Preparation And Evaluation Of Concentrated Benzoic Acid And Salicylic Acid Ointments With PEG As The Matrix

Purpose:With the main purpose for solving the unqualified granularity problem of ointment while ensuring that it meets the standards referred to in all the provisions about ointment in Appendix of Chinese Pharmacopoeia2010Edition (Volume Ⅱ), we determined the best prescription through screening from concentrated benzoic acid and salicylic acid ointments, and established quality control system thereof accordingly.Methods:The concentrated benzoic acid and salicylic acid ointment was prepared by adding in dissolved benzoic acid and salicylic acid after a melting method was applied, in which ethanol or DMSO was used as the solvent for benzoic acid and salicylic acid, and PEG400and PEG4000was used as the water-soluble ointment matrix; ointment forming performance was controlled by adjusting the ratio of PEG400to PEG4000; cetyl alcohol was added to increase the water absorption of the matrix, and glycerin was added for moisture retention. The best prescription and the preparation process thereof was determined by comprehensively scoring obtained ointment preparations according to all the standards for ointment product described in Chinese Pharmacopoeia, selecting the best matrix ratio for each preparation by orthogonal experiments and based on related data processing results, and comparing them. Contents of benzoic acid and salicylic acid were simultaneously measured by using a HPLC method, in which a Kromasil-C18chromatographic column (150mm x4.6mm,5μm) was used as the static phase; a methanol-0.02mol·l-11KH2PO4(the pH value is adjusted to3.1with H3PO4) solution (50:50, V/V) was used as the mobile phase; the detection wavelength was set at280nm; the flow rate was1.0mL/min; the column temperature was adjusted to20℃; the sample injection volume was10μl; contents were calculated by measuring peak area in an external reference method. In addition, a microbial limit test method and other quality control methods of the ointment was established; and in the end, a permanent stability investigation was conducted to ointment product to determine the storage conditions and the expiry date, and a preliminary clinical observation was carried out to ensure its therapeutic effect.Results:1. The best prescription:for every1000g of the ointment,60g salicylic acid,120g benzoic acid,20g cetyl alcohol,125g PEG400,50ml DMSO,100g glycerol and525g PEG4000are contained.2. Preparation process:Solution A was prepared by mixing salicylic acid, benzoic acid, PEG400, glycerin and DMSO, and then continuously stirring them at the room temperature until they were totally dissolved and become clear; Solution B was prepared by heating the mixture of cetyl alcohol and PEG4000until it was dissolved and became clear, then cooling by continuously stirring it. When Solution B was cooled down to the temperature of50℃, Solution A was slowly added into it while it was continuous stirred for cooling the whole system down, then a white and translucent ointment was obtained.3. Granularity:No crystal or grana was observed by a microscope. The visual field of the microscope was transparent.4. Contents measurement by the HPLC method:concentrations of the injected salicylic acid and benzoic acid solutions were in ranges of48-72ug/ml and96-144μg/ml, respectively. Both of the two acid solutions had a good linear relation between the concentration and peak area of them. Recoveries of salicylic acid were respective99.39%,100.17%, and99.69%for a low concentration solution (concentrations of salicylic acid and benzoic acid were48μg/ml and96μg/ml, respectively), a medium concentration solution (concentrations of salicylic acid and benzoic acid were60μg/ml and120μg/ml, respectively), and a high concentration solution (concentrations of salicylic acid and benzoic acid were72μg/ml and144μg/ml, respectively), and those of the benzoic acid were99.87%,100.60and99.59%, respectively.5. Results of the permanent stability investigation showed that, within its validity period, the ointment completely met all the standards of Chinese Pharmacopoeia. And it could be stored at the room temperature for at least six months.6. The preliminary clinical observation indicated a good clinical effect of the ointment.Conclusions:The ointment prepared by this new method has stable and controllable quality, shows a good clinical effect, and meets the standards of Chinese Pharmacopoeia.