title: Diffuse-interface theory for structure formation and release behavior in controlled drug release systems.
abstract: A common method of controlling drug release has been to incorporate the drug into a polymer matrix, thereby creating a diffusion barrier that slows the rate of drug release. It has been demonstrated that the internal microstructure of these drug-polymer composites can significantly impact the drug release rate. However, the effect of processing conditions during manufacture on the composite structure and the subsequent effects on release behavior are not well understood. We have developed a diffuse-interface theory for microstructure evolution that is based on interactions between drug, polymer and solvent species, all of which may be present in either crystalline or amorphous states. Because the theory can be applied to almost any specific combination of material species and over a wide range of environmental conditions, it can be used to elucidate and quantify the relationships between processing, microstructure and release response in controlled drug release systems. Calculations based on the theory have now demonstrated that, for a characteristic delivery system, variations in microstructure arising due to changes in either drug loading or processing time, i.e. evaporation rate, could have a significant impact on both the bulk release kinetics and the uniformity of release across the system. In fact, we observed that changes in process time alone can induce differences in bulk release of almost a factor of two and typical non-uniformities of +/-30% during the initial periods of release. Because these substantial variations may have deleterious clinical ramifications, it is critical that both the system microstructure and the control of that microstructure are considered to ensure the device will be both safe and effective in clinical use.
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Silver Spring, MD 20903, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Saylor
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patwardhan
authors.forename: James A
authors.initials: JA
authors.lastname: Warren
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D007700:Kinetics; D011336:Probability
chemical_list: D004337:Drug Carriers