SOLUBILITY ENHANCEMENT OF GLIBENCLAMIDE USING MESOPOROUS SILICA
Glibenclamide is a BCS Class II drug and poses a major problem during formulation development. In the present study, adsorption onto various carriers was used to enhance the solubility of glibenclamide. It was observed that solubility of glibenclamide was greatly enhanced by adsorbing onto mesoporous silica. The increase in solubility of poorly soluble drugs is often associated with the generation of supersaturation, which results in the risk of drug precipitation. HPMC E5 was used as precipitation inhibitor to maintain sink condition for a longer duration. A 32 full factorial design was adopted to optimize the ratio of glibenclamide (X1) and mesoporous silica as a carrier (X2) and the effect of different ratios was studied on percent yield, percent drug loading, and percent drug release. X-ray powder diffraction (XRPD) and Differential scanning calorimetry studies were performed to investigate any possible interaction in between glibenclamide and mesoporous silica. An optimum batch of drug adsorbate was used to prepare immediate-release tablets. The tablets prepared were evaluated for thickness, uniformity of weight, hardness, friability, in-vitro disintegration time, and in vitro drug release study.
(2) Kawabata, Y.; Wada, K.; Nakatani, M.; Yamada, S.; Onoue, S. Formulation Design for Poorly Water-Soluble Drugs Based on Biopharmaceutics Classification System: Basic Approaches and Practical Applications. Int. J. Pharm.2011, 420 (1), 1–10.
(3) Xu, W.; Riikonen, J.; Lehto, V. P. Mesoporous Systems for Poorly Soluble Drugs. Int. J. Pharm. 2013, 453 (1), 181–197.
(4) Savjani, K. T.; Gajjar, A. K.; Savjani, J. K. Drug Solubility: Importance and Enhancement Techniques. ISRN Pharm.2012, 2012 (100 mL), 1–10.
(5) O’Shea, J. P.; Nagarsekar, K.; Wieber, A.; Witt, V.; Herbert, E.; O’Driscoll, C. M., et.al., Mesoporous Silica-Based Dosage Forms Improve Bioavailability of Poorly Soluble Drugs in Pigs: Case Example Fenofibrate. J. Pharm. Pharmacol.2017, 69 (10), 1284–1292.
(6) Tahvanainen, M.; Rotko, T.; Mäkilä, E.; A. Santos, H.; Neves, D.; Laaksonen, T.et al., Tablet Preformulations of Indomethacin-Loaded Mesoporous Silicon Microparticles. Int. J. Pharm. 2012, 422 (1–2), 125–131.
(7) Van Speybroeck, M.; Mols, R.; Mellaerts, R.; Thi, T. Do; Martens, J. A.; Humbeeck, J. Van et al., Combined Use of Ordered Mesoporous Silica and Precipitation Inhibitors for Improved Oral Absorption of the Poorly Soluble Weak Base Itraconazole. Eur. J. Pharm. Biopharm. 2010, 75 (3), 354–365.
(8) Guzman, H. R.;Tawa, M.; Zhang, Z.; Ratanabanangkoon, P.; Shaw P.;Gardner, C. R. et al., Combined Use of Crystalline Salt Forms and Precipitation Inhibitors to Improve Oral Absorption of Celecoxib from Solid Oral Formulations Journal of Pharmaceutical Sciences 2007, Vol. 96, 2686–2702.
(9) Brouwers, J.; Brewster, M. E.; Augustijns, P. Supersaturating Drug Delivery Systems: The Answer toSolubility-Limited Oral Bioavailability J Pharm Sci 2009 Aug;98(8):2549-7.
(10) Balaji, A.; Kumari, M. H. International Journal of Pharmacy and Industrial. Int. J. Pharm. Ind. Res. 2013, 3 (4), 335–345.
(11) Nikghalb, L. A.; Singh, G.; Singh, G.; Kahkeshan, K. F. Solid Dispersion: Methods and Polymers to Increase the Solubility of Poorly Soluble Drugs. J. Appl. Pharm. Sci. 2012, 2 (10), 170–175.
(12) Sambasevam, K. P.; Mohamad, S.; Sarih, N. M. Synthesis and Characterization of the Inclusion Complex of ? -Cyclodextrin and Azomethine. 2013, 3671–3682.
(13) Development, D.; Pharmacy, I. Its Derivatives With. 1994, 20 (7), 1275–1283.
(14) McCarthy, C. A.; Ahern, R. J.; Dontireddy, R.; Ryan, K. B.; Crean, A. M. Mesoporous Silica Formulation Strategies for Drug Dissolution Enhancement: A Review. Expert Opin. Drug Deliv. 2016, 13 (1), 93–108.
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