Statistically Designed Spheronization and Scale-Up of Ibuprofen Microparticulates Using the Rotor Disk Fluid-Bed Technology: Coating for Prolonged Release and Hard Gelatin Encapsulation of Microparticulates
Moji Christianah Adeyeye
James K. Drennen
David A. Johnson
Frank J. D'Amico
N. K. Ebube
The aim was to develop uncoated and coated ibuprofen microparticulates in a one-step fluid-bed machine with rotor-disk insert, for immediate and prolonged drug delivery. Feasibilty studies using ibuprofen: Avicel (RC-581; 50:50), sodium lauryl sulfate (1%) as surfactant and water as binder in FLM-15 Vector Flo-coater with 12" stainless-steel and waffle-disk inserts showed that amount of binder, plate type and the presence of surfactant affected most of spheroid characteristics. These variables were used in a 2x2x3 full factorial (replicated) experiment. Blocking was used to study batch-to-batch reproducibility of the process and product variables. Our results confirmed that the binder amount, plate-type and the presence of surfactant were important variables in rotor-disk spheronization. The amount of binder was the most critical. The batch with the most acceptable product characteristics was chosen as the optimized formulation, and used to statistically study the effects of other formulation variables viz, drug particle size (20 µm, 40 µm) and drug load (50%, 65%, 80%) in a 2x3 factorially designed (replicated) experiment. The two ibuprofen particle sizes and the three drug loads were spheronizable. However, spheronization of the higher drug load was more difficult and yielded larger sized microparticulates that consequently retarded drug release. The 65% drug load was therefore used for intermediate size scale-up, which resulted in spheroids with good product characteristics.
The optimized scaled-up batch was used in a 2x3 factorially designed (replicated) experiment to study the effects of polymer type (Surelease, Eudragit NE-30D) and level (low, medium, high) on the developed microparticulates. Coating level was found to be inversely related to the drug release. The batch coated with the highest Surelease level yielded the most acceptable spheroid characteristics, including most prolonged release. The latter and the uncoated spheroids were encapsulated using a 2x2x3 experiment in Romaco Index-K150i machine. The average fill-weight of the encapsulated spheroids was mostly affected by the formulation type. Encapsulation of the microparticulates had no undesirable effects on the qualities of both the uncoated and coated pellets.
This study provides spheronized ibuprofen microparticulates that can be sold as ready-to-use modified ibuprofen to pharmaceutical companies owing to their lots of pharmaceutical market potentials.
Chukwumezie, B. (2003). Statistically Designed Spheronization and Scale-Up of Ibuprofen Microparticulates Using the Rotor Disk Fluid-Bed Technology: Coating for Prolonged Release and Hard Gelatin Encapsulation of Microparticulates (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/407