Crystallization of poly(ethylene oxide) with acetaminophen - A study on solubility, spherulitic growth, and morphology in memory of Prof. Peng Wang, a brilliant scientist, an enthusiastic teacher, and the dearest friend.

Min Yang, Costas Gogos

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

A simple, sensitive, efficient, and novel method analyzing the number of spherulitic nuclei was proposed to estimate the solubility of a model drug acetaminophen (APAP) in poly(ethylene oxide) (PEO). At high crystallization temperature (323 K), 10% APAP-PEO had the same low number of spherulitic nuclei as pure PEO, indicating that APAP and PEO were fully miscible. At low crystallization temperature (303 K), the number of nuclei for 10% APAP-PEO was significantly higher, suggesting that APAP was oversaturated and therefore recrystallized and acted as a nucleating agent. Based on the results obtained, the solubility of APAP in PEO is possibly between the concentration of 0.1% and 1% at 303 K. The spherulitic growth rate G of PEO was found to decrease with increasing APAP concentration, suggesting that APAP is most likely functioning as a chemical defect and is either rejected from or included in the PEO crystals during chain folding. APAP could possibly locate in the inter-spherulitic, inter-fibrillar, inter-lamellar, or intra-lamellar regions of PEO. At 323 K, the morphology of 10% APAP-PEO is more dendritic than spherulitic with large unfilled space in between dendrites and spherulites, which is a sign of one or the combination of the four modes of segregation. An extensive spherulitic nucleation and growth kinetics study using the classical theoretical relationships, for example, the Hoffman-Lauritzen (HL) and Avrami theories, was conducted. Both microscopic and differential scanning calorimetric (DSC) analysis yielded similar values for the nucleation constant Kg as well as the fold surface free energy σe and work of chain folding q. The values of σe and q increased with APAP concentration, indicating that the chain folding of PEO was hindered by APAP.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume85
Issue number3 PART B
DOIs
StatePublished - Nov 2013

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Keywords

  • Acetaminophen
  • Avrami theory
  • Crystallization kinetics
  • Hoffman-Lauritzen theory
  • Morphology
  • Poly(ethylene oxide)
  • Solid dispersion
  • Solubility
  • Spherulite

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