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Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension: Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using Box–Behnken Design

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  • Theme: Recent Trends in the Development of Chitosan-Based Drug Delivery Systems
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Abstract

Lacidipine (LCDP) is a highly lipophilic calcium channel blocker of poor aqueous solubility leading to poor oral absorption. This study aims to prepare and optimize LCDP nanosuspensions using antisolvent sonoprecipitation technique to enhance the solubility and dissolution of LCDP. A three-factor, three-level Box–Behnken design was employed to optimize the formulation variables to obtain LCDP nanosuspension of small and uniform particle size. Formulation variables were as follows: stabilizer to drug ratio (A), sodium deoxycholate percentage (B), and sonication time (C). LCDP nanosuspensions were assessed for particle size, zeta potential, and polydispersity index. The formula with the highest desirability (0.969) was chosen as the optimized formula. The values of the formulation variables (A, B, and C) in the optimized nanosuspension were 1.5, 100%, and 8 min, respectively. Optimal LCDP nanosuspension had particle size (PS) of 273.21 nm, zeta potential (ZP) of −32.68 mV and polydispersity index (PDI) of 0.098. LCDP nanosuspension was characterized using x-ray powder diffraction, differential scanning calorimetry, and transmission electron microscopy. LCDP nanosuspension showed saturation solubility 70 times that of raw LCDP in addition to significantly enhanced dissolution rate due to particle size reduction and decreased crystallinity. These results suggest that the optimized LCDP nanosuspension could be promising to improve oral absorption of LCDP.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr el Aini street, Cairo, Egypt

    Mohamed A. A. Kassem, Aliaa N. ElMeshad & Ahmed R. Fares

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  1. Mohamed A. A. Kassem
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  2. Aliaa N. ElMeshad
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  3. Ahmed R. Fares
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Correspondence to Ahmed R. Fares.

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Guest Editors: Claudio Salomon, Francisco Goycoolea, and Bruno Moerschbacher

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Kassem, M.A.A., ElMeshad, A.N. & Fares, A.R. Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension: Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using Box–Behnken Design. AAPS PharmSciTech 18, 983–996 (2017). https://doi.org/10.1208/s12249-016-0604-1

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