Displaying items by tag: Solubility
Problems related to low oral bioavailability due to poor solubility of new drug candidates are an increasing challenge in pharmaceutical research and formulation development. One efficient way to improve solubility is the utilization of nanocrystallization techniques: pharmaceutical nanocrystals are solid drug particles covered by a stabilizer layer with approximated size typically between 100 and 500 nm. Nanocrystal studies have been conducted since the beginning of the 1990’s and the first product entered the market after 10 years of intensive research. At first, nanocrystals were utilized purely for improved dissolution, but today also controlled release applications are in use.
Solid dispersions are an intensively investigated enabling technology to formulate poorly soluble drugs. Many contributions already studied their higher solubility and resulting dissolution rate as well as the challenges at the level of physical stability due to their high intrinsic energy. Whereas the vast majority of these studies focus on the bulk characteristics of the samples, we are convinced that the (often distinct) properties of the sample surface should not be overlooked.
The structural and physical stability of solid dispersions have not been adequately explored during post spray drying manufacturing processes. Solid dispersions are preferentially formulated as solid dosage forms such as tablets and capsules. Formulation parameters of spray drying may lead to differences in physical form and amorphous content of solids in single component systems . However, there is limited understanding on the effect of spray drying processes and formulation variables on drug-polymer mixing in solid dispersions and this limitation also extends to the unit operations such as milling and tabletting. The drug-polymer mixing in solid dispersions was evaluated in two different laboratory spray dryers, the Buchi-mini spray dryer and Pro-C-epT Micro spray dryer (Figure 1). The effect of compression on the structural and the physical stability of the spray dried solid dispersions was investigated as a major scope of this study.
Formulation of co-amorphous drug systems
Using the amorphous form of a drug, instead of its crystalline counterpart is one way to enhance the bioavailability of poorly water-soluble drugs. However, in order to fully benefit from the solubility advantages of amorphous drugs, one needs to overcome phyisco-chemical limitations including poor physical stability associated with the amorphous form. Co-amorphous drug formulations are a novel and one of the most promising formulation approaches in this context, where the drug in its amorphous form is stabilized through strong intermolecular interactions with its co-amorphous low molecular weight partner molecule.