Experimental observations and dissipative particle dynamic simulations on microstructures of pH-sensitive polymer containing amorphous solid dispersions.

Autor: Sun M; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China., Li B; Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China., Li Y; Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China., Liu Y; Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China., Liu Q; Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States., Jiang H; Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Wenhua Road, No. 103, Shenyang 110016, China., He Z; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China., Zhao Y; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China. Electronic address: zhao09081@163.com., Sun J; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China. Electronic address: sunjin66@21cn.com.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2017 Jan 30; Vol. 517 (1-2), pp. 185-195. Date of Electronic Publication: 2016 Nov 25.
DOI: 10.1016/j.ijpharm.2016.11.049
Abstrakt: Amorphous solid dispersion (ASD) technique is an effective strategy to increase the dissolution rate of poorly soluble drugs. However, it is inherently unstable, and the molecular basis for achieving kinetic stability is not well understood. In this study, lacidipine-Eudragit_E_100 solid dispersions with 20% drug loading were prepared using the solvent evaporation. Dissolution tested showed that ASD had a significantly high rate, which was dependent on the pH of the medium. Based on time-dependent measurement of supersaturation and particle size, inhibition of crystal growth by Eudragit_E_100 differed at pH 1.2 and 6.8 to a great extent. Dissipative particle dynamic (DPD) simulation revealed that at pH 1.2, the swollen microstructures of the particles were associated with rapid drug release. At pH 6.8, a compacted microstructure of small amorphous particle-aggregated large particles was associated with slow dissolution. The DPD simulation provides insight into the structural basis for experimental observations, and thus is a useful tool to investigate the microstructures of ASD.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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