(311a) Statistical Modeling On Formulation and Processing Conditions for Drug-Laden Strip Films

Purpose: Strip films as carrying fine API particles offer the advantages of easy online quality control as well as pediatric dosing. Polymer films provide an effective configuration for maintaining small particles in a non-agglomerated form, making them a promising alternative for enhancing drug bioavailability. This work is focused on the the impact of film formulation and processing conditions on the products' pharmaceutical and engineering properties.

Methods: A full response surface design for three factors was constructed. The factors explored were drug/polymer ratio, plasticizer level and ratio organic cosolvent/water. A half response surface design for five factors was constructed. Two additional factors were introduced, including wet film thickness and drying temperature. The model drug used was Griseofulvin and polymer was hydroxypropylmethylcellulose.

Viscosity and dry film thickness were determined at different areas of the film at 25°C. Particle size distribution was obtained by microscopy and image analysis. Disintegration time was determined by applying a visual-based method (Int. J. Pharm., 368: 98-102, 2009) with multiple replicates. Tensile strength and elasticity were determined according to ASTM method.

Results:

The most relevant linear factors affecting the viscosity were drug/polymer ratio and plasticizer (glycerin) content. The viscosity decreased with the increase of drug/polymer ratio and increased when the ratio organic solvent/water increased. Within the ranges employed, there was no significant difference in the particle sizes obtained. For disintegration time, the most relevant linear factors were plasticize content, solvent/water ratio and drying temperature. These factors were all negatively related to the film disintegration time. For tensile strength, the most important linear factors were drug/polymer and solvent/water ratios.

Conclusions: In this study, parameters selected for measuring both formulation and processing conditions were shown to influence almost every property of the strip films in both engineering and pharmaceutical aspects. Linear, quadratic and interaction effects were systematically analyzed. It is noteworthy that under our testing conditions, particle size distribution was the only property that didn't vary significantly with the change of input parameters.

Acknowledgement: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOP).