(594d) Solvent-Polymer Interactions of Ethylcellulose Films for Pharmaceutical Applications

Ethylcellulose (EC) has been widely used as a water-insoluble, rate-controlling polymer for coating oral solid dosage forms, as an excipient for amorphous solid dispersions of the active, for buccal and transdermal drug delivery systems, and for 3D printing applications. The interaction of alcohol/water mixture with EC films will ultimatively impact the drug delivery of the dosage form and thus the therapeutic and prophylactic outcome of the actives. The affinity of the spray solvent for EC can also impact drying rate, secondary drying rate (removal of residual solvent in a secondary batch process), and the glass transition temperature of the spray-dried dispersion. This study is to understand the interaction of alcohol/water mixture with EC films of various molecular weights being cast from various organic solutions. These understandings can also help pharmaceutical scientists design coating formulations for protecting and/or modifying the release of active pharmaceutical ingredients (APIs) with potential alcohol exposure upon ingestion.

Films were cast from organic solution of ethylcellulose polymers with viscosities ranging from 21 to 29 cps. Solvent vapor transmission rates (SVTR) and equilibrium solvent content were determined with a Dynamic Vapor Sorption analyzer (DVS-Resolution). Various EC films were analyzed over a relative partial pressure (P/P₀) range of 0-90%. The vapor program began by exposing the sample to dry air to establish the dry mass. Then, the vapor concentration was increased in 10% P/Po steps to 90% P/Po. The vapor concentration is then decreased in a similar manner to accomplish a full sorption/desorption cycle. Fickian, 1-D diffusion coefficients were determined at each relative partial pressure level.

Solvent vapor transmission rate (SVTR) was measured with two ethanol/water solvent systems (50/50 and 65/35 ethanol/water) at 50% P/P₀ and at temperatures from 20 to 52°C. It was found that the SVTR of ETHOCELâ„¢ film increases at elevated temperatures and higher ethanol concentration of the diffusant. The equilibrium solvent content of ETHOCELâ„¢ films also increases with increasing temperature and ethanol concentration. Additionally, the influence of EC viscosity on SVTR is more pronounced at the higher ethanol level. The diffusion coefficient of ethanol/water vapor is also higher at elevated temperatures and higher ethanol concentration of the diffusant.

In conclusion, ETHOCEL^TM film can serve as a good ethanol/moisture barrier but needs to be enhanced when temperature or ethanol concentration increase. Understanding the interaction between organic solvent and EC excipients will help formulation scientists design formulations which can be used to protect APIs, to improve the spray-dry dispersion process and to advance 3D printing processes.

References

1. Dynamic Vapour Sorption for Organic Solvent Sorption by Surface Measurement Systems. https://azom.com/article.aspx?ArticleID=5181