Browsing Theses and Dissertations by Subject "Zero-order Release Kinetics"
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Development of a novel gastro-retentive delivery system using alfuzosin HCl as a model drugThe objectives of this project encompass the design and development of a drug delivery system to continuously deliver therapeutic agents from the stomach to the proximal region of the intestine. The delivery system designed would have sufficient gastric residence time together with near zero-order release kinetics. The physicochemical properties pertaining to the formulation development of the model drug (alfuzosin HCl) were evaluated. Excipients were selected based on the studies of their physicochemical properties and compatibility with the active ingredient. Gastro-retentive dosage forms have been the topic of interest in recent years as a practical approach in drug deliveries to the upper GI tract or for release prolongation and absorption. These dosage forms are particularly suitable for drugs that have local effects on the gastric mucosa in the stomach. Other candidates include drugs that are likely to be absorbed in the upper small intestine, or drugs that are unstable in basic environment of distal intestine and colon or those with low solubility at elevated pH conditions (i.e. weak bases). To develop a gastro-retentive delivery system the following steps were taken. First, to investigate the possible incompatibility issues between the model drug and excipients to be used for the delivery system. Stability and physicochemical properties of the active agent and its mixture with excipients were studied using analytical techniques such as Raman spectroscopy and Differential scanning calorimetry (DSC). No incompatibility issues were detected. Second, Kollidon SR as a relatively new release-rate controlling polymer was incorporated in the final formulation. For solid dosage form the ability of the final powder mix to flow well during manufacturing and the intrinsic characteristics that make it compressible are critical. The in-depth compaction study of Kollidon SR was assessed with the help of a compaction simulator. The flowability, swelling and erosion behavior together with release-rate retarding properties of Kollidon SR were also assessed. The final oral delivery system was based on Kollidon SR and Polyethylene Oxide (PEO) 303 as a monolithic matrix system. The noneffervescent monolithic matrix was made by direct compression. In vitro evaluation of the designed system released the active content in a near zero manner. The dosage form was bouyant in pH 2.0 acidic buffer with no floatation lag time which minimizes the possibility of early gastric emptying.