The Stability and Blanching Efficiency of Some Betnelan-V® Cream Dilutions

Abstract

In this study Betnelan-V@ cream was diluted with Beeler's basis and Cold cream@. Cold Cream@ reduced the skin-blanching activity of the original cream more than Beeler's base. T h e stability of betamethasone-17-valerate was better in a Beeler's basis dilution than in a Cold cream@ dilution. I N T R O D U C T I O NAlthough the extemporaneous dilution of creams may lead to problems such as drug degradation or non-homogeneity, physicians still prescribe diluted corticosteroid topical preparations in order to obtain a less potent preparation (1,2). Since the release and the chemical stability of corticosteroid topical preparations depend on the vehicle, dilution with bases different from those used by the manufacturer may lead to instability (3-5).Bases such as Emulsifying ointment BP and Plastibase were unsuitable as diluents for Betnovatea ointment due to rearrangement to betarnethasone-21-valerate and hydrolysis to betamethasone (Mi). Unguentum Merck@ and white soft paraffin produced stable dilutions but the potency was equivalent to the undiluted ointment (6,9-10). However, when the new formulation of Betnovatea ointment was diluted with white soft paraffin, the potency was reduced to the same extent as the proprietary diluted ointment. This difference in potency of the extemporaneously diluted products clearly shows the effect of vehicle composition on the release of betamethasone-17-valerate (1 1-12). Betnovatem cream diluted in several cream bases shows good stability and the potency of the dilutions was equivalent to the undiluted cream (13)(14).Since dilutions do not always produce a less potent preparation, the aim of the study was to verify the stability and the clinical effectiveness of Betnelan-V@ cream diluted with Beeler's basis and Cold cream@ containing 5 O , w/w urea. The skin blanching test was used to assess the clinical effectiveness of the dilution. This test is a precise and reproducible method for predicting the topical effect of corticosteroids when carried out under standard conditions (15)(16)(17)(18).

Formulation factors affecting the isomerization rate of betamethasone-17-valerate in a developmental hydrophilic cream – a HPLC and microscopy based stability study

“…The purpose of diluting corticosteroid preparations is usually to reduce the side-effects associated with their use, such as skin atrophy and pigmentation loss 6 . The practice of dilution of marketed corticosteroids appears in principle to be justified, since numerous studies have shown that the relationship between concentration and activity of topically applied glucocorticoids is not linear 6,7 , with much weaker dilutions often demonstrating similar activity to the undiluted product in vasoconstriction assays [8][9][10][11] . However, since in many cases the diluted product is not analyzed and little is known regarding its stability, there may be potential issues regarding safety and efficacy of the active substances in such dilutions.…”

“…In most cases, the increased rate of isomerization was attributed to an increased pH of the diluted preparation, without consideration of other factors. Boonsaner et al 8 studied the stability of BV in Beeler's Basis and Cold Cream Õ . They came to the conclusion that the degradation rate cannot be solely dependent on the pH alone and that other unknown factors must be involved.…”