ABSTRACT
A novel method to convert S- and racemic (RS-) ibuprofen (Ibu) into an oily state at ambient temperature (25 degrees C) was developed. Using menthol and aqueous isopropanol (IPA) as melting point depressing agents, the two-phase melt systems (TMSs) of Ibu consisting of a homogeneous oily phase and a homogeneous aqueous phase were obtained. In TMS with a high S-Ibu: menthol ratio and a low IPA content, the oily phase primarily consisted of Ibu and menthol, whereas the majority of the aqueous phase was IPA and buffer. Using this method, the S-Ibu concentration in the oily phase reached as high as 70% (w/w). The compositional phase diagram was obtained using a titration method to study the relationship between the melting states of the solid components and system composition. S- and RS-Ibu showed different phase diagrams, and the maximum concentration of S-Ibu measured in the oily phase of TMS was much greater than that of RS-Ibu. The permeation study of a series of TMS and non-TMS systems showed that S-Ibu penetrated through shed snake skin faster than RS-Ibu, and the contents of IPA and menthol significantly affected the permeation rates of ibuprofen across shed snake skin, which may be attributed to the higher lipophilicity, and thus, higher solubility of S-Ibu in the skin than RS-Ibu. Such results support the use of S-Ibu TMS for topical formulation development.
Subject(s)
Drug Stability , Ibuprofen/metabolism , Administration, Cutaneous , Animals , Calorimetry, Differential Scanning/methods , Cell Membrane Permeability/drug effects , Cell Membrane Permeability/physiology , Chemistry, Pharmaceutical/methods , Chemistry, Physical/methods , Chromatography, High Pressure Liquid , Excipients/chemistry , Excipients/pharmacology , Ibuprofen/chemistry , Ibuprofen/pharmacology , Korea , Materials Testing/methods , Menthol/chemistry , Oils , Skin/drug effects , Skin Absorption/drug effects , Snakes , Solutions , Stereoisomerism , Technology, Pharmaceutical/methods , Temperature , WaterABSTRACT
Local anesthetics (lidocaine or tetracaine) spontaneously melted at 25 degrees C when mixed with thymol and aqueous isopropyl alcohol solution (IPA) at proper ratios and formed novel two-phase melt systems (TMS). The TMS consisted of a homogeneous oil phase containing primarily a local anesthetic agent (lidocaine or tetracaine) and thymol, and a homogeneous aqueous phase containing primarily IPA and pH 9.2 buffer. The relationship between melting of the solid components and system composition was determined from the phase diagram obtained by a titration method. A select TMS of a local anesthetic agent (lidocaine or tetracaine) was directly emulsified to prepare an O/W cream and tested for the anesthetic efficacy on intact human skin. While both lidocaine (6%) and tetracaine (4%) creams were highly effective for dermal anesthesia with a similar onset time, the tetracaine cream exhibited a significantly longer duration of action than the lidocaine cream. An accelerated stability study indicated that lidocaine was significantly more stable than tetracaine in the creams.
