ABSTRACT
Griseofulvin, an antifungal agent, is a BCS class II drug slowly, erratically, and incompletely absorbed from the gastrointestinal tract in humans. The clinical failure of the conventional oral therapy of griseofulvin is most likely attributed to its poor solubility and appreciable inter- and intra-subject variation in bioavailability from different commercial products. Moreover, the conventional oral therapy is associated with numerous adverse effects and interactions with other drugs. The purpose of the study was to formulate a topical application of griseofulvin which would deliver the drug locally in a therapeutically effective concentration. Griseofulvin was solubilized in ethanol, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and combinations of ethanol with varying amounts of TPGS; then, it was incorporated in the Carbopol (980 NF) base. The formulations were characterized and evaluated ex vivo using Laca mice skin, microbiologically against Microsporum gypseum and Microsporum canis and clinically in a small group of patients. The current study suggested that TPGS and ethanol synergistically enhanced the drug permeation and drug retention in the skin. The selected formulation F VII was found to be effective against M. gypseum and M. canis, non-sensitizing, histopathologically safe, stable at 4°C, 25°C, and 40°C with respect to percent drug content, permeation characteristics, pH, transparency, feel, viscosity, and clinically effective in a small group of subjects. The proposed topical formulation of griseofulvin may be an effective and convenient alternative to the currently available oral therapy for the treatment of superficial fungal infections.
Subject(s)
Griseofulvin/administration & dosage , Griseofulvin/chemical synthesis , Skin Absorption/drug effects , Vitamin E/analogs & derivatives , Administration, Cutaneous , Adult , Animals , Drug Evaluation, Preclinical/methods , Female , Griseofulvin/metabolism , Humans , Male , Mice , Mycoses/drug therapy , Mycoses/metabolism , Mycoses/pathology , Patch Tests/methods , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/metabolism , Skin Absorption/physiology , Vitamin E/administration & dosage , Vitamin E/chemical synthesis , Vitamin E/metabolism , Young AdultABSTRACT
BACKGROUND: Vitiligo is a cosmetically disfiguring acquired depigmenting disorder caused by the loss of functional melanocytes from the epidermis. Various approaches that have been used for the treatment of vitiligo can be classified as medical and surgical therapies. Noncultured autologous melanocyte transplantation is a new and effective surgical treatment for stable vitiligo. OBJECTIVES: To compare the repigmentation results in stable vitiligo of transplantation of autologous noncultured melanocytes suspended in normal saline with that of those suspended in the patient's own serum. METHODS AND MATERIALS: Twenty-five patients with 36 lesions of stable vitiligo were randomized into two groups for noncultured melanocyte transplantation. Patients in Group A received melanocytes suspended in normal saline, and those in Group B received melanocytes suspended in their own serum. RESULTS: Statistically significant difference in repigmentation results and reduction in Dermatology Life Quality Index (DLQI) score was observed between the two groups 16 weeks after surgery. Repigmentation results were excellent (>90%) and very good to excellent (>75%) in 44.4% and 66.7% of lesions, respectively, in Group A and 88.8% and 94.4% of lesions, respectively, in Group B. There was also a significant (p=.002) decline in DLQI score in both groups, with the mean reduction being significantly greater in Group B than Group A (p=.005). CONCLUSION: Results of noncultured melanocyte transplantation can be improved significantly more by suspending the melanocytes in the patients' autologous serum than in normal saline. This could be an important innovation in the surgical management of patients with stable vitiligo.
