Solid-State Stability and Characterization of Hot-Melt Extruded Poly(Ethylene Oxide) Films SUNEELA PRODDUTURI, 1 RAHUL V. MANEK, 2 WILLIAM M. KOLLING, 2 STEVEN P. STODGHILL, 3 MICHAEL A. REPKA 3 1 Food and Drug Administration, Division of Pharmaceutical Analysis, St. Louis, Missouri 63101 2 Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209 3 Department and Pharmaceutics and The National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, Mississippi 38677 Received 4 March 2005; revised 20 May 2005; accepted 26 May 2005 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.20437 ABSTRACT: Poly(ethylene oxide) (PEO) was used to prepare thin polymer films con- taining clotrimazole (CT) utilizing hot-melt extrusion (HME) technology. Films contain- ing PEOs of two different molecular weights and the drug were investigated for solid- state characteristics, moisture-sorption, bioadhesivity, mechanical properties, release characteristics, and physical and chemical stability of the drug within the HME films. The solid-state characterization of the drug and the polymer were performed utilizing differential scanning calorimetry and X-ray diffractometry. A Texture analyzer was utilized to study the bioadhesive and mechanical properties of the HME films. Physical and chemical stability of the films, stored at 258C/60% RH, was studied for up to 12 months. XRD profiles indicated that the drug was physically unstable (recrystalliza- tion of the drug occurred) after storage for 3 months at 258C/60% RH. Based on the DSC studies, it has been proposed that the recrystallization of the drug may be due to the folding (due to HME) and unfolding (upon storage) of the linear PEO chains. Desirable bioadhesive, mechanical, and thermoplastic properties of PEO qualify it as a promising and potential drug carrier. However, further investigation is necessary to enhance the physical stability of these PEO–drug systems. ß 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2232–2245, 2005 Keywords: hot-melt extrusion; solid solutions; polymers; solid state stability; thermal analysis; crystallinity INTRODUCTION Poly(ethylene oxide) (PEO), a thermoplastic, semi-crystalline (melting range of 57–738C), water-soluble resin was utilized in this study as a matrix-forming mucoadhesive polymer. PEO is a non-ionic bioadhesive polymer, which is among the fastest hydrating water-soluble polymers used in pharmaceutical systems. This property of the polymer can be advantageous when fabri- cating a delivery system for poorly soluble drugs. PEO based on its molecular weight, quickly forms a hydrogel that initiates and regulates the release of active ingredients in case of water-soluble drugs. Hence, while formulating poorly soluble drugs, lower molecular weight PEOs, which do not gel to a greater extent, may be advantageous due to the lower diffusion path length for the drug. An appropriate choice of polymer molecular weight (chain length) may result in a desired erosion rate and hence a release rate that pro- vides required salivary or blood levels of the drug. PEO has been used extensively as a matrix for drug delivery systems. 1–5 PEO has been widely 2232 JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 94, NO. 10, OCTOBER 2005 Correspondence to: Michael A. Repka (Telephone: 662-915- 1155; Fax: 662-915-1177; E-mail: marepka@olemiss.edu) Journal of Pharmaceutical Sciences, Vol. 94, 2232–2245 (2005) ß 2005 Wiley-Liss, Inc. and the American Pharmacists Association