PharmaTutor PRINT ISSN: 2394-6679 | E-ISSN: 2347-7881 17 Recent industrial development in Oral Thin Film Technology: An Overview Kh. Hussan Reza 1*, Pranabesh Chakraborty2 1 Department of Pharmacy, Bengal School of Technology, Sugandha, Hooghly, West Bengal, India 2 Director, Department of Pharmacy, Bengal School of Technology, Sugandha, Hooghly, WB, India *[email protected] ABSTRACT Oral route of administration is most convenient route but often is disadvantageous for administering to geriatric and paediatric patients. Orally disintegrating film is found to be effective in delivering rapid drug action by dissolving the drug in buccal cavity. Since a decade oral thin films has got commercial importance in generic and non generic market projecting it as a multinational business asset. Current research in this field is found to be associated with industrialization and commercialization. Current article make an overview of not only technological changes in research and manufacturing but also gives an insight about growing market worldwide. Keywords: Oral Thin Film Technology, oral dissolving film, mucoadhesion INTRODUCTION upon placing on tongue instantly dissolves or The oral route is most popular route for the disintegrate the medication without the need of administration of therapeutic agents because of the water. Thus suitable for patients: paediatrics and low cost of therapy and ease of administration lead geriatrics, avoiding-nausea, vomiting and to high levels of patient compliance. The most dysphasia[6]. This system is found to be equally viable popular oral solid dosage forms are tablets and for unconscious or dementia patients as this system capsule[1]. Generally geriatric, paediatric and is capable to secrete saliva and get dissolved. bedridden patient experience difficulties in swallowing the conventional oral dosage form. To The concept of the oral dissolving film [6] overcome this problem a novel formulation was 1. This delivery system consists of a thin film. developed i.e. oral fast dissolving films or oral thin 2. After placing it on the top of the tongue, the film films[2]. Oral thin film was initially first developed in dissolves within seconds, promoting first pass 1970 as a novel initiative of current dosage form[4]. metabolism as compared to tablet and other Oral thin films were first launched in 2004 for immediate release oral solid dosage forms, and may systemic drug delivery and are now widely increase the bioavailability of drug. accepted[3]. [2, 7] Drug delivery via the oral mucosa is a promising Special Features route, when one wishes to achieve a rapid onset of 1. Thin elegant film. action or improved bioavailability for drugs with high 2. Available in various size and shapes. first pass metabolism. Thus, there is a growing 3. Unobstructive. interest in developing alternative dosage forms, i.e. 4. Excellent mucoadhesion. orally fast disintegrating strip, which allow a rapidly 5. Fast disintegration and Rapid release. dissolving drug to absorb directly into the systemic 6. They are made up of water soluble polymers that circulation through the oral mucosa. These kinds of are inert to the drug substances incorporated, most dosage forms are also convenient for children, commonly used polymers include- Hydroxy Propyl elderly patients with swallowing difficulties, and in Methyl Celullose, Pullulan, Poly Ethylene Oxide,Poly the absence of portable liquids[1]. As mentioned in a Vinyl Alcohol, Maltodextrine, Starch, etc. study of 1576 patients 26 % faced difficulty in [1, 7] swallowing due to size, surface and taste[5]. Oral thin Criteria of Oral Dissolving Film films are made up of water a soluble polymer which Fast dissolving film should How to cite this article: Reza KH, Chakraborty P; Recent industrial development in Oral Thin Film Technology: An Overview; PharmaTutor; 2016; 4(8); 17-22 Vol. 4, Issue 8 | magazine.pharmatutor.org PharmaTutor PRINT ISSN: 2394-6679 | E-ISSN: 2347-7881 18 1. Have a pleasant mouth feel. A. EXICIPENT: The excipients used are generally 2. Not require water to swallow, but it should referred from official monographs and other used dissolve or disintegrate in the mouth in matter of within the limits permissible in general the inactive seconds. ingredient list or IIG issued by FDA serves to us as a 3. The drug should have pleasant taste. limit justified to be incorporated in formulations. The 4. Be compatible with taste masking. commonly used excipients are as follows: 5. Leave minimum or no residue in the mouth after oral administration. i. Polymers [11,12,13] 6. Exhibit low sensitivity to environmental conditions To obtain the desired matrix of film, polymers can such as temperature and humidity. be used alone or in combination. In general water- 7. The drug to be incorporated should have low soluble polymers are used as film formers as they dose. undergo rapid disintegration, good mouth feel and 8. Have the ability to permeate oral mucosal tissue. mechanical properties to the films. The strength of the film depends on the type of polymer and the Advantages of Oral Dissolving Film [1, 2, 8, 9, 10] amount in the formulation. By increasing the 1. Improved patient compliance by enhancing of molecular weight of polymer film bases, administration to pediatric, geriatric, bedridden disintegration rate of the polymer decreases. patients and psychiatric patients who refuse to Polymers frequently used as film formers are water swallow tablets. soluble grades of cellulose ethers, polyvinyl alcohol, 2. No need of water to swallow or chew. polysaccharides, polyvinyl pyrrolidone K-90, 3. No risk of chocking. polyethylene glycols, pullulan, gelatin, carboxmethyl 4. Good mouth feel. cellulose cekol 30, hydroxy propyl methyl cellulose E- 5. No special training is required for the 3 and K-3, methyl cellulose A-3, A-6 and A-15, pectin, administration of dosage form. sodium alginate, hydroxypropylcellulose of grades E- 6. Bypassing the first pass effect leads to reduction in 5 ,E15 and LV grades, maltodextrins and eudragit the dose which can lead to reduction in side effects RD10. Recent as per some patents event the use of associated with the molecule. starch as modified starch, pea starch is also reported. 7. Precision in the administered dose. Polymers generally forms about 40% to 50% of the 8. Larger surface area promotes rapid disintegration film matrix. and dissolution in the oral cavity. 9. Oral films are flexible and thus less fragile as ii. Plasticizers [11,14,15] compared to orally dissolving films. Hence, there is Plasticizer enhances mechanical properties or ease of transportation and during consumer handling durability of matrix such as tensile strength and and storage. elongation to the film by reducing the glass 10. Easy transportation. transition temperature of the polymer. It also reduces brittleness of the strip by fixing itself in Limitations of Oral Dissolving Film [1, 2, 9] between the polymer chains acting as a hinge to the 1. Drugs which are unstable at buccal pH cannot be support, as a result improves its flexibility. Choice of administered. plasticizer depends upon type of solvent used and its 2. These dosage forms are moisture sensitive. compatibility with the polymer. Some of the 3. They require special packaging for the products commonly employed plasticizers are phthalate stability and safety. derivatives like dimethyl, diethyl and Dibutyl 4. High dose cannot be incorporated into the oral phthalate, glycerol mono oleate and low molecular film. weight polyethylene glycols, castor oil, citrate derivatives like tributyl, triethyl, acetyl citrate, PHARMACEUTCIAL ASPECT triacetin and glycerol. The phthalates, since it shows The pharmaceutical aspect generally includes the carcinogenegity are not used currently for excipients used and the manufacturing process formulation. Incorrect use of plasticizer may followed in the development of oral thin film, A brief cause blooming, film cracking, splitting and peeling general overview of the process is given below. Vol. 4, Issue 8 | magazine.pharmatutor.org PharmaTutor PRINT ISSN: 2394-6679 | E-ISSN: 2347-7881 19 of the films. Plasticizers generally forms around 0-20 preferred more. Flouring agents are used along with % of the film composition. menthol that provides a typical cooling sensation to the flavor. Apart from regular oil soluble flavors iii. Surfactant [12,14] some volatile flavors are also used as eucalyptol, Surfactants are used multi dimentionally as eugenol, thymol. Some exotic flavors such as vanilla, solubilising agent, emulsifying agent, dispersing chocolate, coffee are also used depending upon the agent. Nonionic surfactants are in general preferred. targeted market. The commonly used surfactants include Tweens, Sodium Laurly Sulphate, Cremophor, Polaxomer. vii. Colouring agents Generally incorporated colouring agents are FD&C [16] iv. Taste masking agents colours, natural colours, pigments such as titanium As most of the drugs are bitter, it’s a challenge to dioxide. The colour selection is generally done based develop an oral thin film with a good acceptable on the formulation and its colour acceptable in the taste. The taste masking techniques used involves market by customers. complexation and use of artificial and natural sweeteners. The complexation of drug generally B. MANUFACTURING PROCESS: involves the use of pollacryline potassium, To manufacture fast dissolving oral films, following cyclodextrine, tannic acid, chitosan. Various artificial methods are generally employed: sweeteners used are