title: Experimental observations and dissipative particle dynamic simulations on microstructures of pH-sensitive polymer containing amorphous solid dispersions.
abstract: 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.
authors.affiliation: Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors.forename: Mengchi
authors.initials: M
authors.lastname: Sun
authors.affiliation: Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yangdan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Wenhua Road, No. 103, Shenyang 110016, China.
authors.forename: Hailun
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China. Electronic address: zhao09081@163.com.
authors.forename: Yongshan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China. Electronic address: sunjin66@21cn.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D003460:Crystallization; D004095:Dihydropyridines / Q000737:chemistry / Q000493:pharmacokinetics*; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D062105:Molecular Docking Simulation; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*
chemical_list: D000179:Acrylates; D004095:Dihydropyridines; C477020:Eudragit E100; D011108:Polymers; C060285:lacidipine
keywords: Amorphous solid dispersion; Dissipative particle dynamics; Microstructures; Molecular basis