Supersaturated Systems For Enhanced Topical Salicylic Acid Delivery

Supersaturating transdermal delivery system is an emerging concept oftransdermal delivery system in recent years, it can increase the steady-state drug fluxthrough the skin by preparing supersaturated system, it has the following advantages:it can increase skin penetration, it doesn’t elicit the skin irritation, it doesn’t modifythe property of skin. But a supersaturated drug solution is thermodynamically unstableand has the tendency to return to the equilibrium state by drug precipitation. In orderto take advantages of the supersaturated drug solution, we can use precipitationinhibitions to stabilize the system.In this paper, we systematic studied supersaturated salicylic acid transdermaldrug delivery system, specifically: established the in vitro high performance liquidchromatography (HPLC) analysis method of salicylic acid; choosed three solventsystems to determine the solubility of salicylic acid in which the three solvent systemswere: buffer of different pH values (pH2.19, pH2.95, pH4.00, pH6.00, pH8.00),different proportions of the propylene glycol (PG)-aqueous solution and differentproportions of glycofurol (GLY)-aqueous solution, and drawed out of the solubilitycurves; prepared supersaturated salicylic acid solutions of the above three solventsystems, screened a series of different types of different concentrations ofprecipitation inhibitor, comprising: HPMC4000, HPMC65SH-50, PVPK-30,PVPK-90to observe the effect of inhibitting the precipitate. When we used differentproportions of the propylene glycol (PG)-aqueous solution and different proportionsof glycofurol (GLY)-aqueous solution, although we had tried different concentrationsof different types of precipitation inhibitors, it can not effectively inhibit theprecipitation, but in different pH values buffer solvent system, the preparedsupersaturated salicylic acid solutions remained stable state in32℃water bath for amonth without precipitation inhibitors. Therefore we only used supersaturatedsalicylic acid solutions prepared in different pH values buffer solvent system for thein vitro permeation experiments of the next step.Polydimethylsiloxane membrane (PDMS) and isolated pig skin permeationexperiments were carried out, we found that the flux of PDMS membrane permeationexperiments was less than the theoretical value calculated by Higuchi equation, inorder to explore the reasons, we emphatically carried out a series of tests of the PDMSmembrane after permeation experiments, including: Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectroscopy, differential scanningcalorimetry, found that: both spectroscopic and thermal analysis showed that salicylicacid could interact with PDMS membrane when formulated in a supersaturatedsystem, the extent of interaction increased with degree of saturation, which lead to thealteration of PDMS barrier property and reduced solute flux under supersaturatedcircumstances; this study implied that apart from considering the vehicle–membraneand vehicle–drug interactions the drug–membrane interaction(s) should also be takeninto account when designing and formulating supersaturated skin drug deliverysystems.