FABRICATION OF BIOADHESIVE OCUSERT WITH DIFFERENT POLYMERS: ONCE A DAY DOSE
Keywords:Polymeric matrix, Ocuserts, In vivo tests, Once-daily
Objective: The objective of this current study is to fabricate ocuserts to control the drug release from chosen bioadhesive polymeric matrixes to enhance patient compliance. Ciprofloxacin HCl (CFX HCl) was selected as a model drug.
Methods: Different bioadhesive polymers with different film forming capabilities namely Hydroxy Propyl Methyl Cellulose (HPMC K4M), Poly Vinyl Alcohol (PVA), Sodium Carboxy Methyl Cellulose (Na CMC), Hydroxy Propyl Cellulose (HPC), Sodium Alginate (Na Alg.), pullulan and Xanthan Gum (XG) in different ratios were used in fabricating ocuserts using solvent-casting technique. Propylene Glycol (PG) was used as a plasticizer to facilitate the fabrication process. Characterization tests of the developed ocuserts were performed as well as bioadhesive tests and in vitro release studies of the incorporated drug. The obtained results were analysed using different release kinetic models. Stability of the selected ocuserts was investigated at 40Â±0.5 Â°C and 75Â±5% Relative Humidity (RH) for three months' storage period. In vivo ocular irritation test was performed to investigate the safety of the formula in rabbits' eyes as well as to test the release profile and thus to estimate In vitro In vivo correlation.
Results: All the prepared ocuserts showed the uniformity of film characterization and bioadhesion strength ranged from 240Â±66 and 158Â±52dyne/cm2. Selected formula from the in vitro release study tested for in vivo study showed the slow release of ciprofloxacin drug up to 24 h with no signs of eye irritancy. Results for In vitro In vivo correlation showed an excellent correlation with R2 value of 0.9982.
Conclusion: PVA based ocuserts proven to be a promising once-daily, effective and safe ocular delivery system of the drug.
Peneva PT. Non-steroidal anti-inflammatory drugs for topical ophthalmic administration: contemporary trends. Int J Pharm Pharm Sci 2015;7:13-9.
Sharma PK, Kumar A, Bajpai M, Sachdeva M, Kumar P. Formulation, optimization and evaluation of ocular inserts of ciprofloxacin hydrochloride. Biosci Biotechnol Res Asia 2008;5:757-62.
Alany RG, Rades T, Nicoll J, Tucker IG, Davies NM. W/O microemulsions for ocular delivery: Evaluation of ocular irritation and precorneal retention. J Controlled Release 2006;111:145-52.
Nanjawade BK, Manvi FV, Manjappa AS. In situ-forming hydrogels for sustained ophthalmic drug delivery. J Controlled Release 2007;122:119-34.
Sahoo KS, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discovery Today 2008;13:144-51.
Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 2009;71:505-18.
Amar A, Ashish K, Ajaykumar P, Anand J. Formulation and evaluation of controlled release ocuserts of betaxolol hydrochloride. IOSR J Pharm 2012;2:34-8.
Abdou EM, Kandil SM. Formulation and evaluation of dorzolamide and timolol ocuserts. Int J Pharm Sci Res 2017;8:915-24.
Tofighia P, Soltani S, Montazam SH, Montazam SA, Jelvehgari M. formulation of tolmetin ocuserts as carriers for ocular drug delivery system. Iran J Pharm Res 2017;16:432-41.
Chourasia A, Agrawal S. Development and evaluation of ciprofloxacin hydrochloride loaded ocular insert by using PLANTAGO OVATAâ€ as a natural polymer. Int J Curr Pharm Res 2018;10:79-88.
Shah HP, Prajapati ST, Patel CN. Gastroretentive drug delivery systems: from conception to commercial success. J Crit Rev 2017;4:10-21.
Kharenko EA, Larionova NI, Demina NB. Mucoadhesive drug delivery systems (Review). Pharm Chem J 2009;43:200-8.
Koelwel C, Rothschenk S, Fuchs Koelwel B, Gabler B, Lohmann C, Gopferich A. Alginate inserts loaded with epidermal growth factor for the treatment of keratoconjunctivitis sicca. Pharm Dev Technol 2008;13:221-31.
Deshpande PB, Dandagi P, Udupa N, Gopal SV, Jain SS, Vasanth SG. Controlled release polymeric ocular delivery of acyclovir. Pharm Dev Technol 2010;15:369-78.
Blondeau JM. Fluoroquinolones: mechanism of action, classification, and development of resistance. Surv Ophthalmol 2004;49:S73â€“S8.
Shazly GA. Ciprofloxacin controlled-solid lipid nanoparticles: characterization, in vitro release, and antibacterial activity assessment. Biomed Res Int 2017:1-9. Doi:10.1155/2017/ 2120734.
Abhilash AS, Jayaprakash S, Nagarjan M, Dhachinamoorthi D. Design and evaluation of timolol ocuserts. Indian J Pharm Sci 2005;67:311-4.
Nayak BS, Patnaik SC, Sethy S, Ellaiah P, Sarangi BK. Formulation design and in vitro-in vivo evaluation of moxifloxacin ophthalmic insert. Am J Phytomed Clin Ther 2015;3:302-12.
Abul Ella SS. A pharmaceutical study on an antihistaminic drug absorbed from the buccal cavityâ€, [MSc Thesis], Misr university for science and technology (MUST). 6th of October governorate, Egypt; 2011.
Balasubramaniam J, Srinatha A, Pandit JK. In vitro microbiological evaluation of polyvinyl alcohol-based ocular inserts of ciprofloxacin hydrochloride. Indian J Pharm Sci 2006;68:626-30.
Kaul S, Kumar G, Kothiya P. Design and evaluation of soluble ocular drug insert for controlled release of acyclovir. Int J Drug Res Tech 2012;2:393-8.
Sharma J, Sharma S, Kaura A, Durani S. Formulation and in vitro evaluation of moxifloxacin ocular inserts. Int J Pharm Pharm Sci 2014;6:177-9.
Ale A, Sharma SN. Fabrication of a through-flow apparatus for in vitro determination of drug from ophthalmic preparations. Ind Drugs 1991;29:157-60.
Ashture A, Kankudte A, Patil A, Joshi A. Formulation and evaluation of controlled release ocular inserts of betaxolol hydrochloride. IORS J Pharm 2012;2:34-8.
Gilhotra RM, Gilhotra N, Mishra DN. Piroxicam bioadhesive ocular inserts: physicochemical characterization and evaluation in prostaglandin-induced inflammation. Curr Eye Res 2009;34:1065-73.
Ikram M, Gilhotra N, Gilhotra RM. Formulation and optimization of mucoadhesive buccal patches of losaratan potassium by using response surface methodology. Adv Biomed Res 2015;4:239.
Patel VM, Prajapati BG, Patel MM. Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharm 2007;57:61â€“72.
Higuchi T. Mechanism of rate of sustained-action medication. J Pharm Sci 1963;52:1145-9.
Grattarda N, Perninb M, Martyb B, Roudauta G, Champion D. Study of the release kinetics of small and high molecular weight substances dispersed into spray-dried ethylcellulose microspheres. J Controlled Release 2002;84:125-35.
Dave V, Paliwal S, Yadav S. Formulation and evaluation of controlled delivery of aceclofenac through the ocular insert. Turk J Pharm Sci 2013;10:205-20.
Guidance for Industry Q1A (R2) Stability testing of new drug substances and products; 2003.
Al shawwa SZ, Obaidat A, Sallam A, Salem MS. In vivo study of promising formulated ocular bio-adhesive inserts of ciprofloxacin hydrochloride combination with xanthan gum and carbopol. Int J Pharm Pharm Sci 2017;9:229-5.
Abdelkader H, Piercionek B, Alany RG. Novel in situ gelling ocular films for the opioid growth factor-receptor antagonist-naltrexone hydrochloride: Fabrication, mechanical properties, mucoadhesion, tolerability and stability studies. Int J Pharm 2014;477:631-42.
Peyman GA, Paque JT, Meisels HI, Bennett TO. Postoperative endophthalmitis: a comparison of methods for treatment and prophlaxis with gentamicin. Ophthalmic Surg 1975;6:45-55.
Pawar PK, Katara R, Majumdar DK. Design and evaluation of moxifloxacin hydrochloride ocular inserts. Acta Pharm 2012;62:93â€“104.
Sankar V, Chandrasekaran AK, Durga S, Geetha G, Ravichandran VA. Design and evaluation of diclofenac sodium ophthalmic inserts. Acta Pharm Sci 2006;48:5-10.
Shanmugam S, Valarmathi S, Satheesh K. Sterility testing of procedure of ophthalmic ocuserts acyclovir used for treating herpes simplex virus. Asian J Pharm Clin Res 2017;10:344-6.
Sarath CC, Shirwalkar A, Kiron SS. Development and evaluation of chitosan containing ciprofloxacin Î²-CD complex. Int J Pharm Tech Res 2010;2:246-52.
Attia MA, Al-Azizi M, Hashish MS. Design and evaluation of ciprofloxacin hydrochloride ocular inserts. Int J Pharm Tech Res 2011;3:1750-63.
Sudeendra BR, Umme H, Gupta RK, Shivakumar HG. Development and characterization of bioadhesive vaginal films of clotrimazole for vaginal candidiasis. Acta Pharm Sci 2010;52:417-26.
Yoo JW, Dharmala K, Lee CH. The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system. Int J Pharm 2006;309:139-45.
Karavas E, Georgarakis E, Bikiaris D. Application of PVP/HPMC miscible blends with enhanced mucoadhesive properties for adjusting drug release in predictable pulsatile chronotherapeutics. Eur J Pharm Biopharm 2006;64:115-26.
Joshi HN, Wilson TD. Calorimetric studies of dissolution of hydroxypropyl methylcellulose E5 (HPMC E5) in water. J Pharm Sci 1993;82:1033â€“8.
Wu K, XU ZL, Wei YM. Sodium alginate-polyvinyl alcohol/polysulfone (SA-PVA/PSF) hollow fiber composite pervaporation membrane for dehydration of ethanol-water solution. J Shanghai Univ (English Ed) 2008;12:163-70.
Kodavaty J, Deshpande AP. Mechanical and swelling properties of poly (vinyl alcohol) and hyaluronic acid gels used in biomaterial systems a comparative study. Def Sci J 2014;64:222-9.
Siepmann J, Siegel RA, Rathbone MJ. Fundamentals and applications of controlled release drug delivery. Springer: NY, USA; 2012. p. 493-516.
Indian Pharmacopoeia. Vol. I and II; 1996.
Manjula BS, Srinatha A, Sridhar BK. Evaluation of hydrophilic polymers and their combinations in the formulation of sustained-release matrix tablets of a water-soluble drug. Indian J Pharm Edu Res 2014;48:48-69.
Nithiyananthan TS, Shankarananth V, Rajasekhar KK, Jyothikrishna K, Mukesh O, Vikram KE. Preparation and evaluation of ciprofloxacin ocuserts. J Pharm Res 2009;2:1496-9.
Sreenivas SA, Hiremanth SP, Godbole AM. Ofloxacin ocular inserts: design, formulation, and evaluation. Iran J Pharmacol Ther 2006;5:159â€“62.
Mundada A, Shrikhande BK. Formulation and evaluation of ciprofloxacin hydrochloride soluble ocular insert. Curr Eye Res 2008;33:469â€“75.