ORAL BIOAVAILABILITY ENHANCEMEMENT OF BROMOCRYPTINE MESYLATE BY SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM (SMEDDS)
Objective: The purpose of this work was to enhance oral bioavailability of Bromocryptine Mesylate by preparing SMEDDS (self-micro emulsifying drug delivery system)
Methods: Screening of oils, surfactants and co-surfactants were done by solubility study & pseudo ternary diagram. The batches of Bromocryptine Mesylate (BM)â€“SMEDDS were prepared and evaluated for droplet size analysis, poly dispensability index (PDI), robustness to dilution, zeta potential, in vitro dissolution. The optimized batch was compared with commercially available quick release tablets of BM (BrainstarÂ®, 0.8 mg/tablet) by in vivo study (Pharmacodynamic study in rats).
Results: Based on the drugâ€™s solubility study, Akoline MCM, Tween80 and PEG400 were selected as oil, surfactant and co-surfactant, respectively. By pseudo ternary diagram, the componentsâ€™ ratios were screened. In vitro drug release of the optimized batch was lower than the commercial preparation but in in vivo study, optimized batch was similar with commercial tablets.
Conclusion: From the study, it was concluded that the group treated with optimized BM-SMEDDS showed better and sustained reduction in blood sugar as compared to control group and the group treated with marketed formulation, indicated improvement in bioavailability of drug.
Keywords: Bromocryptine Mesylate, Typeâ€“II Diabetes, Self micro emulsifying drug delivery system, Bioavailability, Pharmacodynamic study
2. CM O'Driscolland BT Griffin. Biopharmaceutical challenges associated with drugs with the low aqueous solubility-The potential impact of lipidâ€“based formulations. Adv Drug Delivery Rev 2008;60:617â€“24.
3. S Yang, RN Gursoy, G Lambert, S Benita. Enhanced oral absorption of paclitaxel in a novel self-micro emulsifying drug delivery system with or without concomitant use of p-glycoprotein inhibitors. Pharm Res 2004;21:261â€“70.
4. PP Constantinides, KM Wasan. Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: In vitro/In vivo case studies. J Pharm Sci 2007;96:235â€“48.
5. P Zhang, X Zhang, J Brown, D Vistisen, R Sicree, J Shaw, et al. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87:293â€“301.
6. SOH Pijl, M Matsuda, Y Miyazaki, A Mahankali, V Kumar, R Pipek, et al. Bromocriptine: a novel approach to the treatment of type-II diabetes. Diabetes Care 2000;23:1154â€“61.
7. European Pharmacopoeia: European Directorate for the Quality of medicines and healthcare; 2011. p. 1509.
8. MK Juergendrewe, P Guitard, Andre pellet, Britton Johnston, Christophbeglinger. The relevance of pH dependency on in vitro release of bromocriptine from a modifiedâ€“release formulation. J Pharm Sci 1991;80:160â€“3.
9. CW Poulton and, CJH Porter. Formulation of lipid-based delivery systems for oral administration: Materials, methods, and strategies. Adv Drug Delivery Rev 2008;60:625â€“37.
10. M Joshi, S Pathak, S Sharma, V Patravale. Solid microemulsion preconcentrate (NanOsorb) of artemether for effective treatment of malaria. Int J Pharm 2008;362:172â€“8.
11. CJH Porterand, WN Charman. Intestinal lymphatic drug transport: an update. Adv Drug Delivery Rev 2001;50:61â€“80.
12. SJR Adhvait R Dixit, Samir G Patel. Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS Pharm SciTech 2010;11:314â€“21.
13. T Gershanik, Haltner E, Benita S. Charge-dependent interaction of self-emulsifying oil formulations with CACOâ€“2 cell monolayers: binding, effects on barrier function and cytotoxicity. Int J Pharm 2000;211:29â€“36.
14. Goyal BR, Solanki N, Goyal RK, Mehta AA. The investigation into the cardiac effects of spironolactone in the experimental model of type 1 diabetes. J Cardiovasc Pharmacol 2009;54:502-9.
15. Subhrojit Sen, Moumita Roy, Abhay Sankar Chakraborti. Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats. J Pharm Pharmacol 2011;63:287â€“96.
16. Nahla S Barakat, Alanood S Almurshedi. Design and development of gliclazide-loaded chitosan microparticles for oral sustained drug delivery: inâ€“vitro/inâ€“vivo evaluation. J Pharm Pharmacol 2011;63:169â€“78.
17. BS Gursoy RN. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother 2004;58:173â€“82.
18. RJ Barry, Eggenton J. Membrane potentials of epithelial cells in small rat Intestine. J Physiol 1972;227:201-16.