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Design and In Vitro Performance Evaluation of Purified Microparticles of Pravastatin Sodium for Intestinal Delivery

  • Research Article
  • Theme: Advanced Technologies for Oral Controlled Release
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Abstract

The purpose of research was to develop a mucoadhesive multiparticulate sustained drug delivery system of pravastatin sodium, a highly water-soluble and poorly bioavailable drug, unstable at gastric pH. Mucoadhesive microparticles were formulated using eudragit S100 and ethyl cellulose as mucoadhesive polymers. End-step modification of w/o/o double emulsion solvent diffusion method was attempted to improve the purity of the product, that can affect the dose calculations of sustained release formulations and hence bioavailability. Microparticles formed were discrete, free flowing, and exhibited good mucoadhesive properties. DSC and DRS showed stable character of drug in microparticles and absence of drug polymer interaction. The drug to polymer ratio and surfactant concentration had significant effect on mean particle size, drug release, and entrapment efficiency. Microparticles made with drug: eudragit S100 ratio of 1:3 (F6) exhibited maximum entrapment efficiency of 72.7% and ex vivo mucoadhesion time of 4.15 h. In vitro permeation studies on goat intestinal mucosa demonstrated a flux rate (1,243 μg/cm2/h) that was 169 times higher than the flux of pure drug. The gastric instability problem was overcome by formulating the optimized microparticles as enteric-coated capsules that provided a sustained delivery of the highly water-soluble drug for 12 h beyond the gastric region. The release mechanism was identified as fickian diffusion (n = 0.4137) for the optimized formulation F6. Conclusively, a drug delivery system was successfully developed that showed delayed and sustained release up to 12 h and could be potentially useful to overcome poor bioavailability problems associated with pravastatin sodium.

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Acknowledgments

The authors wish to thanks IIT Delhi, India for providing SEM and DSC facilities.

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Authors and Affiliations

  1. Department of Pharmaceutics, Rajiv Academy for Pharmacy, N.H. #2, P.O. Chattikkara, Mathura, 281001, India

    Yogesh Garg & Kamla Pathak

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  1. Yogesh Garg
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  2. Kamla Pathak
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Correspondence to Kamla Pathak.

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Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

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Garg, Y., Pathak, K. Design and In Vitro Performance Evaluation of Purified Microparticles of Pravastatin Sodium for Intestinal Delivery. AAPS PharmSciTech 12, 673–682 (2011). https://doi.org/10.1208/s12249-011-9626-x

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  • DOI: https://doi.org/10.1208/s12249-011-9626-x

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