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Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs

  • Research Article
  • Theme: Next Generation Formulation Design: Innovations in Material Selection and Functionality
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ABSTRACT

Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.

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Acknowledgments

This work has been supported by the Australian Research Council (ARC) under DP120101065. The University of South Australia and Ian Wark Research Institute are acknowledged for the scholarship funded to Rokhsana Yasmin. Also Mr. Achal Bhatt and Mr. Vaskor Bala are acknowledged for advice and assistance during manuscript writing.

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Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, City East Campus, Adelaide, South Australia, 5000, Australia

    Rokhsana Yasmin, Shasha Rao, Kristen E. Bremmell & Clive A. Prestidge

Authors
  1. Rokhsana Yasmin
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  2. Shasha Rao
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  3. Kristen E. Bremmell
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  4. Clive A. Prestidge
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Correspondence to Clive A. Prestidge.

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Guest Editors: Otilia M. Koo, Panayiotis P. Constantinides, Lavinia M. Lewis, and Joseph Reo

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Yasmin, R., Rao, S., Bremmell, K.E. et al. Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs. AAPS J 18, 876–885 (2016). https://doi.org/10.1208/s12248-015-9864-z

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  • DOI: https://doi.org/10.1208/s12248-015-9864-z

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