Kevin Macias and M. Teresa Carvajal. Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907
Purpose: To develop an in-line method for the determination of particle size during a high-shear wet granulation process. The utility in such a method would be highly desirable for determining granulation growth rates during the process in order to determine and validate coalescence and breakage kernels used in population balance equations. Methods: Placebo wet granulations were performed in a Diosna six-liter high-shear granulator equipped with a bottom driven impeller and side mounted chopper. Granulations of lactose monohydrate (Vopak North America, TX) and pre-gelatinized maize starch (Cargill Food & Pharma Specialties, IA) were prepared using a 5% w/w aqueous solution of poly-vinylpyrrolidone (K~30-BASF, NJ). Operational conditions were held constant for each experiment with an impeller speed of 150 RPM, chopper speed of 1000 RPM and delivery rate of binder solution at 150 grams per minute. During the granulation process, monitoring with Lasentec focused beam reflectance method (FBRM) occurred. In addition, incremental granulations were completed to represent the progression of the granulation process. The latter granulations were fractionated using sieve analysis in order to monitor the change in particle size distribution for each subsequent granulation. Results: Focused beam reflectance method (FBRM) has been used to follow changes chord length distribution of granule growth during the wet granulation process. From the FBRM data, movement of material between size bins was calculated. Employing incremental granulations, changes in particle size distributions were measured using sieve analysis. Qualitatively, the results from each experimental procedure describe similar growth kinetics and mechanisms during the granulation process. Conclusions: The in-line method using FBRM appears to provide similar information compared to measuring agglomerate growth using off-line method. The methods put forth have been established to provide kinetic information of the granulation process. This provides methods that will contribute to experimental determination of appropriate coalescence kernels and subsequent verification of population balance equations.