Formulation and In vivo studies of Clopidogrel by Self-Nanoemulsifying Drug Delivery System
Abstract
A self-nano emulsifying drug delivery system (SNEDDS) has been explored to improve poorly water-soluble drug clopidogrel’s solubility and dissolution rate. Different formulations were prepared using oil, surfactant, and co-surfactant in varying ratios. From the ternary phase diagram resultant formulations were investigated for clarity, phase separation, drug content, % transmittance, globule size, freeze-thaw, in vitro dissolution studies, particle size analysis, and zeta potential. Based on particle size, zeta potential and dissolution profile, and other studies, F6 was the best formulation of clopidogrel SNEDDS. The particle size of the optimized SNEDDS formulation was found to be 5.2 nm, and zeta potential was found to be -29 mV which complies with the requirement of the zeta potential for stability. The % release from optimized SNEDDS formulation F6 was highest (98.93%) and faster than other SNEDDS formulations and pure drug substance (32%), indicating the influence of droplet size on the drug dissolution rate. FTIR data revealed no physicochemical interaction between drug and excipients. In vivo bioavailability studies were carried out on the optimized formulation (F6), mean time to attain peak drug concentration (Tmax) was 0.5 ± 0.53 and 1.5 ± 0.72 minutes for the optimized and pure drug, respectively, while means maximum drug concentration (Cmax) was 6.77 ± 1.73 ng/mL and 2.10 ± 0.39 ng/mL respectively. AUC0-α and AUC0-t for the optimized formulation were significantly higher (p<0.05) 20.5 ± 2.48 ng.h/mL than the pure drug 6.34 ± 1.73 ng h/mL, respectively. Thus, the results indicate clopidogrel with SNEDDS formulation may be used to improve solubility and dissolution rate for the effective management of heart disease.
Keywords:
Clopidogrel, myocardial infarction, Acrysol K150, Solubility, Self-nano emulsifying drug delivery systemDOI
https://doi.org/10.25004/IJPSDR.2021.130504References
Patwekar SL, Baramade MK. Controlled release approach to novel multiparticulate drug delivery system. Int J of Pharm and Pharmaceul Sci. 2012; 4(3):757–763.
Sharma M, Sharma R, Jain DK. Nanotechnology based approaches for enhancing oral bioavailabilit y of poorly water-soluble antihypertensive drugs. Scientifica. 2016; 1:1-11.
Bang LM, Chapman TM, Goa KL. Clopidogrel: A review of its efficacy in the management of hypertension. Drugs. 2003; 63:2449-72.
Borghi C. Clopidogrel in Hypertension. Vasular Health and Risk Management. 2005; 1 (3):173-182.
Herbette LG, Vecchiarelli M, Sartani A. Clopidogrel: short plasma half-life, long duration of action and high cholesterol tolerance updated molecular model to rationalize its pharmacokinetic properties. Blood Press Suppl. 1998; 2:10–17.
Patel J, Kevin G, Anjali P, Mihir R, Navin S. Design and development of a self-nanoemulsifying drug delivery system for Telmisartan for oral drug delivery. Int J Pharm Investig. 2011; 1(2):112-118.
Sermkaew N, Ket jinda W, Boonme P, Phadoongsombut N, Wiwattanapatapee R. Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from crude extract of Andrographispaniculata. Eur J Pharm Sci. 2013;50(3–4):459–66.
Gurjeet K, Pankaj C, Harikumar SL. Formulation Development of Self Nanoemulsifying Drug Delivery System (SNEDDS) of Celecoxib for Improvement of Oral Bioavailability. Pharmacophore. 2013; 4(4):120-133.
Rajinikanth PS, Neo WK, Sanjay G. Self-nanoemulsifyingdrug delivery systems of Valsartan: preparation and in-vitro characterization. Int J of Drug Deliv. 2012; 4(2):153–163.
Zhongcheng K, Xuefeng H, Xiao-bin J. Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D. Drug Des Devel Ther. 2016; 10: 2049- 2060.
Chirag R, Neha J, Jitendra P, Upadhyay UM. Enhanced oral bioavailability of olmesartan by using novel solid SEDDS. Int J of Advan Pharma. 2012; 2:82-92.
Gupta AK, Mishra DK, Mahajan SC. Preparation and in-vitro evaluation of self-emulsifying drug delivery system of antihypertensive drug Valsartan. Int J Pharm Life Sci. 2011; 2 (3): 633-639.
Bhikshapathi DVRN, Madhukar P, Dilip KB, Aravind KG. Formulation and characterization of Pioglitazone HCl self-emulsifying drug delivery system. Scholars Research Library. 2015; 5 (2):292-305.
Shaikh FI, Patel VB. Enhancement of dissolution of Clopidogrel Hydrochloride using solid dispersion technique. Research journal of recent sciences. 2015; 4: 299- 307.
Vanita SS, Subhashini NJP. Novel self-nanoemulsion drug delivery system of fenofibrate with improved bio-availability. Int J Pharm Bio Sci. 2013; 4(2):511-521.
Vijaykumar N, Zhijun W, Guru VB. Pharmacokinetic Evaluation of Improved Oral Bioavailability of Valsartan: Proliposomes versus Self-nanoemulsifying drug delivery systems. AAPS Pharm Sci Tech. 2016; 17 (4): 851-862.
Ruan G, Feng SS. Preparation and Characterization of Poly (lactic acid) - poly (ethylene Glycol)-poly lactic acid (PLA-PEG-PLA) microspheres for the controlled release of Paclitaxel. Biomate. 2003; 24: 5307-44.
Lalit KT, Mohan LK. Stability Study and In-vivo Evaluation of Lornoxicam Loaded Ethyl Cellulose Microspheres. IJPSDR. 2014; 6(1): 26-30.
Jinjie Zhang, Qiang Peng, sanjun shi1 Qiang Zhang, Xun sun, Tao gong1 Zhirong Zhang. Preparation, characterization, and in vivo evaluation of a self-nano emulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex. Int J Nanomed. 2011; 6:3405- 16.
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): 2118–2129.
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