which the film sticks to any piece of paper placed against the strip. Set-to-touch, dust-free, tack-free, dry-to-touch, dry-hard, dry-through, dry-to-recoat, and dry paper-free are the eight steps in the film drying process. Numerous tools are now available for measuring these attributes. Press your thumb against the film at lab scale to do this.

b. Tensile strength:

The greatest stress applied to the point at which the film specimen breaks is known as the tensile strength. The following formula, which takes the average of three measurements and the fractured film's cross-sectional area, can be used to calculate the applied load at rupture.

Tensile strength = [Breaking force /Cross sectional Area of sample]

c. Percentage elongation:

Elongation is one type of deformation. Anything that is under stress undergoes a simple form shift that may be quantified using a texture analyzer. In other words, a sample subjected to tensile stress elongates, lengthens, or deforms. You can use the following formulas. to calculate it by calculating the lengthening of the film after the tensile measurement:

Percent Elongation = [L-L0] X 100 / L0

Where L be the final length and L0 is initial length.        

d. Young’s Modulus:

The elastic modulus of a film, sometimes referred to as Young's modulus, is used to quantify its stiffness. The methods for measuring tensile strength may also be used here. The following ratio of applied stress to strain in the elastic deformation area might be used to illustrate it.

                   Young’s Modulus= Slope x 100/ Film thickness x cross head Speed

A hard, brittle film with little elongation exhibits a high Young’s modulus and tensile strength.

e. Tear Resistance:

The ability of plastic film or sheeting to withstand tearing is a complex consequence of its ultimate resistance to rupture. 51 (2 in.) /min, a relatively low rate of loading, is essentially used to estimate the force needed to initiate tearing. The maximal stress or force required to tear the specimen, which is frequently discovered near the start of tearing, is represented by the tear resistance value in Newtons (or pounds-force).

f. Folding endurance:

The flexibility of the film is a crucial physical feature needed for easy deployment on the administration site. Folding endurance is a quantitative way to measure the film's flexibility. The film is folded 300 times without breaking or repeatedly at a 180° angle to the same plane until it breaks to determine this. The number of times the film can be folded without breaking is used to compute the folding endurance value.^(39-40)

4. In-vitro Dissolution test:

Any of the pharmacopoeia's conventional basket or paddle apparatus can be used for dissolution testing. In essence, the greatest dose of the API and sink circumstances will determine which dissolution media is used. Because the strip has a propensity to float onto the dissolving medium when the paddle equipment is used, the dissolution test can frequently be challenging.⁽⁴¹⁾

Table 3:  Some of the examples of marketed Fast Dissolving Oral Films.⁽⁴²⁾

CONCLUSION:

Mouth-dissolving films (MDFs) represent a cutting-edge advancement in drug delivery, offering rapid onset of action, enhanced patient convenience, and improved therapeutic efficacy. Their ability to dissolve instantly in saliva without the need for water makes them particularly beneficial for individuals with dysphagia, pediatric and geriatric patients, and those requiring immediate drug action. With continuous innovations in polymer science, nanotechnology, and bioadhesive formulations, MDFs are evolving beyond traditional oral medications, enabling precise dosing, controlled drug release, and incorporation of novel active ingredients. Future developments in personalized medicine and smart film technologies will further expand their potential, revolutionizing the way medications are administered.

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