Many of the new drug delivery systems (DDS) are designed to deliver drug at a controlled rate over an extended period of time. This extended drug delivery results in plasma drug levels within the therapeutic range longer than expected from the biological half-life of the drug, thereby prolonging the pharmacological benefits of the drug, while minimizing ineffective or toxic concentrations. The DDS should maintain a constant (zero-order) drug delivery rate for 10 to 14 hours, and be easily adaptable to a variety of drugs, requiring different delivery rates. One such design involves press-coating a drug core with a rate controlling membrane. The rate of drug delivery is modified by altering the porosity of the coating, which changes and rate of water penetration, and thus alters the core dissolution profile and rate of drug release. To predictably modify drug delivery rate by incorporation of porosity modifiers in the coating, requires an understanding of the interplay between physical-chemical properties of the porosity modifier and the change in DDS porosity/surface area. This proposal investigates relationships between properties of porosity modifiers and coating porosity/surface area, which are used in the design of a cost effective press-coated DDS. Powder characteristics and compression profiles of core and coating materials are used in the selection of proper approaches to the initial DDS design. To alter drug release, porosity modifiers of different properties are incorporated into the coating. The dependence of the rate and extent of porosity/surface area modifications on the porosity modifier properties and subsequent influence on drug delivery rate will be studied. The relationships will be tested by determining the accuracy with which drug delivery profile can be predicted by apriori selection of porosity modifier with cores of varying dissolution profiles. Future studies will involve a series of drugs with different properties and the in-vivo evaluation of the DDS. The relationships developed in this investigation will allow use of the same DDS housing, which is adaptable to drugs requiring different delivery rates. This reduces the time and cost involved in developing DDS for new drug entities.
