Content uniformity of captopril, furosemide, nadolol and propranolol hydrochloride powder packets extemporaneously compounded from tablets

The content uniformity of captopril, furosemide, nadolol, and propranolol hydrochloride in extemporaneously compounded single-dose powder packet forms was evaluated. The powders prepared from crushing and trituating commercial tablets with acetylcysteine granules, lactose powder, or lactofermin tablets were divided and packed into 40 single-doses using a packing system in the hospital pharmacy. The coefficients of variation (CVs) of the weight distribution in each of 40 packets from the twelve batches ranged from 4.4% to 36.6%, with a tendency for larger mean weights to have smaller CVs. The CVs of the content of active ingredients, determined for ten packets randomly sampled from each 40-dose batch, was between 5.3% and 68.5%. Moreover, the mean content of active ingredients from all the batches was less than the theoretical content of the powder packets. Among the twelve batches evaluated, only the two batches prepared by mixing furosemide with lactose powder and nadolol with lactofermin tablets met the Ch.P. specifications for uniformity of dosage units. When powder concentration was calculated by dividing the content of active ingredient in each packet by it own weight, the CVs of the powder concentrations of the active ingredients varied from 3.4% to 23.8%. It appeared that both mixing homogeneity and minimal weight variation were essential for content uniformity of those preparations. Reducing the number of packing units didn't affect the weight variation, content uniformity and mixing homogeneity of the powder packet preparations. Such extemporaneously compounded powder packet forms can cause considerable problems of dose uniformity for pediatric use.