Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer.
Various processing variables that can influence granulation characteristics of a lactose-based formulation were evaluated using a Plackett-Burman experimental design. These parameters were impeller speed, granulating solution addition rate, total amount of water added in the granulation step, wet massing time, moisture content of the granulation after drying, and screen size used for the dry milling. Results showed that granulation growth was enhanced by the increase in the amount of added water, high impeller speed, and short wet massing time. On the other hand, moisture content had the largest impact on granulation compressibility, followed by the wet massing time and impeller speed. Increasing moisture content of the granulation and decreasing wet massing time or impeller speed increased granulation compressibility. Increasing impeller speed and/or wet massing time decreased granule porosity and fragmentation propensity, which led to decreased granulation compressibility. Granulation compressibility was extremely sensitive to processing conditions. Tablets from all runs showed acceptable weight variation and friability, suggesting that the parameters evaluated had little effect on these responses in the ranges tested.
Badawy
S I
SI
Pharmaceutical R and D, DuPont Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0400, USA.
Menning
M M
MM
Gorko
M A
MA
Gilbert
D L
DL
D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D004345:Drug Industry; D006813:Humidity; D007785:Lactose; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D016062:Porosity; D011208:Powders; D012044:Regression Analysis
D011208:Powders; D007785:Lactose