Formulation of extemporaneous amphotericin b topical preparations containing high amount of dimethyl sulfoxide for the treatment of onychomycosis

Abstract

The main purpose of this research was to formulate the stable extemporaneous Amphotericin B topical preparation in a treatment onychomycosis and to determine beyond-use date of the product. To date, there is no marketed topical Amphotericin B product available in Thailand and no data available on stability of these preparations. The formulations in this study were prepared from a commercial Amphotericin B for injection. Three Amphotericin B topical preparations; i.e. o/w emulsion, hydrophilic ointment and gel, were developed. The preparations were formulated with high amount of dimethyl sulfoxide (DMSO) as a nail permeation enhancer and use Tris-hydrochloride buffer for controlling pH value of the preparation at pH 7. The physical stabilities of these formulations were tested by heating-cooling method (4°C for 48 hours – 45°C for 48 hours) and also monitored for appearance changes. The amphotericin B gel lost its viscosity and showed visible non-uniformity due to precipitation of Amphotericin B after stability testing. The preparations were storage at 30±2oC up to 60 days. During that time, Amphotericin B was quantified by high-performance liquid chromatography (HPLC). The extemporaneous Amphotericin B cream and ointment containing 30% concentrations of DMSO were stable for 60 days. Moreover, the In vitro permeation to clipping nail plates from healthy human volunteer showed that Amphotericin B in cream and ointment could permeate into nail plate when compared with the self-base formulation. The ointment formulation was better than cream (p < 0.05). The stable cream and ointment containing 3% Amphotericin B were obtained for further clinical study to evaluate the therapeutic and adverse effects, including the patient’s satisfaction.