IN SITU GEL AS PLATFORM FOR KETOCONAZOLE SLOW RELEASE DOSAGE FORM
Keywords:Ketoconazole, In-situ floating gel, Sodium alginate, Guar gum, HPMCK4M, HPMCK15M
Objective: The aim of this study was to formulate ketoconazole (keto) as oral floating in situ gel to slow the release of keto in the stomach.
Methods: Sodium alginate (Na alginate) was used as a primary polymer in the preparation of the in situ gel and was supported by the following polymers: guar gum (GG), hydroxypropyl methylcellulose (HPMC) K4M, K15M and carbapol 940 as viscosity enhancing agents. As a consequence, and to complete the gelation process of above formulations was by adding the calcium carbonate (CaCO3). The in situ gels were investigated by the following tests: floating lag time, floating duration, viscosity, drug content, in vitro gelling studies and in vitro release study.
Results: The study showed that the faster release was obtained with F1 which contained Na alginate alone. Additionally, reduction in Na alginate concentration resulted in significant increase in drug release. It was also noted that the increase in GG (viscosity enhancing polymer) concentration resulted in non-significant decrease in percent drug release and the reduction in CaCO3 concentration led to significant increase in drug release. Moreover, the release of drug was also affected by grade of viscosity enhancing polymer, the faster release was observed with the formula which contained a polymer of low viscosity (HPMC K4M) and an opposite result was with the high viscosity polymer (HPMCK15M).
Conclusion: This study showed the formulation of Na alginate with GG and CaCO3, led to gain floating in situ gel and a sustained release of keto.Â
Nayak AK, Malakar J, Sen KK. Gastroretentive drug delivery technologies: current approaches and future potential. J Pharm Educ Res 2010;1:1-12.
Lopesa CM, Bettencourta C, Rossib A, Francesca Buttinib F, Barataa P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharm 2016;510:144â€“58.
Pawar VK, Kansa S, Garg G, Awasthi R, Singodia D, Giriraj T, et al. Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems. Drug Delivery 2011;18:97â€“110.
Bhardwaj L, Sharma PK, Malviya R. A short review on gastro retentive formulations for stomach specific drug delivery: special emphasis on floating in situ gel systems. Afr J Basic Appl Sci 2011;3:300-12.
Rajinikanth PS, Balasubramaniam J, Mishra B. Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori. Int J Pharm 2007;335:114â€“22.
Darekar AB, Patil VA, Gondkar SB, Saudagar RB. Development and characterization of novel in-situ floating gel of levocetirizine dihydrochloride for oral drug delivery system. Der Pharm Lett 2016;8:188-96.
Rosenfeld GC, Loose DS. Pharmacology 6th ed. Lippincott Williams and Wilkins, a Wolters Kluwer business; 2014. p. 280.
Finkel, Richard, Clark, Michelle A, Cubeddu, Luigi X. Lippincott's illustrated reviews: pharmacology. 4th ed. Lippincott Williams and Wilkins; 2009. p. 410.
Sweetman SS. Martindale: the complete drug refrance. 36th ed. London: Pharmaceutical Press; 2009. p. 539.
Hasan MJ, Kamal BA. Formulation and evaluation of rantidine hydrochloride as floating in situ gel. Int J Pharm Pharm Sci 2014;6 Suppl2:401-5.
Prasad RaoMR, Shelar SU. Controlled release ion sensitive floating oral in situ gel of a prokinetic drug using gellan gum. Indian J Pharm Educ Res 2015;49:158-68.
Kubo W, Miyazaki S, Attwood D. Oral sustained delivery of paracetamol from In situ gelling gellan and sodium alginate formulations. Int J Pharm 2003;258:55-64.
Vipul V, Basu B. Formulation and characterization of novel floating in-situ gelling system for controlled delivery of ramipril. Int J Drug Delivery 2013;5:43-55.
Prasanthi S, Vidyavathim. Formulation and optimization of buoyant in situ gelling system of valsartan using natural polymer. Int J Pharm Pharm Sci 2017;9:128-36.
Thomas LM. Formulation and evaluation of floating oral in situ gel for metronidazole. Int J Pharm Pharm Sci 2014;6:265-9.
Jaafar IS. Formulation and in vitro evaluation of fast dissolving film of metoclopramide hydrochloride. Int J ChemTech Res 2017;10:26-38.
Rao M, Shelarl SU, Yunusil A. Controlled release floating oral in situ gel of itopride hydrochloride using pH sensitive polymer. Int J Pharm Pharm Sci 2014;6:338-43.
Hoi BY, Park HJ, Hwang SJ, Park JB. Preparation of alginate beads for floating drug delivery system: effect of CO2 gas forming agents. Int J Pharm 2002;239:81â€“91.
Kadivar A, Kamalidehghan B, Javar HA, Davoudi ET, Zaharuddin ND, Sabeti B, et al. Formulation and In vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet. PLOS One 2015;10:1-23.
TheUnited State Pharmacopeia (USP) 30, NF28, USA: The United State Pharmacopeial Convention Inc; 2010.
Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Controlled Release 2000;63:235â€“59.
Varshosaz J, Tavakoli N, Roozbahani F. Formulation and in vitro characterization of ciprofloxacin floating and bioadhesive extended-release tablets. Drug Delivery 2006;13:277â€“85.
De Wit D, van Erp NP, Khosravan R, Wiltshire R, Allred R, Demetri GD, et al. Effect of gastrointestinal resection on sunitinib exposure in patients with GIST. BMC Cancer 2014;14:1-8.
Swathi G, Lakshmi PK. Design and optimization of hydrodynamically balanced oral in situ gel of glipizide. JAPS a 2015;5 Suppl 1:31-8.
Kumar KK, Swathi M, Srinivas L, Naseeb Basha S. Formulation and evaluation of floating in situ gelling system of losartan potassium. Der Pharm Lett 2015;7:98-112.
Rohith G, Sridhar BK, Srinatha A. Floating drug delivery of a locally acting H2-antagonist: An approach using an in situ gelling liquid formulation. Acta Pharm 2009;59:345â€“54.
Maheswaran A, Padmavathy J, Nadhini V, Saravanan D, Angel P. Formulation and evaluation of Floating oral in situ gel of diltiazem. Int J Appl Pharm 2017;9:50-3.
Nassoura L, Hasana I, El-Hammadia M, Abboudb H. Floating in-situ-gelling gellan formulations of metformin hydrochloride. J Chem Pharm Res 2014:6:1509-17.
Li S, Lin S, Daggy BP, Mirchandani HL, Chien YW. Effect of HPMC and carbopol on the release and floating properties of gastric floating drug delivery system using factorial design. Int J Pharm 2003;253:13-22.