Presented byMr. MAYUR R. KHINVASARA

(M. Pharm. Sem. II)Roll No. A-11

Department of PharmaceuticsS. S. D. J. COLLEGE OF PHARMACY,CHANDWAD

BUCCAL FILM : INNOVATIVE DRUG DELIVERY SYSTEM

BDDS

CONTENTS♪ INTRODUCTION♪ ANATOMY AND PHYSIOLOGY OF

ORAL CAVITY.♪ ADVANTAGES♪ DISADVANTAGES♪ ROLE OF SALIVA ♪ ROLE OF MUCUS♪ TRANSPORT OF MATERIAL ACROSS

THE ORAL MUCOSA♪ FORMULATION♪ METHODS OF PREPARATION♪ EVALUATIONS♪ REFERENCES

INTRODUCTION• A drug can be administered via many different routes to

produce a systemic pharmacologic effect.• The most common method of drug administration is via the

peroral route, in which the drug is swallowed and enters the systemic circulation primarily through the membranes of the small intestine.

• Although this type of drug administration is commonly termed oral. peroral is a better term because oral administration more accurately describes drug absorption from the mouth itself.

• In general, buccal DDS drugs penetrate the mucous membrane by simple diffusion and are carried in the blood, which richly supplies the salivary glands and their ducts, into the systemic circulation via the jugular vein.

• Buccal drug delivery has lately become an important route of drug administration.

Continued…

• Buccal film drug-delivery systems were first developed in the late 1970s as based on the technology of the transdermal patch. an alternative to tablets, capsules, and syrups for pediatric and geriatric patients who experienced difficulties in swallowing traditional oral solid-dosage forms.

• This delivery system consists of a thin film, which is simply placed on the patient’s tongue or mucosal tissue, instantly wet by saliva; the film rapidly dissolves.

• Then it rapidly disintegrates and dissolves to release the medication for oral mucosal absorption.

• Buccal film is prepared using hydrophilic polymer that rapidly dissolves on the tongue or buccal cavity.

ANATOMY AND PHYSIOLOGY OF ORAL CAVITY The different anatomical

regions of the oral cavity and mucosal tissues.

The various target sites for drug delivery may include- The inner surfaces of

the upper and lower lips.

Gums (gingiva), Hard and soft palate, Floor of the mouth

(sublingual), Tongue and buccal

mucosal tissue (cheek).

Fig. The anatomic regions of the oral cavity.

• Oral cavity offers a unique environment for delivering the drugs.

• The oral mucosal tissue consists of a keratinized epithelium in the masticatory region consisting of the gums (gingivae), palatal mucosa, and inner sides of the lips.

• The sublingual (floor of mouth) and the buccal mucosa are nonkeratinized.

• The keratinized areas of the hard palate and gingival tissue resist shear forces and abrasion caused by food materials.

• The masticatory regions have an underlying submucosa in the hard palate. Submucosa is absent in the gingiva.

• Submucosa contains mucus salivary glands, greater palatine nerves, and blood vessels.

• It serves to anchor the buccal mucosa to the periosteum of the maxillae and palatine bones.

Continued…

ADVANTAGES• No need of water to swallow or chew• Available in various size and shapes.• Hydrate and dissolves in the buccal cavity within a fraction

of seconds.• Fast disintegration or dissolution.• Polymer used should be non toxic and non irritant.• Taste masking.• Enhanced stability.• Small size for improved patient compliance.• Ease of handling and transportation.• No risk of chocking.• Rapid onset of action.• To avoid first-pass metabolism.

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

o Packaging of films requires special equipments and it is difficult to pack.

o High dose cannot be incorporated into the oral film.o Eating and drinking may become restricted.o Buccal films are moisture sensitive.

DISADVANTAGES

ROLE OF SALIVA • Continuous mineralization / demineralization of the tooth enamel • Protective fluid for all tissues of the oral cavity• To hydrate oral mucosal dosage forms

ROLE OF MUCOS• Bioadhesion of mucoadhesive drug delivery systems• Made up of proteins and carbohydrates.• Lubrication.

TRANSPORT OF MATERIAL ACROSS THE ORAL MUCOSA

The majority of drugs move across epithelial membranes, including the oral epithelia, by passive mechanisms which governed primarily by the law of diffusion.

Diffusion layer

Mucosal membrane

In the case of simple diffusion, two potencial routes of material transports across the epithelium are-

1. Transcellular pathways2. Paracellular pathways.

In Transcellular routes involves transport into and across cells.

In Paracellular routes involves the passages of molecules through intercellular space

FORMULATIONS

S. No. INGREDIENTS AMOUNT (w/w)1. Drug 1-30%2. Film forming polymer 40-50%3. Plasticizer 0-20%4. Saliva stimulating agent 2-6%5. Sweetening agent 3-6%6. Flavoring agent q.s.7. Surfactant q.s.8. Colors, Filler q.s.

DRUG (ACTIVE PHARMACEUTICAL INGREDIENT)

• Different type of API can be successfully incorporated in the buccal film.

• Micronized API can improve the texture of the film and also dissolution and uniformity of the oral fast dissolving film.

• Taste of bitter drug need to be masked for that cyclodextrins or resins can be used; they prevent the direct contact of API with the saliva.

• The dug should have high solubility and high permeabilility (BCS class I).

• The drug should have low dose• It includes-

• Cough/Cold Remedies (antitussive, Expectorants)- Ambroxol HCL.• CVS Agent- Valsartan, Verapamil.• Antihistamines- Levocetrizine HCL, • Antiasthamatics- Salbutamol sulphate, Montelukast sodium.• Nausea- Domperidone,• Pain- NSAIDS (Paracetamol, Tramadol, Ibuprofen, Nimusulide)

FILM FORMING POLYMER• Polymers play an important role in the film formation.• Hydrophilic polymers are used in the preparation.• Now a day’s both natural and synthetic polymers are used in the oral

cavity.• Natural polymers are safe, effective and devoid of side effect so more

preferred than synthetic polymers.• Ideal properties-

It should be inexpensive and readily available It should have good wetting and spreadibility property.

Natural polymer Synthetic polymerPullulan Hydroxypropylmethyl cellulose

(HPMC)Starch Polyvinyl pyrrolidone (PVP)Pectin KollicoatSodium alginate Hydroxypropyl celluloseMaltodextrin Carboxy methyl cellulose (CMC)Lycoat NG 73 Poly ethylene oxide

PLASTICIZERS• Plasticizers are the important excipient of the oral film.• The selection of film forming polymers, is one of the most important

and critical parameter for the successful development of film formulation.

• It improves the flexibility and a mechanical property of the film like tensile strength and elongation and reduces the brittleness of the strip.

• Plasticizer significantly improves the strip properties by reducing the glass transition temperature of the polymer.

• A plasticizer should be selected so that it must be compatible with the drug.

• Plasticizer can improve the flow and enhances the strength of polymer.

• Different plasticizers used in the preparation of the oral films are Glycerol, propylene glycol, polyethylene glycol 400, dimethyl, dibutyl, diethyl phthalate, actyl citrate, triacetin and castor oil.

SALIVA STIMULATING AGENTΩ These are used to increase the secretion of saliva so that the

oral film disintegrate and dissolve faster in the oral cavity.Ω The acids which are used in the preparation of food are

generally used as saliva stimulators.Ω Citric acid, malic acid, lactic acid, ascorbic acid, tartaric acid

are the saliva stimulating agent.

† Sweeteners are used for the taste masking of bitter drugs so that drugs are palatable.

† Natural as well as artificial sweeteners are used in the preparation of oral film.

† Natural sweeteners used are xylose, ribose, glucose, sucrose, maltose, steviosides, dextrose, fructose, liq. Glucose.

† Fructose is sweeter than sorbitol and mannitol and thus widely used as a sweetner.

† Artificial sweetners used in oral films are sodium or calcium saccharine salts.

† Sucralose have more than 200-600 times sweet.† Neotame & Altitame have more than 2000- 8000 times sweetening

power as compared to sucrose.

SWEETENING AGENT

FLAVORING AGENT• Flavouring agent are those ingredients which impart flavour to any

of the formulation.• Any US-FDA approved flavour can be added to the formulation

according to the choice of the individuals of different age groups.• The flavours liking changes with the age as geriatric population like

menthol, mint or orange flavour while young generation like fruit, raspberry, strawberry flavour.

• Flavouring agent should be compatible with the drug and other excipients.

• Flavouring agent can be extracted from different part of the plant like leaves, flower, fruit, bark, and seeds.

SURFACTANT Surfactant are used as a solubilizing or wetting or dispersing

agent so that the film gets dissolve within seconds and release the active agent instantly.

One of the most important surfactant is poloxamer 407 that is used as solubilizing, wetting and dispersing agent.

Some of the commonly used surfactants are sodium lauryl sulphate, tweens, span.

METHOD OF PREPARATION

• Buccal film can be prepared by five methods:1. Solvent casting method2. Semisolid casting method3. Hot melt extrusion4. Solid dispersion technique.5. Rolling method

• Generally Solvent casting method is most preferred for the manufacture of fast dissolving film.

SOLVENT CASTING METHOD

1.• In solvent casting method

excipients are dissolved in water. Then water soluble polymers and in last drug is added.

2.• Solution are stirred with help

of magnetic stirrer for 5 mins to form a homogenous solution

3.• Finally casted in to the Petri

plate and dried at 40°C temp in hot air oven.

SEMISOLID CASTING METHOD

1. In semisolid casting method firstly a solution of water soluble film forming polymer is prepared.

2. 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.

3. Then appropriate amount of plasticizer is added so that a gel mass is obtained.

4. Finally the gel mass is casted in to the films or ribbons using heat controlled drums.

5. 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.

HOT MELT EXTRUSION1. The drug is mixed with carriers in solid form.2. Then the extruder having heaters melts the mixture.Finally the melt is shaped in to films by the dies. There

are certain benefits of hot melt extrusion.• Fewer operation units• Better content uniformity• An anhydrous process

1) A solution or suspension containing drug is rolled on a carrier. 2) The solvent is mainly water and mixture of water and alcohol.3) The film is dried on the rollers and cutted in to desired shapes

and sizes. 4) Other ingredients including active agent are dissolved in small

portion of aqueous solvent using high shear processor. 5) Water soluble hydrocolloids dissolved in water to form

homogenous viscous solution.

ROLLING METHOD

SOLID DISPERSION TECHNIQUE.

1. The term solid dispersions refer to the dispersion of one or more active ingredients in an inert carrier in a Solid state in the presence of amorphous hydrophilic polymers.

2. Drug is dissolved in a suitable liquid solvent3. Incorporated solution into the melt of polyethylene

glycol, below 70°C4. Solid dispersions are shaped into the films by

means of dies.

EVALUATION OF THE BUCCAL FILM1. Mechanical propertiesA. ThicknessB. Dryness/tack testC. Tensile strengthD. Percent elongationE. Young’s modulusF. Folding endurance

2. Organoleptic test3. Swelling test4. Surface pH test5. Contact angle6. Transparency7. Assay/ content uniformity8. Disintegration test9. In-vitro dissolution test

MECHANICAL PROPERTIES1. Thickness• The thickness of film is measured by micrometer screw gauge or

calibrated digital Vernier Callipers. • The thickness of film should be in range 5-200 μm. The thickness

should be evaluated at five different locations (four corners and one at centre) and it is essential to ascertain uniformity in the thickness of film as this is directly related to accuracy of dose distribution in the film.

2. Tensile StrengthThe maximum stress applied to a point at which the strip breaks is called as tensile strength. Was calculated by equation- Load at breakStrip break × Strip Width

3. Folding EnduranceFolding endurance is measured by Manual repeated folding of film at same place till it broke. The number of time the film is folded without breaking is known as the folding endurance value.

Tensile strength =

4. Young’s Modulus The measure of stiffness of the strip is young’s modulus. It is measured by using houns field universal testing

machine. It is represented by equation-slope × 100strip thickness ×cross-head speed

5. Percent ElongationWhen 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 increases.Percent elongation= L*100/L0

L = Increase in length of filmL0 = Initial length of film

Young modulus =

SWELLLING TEST1) Film swelling studies is conducted using simulated saliva solution.2) Each film sample is weighed and placed in a preweighed stainless

steel wire mesh.3) The mesh containing film sample is submerged into 15ml

medium in a plastic container.4) 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 by

• W= Wt-Wo/Wo• Where,• Wt- is weight of film at time t,• Wo is weight of film at time zero.

IN VITRO DISSOLUTION TIME

• The in vitro dissolution study is carried out in simulated saliva solution pH 6.4 phosphate buffer using USP paddle apparatus at 37±0.5°C.

• Samples are withdrawn at regular time interval and analyzed by UV-Visible spectrophotometer.

ASSAY/DRUG CONTENT AND CONTENT UNIFORMITY

Drug content is determined by any standard assay method which is described for the particular API in any standard pharmacopoeia. Limit of content uniformity is 85-115%

TRANSPARENCYThe measurement of the oral film transparency can be

determined by using a simple UV spectrophotometer.Cut the film sample into rectangles and placed on the internal

side of the spectrophotometer cell. Now determine the transmittance of the film at 600 nm. The transparency of film was calculated as follows-

Transparency = (logT600)/b = CWhere,

T600 = Transmittanceb = Film thicknessC = Concentration

IN VITRO DISINTEGRATION TEST

Disintegration time is the time when an oral film starts breaking when brought in contact with water or saliva.

For a fast dissolving film, the time of disintegration should be in range of 5-30s.

United State Pharmacopoeia (USP) disintegration apparatus can be used to study disintegration time.

In another method, the disintegration time can be visually determined by dipping the film in 25 ml water in a beaker.

The beaker should be shaken gently and the time was noted when the film starts to breaks or disintegrates.

SURFACE PH TEST• The surface pH of buccal film can cause side effects to the oral

mucosa, so it is necessary to evaluate the surface pH of film.• The surface pH of film should be 7 or close to neutral.• For this purpose, a combined pH electrode can be used with the

help of water, buccal film was made slightly wet and the pH was measured by bringing electrode in contact with surface of oral film.

• This study should be done on at least six films of each formulation and their mean ± SD can be calculated.

• In another method to determine the surface pH, the films are placed on the 1.5%w/v agar gel and then the pH paper are placed on the film, change in color of pH paper gives surface pH of the film.

MARKETED FORMULATIONS

REFERENCES

1) Arya Arun, Chandra Amrish, Sharma Vijjay, (2010). Fast Dissolving Oral Films: An Innovative Drug. International Journal of ChemTech Research. 2 (1), pp.576-583.

2) Varma Shubham, Kumar Nitin, Sharma Promod Kumar, (2014). Buccal Film: An Advance Technology for Oral Drug Delivery. Advances in Biological Research. 8 (6), pp.260-267.

3) Thakur Nishi, Bansal Mayank, Sharma Neha,, (2013). Overview “A Novel Approach of Fast Dissolving. Advances in Biological Research. 7 (2), pp.50-58.

4) Jain N.K., (2005). Controled and Novel Drug Delivery. 1st ed. New Delhi: CBS Publishers and Distributers. pp- 52-56.

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