Relationship of film properties to drug release from monolithic films containing adjuvants.

The rate of drug release from a polymeric matrix system was influenced by the physical and chemical properties of the monolithic films. The model drugs, salicylic acid and chlorpheniramine maleate, and two poly(methyl methacrylate) copolymers of different permeabilities (Eudragit RL and Eudragit RS), with and without additional adjuvants, were used to form monolithic matrix films for controlled drug release. Adjuvants, including polyethylene glycols (PEG 400 and PEG 8000) and poly(vinylpyrrolidones) (PVP-K15 and PVP-K90), were incorporated into films of Eudragit RL PM and Eudragit RS PM. The moisture permeation constant, glass transition temperature (Tg), tensile strength, and drug release profiles were determined for each acrylic resin slab to correlate the physicochemical and physicomechanical film properties to observed drug release. Faster rates of drug diffusion were observed with the addition of PEG 400 to the films, because of its plasticizing effect and the resultant increased moisture permeability of the matrix. An exception existed with the Eudragit RL PM film containing salicylic acid where drug-polymer interactions inhibited drug diffusion. The small changes in moisture permeability, Tg, and tensile strength observed with incorporation of the PVPs had an insignificant influence on the dissolution results for salicylic acid from Eudragit RS PM films. Increases in the tensile strength and Tg after addition of PVP to the Eudragit RS PM matrix support the observed decreased rate of diffusion for chlorpheniramine maleate. The pores formed by migration of the hydrophilic adjuvants from the films altered the diffusion kinetics of the matrix, compared with that of the nonporous polymer, when only the antihistamine was present.

Physical and chemical factors influencing the release of drugs from acrylic resin films.

An investigation was conducted to evaluate the factors influencing the release of salicylic acid and chlorpheniramine maleate from polymethacrylate amino-ester copolymer films (Eudragits RL PM and RS PM). Differential scanning calorimetry was performed on the films to study the solubility of drug in the polymer and to determine the effect of added drug on the thermal properties of the film. Incorporation of drug into the polymers decreased the glass transition temperature of the polymers. Dissolution of drug from monolithic slabs was followed as a function of temperature, drug concentration in the films, and ionic strength of the release media. In addition, adsorption studies were conducted with each drug:polymer combination to help explain release results and further characterize the drug:polymer interactions that occurred. The rate of drug release increased with increasing temperature. Adsorption of salicylic acid by the polymers was believed to influence the drug release profiles observed for different drug loadings and ionic strengths. Eudragit RL was found to adsorb salicylic acid to a greater extent than the Eudragit RS. Chlorpheniramine maleate was not found to be adsorbed by either polymer.