Crystallization of poly(ethylene oxide) with acetaminophen--a study on solubility, spherulitic growth, and morphology.
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.
['Yang|Min|M|', 'Gogos|Costas|C|']
D000082:Acetaminophen D002152:Calorimetry, Differential Scanning D002626:Chemistry, Pharmaceutical D003460:Crystallization D016503:Drug Delivery Systems D004355:Drug Stability D007700:Kinetics D008853:Microscopy D055095:Optics and Photonics D011092:Polyethylene Glycols D011108:Polymers D012995:Solubility D013499:Surface Properties D013696:Temperature
Poly(ethylene oxide) Solubility Spherulite Morphology Acetaminophen Avrami theory Crystallization kinetics Hoffman–Lauritzen theory Solid dispersion