Review on Oral Fast Dissolving Film Technology: Materials, Methods

Oral route of medicine administration is a most favored route due to its ease of administration, non-invasiveness, rigidity, patient compliance and adequacy. Regarding oral route of  medicine administration, numerous backups have continuously been presented by using recent  new technologies for pediatrics,  elders,  squeamish andnon-compliance cases. Bioadhesive mucosal lozenge forms including  tenacious tablets, gels and patches are  issues of technological development. Among  colorful lozenge forms, the use of polymeric  flicks for delivering  drug into buccal  depression has developed great  eventuality in recent area. Orally disintegrating flicks( ODFs), when placed on  lingo,  incontinently hydrates by soaking  slaver following decomposition and/ or dissolution releasing active pharmaceutical agent from the lozenge form. ODFs are kind of phrasings which are generally prepared using hydrophilic polymers enabling rapid-fire dissolution upon contact with slaver. Oral disintegrating tablets (ODTs) and oral disintegrating flicks( ODFs) are the typical  exemplifications of orally disintegrating  medicine delivery systems. These systems were developed in late 1970 to serve as an  volition to conventional lozenge forms, for case, fast disintegrating tablets and capsules for  elders and pediatric cases having difficulty in swallowing conventional lozenge forms. A typical ODF is  generally equal to the size of a postage stamp ^[1]  In  request place, the  preface of ODT was  explosively associated with comforting of cases about the applicable administration by giving instruction like ‘‘ do not chew/ do not swallow’’ still, in  malignancy of these instructions, incidents regarding biting  and swallowing were  frequently reported.^[2]

1.1 Special features of Dissolving film ^[3]

• Thin elegant film
• Rapid drug release
• Fast disintegration and dissolution

Advantages of oral film ^[4]

• No need of water for administration
• Convenient for pediatric, geriatric and dysphasic patients having difficulty in swallowing.
• Rapid disintegrating and dissolution in the oral cavity due to larger surface area of films.
• Rapid onset of action
• Reduce dose, enhances the efficacy and safety profile of the drug with reduced side effects
• Ease of administration to mentally ill, disabled , uncooperative patients and the patients who are on reduced liquid intake plans

Ideal properties of film forming polymers ^[5]

• The polymers should be inert, nontoxic and non-irritant.
• The polymer should have a better mouth feel property and good shelf-life.
• The polymer should exhibit good spread ability and wetting property.
• The polymers need to possess sufficient tensile, shear and peel strengths.
• The polymer should be economical and readily available.

2. Formulation of dissolving film

• Active pharmaceutical ingredient
• Film forming polymers
• Plasticizers
• Sweetening agent
• Saliva stimulating agent
• Surfactants
• Flavouring agent
• Colouring agent

Active pharmaceutical agents: The active substance is may be from any class of pharmaceutically active substances that can be administered orally or through the buccal mucosa respectively. According to literature, API can be added from 5%-25% w/w of total weight of polymer. For the effective formulation, dose of drug should be in mgs (less than 20 mg/day). The drugs which are potent, show high first pass metabolism and patient non- compliant are best candidates for fast dissolving buccal films. Researchers have shown interest in development of fast dissolving films for drugs like: Pediatrics (antitussive, expectorants, antiasthamatics), Geriatrics (antiepileptic, expectorants), Gastrointestinal diseases, Nausea (e.g. due to cytostatic therapy), Pain (e.g. migraine), CNS (e.g. antiparkinsonism therapy).

Among which favored active agents include chlorpheniramine maleate, brompheniramine maleate, dexchloropheniramine, triprolidine hydrochloride, acrivastine, azatadine maleate, loratidine, phenylephrine hydrochloride, dextromethorphan hydrochloride, ketoprofen, sumatriptan succinate, zolmitriptan, loperamide, famotidine, nicotine, caffeine, diphenhydramine hydrochloride, and pseudophedrine hydrochloride, and their amounts per strip can be well known in the art.

Polymers A variety of polymers are available for medication of fast dissolving buccal  flicks. The polymers can be used alone or in combination to  gain the asked  film  parcels. The film  attained should be tough enough so that there will not be any damage while handling or during transportation. The robustness of the strip depends on the type of polymer and the  quantum in the expression. The  colourful polymers to make fast dissolving  flicks include cellulose or cellulosederivatives, pullulan, Gelatin, hydroxypropyl methyl cellulose,hydroxyethylcellolose,hydroxypropyl cellulose, polyvinylpyrrolidone, carboxymethylcellulose, polyvinylalchohal, sodium alginate, xanthine goo, tragacanth goo, guar goo, acacia goo, methylmethacrylate copolymer and hypromellose are most generally used for medication of fast dissolving  flicks. Modified beans are also used for medication. Due to low cost of this excipient it's used in combination of pullulan to  drop the overall cost of the product. Pullulan is a natural polymer  attained from nonanimal origin and does n't bear chemical  revision. About 50 to 80 percent w of pullulan can be replaced by  bounce in the  product of fast dissolving  flicks without loss of  needed  parcels of Pullulan. Combination of microcrystalline cellulose and maltodextrin has also been used to formulate fast dissolving  flicks. Kulkarni et al., 2010 explored different polymers for use in  expression of oral fast dissolving strips. Different polymers viz., HPMC E15, HPMC K4M, HPMC E5, PVP, PVA, gelatin, eudragit RL100 and pullalan were used to formulate  presto dissolving buccal  flicks; by solvent casting  system. Results  verified that pullalan is stylish polymer for oral fast dissolving strips ^[6]

Plasticizers: Plasticizer 7- 8 is a vital  component of the fast dissolving buccal  flicks  expression. The mechanical  parcels  similar as tensile strength and  extension to the  flicks can be  bettered by the addition of the plasticizer. Variations in their  attention affect these  parcels. The selection of the plasticizer will depend upon its  comity with the polymer and also the type of solvent employed in its casting. Plasticizers include glycerine, sorbitol, propylene glycol, polyethylene glycol, triacetin, di- butylpthalate, triethyl citrate, acetyl triethyl citrate and other citrate esters. generally the plasticizers are used in the  attention of 0- 20 w/ w of the dry polymer weight ^[7]. unhappy use of the plasticizer may lead to film cracking,  unyoking,  shelling of the strip and it may also affect the  immersion rate of the  medicine.

 Surfactants: Surfactants are used as solubilizing or wetting or dispersing agents so that the film gets dissolved within seconds and release active agent  incontinently. Surfactants also ameliorate the solubility of  inadequately answerable  medicines in fast dissolving buccal  flicks. Some of the generally used are polaxamer 407, sodium lauryl sulfate, benzalkonium chloride, benzthonium chloride, tweens and spans etc ^[8]

Sweetening agents: Sweeteners have come the important part of pharmaceutical products intended to be disintegrated or dissolved in the oral  depression. The classical source of sweetener is sucrose, dextrose, fructose, glucose, liquid glucose. The  agreeableness of fructose is perceived  fleetly in the mouth as compared to sucrose and dextrose. Fructose is sweeter than sorbitol and mannitol and  therefore used extensively as a sweetener. Polyhydric alcohols  similar as sorbitol, mannitol can be used in combination as they  also  give good mouth ‐  sense and cooling sensation. Polyhydric alcohols are less carcinogenic and don't have bitter after taste which is a vital aspect in formulating oral medications. The artificial sweeteners have gained generation of the artificial sweeteners followed by acesulfame ‐ K, sucralose, alitame and neotame which fall under the alternate generation artificial sweeteners. Acesulfame ‐ K and sucralose have further than 200 and 600 time agreeableness. Neotame and alitame have  further than 2000 and 8000 time  enhancing power as compared to sucrose. Rebiana which is a herbal sweetener, deduced from factory Stevia rebaudiana( South American factory) has  further than 200 ‐ 300 time  agreeableness ^[9]

Saliva Stimulating Agents: The purpose of using slaver stimulating agents is to increase the rate of  product of  slaver that would  prop  in the  briskly decomposition of the  rapid-fire dissolving strip  phrasings. Generally acids which are used in the medication of food can be  employed as salivary  instigations. Citric acid, malic acid, lactic acid, ascorbic acid and tartaric acid ¹⁰ are the many  exemplifications of salivary  instigations, citric acid being the most  favored amongst them.

Flavoring agents: seasoning agents can be  named from the synthetic flavor canvases, oleo resins, excerpt  deduced from  colorful  corridor of the  shops like leaves, fruits and flowers. Flavors can be used alone or in the combination. Any flavor can be added  similar as essential canvases  or water answerable excerpts of menthol,  violent mints  similar as peppermint, sweetmint, spearmint, wintergreen, cinnamon, clove, sour fruit flavor  similar as bomb, orange or sweet confectionery flavors ¹¹ similar as vanillin, chocolate, or fruit  substance like apple,  jeer, cherry, pineapple. The  quantum of flavor  demanded to mask the taste depends on the flavor type and its strength.

Coloring agents: A full range of colours is available including FD & C colors, EU colours, natural colouring more fashionability in pharmaceutical medications. Saccharin, cyclamate and aspartame are the firstColoring agents A full range of colours is available including FD & C colors, EU colours, natural colouring agents, and natral juice concentrates,  colors  similar as titanium oxide, silicon dioxide and zinc dioxide and custom pantone- matched colours. These all coloring agents should n't exceed  attention  situations of 1 w/ w. these agents are incorporated when some of the  expression  constituents or  medicines are present in  undoable or  suspense form.

2.1 The ideal chracteristics of drug to be selected

• The drug should have pleasant taste.
• The therapeutic dose of the drug should not be greater than 40 mg.
• The drug should have small molecular size and stability in water as well as in saliva.

Methods of preparation of Films

There are some methods in which oral dissolving films can be prepared, each of the methods are described below

1. Preparation of film using, solvent casting method
2. Semisolid casting
3. Hot melt extrusion
4. Solid dispersion extrusion
5. Rolling method

1. Solvent Casting Method It's one of the generally used  styles for the  expression of film. It's prepared using water-answerable polymers, excipients and  medicine. Due to the  operation of high shear, force a homogenous admixture is formed( Figure 1). The  result  attained is poured into antipode spread with coating  cutter to  gain  invariant consistence ^[12]

Figure 1: Solvent casting method

 

Fig No. 2 Hot melt extrusion

 

Fig No. 3 Semi solid casting method

Fig No. 4.Solid Dispersion Extrusion Method

    REFERENCES

1. Arya A, Chandra A, Sharma V, Pathak K. Fast dissolving oral films: an innovative drug delivery system and dosage form. Int J ChemTech Res. 2010;2:576–583.
2. Bhyan B, Jangra S, Kaur M, Singh H. Orally fast dissolving films: innovations in formulation and technology. Int J Pharm Sci Rev Res. 2011;9(2):9–15.
3. Bala R, Pawar P, Khanna S, Arora S. Orally dissolving strips: a new approach to oral drug delivery system. Int J Pharm Investig. 2013;3(2):67.
4. Jangra PK, Sharma S, Bala R. Fast dissolving oral films: novel way for oral drug delivery. Int J Uni Pharma Bio Sci. 2014;3(1):6–27.
5. Nagar P, Singh K, Chauhan I, Verma M, Yasir M, Khan A, et al. Orally disintegrating tablets: formulation, preparation techniques and evaluation. J Appl Pharm Sci. 2011;1:35–45.
6. Kulkarni AS, Deokule HA, Mane MS, Ghadge DM. Exploration of different polymers for use in the formulation of oral fast dissolving strips. J Curr Pharm Res. 2010;2(1):33–35.
7. Sakellariou P, Rowe RC. Interactions in cellulose derivative films for oral drug delivery. Prog Polym Sci. 1995;20(5):889–942.
8. Mahajan A, Chhabra N, Aggarwal G. Formulation and characterization of fast dissolving buccal films: a review. Der Pharm Lett. 2011;3(1):152–165.
9. Raymond CR, Sheskey PJ, Owen SC. Handbook of Pharmaceutical Excipients. 5th ed. London: Pharmaceutical Press; 2006.
10. Rowe RC, Sheskey PJ, Weller PJ, editors. Handbook of Pharmaceutical Excipients. 6th ed. London: Pharmaceutical Press; 2006. p. 94–96.
11. Prakash I, DuBois GE, Clos JF, Wilkens KL, Fosdick LE. Development of rebiana, a natural, non-caloric sweetener. Food Chem Toxicol. 2008;46(7 Suppl 1):S75–S82.
12. Siddiqui MN, Garg G, Sharma PK. A short review on a novel approach in oral fast dissolving drug delivery system and their patents. Adv Biol Res. 2011;5(6):291–303.
13. Barnhart SD. Thin film oral dosage forms in modified release. Drug Dev Technol. 2007;1:34–35.
14. Nishimura M, Matsuura K, Tsukioka T, Yamashita H, Inagaki N, Sugiyama T, et al. In vitro and in vivo characteristics of prochlorperazine oral disintegrating film. Int J Pharm. 2009;368(1–2):98–102.
15. Mahajan A, Chhabra N, Aggarwal G. Formulation and characterization of fast dissolving buccal films: a review. Der Pharm Lett. 2011;3(1):152–165.
16. Zayed GM, Abd-El Rasoul S, Ibrahim MA, Saddik MS, Alshora DH. In vitro and in vivo characterization of domperidone-loaded fast dissolving buccal films. Saudi Pharm J. 2020;28(3):266–273.
17. Patil H, Tiwari RV, Repka MA. Hot-melt extrusion: from theory to application in pharmaceutical formulation. AAPS PharmSciTech. 2016;17(1):20–42.
18. Thakur RR, Rathore DS, Narwal S. Orally disintegrating preparations: recent advancement in formulation and technology. J Drug Deliv Ther. 2012;2(3):87–96.
19. Goel H, Rai P, Rana V, Tiwary AK. Orally disintegrating systems: innovations in formulation and technology. Recent Pat Drug Deliv Formul. 2008;2(3):258–274.
20. Prabhu SC, Parsekar SD, Shetty A, Monteiro SS, Azharuddin M, Shabaraya AR. A review on fast dissolving sublingual films for systemic drug delivery. Int J Pharm Chem Sci. 2014;3(2):501–511.
21. Daud AS, Sapkal NP, Bonde MN. Development of Zingiber officinale in oral dissolving films: effect of polymers on in vitro, in vivo parameters and clinical efficacy. Asian J Pharm. 2011;5(3).
22. Nair AB, Kumria R, Harsha S, Attimarad M, Al-Dhubiab BE, Alhaider IA. In vitro techniques to evaluate buccal films. J Control Release. 2013;166(1):10–21.
23. Sievens-Figueroa L, Bhakay A, Jerez-Rozo JI, Pandya N, Romañach RJ, Michniak-Kohn B, et al. Preparation and characterization of hydroxypropyl methyl cellulose films containing stable BCS class II drug nanoparticles for pharmaceutical applications. Int J Pharm. 2012;423(2):496–508.
24. Liew KB, Tan YTF, Peh KK. Characterization of oral disintegrating film containing donepezil for Alzheimer disease. AAPS PharmSciTech. 2012;13(1):134–142.
25. Ahmed MG, Charyulu RN, Harish NM, Prabhu P. Formulation and in vitro evaluation of chitosan films containing tetracycline for the treatment of periodontitis. Asian J Pharm. 2009;3(2).
26. Saini S, Nanda A, Dhari J. Formulation, development and evaluation of oral fast dissolving anti-allergic film of levocetirizine dihydrochloride. J Pharm Sci Res. 2011;3(7):1322.
27. El-Setouhy DA, El-Malak NSA. Formulation of a novel tianeptine sodium orodispersible film. AAPS PharmSciTech. 2010;11(3):1018–1025.
28. Lakshmi PK, Sreekanth J, Sridharan A. Formulation development of fast releasing oral thin films of levocetirizine dihydrochloride with Eudragit® EPO and optimization through Taguchi orthogonal experimental design. Asian J Pharm. 2011;5(2).
29. Arya A, Chandra A, Sharma V, Pathak K. Fast dissolving oral films: an innovative drug delivery system and dosage form. Int J ChemTech Res. 2010;2(1):576–583.
30. Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Control Release. 2009;139(2):94–107.
31. Gauri S, Kumar G. Fast dissolving drug delivery and its technologies. Pharma Innov. 2012;1(2 Part A):34