Improving dissolution profile of poorly water-soluble drug using non-ordered mesoporous silica

Year 2018, Volume: 22 Issue: 2, 249 - 258, 27.06.2025

Jyotsana R. Madan Shronavi Patil Dyandevi Mathure Santosh P. Bahirat Rajendra Awasthi , Kamal Dua

Abstract

The aim of the study was to increase dissolution rate of atorvastatin by the use of mesoporous silica SYLOID® 244 FP. The poorly soluble drug atorvastatin was adsorbed on and/or into SYLOID® 244 FP in the ratios 1:1, 1:1.1.5, 1:2, 1:2.5, 1:3 and 1:3.5 via a wetness impregnation method. The absence of crystalline form and presence of hydrogen bond interaction between atorvastatin and SYLOID® 244 FP is done by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The atorvastatin loaded matrix lacked in the crystalline form of atorvastatin and it showed improvement in the dissolution rate of ATC. The flowability of the atorvastatin loaded matrix powder was evaluated by bulk density, Carr’s index and angle of repose. This matrix was then processed into a tablet by direct compression method. A 32 full factorial design was applied to investigate the combined effect of two formulation variables - volume of ethanol and amount of SYLOID® 244 FP. The tablets were evaluated for hardness, friability, drug content and drug dissolution studies. The solubility of atorvastatin-loaded matrix was increased up to 4.28 times. Atorvastatin tablet prepared from drug-loaded silica may provide a feasible approach for development of an oral formulation for this poorly water-soluble drug.

Keywords

Non-ordered mesoporous silica , atorvastatin , wetness impregnation method , factorial design , bioavailability

References

• [1] Madan JR, Pawar KT, Dua K. Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy. Int J Pharm Investig. 2015; 5(2): 114-120.
• [2] Singh R, Bharti N, Madan J, Hiremath SN. Characterization of cyclodextrin inclusion complexes - A review. J Pharm Sci Technol. 2010; 2(3): 171-183.
• [3] Madan J, Sudarshan B, Kadam V, Dua K. Formulation and development of self-microemulsifying drug delivery system of pioglitazone hydrochloride. Asian J Pharm. 2014; 27-34.
• [4] Madan JR, Ghuge NP, Dua K. Formulation and evaluation of proniosomes containing lornoxicam. Drug Deliv Transl Res. 2016; 6(5): 511-518.
• [5] Madan JR, Khude PA, Dua K. Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery. Int J Pharm Investig. 2014; 4(2): 60-64.
• [6] Ahuja G, Pathak K. Porous carriers for controlled/modulated drug delivery. Indian J Pharm Sci. 2009; 71(6): 599-607.
• [7] Wang Y, Zhao Q, Hu Y, et al. Ordered nanoporous silica as carriers for improved delivery of water insoluble drugs. Int J Nanomedicine. 2013; 8: 4015-4031.
• [8] Vallet-Regí M, Balas F, Arcos D. Mesoporous materials for drug delivery. Angew Chem Int Ed Engl. 2007; 46(40): 7548-7558.
• [9] Zhao Z, Wu C, Zhao Y, et al. Development of an oral push-pull osmotic pump of fenofibrate-loaded mesoporous silica nanoparticles. Int J Nanomedicine. 2015; 10: 1691-1701.
• [10] Vialpando M, Smulders S, Bone S, et al. Evaluation of three amorphous drug delivery technologies to improve the oral absorption of flubendazole. J Pharm Sci. 2016; 5: 2782-2793.
• [11] Coasne B, Galarneau A, Pellenq RJ, Di Renzo F. Adsorption, intrusion, and freezing in porous silica; the view from the nanoscale. Chem Soc Rev. 2013; 42: 414-417.
• [12] Tarn D, Ashley CE, Xue M, et al. Mesoporous silica nanoparticle nanocarriers: biofunctionality and biocompatibility. Acc Chem Res. 2013; 46(3): 792-801.
• [13] Hillerstrom A, Andersson M, Samuelsson J, van Stam J. Solvent strategies for loading and release in mesoporous silica. Colloid Interface Sci Commun. 2014; 3: 5-8.
• [14] Santosh PB, Neeraj R. Increasing the oral bioavailability of poorly water-soluble valsartan using nonordered mesoporous silica microparticles. Asian J Pharm. 2016; 10(2): S86-S95.
• [15] Kiekens F, Eelen S, Verheyden L, et al. Use of ordered mesoporous silica to enhance the oral bioavailability of ezetimibe in dogs. J Pharm Sci. 2012; 101(3): 1136-1144.
• [16] Jammaer JAG, Aerts A, D’Haen J, et al. Convenient synthesis of ordered mesoporous silica at room temperature and quasi-neutral pH. J Mater Chem. 2009; 19: 190-198.
• [17] Tiwari R, Pathak K. Statins therapy: A review on conventional and novel formulation approaches. J Pharm Pharmacol. 2011; 63: 983-998.
• [18] Shayanfar A, Ghavimi H, Hamishehkar H, Jouyban A. Coamorphous atorvastatin calcium to improve its physicochemical and pharmacokinetic properties. J Pharm Pharm Sci. 2013; 16(4): 577-587.
• [19] Maheshwari RK, Jagwani Y. Mixed hydrotropy: Novel science of solubility enhancement. Indian J Pharm Sci. 2011; 73: 179-183.
• [20] Jayakumar C, Morais AP. Solubility enhancement of theophylline drug using different solubilization techniques. Int J Pharm Sci. 2012; 2: 7-10.
• [21] Kinnari P, Makila E, Heikkila T, et al. Comparison of mesoporous silicon and nonordered mesoporous silica materials as drug carriers for itraconazole. Int J Pharm. 2011; 414: 148-156.
• [22] Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instr. 1965; 4: 117-122.
• [23] Patel DM, Patel MM. Optimization of Fast dissolving etoricoxib tablets prepared by sublimation technique. Indian J Pharm Sci. 2008; 70: 71-76.
• [24] Lachman L, Libermann HA, Kanig JL. The theory and practice of industrial pharmacy, 3rd ed. New Delhi: Varghese Publishing House, 1991.
• [25] Madan J, Sharma AK, Singh R. Fast dissolving tablets of aloe vera gel. Trop J Pharm Res. 2009; 8(1): 63-70.
• [26] Limnell T, Santos HA, Makila E, et al. Drug delivery formulations of ordered and nonordered mesoporous silica: Comparison of three drug loading methods. J Pharm Sci. 2011; 100: 3294-3306.