Rheological study of the mixture of acetaminophen and polyethylene oxide for hot-melt extrusion application

• Published in: European journal of pharmaceutics and biopharmaceutics 2011-08, Vol.78 (3), p.506-512
• Main Authors: Suwardie, Herman, Wang, Peng, Todd, David B., Panchal, Viral, Yang, Min, Gogos, Costas G.
• Format: Article
• Language: English
• Subjects: Acetaminophen - analysis; Acetaminophen - chemistry; Analgesics, Non-Narcotic - analysis; Analgesics, Non-Narcotic - chemistry; Biological and medical sciences; Cold Temperature; Drug Carriers - chemistry; Drug Compounding - methods; Drug Delivery Systems; General pharmacology; Hot Temperature; Hot-melt extrusion; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Polymers - chemistry; Rheology; Rheometer; Solubility; Viscoelasticity; Viscosity
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.03.013

Reduced viscosity of APAP-PEO mixture at different temperature. The drug’s solubility in the molten polymer is given by the lowest point of each curve. There is a growing interest of extrusion drug and polymer together to manufacture various solid dosages. In those cases, the drug’s release profiles are greatly affected by the miscibility of two materials. The goal of this study is to test the drug’s solubility in molten polymer and obtain the mixture’s rheological properties for the purpose of optimizing the extrusion process. The dynamic and steady viscosities of APAP–PEO mixture were determined using oscillatory and capillary rheometers. The curves of viscosity vs. drug loading generally have a “V” shape, and the minimal point gives the APAP’s solubility in PEO. The test results suggest that different dynamic methods lead to essentially the same solubility data. At high shear rates, the mixtures show shear thinning behavior and the viscosity becomes less sensitive to the drug loading. In other words, it is desirable to use a low shear rate in order to deduce the drug’s solubility in polymer from the viscosity data. On the other hand, viscosity data at high shear rates are more representative of the materials’ rheological properties during extrusion.