Dilutions of corticosteroid creams and ointments — a stability study

Cornarakis-Lentzos, M.; Cowin, P.R.

doi:10.1016/0731-7085(87)80084-5

Cited by 8 publications

(9 citation statements)

References 8 publications

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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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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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“…A number of other studies found significant destabilization of the mixed preparations (e.g., phase separation into distinct layers and bleeding of oil components). 1,3,13,14) In the present study, we focused on the compatibility of moisturizing creams with an ointment base. We tested various commercial creams that are popularly used in Japan.…”

Section: H-nmr Spectra Of Each Phase-separated Layer Acquired From Thmentioning

confidence: 99%

“…[1][2][3][4] This mixing is aimed at improving the patient compliance by reducing the frequency of application and modifying the texture of the preparations. Cream preparations are thermodynamically unstable emulsions; therefore, to prepare a stable mixed preparation, appropriate selection of the moisturizing cream is crucial.…”

Section: H-nmr Spectra Of Each Phase-separated Layer Acquired From Thmentioning

confidence: 99%

“…Dermatologists frequently prescribe moisturizing creams mixed with steroid ointments. [1][2][3][4] This treatment approach is based on the concept that moisture retention of the skin is important for the treatment of atopic dermatitis, as is steroid therapy. To facilitate application of the cream and ointment, they are mixed in an operation that is widely performed at pharmacy level.…”

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confidence: 99%

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Stability of Mixed Preparations Consisting of Commercial Moisturizing Creams with an Ointment Base Investigated by Magnetic Resonance Imaging

Onuki

Funatani

Yamamoto

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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A moisturizing cream mixed with a steroid ointment is frequently prescribed to patients suffering from atopic dermatitis. However, there is a concern that the mixing operation causes destabilization. The present study was performed to investigate the stability of such preparations closely using magnetic resonance imaging (MRI). As sample preparations, five commercial moisturizing creams that are popular in Japan were mixed with an ointment base, a white petrolatum, at a volume ratio of 1 : 1. The mixed preparations were stored at 60°C to accelerate the destabilization processes. Subsequently, the phase separations induced by the storage test were monitored using MRI. Using advanced MR technologies including spin-spin relaxation time (T 2 ) mapping and MR spectroscopy, we successfully characterized the phase-separation behavior of the test samples. For most samples, phase separations developed by the bleeding of liquid oil components. From a sample consisting of an oil-in-water-type cream, Urepearl Cream 10%, a distinct phase-separation mode was observed, which was initiated by the aqueous component separating from the bottom part of the sample. The resultant phase separation was the most distinct among the test samples. To investigate the phase separation quantitatively and objectively, we conducted a histogram analysis on the acquired T 2 maps. The water-in-oil type creams were found to be much more stable after mixing with ointment base than those of oil-in-water type creams. This finding strongly supported the validity of the mixing operation traditionally conducted in pharmacies.Key words mixed external preparation; magnetic resonance imaging; quantitative T 2 map; emulsion stability Atopic dermatitis is one of the most common skin disorders in Japan. Dermatologists frequently prescribe moisturizing creams mixed with steroid ointments.1-4) This treatment approach is based on the concept that moisture retention of the skin is important for the treatment of atopic dermatitis, as is steroid therapy. To facilitate application of the cream and ointment, they are mixed in an operation that is widely performed at pharmacy level.Moisturizing creams are classified into two types: oilin-water (o/w) emulsions, which are composed of small oil droplets dispersed in a continuous aqueous phase, while water-in-oil (w/o) creams are composed of small water droplets dispersed in a continuous oily phase.5) The basic concept concerning the compatibility of the different types of emulsions with steroid ointments is described in the dispensing guidelines in Japan, Chozai Shishin.6) The guidelines show a greater preference for w/o-type moisturizing creams in mixing creams with ointments than for o/w-type creams. This description is often used as a rationale to argue that the mixing operation performed in the pharmacy is appropriate. However, as a whole, pharmaceutical emulsions are not designed under the assumption that they would be mixed with other preparations. Therefore, it remains a concern that the mixing operation could be a...

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“…The mixing operation is aimed at improving patient compliance; the admixture allows the patients to reduce the frequency of application and modify the sticky and uncomfortable texture of the ointment base. [1][2][3][4][5] For the mixing operation, a centrifuge-type apparatus called "a revolution/rotation" hybrid mixer is widely used in pharmacy. 6) This apparatus comprises a main rotary head mounted on a vertical axis for the rotation motion and a secondary rotor mounted in bearings on the main head for the revolution motion.…”

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confidence: 99%

MRI Monitoring of the Mixed State of Admixtures Consisting of Moisturizing Cream and Steroid Ointment during the Mixing Process by a Revolution/Rotation-Type Hybrid Mixer

Yokokawa

Setoyama

Okada

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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The admixture of a steroid ointment and a moisturizing cream is frequently prescribed to patients suffering from atopic dermatitis. For the mixing operation, a revolution/rotation-type hybrid mixer is widely used in pharmacy. The purpose of this study was to monitor the mixed state of the admixtures during the mixing process of the hybrid mixer. The key technology used in this study was magnetic resonance imaging (MRI). Two different commercial mometasone furoate-containing ointments were used as a test steroid ointment. After layering the moisturizing cream and the steroid ointment in an ointment bottle, the sample was mixed for a predetermined period using the hybrid mixer. According to MRI transverse relaxation time (T 2 ) mapping for nondestructive monitoring, it was confirmed that the Flumeta ® ointment-containing admixture became homogeneous by mixing for 60 s or more. As for the mometasone furoate ointment 0.1%-containing admixture, the mixed state, after becoming homogeneous, was separated into two layers again by the prolonged mixing process. From the 1 H-NMR spectra of the phase-separated layers, re-separation was caused by removing aqueous components from the bottom of the samples. MRI is a powerful tool for monitoring the mixed state of the admixture during the mixing process. We believe that our findings offer profound insights into the clinical practice of the mixing operation using a hybrid mixer.

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Dilutions of corticosteroid creams and ointments — a stability study

Cited by 8 publications

References 8 publications

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

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

Stability of Mixed Preparations Consisting of Commercial Moisturizing Creams with an Ointment Base Investigated by Magnetic Resonance Imaging

MRI Monitoring of the Mixed State of Admixtures Consisting of Moisturizing Cream and Steroid Ointment during the Mixing Process by a Revolution/Rotation-Type Hybrid Mixer

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