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The transformation of a monohydrate into an anhydrous form of risedronate monosodium (RS) in a methanol and water mixture was investigated. The phase transformation was detected by monitoring the number of particles, particle size, and shape. At the same time, polymorphic forms of crystals were identified by various offline techniques such as XRPD, TGA, and DSC. The kinetics of phase transformation was found to be controlled by three-dimensional nuclear growth. The reaction of water in the solvent mixture was a main factor determining the stability of anhydrate and monohydrate forms. The time required for phase transformation was strongly affected by temperature and agitation rate. The phase transformation could be successfully determined in real time by using an in situ particle measurement system.

Freeze casting is a useful molding technique for the production of porous, fast dissolving tablets of foods and pharmaceuticals. In order to optimize the freeze casting process, the slurries, and also the characteristics of the freeze‐casted products, multifunctional additives are usually employed. For further applications of these procedures in industrial processes, the suspension characteristics should be known. This case study focuses on the rheological properties of paracetamol suspensions. The effects of modified starch as an additive, the solid loadings, and the temperature on the flow behavior and viscosities of the suspensions were investigated. It was found that most suspensions are thixotropic systems. The viscosity of the suspensions is highly sensitive with respect to the studied factors, such as shear rate, shearing time, temperature, solid loading, and additive content. Optimized conditions were found and are recommended for industrial use.

Abstract:The improvement of pharmaceutical dosage forms, such as tablets, towards drug delivery control and cost efficiency is of great importance in formulation technologies. Here, three examples: in situ coating, freeze casting and protein-based biocomposites are presented that address the above mentioned issues and contribute to further developments in formulation technologies. The in situ coating increases the economic efficiency by saving process steps in comparison to a conventional tableting process and provides a crystalline coating for a tailorable drug delivery rate. The freeze casting allows the control over the surface area of a drug delivery system (DDS) by providing different numbers and sizes of pores, which in conjunction with adequate additives offer an efficient instrument for drug delivery control, especially by accelerating the dissolution effect. Protein-based biocomposites are attractive materials for biomedical and pharmaceutical applications that can be applied as a polymeric DDS. They inherently combine degradability in vivo and in vitro, show a good biocompatibility, offer sites of adhesion for cells and may additionally be used to release embedded bioactive molecules. Here, a new approach regarding the incorporation of crystalline active pharmaceutical ingredients (API) into a protein matrix in one process step is presented. All three presented techniques mark decisive progress towards tailor-made drug delivery systems with respect to function, economic efficiency and the generation of additional values.

The transformation from a hemipentahydrate to a monohydrate of risedronate monosodium was studied by seed crystallization in solution. By using the in-line measurement based on ultrasonic measuring technique and the off-line measurements such as optical microscopic and crystallography, transformation of hydrate forms and crystallization of monohydrate were observed. The effect of concentration of solution and solid fraction of suspension on the ultrasonic velocity was found. The hydrate composition, concentration of solution, and supersaturation during the transformation were estimated with elapsed time. The effect of monohydrate seed, agitation rate and temperature on the induction time, transformation, and crystallization was also investigated. Eventually, transformation from hemipentahydrates to monohydrates and crystallization of monohydrate were analyzed successfully from in-line measuring technique.