Engineering Active Pharmaceutical Ingredients by Spray Drying: Effects on Physical Properties and In Vitro Dissolution

Abstract

Active pharmaceutical ingredients have very strict quality requirements; minor changes in the physical and chemical properties of pharmaceuticals can adversely affect the dissolution rate and therefore the bioavailability of a given drug. Accordingly, the aim of the present study was to investigate the effect of spray drying on the physical and in vitro dissolution properties of four different active pharmaceutical ingredients, namely carbamazepine, indomethacin, piroxicam, and nifedipine. Each drug was dispersed in a solution of ethanol and water (70:30) and subjected to single-step spray drying using similar operational conditions. A complete characterization of the spray-dried drugs was performed via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), particle size distribution analysis, solubility analysis, and an in vitro dissolution study. The results from the thermal analysis and X-ray diffraction showed that, except for carbamazepine, no chemical modifications occurred as a result of spray drying. Moreover, the particle size distribution of all the spray-dried drugs significantly decreased. In addition, SEM images showed that most of the particles had an irregular shape. There was no significant improvement in the solubility of the spray-dried drugs compared with the unprocessed compounds; however, in general, the dissolution rates of the spray-dried drugs showed a remarkable improvement over their non-spray-dried counterparts. Therefore, the results from this study demonstrate that a single spray-drying step may lead to changes in the physical properties and dissolution characteristics of drugs and thus improve their therapeutic action.

Keywords:

• Crystallinity
• In vitro dissolution
• Particle size distribution
• Solubility
• Thermal analysis

ACKNOWLEDGMENTS

Financial support from FAPESP (08/02848-9 and 08/07115-0) and CNPq (PQ-2) are gratefully acknowledged.

Notes

*Student's t-test shows significance (p < 0.05). Values represented by different letters were significantly different.

*Student's t-test shows significance (p < 0.05). Values represented by different letters were significantly different.