Influence of Chlorpheniramine Maleate on Topical Hydroxypropylcellulose Films Produced by Hot-Melt Extrusion

Abstract

The objective of this investigation is to study the influence of chlorpheniramine maleate (CPM) on the chemical and physical–mechanical properties of hydroxypropylcellulose (HPC) hot-melt extruded films without the use of a traditional plasticizer. HPC films containing CPM in concentrations of 1, 5, and 10 wt% were prepared by hot-melt extrusion utilizing a Randcastle Microtruder® (Model #RCP-0750) with a 6-in. flex-film die. The physical–mechanical properties including tensile strength and percent elongation were determined on an Instron according to the ASTM standards. Glass transition temperatures and thermal analysis of the extruded films were determined utilizing a DSC 2920 Modulated DSC and Thermal Analyst 2000 software. The crystalline properties of the drug, polymer, and extruded films were studied via wide angle X-ray diffraction (XRD) using a Philips Vertical Scanning Diffractometer (Type 42273, Philips Electronic Instrument, Mount Vernon, NY). Gel permeation chromatography was used to study the stability of the polymer matrix as a function of different concentrations of CPM and processing conditions. CPM functioned as an effective plasticizer, increasing percent elongation and decreasing tensile strength in a concentration dependent manner. All three concentrations of extruded films exhibited a 10- to 12-fold decrease in tensile strength in contrast to a fourfold increase in percent elongation when testing was performed perpendicular to flow vs. in the direction of flow. The drug was also shown by XRD and DSC data to be in solution in the HPC matrix within the films up to the 10% level. In addition, CPM functioned as a processing aid in the extrusion of hot-melt films, stabilizing the weight-average molecular weight of HPC and allowing for film processing at lower temperatures. CPM could potentially be a candidate antihistamine for transdermal or transmucosal applications in film devices prepared by hot-melt extrusion technology.