(30d) Micron-Sized Drug Release Rate Control From Strip Film Matrix as An Alternative API Carrier

INTRODUCTION Strip films offer a promising composite API configuration and delivery system ideally suited for maintaining small particles in an immobilized, non-agglomerated form. This work focuses on the impact of film formulation on dissolution rate of strip films. To understand the macroscopic behavior of the films, our research also covered microscopic level characterization including the drug particle size distribution in the matrix and microscopic topographical/chemical relationship. EXPERIMENTAL METHODS Film strips made from hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA) containing dispersed griseofulvin microparticles were prepared by film casting. Several factors from the film formulation and processing were varied to understand their effect on the drug release rate. Analysis of particle size distribution within the films was conducted by using Coherent anti-Stokes Raman scattering (CARS). The microscopic structural-chemical relationship of mixed polymers was studied using Atomic Force Microscopy (AFM). RESULTS AND DISCUSSION Drug particle size distribution within the film was effectively evaluated using CARS showing the majority of the API particles had a size of less than 5 microns under the film formation conditions employed. The dissolution rate of the drug was dramatically enhanced by the polymer matrices compared to the non dispersed drug. Effects of formulation and processing factors on dissolution rate were also evaluated. Enhanced dissolution rate was obtained with decreased molecular weight of the polymer, reduced film thickness as well as elevated drying temperature. Composite films made from HPMC and SA can also be used to fine tune performance, in this case, by changing the proportion of each polymer composition. Its micron-scale spinodal microstructure was evidenced by AFM. CONCLUSIONS Particle-laden polymer strip films can effectively prevent the agglomeration of micron or sub-micron sized drug particles. Formulation and processing conditions of the films can be changed to engineer the drug release rates. CARS and AFM are effective tools to assist in analyzing the films' microstructure.