Jw Kennerley

Scintigraphic assessment of the in vivo dissolution rate of a sustained release tablet

Abstract The release of [ 99m Tc]diethylenetriaminepentaacetic acid ([ 99m Tc]DTPA) from a matrix tablet formulation was measured by external scintigraphy in 4 healthy male volunteers. The rate determined was compared with that observed in vitro using a U.S.P. dissolution apparatus. The in vitro release rate of [ 99m Tc]DTPA was similar to that of chlorpheniramine, and therefore the labelled compound was used to model the release of this drug in vivo. The in vitro release of [ 99m Tc]DTPA was pH-independent.

The compaction properties of polyethylene glycols

The mechanical properties of polyethylene glycol (PEG) powders of different average molecular weights have been characterized in terms of their yield pressure, determined from the densification of compacts by the method of Heckel. The yield pressure was found to be proportional to the molecular weight of the PEG. The densification which occurred during compaction was greater the lower the molecular weight. In terms of compact tensile strength, PEG 10000 produced the greatest strength for a given pressure. This arises from its ability to deform plastically to form a compact and be of sufficient intrinsic strength to resist fracture during the diametral compression test. Higher molecular weights PEGs do not allow sufficient plastic flow during consolidation for their inherent higher strength to be used.

A modified Weibull treatment for the analysis of strength-test data from non-identical brittle specimens

Powder compacts (e.g., pharmaceutical tablets) manufactured on commerically available machines are not strictly identical but show inevitable variability in their weights, thicknesses and compaction pressures. Consequently, the variability in fracture-stress data obtained from such brittle specimens is greater than that due to the inherent strength variability of the material itself. A modified Weibull analysis has been developed so that a more accurate estimate of the inherent variability of the mechanical strength of the material can be derived from test data obtained from commercially produced compacts; its application is illustrated.

An evaluation of the relative importance of formulation and process variables using factorial design

A factorial design method for assessing the relative importance of various formulation and process factors and their interactions in model paracetamol tablets is described. The design was a 2 times 2 × 2 times 3 type using mixing time, starch concentration, drug particle size and compaction pressure respectively. The starch concentration was the most significant factor in affecting the dissolution rate but the larger drug particle size also gave a significant increase in drug release rate. Interactions between starch concentration and drug size and between these and mixing time were also observed. The most significant factor affecting the tensile fracture stress of the tablets was the mixing time, followed in order by the drug particle size, starch concentration and compaction pressure.