DEVELOPMENT OF OLMESARTAN MEDOXOMIL-LOADED CHITOSAN MICROPARTICLES: A POTENTIAL STRATEGY TO IMPROVE PHYSICOCHEMICAL AND MICROMERITIC PROPERTIES
Keywords:
Olmesartan medoxomil, Chitosan, Microparticles, Factorial designAbstract
Objective: The objective of the present research was to improve physicochemical and micromeritic properties of Olmesartan Medoxomil (OLM), BCS class II antihypertensive drug by loading in Chitosan (CH) microparticles.
Methods: The 32 full factorial design was assigned for microparticles prepared by single emulsion technique method using CH, a natural polymer and Glutaraldehyde (GA) as cross linking agent. Developed microparticles were characterized for Micromeritic properties, morphology by Scanning Electron Microscopy (SEM), drug entrapment efficiency, in vitro drug release, and interaction studies Fourier transfer infrared spectroscopy (FTIR) & Differential Scanning Calorimetry (DSC), drug crystallinity study by X-ray diffractometry (XRD) & DSC.
Results: Maximum entrapment efficiency was found 61.76% for maximal CH and lower GA concentration. Saturation solubility of microparticles was increased by 13.74 times to that of pure OLM. FTIR showed compatibility between drug and polymer. XRD, DSC and SEM studies confirmed reduction in crystallinity of drug. It led to increase in dissolution profile of the drug and showed 92.61% of drug release in 120 min. These microparticle preparations also helped in improving micromeritic properties like bulk density, tapped density, the angle of repose, Hausner's ratio and Carr's index.
Conclusion: The results obtained in the present work demonstrate the potential use of CH to modulate physicochemical and micromeritic properties of OLM especially obtaining significant improvement in dissolution rate.
Â
Downloads
References
United States Pharmacopoeia XXXI, The official compendia of standards, The United States Pharmacopoeial Convention, Rockville: 2008.
Rowe R, Shesky P, Owen S. Hand book of Pharmaceutical Excipients. 4thEdition. Chicago. Pharmaceutical Press; 2003. p. 210-11, 345-7.
Gavhane YN, Gurav AS, Yadav AV. Chitosan and its applications: a review of literature. Int J Pharm Biomed Sci 2003;4(1):312-31.
Vyas SP, Khar RP. Targeted and controlled drug delivery. 1st edition. chap. 9, CBS Publishers and distributors: New Delhi; 2002. p. 331-85.
Jia-You F, Chia-Lang F, Chi-Hsien L, Yu-Han S. Solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm 2008;70:633-40.
Kretuer J. Nanoparticulate systems for brain delivery of drugs. Adv Drug Delivery Rev 2001;47:65-81.
Sathali A, Jayalakshmi J. Enhancement of solubility and dissolution rate of olmesartan medoxomil by solid dispersion technique. J Curr Chem Pharm Sci 2013;3(2):123-34.
Yadav AA, Yadav DS, Karekar PS, Pore YV, Gajare P. Enhanced solubility and dissolution rate of Olmesartan medoxomil using crystallo-co-agglomeration technique. Pharm Sin 2012;3(2):160-9.
Singh S, Pathak K, Bali V. Product development studies on surface-adsorbed nanoemulsion of olmesartan medoxomil. Capsular Dosage Form 2012;13(4):1212-21.
Agnihotri A, Nadagouda NMA, Aminabhavi A. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Controlled Release 2004;100:5-28.
Alagusundaram M, Chetty C, Umashankari K, Attuluri V, Lavanya C, Ramkanth S. Microspheres as a novel drug delivery system-a review. Int J ChemTech Res 2009;3(1):526-34.
Nair R, Reddy B, Ashok Kumar CK, Jayraj K. Application of chitosan microspheres as drug carriers: a review. J Pharm Sci Res 2009;2(1):1-12.
Ju-Hwan P, Hyo-Eon J, Dae-Duk K, Suk-Jae C, Won-Sik S, Chang-Koo S. Chitosan microspheres as an alveolar macrophage delivery system of ofloxacin via pulmonary inhalation. Int J Pharm 2013;441:562–9.
Cui-Yun Y, Xi-Chen Z, Fang-Zhou Z, Xian-Zheng Z, Si-Xue C, Ren-Xi Z. Sustained release of antineoplastic drugs from chitosan-reinforced alginate microparticle drug delivery systems. Int J Pharm 2008;357:15–21.
Rawat S, Jain S. Solubility enhancement of celecoxib using beta cyclodextrin inclusion complexes. Eur J Pharm Biopharm 2004;57:263-7.
Dixit M, Kini A, Kulkarni P. Enhancing solubility and dissolution of celecoxib by spray drying using pluronic F127. Indian J Pharm Educ 2011;45(4):346-52.
Ko JA, Park HJ, Hwang SJ, Park JB, Lee JS. Preparation and characterization of chitosan microparticles intended for controlled drug delivery. Int J Pharm 2002;249:165-74.
Jagdale SC, Patil SA, Kuchekar BS. Design, development and evaluation of floating tablets of tapentadol hydrochloride using Chitosan. Asian J Pharm Clin Res 2012;5(4):163-8.
Maestrelli F, Zerrouk N, Cirri M, Mennini N, Mura P. Microspheres for colonic delivery of ketoprofen-hydroxypropyl-cyclodextrin complex. Eur J Pharm Sci 2008;34:1–11.
Labhasetwar V, Deshmukh S, Dorle A. Studies on some crystalline forms of Ibuprofen. Drug Dev Ind Pharm 1993;19:631–41.
Gavini E, Hegge A, Rassu G, Sanna V, Testa C, Pirisino G, et al. Nasal administration of Carbamazepine using chitosan microspheres: In vitro/in vivo studies. Int J Pharm 2006;307:9–15.
Gavhane YN, Yadav AV. Improvement in physicochemical properties of aceclofenac by using chitosan and water soluble chitosan. Int J Pharm Pharm Sci 2013;5(1):414-9.