COMPARATIVE EVALUATION OF THE RELEASE PROPERTIES OF VERAPAMIL HCL AND CARBAMAZEPINE FROM MICROCRYSTALLINE CELLULOSE II PELLETS

Objective: To study microcrystalline cellulose II (MCCII) as new pelletization aid for a high and low solubility drugs such as verapamil. HCl and carbamazepine, respectively.Methods: Approximately, 30 g of MCCII and drug mixtures were hydrated passed through a # 20 mesh sieved and spheronizated at a frequency of 6 Hz and residence time of 480 s. A microscopy analysis was used to evaluate the shape and size descriptors. Pellets properties such as compressibility, friability, density, flowability and product yield were also evaluated. Drug release properties were tested according to the USP specifications and compared to those of MCCI.Results: The wetting level of the excipients depended on drug loading and drug solubility. Thus, a high drug loading (>50%) rendered pellets having a low yield, flowability and caused a detriment on size descriptors. Likewise, the regular morphology and strength of MCCII-based pellets was highly affected by increasing drug loads. Verapamil. HCl pellets were less friable and compressible and showed better flowability than carbamazepine pellets. Regardless of drug loading and drug solubility, MCCII-based pellets released more than 80% of verapamil. HCl within 10 min, whereas released more than 75% of carbamazepine within 15 min. Conversely, MCCI pellets had a satisfactory verapamil. HCl release, but ~30% carbamazepine release within 1h.Conclusion: MCCII proved to be a better excipient than MCCI to yield beads having optimal pellet characteristics and rendered an immediate release profile for verapamil. HCl and carbamazepine.

ASSESSMENT OF THE PRODUCTION VARIABLES ON THE PELLETIZATION PROPERTIES OF MICROCRYSTALLINE CELLULOSE II (MCCII)

Objective: To study microcrystalline cellulose II (MCCII) as new pelletization aid using the extrusion/spheronization technology.Methods: The effect of the spheronization rate and spheronization time was assessed by a response surface design. The shape descriptors and physical properties of pellets were taken as response variables. Approximately, 30 g of MCCII were hydrated, passed through a # 20 mesh sieve and spheronizated at frequencies of 6, 9 and 12 Hz and residence times of 15, 240 and 480 s in 9 experimental runs. In a separate experimental set, moisture levels of 25, 50, 75, 100 and 125% were employed at the optimal operating conditions of 6 Hz and 480 s. A microscopy analysis was used to evaluate the shape descriptors. Pellets properties such as compressibility, friability, porosity, strength, flow rate and mass were also evaluated.Results: Pellets having a small size and a high value of shape descriptors related to morphology were obtained employing a spheronization rate and spheronization time of 6Hz and 480s and 100% wetting level. The spheronization time increased pellet densification but decreased the total porosity. Pellet mass was also favoured by using high spheronization rates. A high moisture level (>100%) rendered pellets having a large size, mass, low porosity and good yield. Conversely, pellet size decreased as sample load increased, whereas porosity and compressibility increased as sample load augmented.Conclusion: MCCII offers the potential for use as an alternative pelletization agent rendering pellets having a good flowability, high mechanical strength and low friability at the optimal operational conditions.