BIOAVAILABILITY ENHANCEMENT BY FLOATING MICROBALLOONS OF DIPYRIDAMOLE AND CLOPIDOGREL: IN VIVO PHARMACOKINETIC STUDY

SEELAM RAMYA KRISHNA; A. RAMU; S. VIDYADHARA; A. PRAMEELA RANI

doi:10.22159/ijap.2021v13i6.42316

Authors

SEELAM RAMYA KRISHNA Department of Pharmaceutics, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur 522510, Andhra Pradesh, India
A. RAMU Department of Pharmaceutics, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur 522510, Andhra Pradesh, India
S. VIDYADHARA Department of Pharmaceutics, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur 522510, Andhra Pradesh, India
A. PRAMEELA RANI Department of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India

DOI:

https://doi.org/10.22159/ijap.2021v13i6.42316

Keywords:

Clopidogrel bisulfate, Dipyridamole, HPLC, Bioavailability enhancement, Pharmacokinetic studies

Abstract

Objective: In vivo pharmacokinetic studies of clopidogrel and dipyridamole floating microballoons to check their bioavailability enhancement.

Methods: The bioanalytical method development was carried by using HPLC with column Poroshell 120 EC-C 18; 4.6x100 mm. The in vivo pharmacokinetic studies were performed in Wistar male rats and the obtained data from the pharmacokinetic parameters were analyzed using PK Solver software.

Results: The developed bioanalytical method was found to be linear in the concentration range of 1-100 ng/ml for clopidogrel bisulfate and 0.02-4µg/ml for dipyridamole with correlation coefficient of 0.9993 and 0.9987 respectively. The study results showed that the method was simple, linear, accurate and precise. The in vivo studies indicated that the AUC was found to be increased by 33.3% and 154.5% for clopidogrel and dipyridamole micro balloons, respectively, when compared to their pure drugs.

Conclusion: The bioanalytical methods development and their validation parameters indicated that the methods are accurate, precise and linear in the studied range of concentrations. In vivo test results infer to the effective, sustained release of both the drugs when formulated as micro balloons and increase in the absorption, thereby enhancing the bioavailability of the drugs. The pharmacokinetic studies also confirmed the increase in the mean residence time of the drugs when formulated as floating microballoons.

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References

Bazzo GC, Pezzini BR, Stulzer HK. Eutectic mixtures as an approach to enhance solubility, dissolution rate and oral bioavailability of poorly water-soluble drugs. Int J Pharm. 2020;588:119741. doi: 10.1016/j.ijpharm.2020.119741.

Beg S, Swain S, Rizwan Md, Irfanuddin Md, Malini DS. Bioavailability enhancement strategies: basics, formulation approaches and regulatory considerations. Curr Drug Delivery. 2011;8(6):691-702. doi: 10.2174/156720111797635504, PMID 21864253.

Jain HK, Deere DD. Bioanalytical method development and validation for estimation of clopidogrel bisulfate in human plasma by RP-HPLC. Int J Appl Pharm. 2016;8:18-21.

Vanshiv SD, Joshi HP, Aware AB. Formulation and development of gastroretentive dipyridamole microspheres: proof of concept by in vitro in vivo assessment. Pharm Sci. 2018;80(1):181-91. doi: 10.4172/pharmaceutical-sciences.1000343.

Joseph NJ, Lakshmi S, Jayakrishnan A. A floating-type oral dosage form for piroxicam based on hollow polycarbonate microspheres: in vitro and in vivo evaluation in rabbits. J Controlled Release. 2002;79(1-3):71-9. doi: 10.1016/s0168-3659(01)00507-7, PMID 11853919.

Javed MK, Iqbal Z, Khan A, Khan A, Shah Y, Ahmad L. Development and validation of HPLC-UV method for the determination of clopidogrel in pharmaceutical dosage form and human plasma. J Liq Chromatogr Relat Technol. 2011;34(18):2118-29. doi: 10.1080/10826076.2011.585482.

Qin T, Qin F, Li N, Lu S, Liu W, Li F. Quantitative determination of dipyridamole in human plasma by high-performance liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study. Biomed Chromatogr. 2010;24(3):268-73. doi: 10.1002/bmc.1283, PMID 19630071.

Nagavi JB, Gurupadayya B. Simultaneous estimation of clopidogrel and atorvastatin in human plasma using bioanalytical RP-Ultra fast liquid chromatographic method. Int J Curr Pharm Res. 2015;7:30-5.

Housheh S, Ali D, Trefi S, Mohammad H, Chehna MF. Optimization of RP-HPLC assay for pharmaceutical analysis of clopidogrel. Int J Pharm Sci Nanotechnol. 2014;7(1):2371-6. doi: 10.37285/ijpsn.2014.7.1.9.

International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Validation of analytical procedures: Text and Methodology. ICH-Q2B. Geneva; 1996.

Awasthi R, Kulkarni GT, Pawar VK, Garg G. Optimization studies on gastroretentive floating system using response surface methodology. AAPS PharmSciTech. 2012;13(1):85-93. doi: 10.1208/s12249-011-9730-y, PMID 22135108.

Yang Z, Song B, Li Q, Fan H, Ouyang F. Preparation of microspheres with microballoons inside for floating drug-delivery systems. J Appl Polym Sci. 2004;94(1):197-202. doi: 10.1002/app.20856.

Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27-31. doi: 10.4103/0976-0105.177703, PMID 27057123.

Kamala G, Vadrevu S, Valli KN. Development and validation of RP-HPLC method for simultaneous estimation of lamivudine and zidovudine in bulk. Int J Curr Pharm Sci. 2016;8:28-33.

Sahai M, Devanna N. Validated stability-indicating HPLC approach for quantifying tricholine citrate and cyproheptadine simultaneously in syrup forms. Int J Appl Pharm. 2021;13:207-13.

Patil PM, Bobade AS. Development and validation of stability indicating RP-HPLC for determination of atorvastatin calcium and ezetimibe in bulk and pharmaceutical dosage forms. Int J Pharm Pharm Sci. 2016;8:38-2.

Grace AC, Prabha T, Jagadeeswaran M, Srinivasan K, Sivakumar T. Analytical method development for simultaneous determination of ubidecarenone and vitamin E acetate in capsule dosage form by HPLC. Int J Pharm Pharm Sci. 2019;11:79-84. doi: 10.22159/ijpps.2019v11i1.30054.

PK, Dvrn B. Development and in vivo evaluation of mucoadhesive microspheres using pirenzepine. Asian J Pharm Clin Res. 2018;11:296-302.

PP, KA, KM. Gastro-floating tablets of repaglinide: preparation and in vivo evaluation. Asian J Pharm Clin Res. 2018;11:291-5.

Husseiny RA, Abu Lila AS, Abdallah MH, Hamed EE, El-ghamry HA. Design, in vitro/in vivo evaluation of meclizine HCl-loaded floating microspheres targeting pregnancy-related nausea and vomiting. J Drug Delivery Sci Technol. 2018;47:395-403. doi: 10.1016/j.jddst.2018.08.012.