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In vitro and in vivo evaluation of ordered mesoporous silica as a novel adsorbent in liquisolid formulation

Authors Chen B, Wang Z, Quan G, Peng X, Pan X, Wang R, Xu Y, Li G, Wu C

Received 3 October 2011

Accepted for publication 24 November 2011

Published 16 January 2012 Volume 2012:7 Pages 199—209

DOI https://doi.org/10.2147/IJN.S26763

Review by Single-blind

Peer reviewer comments 3

Bao Chen1,2, Zhouhua Wang1, Guilan Quan1, Xinsheng Peng1, Xin Pan1, Rongchang Wang1, Yuehong Xu1, Ge Li2, Chuanbin Wu1,2
1School of Pharmaceutical Sciences, 2Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China

Background: A liquisolid technique has been reported to be a new approach to improve the release of poorly water-soluble drugs for oral administration. However, an apparent limitation of this technique is the formulation of a high dose because a large amount of liquid vehicle is needed, which finally results in a low-dose liquisolid formulation. Silica as an absorbent has been used extensively in liquisolid formulations. Although nanoparticle silica can be prepared and used to improve liquid adsorption capacity, loading a high dose of drug into a liquisolid is still a challenge. With the aim of improving adsorption capacity and accordingly achieving high drug loading, ordered mesoporous silica with a high surface area and narrow pore size distribution was synthesized and used in a liquisolid formulation.
Methods: Ordered mesoporous silica was synthesized and its particle size and morphology were tailored by controlling the concentration of cetyltrimethyl ammonium bromide. The ordered mesoporous silica synthesized was characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, small-angle x-ray diffraction, wide angle x-ray diffraction, and nitrogen adsorption-desorption measurements. The liquid adsorption capacity of ordered mesoporous silica was subsequently compared with that of conventional silica materials using PEG400 as the model liquid. Carbamazepine was chosen as a model drug to prepare the liquisolid formulation, with ordered mesoporous silica as the adsorbent material. The preparation was evaluated and compared with commercially available fast-release carbamazepine tablets in vitro and in vivo.
Results: Characterization of the ordered mesoporous silica synthesized in this study indicated a huge Brunauer–Emmett–Teller surface area (1030 m2/g), an ordered mesoporous structure with a pore size of 2.8 nm, and high adsorption capacity for liquid compared with conventional silica. Compared with fast-release commercial carbamazepine tablets, drug release from the liquisolid capsules was greatly improved, and the bioavailability of the liquisolid preparation was enhanced by 182.7%.
Conclusion: Ordered mesoporous silica is a potentially attractive adsorbent which may lead to a new approach for development of liquisolid products.

Keywords: ordered mesoporous silica, poorly water-soluble drug, carbamazepine, liquisolid, bioavailability

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