Oral Thin Films - A Review

Introduction:

Recent developments in the pharmaceutical technology have presented viable dosage alternatives from oral route for pediatrics, geriatric, bedridden, nauseous or noncompliant patients. Among these the use of oral thin films for buccal delivery, also known as mouth dissolving film is gaining much attention. A new drug delivery system for the oral delivery of the drugs, was developed based on the technology of the transdermal patch. The delivery system consists of a very thin oral strip, which is placed on the patient’s tongue or any oral mucosal tissue, which instantly gets wet by saliva and the film gets rapidly hydrated and adheres onto the site of application. It then rapidly disintegrates and dissolves to release the medication. OTFs offer fast, accurate dosing in a safe, efficacious format that is convenient and portable, without the need for water. OTFs are typically the size of a postage stamp and disintegrate on a patient's tongue in a matter of seconds for the rapid release of one or more drugs.

Special features of mouth dissolving films:

 • Thin elegant film

• Available in various size and shapes

• Unobstructive

• Excellent mucoadhesion

• Fast disintegration

• Rapid release.

Advantages:

• Convenient dosing.

• No water needed.

 • No risk of chocking.

• Taste masking.

• Enhanced stability.

• Improved patient compliance.

Disadvantages:

·         ODTs are sometimes difficult to carry.

·         Store and handle (fragility and friability).                                                              

·         Special packaging for protection during storage and transportation.

A large number of drugs can be formulated as mouth dissolving films. Innovative products may increase the therapeutic possibilities in the following indications.

Pediatrics (anti-tussives, expectorants, anti-asthamatics)

Geriatrics (antiepileptic, expectorants)

Gastrointestinal diseases

Nausea (e.g. due to cytostatic therapy)

Pain (e.g. migraine)

CNS (e.g. anti-parkinsonism therapy).

Composition of Oral thin films:

Mouth dissolving film is a thin film with an area of 5- 20 cm² containing a drug. The immediate dissolution, in water or saliva respectively, is reached through a special matrix from                   water-soluble polymers. Drugs can be incorporated up to a single dose of 15mg. The formulation considerations (plasticizers etc.) have been reported as important factors which affects the mechanical properties of the films.

Composition:

·         Drug 1-25%

·         Water soluble polymer 40-50%

·         Plasticizers 0-20%

·         Fillers, colors, flavors etc. 0-40%

Drugs:

Several classes of drugs can be formulated as mouth dissolving films including antiulcer (e.g. omeprazole), antiasthamatics (salbutamol sulphate), antitussives, expectorants, antihistaminics, NSAID’S (e.g. paracetamol, meloxicam, valdecoxib)

Water soluble polymers:

Water-soluble polymers are used as film formers. The use of film forming polymers in dissolvable films has attracted considerable attention in medical and nutraceutical application. The water-soluble polymers achieve rapid disintegration, good mouth feel and mechanical properties to the films. The disintegration rate of the polymers is decreased by increasing the molecular weight of polymer film bases. Some of the water soluble polymers used as film former are HPMC E-3 and K-3, Methyl cellulose A-3, A-6 and A-15, Pullulan, CMC, PVA, PVP K-90, Pectin, Gelatin, Sodium Alginate, , and EUDRAGITR D108,9,10,11,12 .

Plasticizers

Formulation considerations (plasticizer, etc.) have been reported as important factors affecting mechanical properties of films. The mechanical properties such as tensile strength and elongation to the films have also been improved by the addition of plasticizers. Variation in their concentration may affect these properties. The commonly used plasticizers are glycerol.

Flavors:

Any flavor can be added, such as intense mints, sour fruit flavors or sweet confectionery flavors. 

Colours:

A full range of colors is available, including FD&C colors, EU Colours, Natural Colors and custom Pantone-matched colors’.

Saliva stimulating agents:

These are also be added to enhance the disintegration and to get rapid release. Some of these agents are citric acid, tartaric acid, malic acid, ascorbic acid and succinic acid.

MANUFACTURING METHODS:

One or combination of the following process can be used to manufacture the mouth dissolving films.

Solvent casting.

Semisolid casting.

Hot melt extrusion.

Solid dispersion extrusion.

Rolling.

Solvent casting method

In solvent casting method water soluble polymers are dissolved in water and the drug along with other excipients is dissolved in suitable solvent then both the solutions are mixed and stirred and finally casted on the petri plate and dried.

Semisolid casting method:

In semisolid casting method, firstly a solution of water soluble film forming polymer is prepared. The resulting solution is added to a solution of acid insoluble polymer (e.g. cellulose acetate phthalate, cellulose acetate butyrate), which was prepared in ammonium or sodium hydroxide. Then appropriate amount of plasticizer is added so that a gel mass is obtained. Finally the gel mass is casted in to the films or ribbons using heat controlled drums. The thickness of the film is about 0.015-0.05 inches. The ratio of the acid insoluble polymer to film forming polymer should be 1:4. Both mixtures are mixed to form homogenous viscous solution degassed under vacuum, bubble free solution is coated on non-treated casting film. Coated film is sent to aeration drying oven and the dried film is cut in to desired shape and size.

Hot melt extrusion:

In hot melt extrusion method firstly the drug is mixed with carriers in solid form. Then the extruder having heaters melts the mixture. Finally the melt is shaped in to films by the dies. The benefits of hot melt extrusion include fewer operation units, better content uniformity and an anhydrous process.

Rolling Method:

In rolling method a solution or suspension containing drug is rolled on a carrier. The solvent is mainly water and mixture of water and alcohol. The film is dried on the rollers and cut in to desired shapes and sizes.

Evaluating parameters:

Mechanical properties:

Mechanical properties of films are evaluated Instron using a TA.XT2 texture analyzer equipment equipped with a 5kg load cell. Films are held between two clamps positioned between 3cm. During measurement the strips were pulled at rate of 2mm/sec. The force and elongation were measured when film breaks. Three mechanical properties namely tensile strength, elastic modulus and % elongation are calculated.

Tensile strength :

Tensile strength is calculated by formula = force at break/ initial cross sectional area of film in mm²

% Elongation :

It is calculated as = Increase in length Original length

Folding endurance :

Folding endurance is determined by folding the films of uniform cross sectional area and thickness until it breaks.

Morphology study :

The morphology of the films is studied using scanning electron microscopy (SEM), at a definite magnification.

Swelling property:

 Film swelling studies is conducted using simulated saliva solution. Each film sample is weighed and placed in a pre weighed stainless steel wire mesh. The mesh containing film sample is submerged into 15ml medium in a plastic container. Increase in the weight of the film was determined at preset time interval until a constant weight was observed. The degree of swelling was calculated using parameters   wt-w0/w0, wt is weight of film at time t, and weight of film at time zero.

 Contact angle :

Contact angle measurements are performed at room temperature with a goniometer. A drop of double distilled water was placed on the surface of the dry film. Images of the water droplet were recorded within 10 seconds of deposition by means of digital camera. A minimum of five measurements, taken at different positions of the film, was carried out. The contact angle was measured on both sides of the drop and averaged.

In vitro disintegration:

In vitro disintegration time is determined visually in a glass dish of 25ml distilled water with swirling every 10 sec. The disintegration time is the time when the film starts to break or disintegrates.

 Packaging :

A variety of packaging options are available for fast dissolving films. Single packaging is mandatory for films, which are pharmaceutical products; an aluminum pouch is the most commonly used packaging format. APR-Labtec has developed the Rapid card, a proprietary and patented packaging system, which is specially designed for the Rapid films. The rapid card has same size as a credit card and holds three raid films on each side. Every dose can be taken out individually.