Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound ...Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qualitative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ketoconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation products, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.展开更多
Corticosteroids are the most widely used class of anti-inflammatory medications in the pharmaceutical industry. There are several pharmaceutical dosage forms available using different corticosteroids. Topical steroids...Corticosteroids are the most widely used class of anti-inflammatory medications in the pharmaceutical industry. There are several pharmaceutical dosage forms available using different corticosteroids. Topical steroids of varying potencies are available in creams, ointments, solutions and other vehicles. Chemical instability and drug degradation are the key quality concerns for these topical dosage forms. Nature of the dosage forms, excipient quality, product composition, and process optimization are some of the common factors which affect the stability of corticosteroids. This article describes drug degradation behavior of three different corticosteroids in different topical dosage forms. Drug degradation patterns of Hydrocortisone, Clobetasol propionate and Desonide formulations observed in stability studies of respective finished drug products under ICH recommended storage conditions were investigated. HPLC, UPLC-MS/MS methods were developed for the separation and characterization of impurities. The structural elucidation of the unknown impurities observed for these steroids and mechanistic consideration of potential degradation pathways has been discussed. Detailed discussion on the analytical methodologies is included as well.展开更多
Background: Calcineurin inhibitors like tacrolimus and pimecrolimus are new modality of treatment of localized vitiligo. Objective: To compare the effectiveness and side effects of 1% pimecrolimus cream in comparison ...Background: Calcineurin inhibitors like tacrolimus and pimecrolimus are new modality of treatment of localized vitiligo. Objective: To compare the effectiveness and side effects of 1% pimecrolimus cream in comparison with 0.05% clobetasol propionate cream as a treatment of localized type of vitiligo. Patients and Methods: Fifty two patients with localized vitiligo were included in this single, blind, comparative therapeutic trial. Full history and examination for each patient was done. Wood’s light was used when needed to confirm the diagnosis. Thirty (57.7%) were females and 22 (42.3%) males, female to male ratio of 1.36:1. Their ages ranged between 3 - 40 (13.15 ± 7.9) years, while disease duration ranged from 6 - 84 (29.62 ± 20.56) months. Total numbers of lesions were 114 lesions with a mean of 2.2 lesions per patient. The surface area of the lesions ranged between 1 - 31 (7.15 ± 6.98) cm2. Vitiliginous patches were most commonly located on face 48 (42.1%) lesions, and lower limbs 35 (30.7%) lesions. Patients were divided in to two groups according to the type of therapeutic modality.?Group?A?consisted of 25 patients (52 lesions) receiving 1% pimecrolimus cream and?Group?B?27 patients (62 lesions) treated with 0.05% clobetasol propionate cream, both used twice daily. The amount of cream per area was applied according to rule of fingertip unit. Measuring the surface area of the lesions and calculating the reduction rate were done every month till the end of the 6th?month. Then patients were asked to stop the use of medication to be re-evaluated again after 3 months without any treatment and to record any local or systemic side effects. Results: After 6 months of treatment there was 79.67% reduction in the surface area of lesions in?Group?A, while inGroup?B?there was 82.59% reduction in the surface area with no statistically significant difference between the two groups. The reduction rate was early as there was statistically significant reduction for both groups after one month of treatment (p value < 0.01). The reduction rates for facial lesions were more than other parts of the body. There was no significant relapse after 3 months of stopping treatment for both groups. Side effects were minimal and tolerable. Conclusions: Topical 1% pimecrolimus is as effective as clobetasol propionate in treatment of localized vitiligo affecting less than 5% of the body surface area but pimecrolimus was more preferred as the side effects of topical steroid could be avoided.展开更多
文摘Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qualitative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ketoconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation products, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.
文摘Corticosteroids are the most widely used class of anti-inflammatory medications in the pharmaceutical industry. There are several pharmaceutical dosage forms available using different corticosteroids. Topical steroids of varying potencies are available in creams, ointments, solutions and other vehicles. Chemical instability and drug degradation are the key quality concerns for these topical dosage forms. Nature of the dosage forms, excipient quality, product composition, and process optimization are some of the common factors which affect the stability of corticosteroids. This article describes drug degradation behavior of three different corticosteroids in different topical dosage forms. Drug degradation patterns of Hydrocortisone, Clobetasol propionate and Desonide formulations observed in stability studies of respective finished drug products under ICH recommended storage conditions were investigated. HPLC, UPLC-MS/MS methods were developed for the separation and characterization of impurities. The structural elucidation of the unknown impurities observed for these steroids and mechanistic consideration of potential degradation pathways has been discussed. Detailed discussion on the analytical methodologies is included as well.
文摘Background: Calcineurin inhibitors like tacrolimus and pimecrolimus are new modality of treatment of localized vitiligo. Objective: To compare the effectiveness and side effects of 1% pimecrolimus cream in comparison with 0.05% clobetasol propionate cream as a treatment of localized type of vitiligo. Patients and Methods: Fifty two patients with localized vitiligo were included in this single, blind, comparative therapeutic trial. Full history and examination for each patient was done. Wood’s light was used when needed to confirm the diagnosis. Thirty (57.7%) were females and 22 (42.3%) males, female to male ratio of 1.36:1. Their ages ranged between 3 - 40 (13.15 ± 7.9) years, while disease duration ranged from 6 - 84 (29.62 ± 20.56) months. Total numbers of lesions were 114 lesions with a mean of 2.2 lesions per patient. The surface area of the lesions ranged between 1 - 31 (7.15 ± 6.98) cm2. Vitiliginous patches were most commonly located on face 48 (42.1%) lesions, and lower limbs 35 (30.7%) lesions. Patients were divided in to two groups according to the type of therapeutic modality.?Group?A?consisted of 25 patients (52 lesions) receiving 1% pimecrolimus cream and?Group?B?27 patients (62 lesions) treated with 0.05% clobetasol propionate cream, both used twice daily. The amount of cream per area was applied according to rule of fingertip unit. Measuring the surface area of the lesions and calculating the reduction rate were done every month till the end of the 6th?month. Then patients were asked to stop the use of medication to be re-evaluated again after 3 months without any treatment and to record any local or systemic side effects. Results: After 6 months of treatment there was 79.67% reduction in the surface area of lesions in?Group?A, while inGroup?B?there was 82.59% reduction in the surface area with no statistically significant difference between the two groups. The reduction rate was early as there was statistically significant reduction for both groups after one month of treatment (p value < 0.01). The reduction rates for facial lesions were more than other parts of the body. There was no significant relapse after 3 months of stopping treatment for both groups. Side effects were minimal and tolerable. Conclusions: Topical 1% pimecrolimus is as effective as clobetasol propionate in treatment of localized vitiligo affecting less than 5% of the body surface area but pimecrolimus was more preferred as the side effects of topical steroid could be avoided.
