Purpose: The main objective of the study was to evaluate the effect of certain critical process parameters during extrusion (screen size) and spheronization (spheronization speed, and spheronization time) on the physical characteristics (shape, bulk and tapped density, particle size distribution) and release profile of a model drug.
Methods: The process involves wet granulation by high shear granulation, extrusion, spheronization, drying and coating using Eudragit RL and Eudragit RS in Hutlin Unilab .
Batches were manufactured using a wet granulation process (Vector high shear granulator) with commonly used excipients (binder, diluent, disintegrant). The preblend was granulated using water as a solvent. The process of wet granulation was common for all batches. Extrusion (Multi granulator MG-55 lab extruder) was performed using 2 different screen sizes (0.6 and 0.8 mm). Extrudate produced with each screen were subdivided into three equivalent subparts and spheronized by varying the speed and spheronization time (residence time) of spheronizer (QJ-400 spheronizer). Following spheronization,each of the sublot drug spheres were coated with Eudragt RL and Eudragit RS in the Hutlin Unilab to a 15% weight gain. The shape of the spheres were observed under microscope, measured for bulk and tapped density using Varian, and particle size distribution was measured using Ro-Tap Sieve shakers.
Results: For the granulation, water and microcrystalline cellulose percentages were optimized to obtain optimal granules required for extrusion. It was observed that the batch load, spheronization speed and time had significant impact on shape of the pellets and generation of fines which in turn affected the release profile of the pellets coated. As a result, the spheronization parameters were optimized. During spheronization, extrudate produced with 0.8 mm screen resulted in spherical pellets with a speed of 1200 rpm and spheronization time of 120 seconds. The dissolution profiles of the Eudragit RS and Eudragit RL coated spheres were also studied and greater than 80% of drug was released within 8 hours.
Conclusion: These studies demonstrated that there are critical process parameters during extrusion and spheronization that affect the pellet size and shape which in turn had direct impact on the release profile of a model drug. These studies also concluded that during extrusion and spheronization, critical process parameters must be optimized to achieve desirable release profile using suitable polymers.
Bruhal Shah– Senior Formulation Scientist, Cambrex, Whippany, New Jersey
Bhavik Patel– Senior Formulation Scientist, HALO PHARMACEUTICAL
Satish Shetty– Director - Product Development, HALO PHARMACEUTICAL
Anthony Qu– Vice President Scientific Affairs, HALO PHARMACEUTICAL