FORMULATION AND EVALUATION OF SIMVASTATIN GASTRORETENTIVE DRUG DELIVERY SYSTEM
DOI:
https://doi.org/10.22159/ijap.2017v9i3.18763Keywords:
GRRDS, Simvastatin, Polymers, Drug releaseAbstract
Objective: The aim of this study was to formulate and evaluate gastro retentive drug delivery system (GRRDS) using an effervescent approach for simvastatin.
Methods: Floating tablets were prepared using directly compressible polymers hydroxypropyl methylcellulose (HPMC) K100M, HPMC K4M and carboxymethylcellulose sodium (NaCMC). The prepared tablets were subjected to pre-formulation studies like Compressibility index, Hausner ratio and post compression parameters like buoyancy/floating test and In vitro dissolution study.
Results: Drug-excipient compatibility studies performed with the help of FTIR instrument indicated that there were no interactions. The DSC thermogram of the formulations revealed that crystalline form of simvastatin existed in the formulation which was confirmed by X-ray powder diffraction. Dissolution studies indicated that there was a decrease in the drug release with an increase in the polymer viscosity. The tablets prepared with low-viscosity grade HPMC K4M exhibited short Buoyancy Lag Time and floated for a longer duration as compared with formulations containing high viscosity grade HPMC K100M. The ‘n' value for dissolution studies for all the formulations was found to be in the range of 0.647 to 0.975 indicating non-Fickian or anomalous drug transport.
Conclusion: The drug release rate and floating duration of tablets depended on the nature of the polymer and other added excipients. The release rate of the drug can be optimized by using different ratios of polymers and other excipients. The formulation F8 achieved the optimized batch and complied with all the properties of the tablets.
Downloads
References
Todd PA, Goa KL. Simvastatin: a review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs 1990;40:583-607.
Duggan DE, Chen IW, Bayne WF, Halpin RA, Duncan CA, Schwartz MS. The physiological disposition of lovastatin. Drug Metab Dispos 1989;17:166-73.
Vickers S, Duncan CA, Chen IW, Rosgay A, Duggan DE. Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug. Drug Metab Dispos 1990;18:138-45.
McClelland GA, Stubbs RJ, Fix JA. Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through the administration of a controlled porosity osmotic pump dosage form. Pharm Res 1991;8:873-6.
Cheng H, Sutton SC, Pipkin JD, Zetner GM. Evaluation of Sustained/Controlled-release dosage forms of 3-hydroxy-3-methylglutaryl–coenzyme an (HMG-CoA) reductase inhibitors in dogs and humans. Pharm Res 1993;10:1683-7.
Babu AK, Ramana MV. Development and in vivo evaluation of gastro retentive floating tablets of antipsychotic drug risperidone. Int J Pharm Pharm Sci 2016;8:43-52.
Sawant K, Patel P, Patel J, Mundada P. Formulation, optimisation, characterization and in vivo anti-ulcer activity of esomeprazole magnesium trihydrate gastroresistant microspheres. Int J Pharm Pharm Sci 2017;9:273-82.
Castellanos RM, Zia H, Rhodes TC. Design and testing in vitro of a bioadhesive and floating drug delivery system for oral application. Int J Pharm 1994;105:65-70.
Shah HP, Prajapati ST, Patel CN. Gastroretentive drug delivery systems: from conception to commercial success. J Crit Rev 2017;4:10-21.
Rao GK, Mandapalli PK, Manthri R, Reddy VP. Development and in vivo evaluation of gastro retentive delivery systems for cefuroxime axetil. Saudi Pharm J 2013;21:53-9.
Kharwade RS, More SM, Mahajan UN. Formulation and evaluation of gastroretentive floating tablet using hibiscus rosa-sinensis mucilage. Asian J Pharm Clin Res 2017;10;444-8.
Upadhye AA, Ambike AA, Mahadik KR, Paradkar A. Application of ion exchange resin in the floating drug delivery system. Drug Dev Ind Pharm 2008;34:1117-24.
Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable gastroretentive dosage forms. J Controlled Release 2003; 90:143-62.
Baumgartner S, Kristl J, Vrecer F, Vodopivec P, Zorko B. Optimization of floating matrix tablets and evaluation of their gastric residence time. Int J Pharm 2000;195:125-35.
Manna S, Jayasri K, Annapurna KR, Kanthal LK. Alginate based gastro-retentive raft forming tablets for enhanced bioavailability of tinidazole. Int J Appl Pharm 2017;9:16-21.
Chavanpatil M, Jain P, Chaudhari S, Shear R, Vavia P. Development of sustained release gastroretentive drug delivery system for ofloxacin: in vitro and in vivo evaluation. Int J Pharm 2005;304:178–84.
Streubel A, Siepmann J, Bodmeier R. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release. Eur J Pharm Sci 2003;18:37–45.
Dave BS, Amin AF, Patel MM. Gastro retentive drug delivery system of ranitidine hydrochloride: formulation and in vitro evaluation. AAPS PharmSciTech 2004;5:1-6.
Nur OA, Zhang JS. Captopril floating and/or bioadhesive tablets: design and release kinetics. Drug Dev Ind Pharm 2000;26:965-9.
Narendra C, Srinath MS, Babu G. Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention. AAPPS PharmSciTech 2006;7:E1-E7.
Zhang Y, Zhang J, Jiang T, Wang S. Inclusion of the poorly water-soluble drug simvastatin in mesocellular foam nanoparticles: drug loading and release properties. Int J Pharm 2011;40:118–24.
Chavanpatil M, Jain P, Chaudhari S, Shear R, Vavia P. Novel sustained release, swellable and bioadhesive gastro retentive drug delivery system for ofloxacin. Int J Pharm 2006;316:86–92.