Journal article
Amorphous Solid Dispersions Containing Residual Crystallinity: Competition Between Dissolution and Matrix Crystallization
The AAPS journal, Vol.23(4), pp.69-69
05/17/2021
DOI: 10.1208/s12248-021-00598-6
PMID: 34002256
Abstract
Crystallinity in an amorphous solid dispersion (ASD) may negatively impact dissolution performance by causing lost solubility advantage and/or seeding crystal growth leading to desupersaturation. The goal of the study was to evaluate underlying dissolution and crystallization mechanisms resulting from residual crystallinity contained within bicalutamide (BCL)/polyvinylpyrrolidone vinyl acetate copolymer (PVPVA) ASDs produced by hot melt extrusion (HME). In-line Raman spectroscopy, polarized light microscopy, and scanning electron microscopy were used to characterize crystallization kinetics and mechanisms. The fully amorphous ASD (0% crystallinity) did not dissolve completely, and underwent crystallization to the metastable polymorph (form 2), initiating in the amorphous matrix at the interface of the amorphous solid with water. Under non-sink conditions, higher extents of supersaturation were achieved because dissolution initially proceeded unhindered prior to nucleation. ASDs containing residual crystallinity had markedly reduced supersaturation. Solid-mediated crystallization (matrix crystallization) consumed the amorphous solid, growing the stable polymorph (form 1). Under sink conditions, both the fully amorphous ASD and crystalline physical mixture achieve faster release than the ASDs containing residual crystallinity. In the latter systems, matrix crystallization leads to highly agglomerated crystals with high relative surface area. Solution-mediated crystallization was not a significant driver of concentration loss, due to slow crystal growth from solution in the presence of PVPVA. The high risk stemming from residual crystallinity in BCL/PVPVA ASDs stems from (1) fast matrix crystallization propagating from crystal seeds, and (2) growth of the stable crystal form. This study has implications for dissolution performance outcomes of ASDs containing residual crystallinity.
Details
- Title: Subtitle
- Amorphous Solid Dispersions Containing Residual Crystallinity: Competition Between Dissolution and Matrix Crystallization
- Creators
- Dana E Moseson - Purdue University West LafayetteIsaac D Corum - Purdue University West LafayetteAndres Lust - Purdue University West LafayetteKevin J Altman - Purdue University West LafayetteTze Ning Hiew - Purdue University West LafayetteAyse Eren - Purdue University West LafayetteZoltan K Nagy - Purdue University West LafayetteLynne S Taylor - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- The AAPS journal, Vol.23(4), pp.69-69
- DOI
- 10.1208/s12248-021-00598-6
- PMID
- 34002256
- ISSN
- 1550-7416
- eISSN
- 1550-7416
- Language
- English
- Date published
- 05/17/2021
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984366016202771
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