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.

Effect of inline filtration on ViaSpan cold-storage solution.

The effect of filtration on the particulate load in ViaSpan cold-storage solution was studied. Commercially available inline blood transfusion filters (SQ40S, Pall Biomedical) were inserted into the delivery-set port of polyvinyl chloride bags of ViaSpan (DuPont Merck Pharmaceutical). Particles in samples collected in particle-free vials before and after filtration were counted by a light-obscuration technique. The compatibility of key ViaSpan ingredients and of three commonly used additives (penicillin G potassium, dexamethasone sodium phosphate, and human insulin) with the inline filter was also investigated. Filtration removed 56% of particles 5-10 microm in diameter, 71% of particles of > 10-25 microm, and > 99% of particles measuring > 25 microm. Flow rates with the filters were more than adequate for clinical use. Concentrations of constituent hydroxyethyl starch, glutathione, adenosine, allopurinol, raffinose pentahydrate, and lactobionic acid were not significantly affected by filtration, nor were the concentrations of any of the drug additives. Inline filtration of ViaSpan effectively reduced fatty acid salt particulates in the solution and had no deleterious effect on flow rate, ingredient concentrations, or concentrations of commonly added drugs.