Drug Content Variation Research Articles

Effect of additives on physical properties of fine ethyl cellulose microcapsules prepared by the Wurster process.

Ethyl cellulose (EC) microcapsules with fine calcium carbonate cores (32-44μm) and drug layers were prepared. The effect of additives on the particle size distribution, the variation in drug content with particle size and the dissolution properties of the products were evaluated.Among eight additives used, cholesterol (CH) most restrained the release of phenacetin, a model drug, which resulted in a saving of coating material and time. For sustained release of phenacetin, only 6.25% or less coating material relative to core material was sufficient. In addition, CH remarkably reduced particle agglomeration. The mean particle size of a product 25% coated with EC : CH=2 : 1 mixture was 58μm. However, the drug content and the phenacetin release were strongly dependent on the particle size of the product. This was the result of retardation of particle recycling in the Wurster chamber due to its adhesion to the well by electrostatic charge. Stearyltrimethyl-ammonium chloride, a cationic surfactant, reduced the particle adhesion when it was added to EC-CH (2 : 1) in a 1% amount on a dry basis. As a result, the particle size distribution became sharper, and there was higher homogeneity of the physical properties. This effect was not observed with polysorbate 80, a nonionic surfactant.

Interactive mixing between agglomerated drug particles and coarse carrier particles

AbstractThe equation of Egermann1 was used to calculate the theoretical coefficient of variation in drug content of completely random interactive mixtures containing furosemide and sodium chloride. These coefficients of variation (CV) were compared to that obtained experimentally. Although no free furosemide agglomerates or aggregates were present in the mixtures, the experimental values were consistently higher. This could only be explained if small furosemide aggregates accumulated in clefts and crevices in the sodium chloride particle surfaces. For the system examined random interactive mixtures were produced with furosemide concentrations between 0.05 and 4%

Relationship between sine random vibrations, resonance and drug content uniformity.

The effect of sine random vibrations on the segregation tendency of 3 ordered power mixes was studied. Ordered mixes containing either Emdex, Dipac or recrystallized lactose carrier particles mixed with 0.5% fine-particle potassium chloride were prepared. It was found that the coefficients of variation of drug content in samples removed from the ordered mixes following random vibration were, in general, lower than those derived from vibration at equivalent single frequencies. Ordered mixes vibrated at low centre-frequencies were found to be most prone to slight demixing and under these conditions, a vibration bandwidth of 30 Hz produced more de-mixing than a 10 Hz bandwidth. Most ordered mixes were considered to be segregation free following random vibration.

Tablet-to-Tablet Variation of Drug Content of Sugar-Coated Tablets Containing Drug in the Sugar Coat

In dosage forms where active drug is added to a sugar coat, it may be shown that the distribution of assays should be normal and the standard deviation should be proportional to the square root of the number of coats.Although, in a series of batches, the standard deviation was found linearly related to the square root of the number of coats, the plot failed to intersect at the origin and did not have the required slope, presumably due to secondary contributions to the variation such as pan build-up.