Ibuprofen-Loaded Calcium Stearate Pellets: Drying-Induced Variations in Dosage Form Properties

• Published in: AAPS PharmSciTech Vol. 13; no. 2; pp. 686 - 698
• Main Authors: Schrank, Simone, Hodzic, Aden, Zimmer, Andreas, Glasser, Benjamin J., Khinast, Johannes, Roblegg, Eva
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2012
• Subjects: Administration, Oral; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calcium; Chemistry, Pharmaceutical; Compressive Strength; Crystallography, X-Ray; Desiccation; Dissolution; Dosage Forms; Drug delivery; Drugs; Drying; Freeze Drying; Ibuprofen; Ibuprofen - administration & dosage; Ibuprofen - chemistry; Kinetics; Lipophilic; Microscopy, Electron, Scanning; Pharmacology/Toxicology; Pharmacy; Porosity; Research Article; Scattering, Small Angle; Solubility; Spectrum Analysis, Raman; Stearic Acids - chemistry; Technology, Pharmaceutical - methods; desiccation; fluid bed; lyophilization; extrusion/spheronization
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-012-9791-6

Pellets intended for oral dosing are frequently produced via extrusion/spheronization followed by drying. Typically, the last active process step, i.e. , drying, is assumed to have little effect on the final dosage form properties ( e.g. , dissolution characteristics). Thus, there exist only a few studies of this subject. In the present study, calcium stearate/ibuprofen pellets were used as model system to investigate the impact of the drying conditions. Lipophilic calcium stearate matrix pellets containing 20% ibuprofen were prepared via wet extrusion/spheronization. Subsequently, desiccation, fluid-bed drying, and lyophilization were applied for granulation liquid removal. The impact of these drying techniques on the final pellet properties was evaluated. The in vitro dissolution behavior was dramatically altered by the drying techniques that were considered. The investigated pellets showed drug release rates that varied as much as 100%. As no polymorphic transitions occurred during drying, we focused on two possible explanations: (a) a change in the drug distribution within the pellets and (b) a change in pellet micro-structure (porosity, pore size). The ibuprofen distribution proved to be homogeneous regardless of the drying conditions. Pellet porosity and pore sizes, however, were modified by the drying process. Our results clearly demonstrate that a single process step, such as drying, can play a crucial role in achieving desired pellet properties and release profiles.