The Effect of Serial Dilution of Betamethasone-17-Valerate on Blanching Potential and Chemical Stability

Ryatt, K.S.; Cotterill, J.A.; Mehta, A. C.

doi:10.1111/j.1365-2710.1983.tb01044.x

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…The degradation pathways of betamethasone-17-valerate in topical pharmaceutical preparations have been documented in the literature [15,16]. Betamethasone-17-valerate undergoes an intra-molecular isomerisation under acidic and basic conditions forming the more thermodynamically stable betamethasone-21valerate.…”

Section: Selectivitymentioning

confidence: 99%

Development and validation of a novel stability-indicating HPLC method for the simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate, methylparaben and propylparaben in a topical cream preparation

Byrne¹,

Velasco‐Torrijos

Reinhardt³

2014

Journal of Pharmaceutical and Biomedical Analysis

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A novel stability-indicating reversed phase high performance liquid chromatographic (RP-HPLC) method for the simultaneous assay of betamethasone-17-valerate, fusidic acid and potassium sorbate as well as methyl- and propylparaben in a topical cream preparation has been developed. A 100mm×3.0mm ID. Ascentis Express C18 column maintained at 30°C and UV detection at 240nm were used. A gradient programme was employed at a flow-rate of 0.75ml/min. Mobile phase A comprised of an 83:17 (v/v) mixture of acetonitrile and methanol and mobile phase B of a 10g/l solution of 85% phosphoric acid in purified water. The method has been validated according to current International Conference on Harmonisation (ICH) guidelines and applied during formulation development and stability studies. The procedure has been shown to be stability-indicating for the topical cream.

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Section: Selectivitymentioning

confidence: 99%

Development and validation of a novel stability-indicating HPLC method for the simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate, methylparaben and propylparaben in a topical cream preparation

Byrne¹,

Velasco‐Torrijos

Reinhardt³

2014

Journal of Pharmaceutical and Biomedical Analysis

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“…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.…”

Section: Introductionmentioning

confidence: 97%

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

1986

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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).

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Byrne

Wyraz

Velasco‐Torrijos

et al. 2016

Pharmaceutical Development and Technology

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The formulation of betamethasone-17-valerate (BV) into topical medicines presents a significant challenge for the formulation chemist. The substance is susceptible to acid and base catalyzed isomerization in aqueous environments, which results in valerate transesterification from carbon 17 to carbon 21 of the steroid ring system. This acyl migration process is of significant clinical importance since the 21-valerate ester possesses only a fraction of the potency of the 17-valerate parent compound. Isomerization of BV should therefore be reduced to a minimum through design of a suitable drug vehicle. In this study, the effect of varying the concentration of several excipient components on the isomerization rate of betamethasone valerate in a model hydrophilic cream has been investigated. These excipients include the emulsifier macrogolstearylether-20/21, the co-emulsifier cetylstearyl alcohol and the thickening agent hydroxyl propyl methylcellulose. Additionally, the influence of pH, the presence of the antioxidant, alpha-tocopherol, as well as the chelating agent, disodium edetate, on the stability of the formulation have been investigated. Trial drug product formulations, which were designed to investigate the influence of the above-mentioned components/parameters were manufactured and their stability was tested according to current ICH Guidelines. The content, purity and crystalline structure of the active substance in these formulations was analyzed by a combination of HPLC and microscopy techniques. The study demonstrates that the rate of isomerization of betamethasone valerate depends significantly on the concentration of emulsifier used in the cream formulation. At higher concentrations of emulsifier the isomerization proceeds rapidly with significant degradation over a period of weeks, whereas at lower concentrations significant degradation may not be observed, even after several years' storage. The influence of the emulsifier has been shown to be independent of the pH value of the aqueous phase of the cream. These findings have not been reported in previous literature reports on this topic, which have tended to focus on the influence of pH. The results are likely to be of interest to pharmaceutical chemists working on the formulation of glucocorticoids as well as to local- and hospital pharmacists who carry out the practice of dilution of proprietary corticoid preparations, where the choice of diluent is likely to be critical for ensuring the stability of the diluted product.

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The Effect of Serial Dilution of Betamethasone-17-Valerate on Blanching Potential and Chemical Stability

Cited by 5 publications

References 6 publications

Development and validation of a novel stability-indicating HPLC method for the simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate, methylparaben and propylparaben in a topical cream preparation

Development and validation of a novel stability-indicating HPLC method for the simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate, methylparaben and propylparaben in a topical cream preparation

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

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

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