Dosage uniformity in hydrocortisone ointment B.P

Abstract

Abstract The content uniformity of hydrocortisone in seven commercially available brands of hydrocortisone ointment B.P. 1% has been investigated. Fifty 5 mg samples were assayed by high pressure liquid chromatography and the results indicated that for 95% confidence levels only two of the ointments exhibited no positive skewness, one exhibited a significant degree of positive skewness and four exhibited a highly significant degree of positive skewness. The extent of the skewed distributions is discussed in relation to previously published particle/ agglomerate distributions for these ointments. The content uniformity in terms of the coefficient of variation CE calculated from the h.p.l.c. data is compared with the coefficient of variation CP that can be predicted from mixing theory on the basis of the particle/agglomerate distribution of the hydrocortisone. The departure from normality in drug content uniformity in the ointment is attributed to the hydrocortisone particles not being individually available for randomization, a large number being in an agglomerated form. That is, the manufacturing process is failing to achieve the full potential of the formulation by dispersing all of the agglomerates. Theoretical and experimental models predict that percutaneous absorption of drug may be enhanced over areas, where agglomerates are located, possibly not only resulting in localized toxicity but increased systemic availability. Drug content variability in small samples (5 mg) of topical steroid formulations could also effect the degree of skin blanching response in Mackenzie-Stoughton type tests since 5 mg portions containing in excess of twice the labelled strength were found. Regulatory control of content uniformity should be considered for certain topical steroids if unintentional over-dosage on small discrete areas is to be avoided.