Impregnation of active pharmaceutical ingredients into porous carriers
Creators: name: Omar, Thamer A.
Publisher: name: No Publisher Supplied
Year: 2019

description: Launching of a new drug into the market consumes significant resources and research effort and it involves a number of complex steps in drug substance and drug product development. The essential component of drug product development is often the optimization of the physical properties of the drug substance. The effect of a drug’s physical properties on pharmaceutical development can be seen from the first step to the final step of development process. For instance, choosing the preferred solid-state form of the drug can influence the early steps of drug manufacturing such as the drug-substance isolation method, and it can also alter some properties of the final dosage form such as the stability and dissolution behavior of the finished product. A simple approach to product development is desirable to shorten the required development steps, preferably by excluding some unit operations. Therefore, it is of interest to develop a pharmaceutical manufacturing method that can simplify drug product development. In this dissertation, the impregnation of drugs into porous carriers is examined as an approach to achieve this aim. This work implemented the essential tools for successful drug impregnation into porous carriers and specified the requirements for equipment and materials, which are necessary to perform this goal. A set of analytical methods to fully characterize the impregnated products was also studied. Preliminary studies regarding the use of a fluidized bed dryer as an impregnation device were presented to illustrate the applicability of this device. Also, a case study of continuous impregnation using a continuous blender as an efficient device for continuous impregnation was carried out. The first aim of this dissertation investigated the impregnation of an active pharmaceutical ingredient (API) into a mesoporous carrier (excipient) in a fluidized bed using different transport solvents. Impregnation and drying occurred simultaneously in the fluidized bed, and this method precluded several challenges encountered in other impregnation methods. Our results showed that the method of fluidized bed impregnation yielded a product with high uniformity and overcame several challenges presented by traditional physical blends. The second aim expanded the use of a fluidized-bed dryer for impregnation of active pharmaceutical ingredients (APIs) to include different porous carriers. Impregnating different porous carriers with the same drug allowed us to answer fundamental questions about impregnation such as drug dissolution and blend uniformity. Since there can be large differences in the prices of porous carriers/excipients, it is also important to investigate how product properties vary with different carriers to allow one to make cost/benefit decisions in terms of the different carriers. The results demonstrated that a fluidized-bed dryer can be successfully used to impregnate Indomethacin into porous carriers with different pore sizes. The resulting impregnated products displayed a significant improvement in some essential properties such as blend uniformity and drug dissolution, which are necessary to develop and formulate APIs into various pharmaceutical dosage forms.The third and last aim investigated the development of a new manufacturing method to continuously impregnate APIs into porous carriers using a Glatt GCG-70 blender. This work focused on the characterization of the GCG-70 blender with consideration to the process parameters (flow rate, impeller rotation), porous carrier type (Neusilin or Fujicalin), and tracer amount (low, medium, and high). The characterization of the continuous blender depended on two main strategies. The first strategy was investigation of the flow behavior of the carriers in the blender. This step was accomplished by conducting residence time distribution measurements, material hold up measurements and strain calculations. The second strategy was evaluation of the blend uniformity of the impregnated products using NIR spectroscopy. These two strategies provided a good understanding of the performance of the GCG-70 blender as a piece of equipment for impregnation.