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Int J Pharm. 2016 Apr 30;503(1-2):238-46. doi: 10.1016/j.ijpharm.2016.01.062. Epub 2016 Feb 8.

Solvent-shift strategy to identify suitable polymers to inhibit humidity-induced solid-state crystallization of lacidipine amorphous solid dispersions.

Author information

1
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
2
Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, China.
3
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, No.103, Shenyang 110016, China.
4
Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Wenhua Road, No. 103, Shenyang 110016, China. Electronic address: jianwang@syphu.edu.
5
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China. Electronic address: sunjin66@21cn.com.

Abstract

The solvent-shift strategy was used to identify appropriate polymers that inhibit humidity-induced solid-state crystallization of amorphous solid dispersions (ASDs). Lacidipine with the polymers, PVP-K30, HPMC-E5 or Soluplus, were combined to form amorphous solid dispersions prepared by solvent evaporation. The formulations were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT-IR) and were subjected to in vitro dissolution testing. The moisture had a significant impact on the amount dissolved for the solid dispersions. Molecular docking studies established that hydrogen bonding was critical for the stabilization of the solid dispersions. The rank order of the binding energy of the drug-polymer association was Soluplus (-6.21 kcal/mol)>HPMC-E5 (-3.21 kcal/mol)>PVP-K30 (-2.31 kcal/mol). PVP-K30 had the highest water uptake among the polymers, as did ASD system of lacidipine-PVP-K30 ASDs. In the Soluplus ASDs, with its strong drug-polymer interactions and low water uptake, moisture-induced solid-state crystallization was not observed.

KEYWORDS:

Drug–polymer interactions; Humidity-induced solid-state crystallization; Molecular docking; The solvent-shift strategy; Water uptake

PMID:
26869398
DOI:
10.1016/j.ijpharm.2016.01.062
[Indexed for MEDLINE]

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