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The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol
Authors:Yanzhu Wang  Lizhang Sun  Tongying Jiang  Jinghai Zhang  Chen Zhang  Changshan Sun
Affiliation:1. Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenhe District Shenyang, Liaoning ProvincePR China;2. Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University ShenyangPR China
Abstract:Objective: To explore the suitable application of MCM-41 (Mobil Composition of Matter number forty-one)-type and MCM-48-type mesoporous silica in the oral water insoluble drug delivery system.

Methods: Cilostazol (CLT) as a model drug was loaded into synthesized MCM-48 (Mobil Composition of Matter number forty-eight) and commercial MCM-41 by three common methods. The obtained MCM-41, MCM-48 and CLT-loaded samples were characterized by means of nitrogen adsorption, thermogravimetric analysis, ultraviolet-visible spectrophotometry, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and powder X-ray diffractometer.

Results: It was found that solvent evaporation method was preferred according to the drug loading efficiency and the maximum percent cumulative drug dissolution. MCM-48 with 3D cubic pore structure and MCM-41 with 2D long tubular structure are nearly spherical particles in 300–500?nm. Nevertheless, the silica carriers with similar large specific surface areas and concentrating pore size distributions (978.66?m2/g, 3.8?nm for MCM-41 and 1108.04?m2/g, 3.6?nm for MCM-48) exhibited different adsorption behaviors for CLT. The maximum percent cumulative drug release of the two CLT/silica solid dispersion (CLT-MCM-48 and CLT-MCM-41) was 63.41% and 85.78% within 60?min, respectively; while in the subsequent 12?h release experiment, almost 100% cumulative drug release were both obtained. In the pharmacokinetics aspect, the maximum plasma concentrations of CLT-MCM-48 reached 3.63?mg/L by 0.92?h. The AUC0–∞ values of the CLT-MCM-41 and CLT-MCM-48 were 1.14-fold and 1.73-fold, respectively, compared with the commercial preparation.

Conclusion: Our findings suggest that MCM-41-type and MCM-48-type mesoporous silica have great promise as solid dispersion carriers for sustained and immediate release separately.
Keywords:Cilostazol  drug release  MCM-41  MCM-48  silica carriers  solid dispersion
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