4.4 Article

The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol

期刊

DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 40, 期 6, 页码 819-828

出版社

TAYLOR & FRANCIS LTD
DOI: 10.3109/03639045.2013.788013

关键词

Cilostazol; drug release; MCM-41; MCM-48; silica carriers; solid dispersion

资金

  1. National Basic Research Program of China (973 Program) [2009CB930300]
  2. National Natural Science Foundation of China [81072605]
  3. Major national platform for innovative pharmaceuticals [2009ZX09301-012]
  4. Key Laboratory of Drug Preparation Design & Evaluation of Liaoning Provincial Education Department [LS2010161]
  5. Shenyang Special Fund for Exploration of Intellectual Resources

向作者/读者索取更多资源

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 m(2)/g, 3.8 nm for MCM-41 and 1108.04 m(2)/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 AUC(0-infinity) 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.

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