Design and in vivo Evaluation of Manidipine by Self-Nanoemulsifying Drug Delivery Systems
Abstract
The current research is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of Manidipine for enhanced solubility and oral bioavailability. The Manidipine SNEDDS are formulated with excipients comprising of Capmul MCM (oil phase), Transcutol P (surfactant) Lutrol L 300 as co-surfactant. The prepared fifteen formulations of Manidipine SNEDDS analysed for emulsification time, percentage transmittance, particle size, in vitro drug release, and stability studies. In vivo pharmacokinetic studies of the optimized formulation were carried out in Wistar rats in comparison with control (pure drug). The morphology of Manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 is 98.24 ± 5.14%. The particle size F14 formulation was 22.4 nm and Z-Average 23.3 nm. The PDI and zeta potential of Manidipine SNEDDS optimized formulation (F14) were 0.313 and-5.1mV respectively. From in vivo bioavailability data the optimized formulation exhibited a significantly greater Cmax and Tmax of the SNEDDS was found to be 3.42 ± 0.46ng/ml & 2.00 ± 0.05 h respectively. AUC0-∞ infinity for formulation was significantly higher (11.25 ± 3.45 ng.h/ml) than pure drug (7.45 ± 2.24ng. h/ml). Hence a potential SNEDDS formulation of Manidipine developed with enhanced solubility and bioavailability.
Keywords:
Manidipine, Hypertension, SNEDDS, Solubility studies, Pharmacokinetic studies.DOI
https://doi.org/10.25004/IJPSDR.2019.110609References
Charman WN, Stella VJ. Transport of lipophilic molecules by the intestinal lymphatic system. Adv Drug Del Rev. 1991; 7:1-14.
O'Driscoll CM. Lipid-based formulations for intestinal lymphatic delivery. Eur J Pharm Sci. 2002; 15:405-415.
Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007; 6:231-248.
Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK. Development and bioavailability assessment of Ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007; 66:227-243.
Attivi D, Ajana I, Astier A, Demoré B, Gibaud S. Development of microemulsion of mitotane for improvement of oral bioavailability. Drug Dev Ind Pharm. 2010; 36:421-427.
Dixit AR, Rajput SJ, Patel SG. Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS PharmSciTech. 2010; 11:314-321.
Nielsen FS, Petersen KB, Müllertz A. Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. Eur J Pharm Biopharm. 2008; 69:553-562.
Wu X, Xu J, Huang X, Wen C .Self-microemulsifying drug delivery system improves curcumin dissolution and bioavailability. Drug Dev Ind Pharm 2011; 37:15-23.
Cui J, Yu B, Zhao Y, Zhu W, Li H. Enhancement of oral absorption of curcumin by self-micro emulsifying drug delivery systems. Int J Pharm. 2009; 371:148-155.
McKeage K, Scott LJ. Manidipine a review of its use in the management of hypertension. Drugs 2004; 64(17):1923-40.
Cheer SM, McClellan K. Manidipine a review of its use in hypertension. Drugs 2001; 61(12):1777-99.
Chaudhari P, Bhalerao A. Method validation for spectrophotometric estimation of cilnidipine. Int J Pharm PharmSci. 2012; 4(5):96-98.
Talegaonkar S, Mustafa G, Akhter S, Iqbal ZI. Design and Development of Oral Oil-in-Water Nanoemulsion Formulation Bearing Atorvastatin: In Vitro Assessment. J DispersSci Technol.2010; 31(5):690-701.
Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W, Wiwattanaptapee R. Development and Characterization of Solid Self-emulsifying Drug Delivery System of Cilnidipine. Eur J Pharm Biopharm. 2010; 76:475–485.
Constantinides PP, Scalart JP, Lancaster C, Marcello J, Marks G, Ellens H, Smith PL. Formulation and Intestinal Absorption Enhancement Evaluation of Water-in-Oil Microemulsions Incorporating Medium-Chain Glycerides. Pharmaceutical Research 1994; 11(10):1385–1390.
Rajinikanth PS, Keat NW, Garg S. Self-nanoemulsifying drug delivery systems of valsartan: Preparation and in-vitro characterization. International Journal of Drug Delivery 2012; 4(2):153-163.
Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001; 13:123–133.
Dixit P, Jain DK, Dumbwani J. Standardization of an ex vivo method for determination of intestinal permeability of drugs using everted rat intestine apparatus. J Pharmacol Toxicol Methods. 2012; 65:13–17.
Shaji J, Jadhav D. Newer Approaches to Self Emulsifying Drug Delivery System. Int J Pharm PharmSci 2010; 2:37–42.
Sonia A, Rishikesh G, Prajapati S. Self-Micro emulsifying Drug Delivery System. Asian J Pharm Clin Res. 2016; 9(2):33-38.
Zhang J, Peng Q, Shi S, Zhang Q, Sun X, Gong T, Zhang Z.. Preparation, characterization, and in vivo evaluation of a self-nanoemulsifying drug delivery system (sNeDDs) loaded with morin-phospholipid complex. Int J Nanotechnol Nanomed. 2011; 6:3405-14.
Jing J, Ren W, Chen X, He H, Zhou W, Zhu X, Sun Y, Wang G. Determination and pharmacokinetics of manidipine in human plasma by HPLC/ESIMS. Biomed Chromatogr. 2007; 21(8): 836–840.
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