ABSTRACT
In can be difficult to maintain the moisture level of small quantities of freeze-dried product contained in vials. We have observed that over a period of time a gradual increase in the residual moisture level in Thrombin vials containing small quantities of the freeze-dried product can sometimes be seen. No change in Thrombin potency has been observed. Investigations into the cause and resolution of this situation resulted in (1) modification of the freeze-drying cycle for vials containing small quantities of Thrombin and (2) incorporation of a special drying cycle for vial stoppers.
Subject(s)
Freeze Drying/methods , Thrombin/isolation & purification , Drug Packaging/methods , Water/analysisABSTRACT
The influence of shear mixing on the in vitro dissolution properties of several experimental capsule formulations containing lubricants was investigated. The studies were carried out in 2.8-liter laboratory V-blender equipped with a high-speed intensifier bar, using nitrofurantoin and procainamide hydrochloride as active drugs, powdered lactose and starch as excipients, and magnesium stearate and magnesium lauryl sulfate as lubricants. These studies revealed a pronounced inhibitory effect on drug dissolution due to shear in powder mixtures containing magnesium stearate; even at the maximum lubricant level of only 2%, high mixing markedly altered the in vitro dissolution rate. In systems with magnesium lauryl sulfate, the shear effect was less pronounced (nitrofurantoin blends) or absent (procainamide hydrochloride blends). The poor dissolution characteristics noted with magnesium stearate--shear combinations seem to result from the formation of a hydrophobic film around the powder mass, preventing wetting and deaggregation.
