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Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy

Authors Kurakula M, El-Helw A, Sobahi TR, Abdelaal MY

Received 18 November 2014

Accepted for publication 7 December 2014

Published 6 January 2015 Volume 2015:10(1) Pages 321—334

DOI https://doi.org/10.2147/IJN.S77731

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J Webster

Mallesh Kurakula,1 AM El-Helw,2 Tariq R Sobahi,1 Magdy Y Abdelaal1

1Polymer Research Lab, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

Abstract: Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CSL, medium CSM, high CSH molecular weights) and Labrasol® in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CSM and CSH; low cationic charge of CSL acted as both electrostatic and steric stabilizer by significant size reduction to 394 nm with charge of 21.5 meV. Solubility of ATR-CSL increased to 60-fold relative to pure ATR and ATR-L. Nanocrystals were characterized for physiochemical properties. Scanning electron microscopy revealed scaffold-like structures with high surface area. X-ray powder diffractometry and differential scanning calorimetry revealed crystalline to slight amorphous state changes after cationic charge size reduction. Fourier transform-infrared spectra indicated no potent drug-excipient interactions. The enhanced dissolution profile of ATR-CSL indicates that sustained release was achieved compared with ATR-L and Lipitor®. Anti-hyperlipidemic performance was pH dependent where ATR-CSL exhibited 2.5-fold higher efficacy at pH 5 compared to pH 6 and Lipitor®. Stability studies indicated marked changes in size and charge for ATR-L compared to ATR-CSL exemplifying importance of the stabilizer. Therefore, nanocrystals developed with CSL as a stabilizer is a promising choice to enhance dissolution, stability, and in-vivo efficacy of major Biopharmaceutical Classification System II/IV drugs.

Keywords: atorvastatin, anti-hyperlipidemia, chitosan, cationic charge, stability, nanocrystals, in-vivo efficacy

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