To study the effect of the spray drying parameters on the spray dried nanosuspensions containing varying concentrations of dispersing agent.

摘要

In the recent years, there has been a steady increase in the percentage of promising drug candidates (about 40%) falling under the BCS class II or IV, thereby decreasing bioavailability. However, enhancing solubility of these drugs using conventional enhancement methodologies has been quite a challenge for formulation scientists. This has necessitated the development and utilization of novel technologies. Nanotechnology has evolved has a promising strategy in overcoming solubility problems, hence improving bioavailability. Improved wetting, dissolution along with similar bioavailability in both fed and fasted conditions has proved nanosuspensions to be very advantageous. However, the high surface area to volume ratio of nanosuspensions renders them instable both physically and chemically. These can however be stabilized by converting crystalline nanosuspensions into solid powders either by spray or freeze drying. Spray drying being widely used in the pharmaceutical industry, optimization and evaluation of the processing conditions is necessary to obtain product with excellent quality and therapeutic efficiency.;The main objective of this research work was to analyze and evaluate the changes occurring in the spray dried nanosuspensions with the changing spray drying processing parameters and mannitol concentration.;Nanosuspensions were prepared using wet-attrition media milling technique. The prepared nanosuspensions with varying concentrations determined by DOE was spray dried at varying spray drying parameters which was also determined using a DOE approach. The obtained spray dried powders were then evaluated for quality attributes namely process yield, outlet temperature and redispersibility behaviour of the nanocrystals. The spray drying process parameters "inlet temperature" and "flow rate" proved to be most significant in affecting the resulting nanocrystals both in quantity and quality. Moreover, Pearson's correlation analysis, Kohonen's self-organizing map and response surface plots were used to understand and visualize the relationship between input variables and quality attributes.;The crystalline nature of the obtained spray dried powders were confirmed using analytical techniques such as modulated differential scanning calorimeter (MDSC), X-ray powder diffraction (XRPD) and Fourier transformed infrared spectroscopy (FTIR). Additionally in-vitro dissolution profiles were generated both in deionised water and pH 1.2 to enable us to understand the effects of changing process parameters on the dissolution rate of nanocrystals.