Study of base influence on the active pharmaceutical ingredients releasing from combined ointments with antimycotic action

Abstract

Questions of mycotic diseases therapy keep staying in focus of clinical dermatology interest that is caused first of all by their considerable prevalence for international population. At the same time the dominating pathologies in this area are foot mycosis including skin, foot web space and nail plate affections. Etiotropic pharmacotherapy of foot skin and web spaces is carried out using topical antifungal medications effective against dermatomycetes. Also taking into account the frequent mixt infections, medicines with antibacterial action are desirable. Also topical antifungal medicines for therapy of foot skin mycosis have to satisfy the next requirements as rapid absorbance, safety and usability besides efficacy. Domestic dermatology for these aims has a great pharmacotherapeutical arsenal proposed by 34 semisolid dosage forms, 15 from them are made in Ukraine and the remainder are imported in our country. At the heart of practically all antimycotic medicines for topical therapy of smooth foot skin (as imported so domestic) imidazole and triazole derivatives are used and because of their high value they limit the therapeutical potential of population with low profit. 2-mercaptobenzothiazole is interesting as biologically active component of ointments not only because of broad spectrum of antifungal and antibacterial action but also exceptional hydrophobic characteristics which provide long adhesion even after washing during hygienic procedures. In this connection creating of semisolid dosage forms for the topical treatment of skin integument and interdigital folds with biologically active substances from the group of nonspecific antifungal matters (2-mercaptobenzothiazole, chinosolum) on the base of domestic technologies is actual for modern pharmaceutical and medical science. During creating of semisolid dosage forms for the external use one of the main experimental fragments is a selection of base which provides high consumer characteristics of medicine and its efficacy. The aim of this work is biopharmaceutical validation of rational composition of semisolid dosage form for external use containing the combination of 2-mercaptobenzothiazole and chinosolum. Materials and methods. As a delivery vehicle for developing pharmacotherapeutical medicine the bases widely used in manufacturing of semisolid dosage forms, providing easy “wipe-off effect after application, non-allergic and non-sensibilic after tracing, available for national producer and described in literature were studied. As the active pharmaceutical ingredients for antimycotic ointment 2-mercaptobenzothiazole and chinosolum in concentration 1% and 1% accordingly providing with suitable level of antifungal activity were used. Taking into account the advisability of high dispersion degree of medical substances in semisolid dosage forms for external use and physical-chemical properties of active pharmaceutical ingredients 2-mercaptobenzothiazole was added in all bases after preliminary dissolution in polyethylenoxyde 400 with heating and chinosolum was added after dissolution in prescribed or minimal amount of water. 2-mercaptobenzothiazole and chinosolum releasing from ointment compositions was studied with equilibrium dialysis method by Kruvchinsky at the temperature 32±0,5˚С through the semipermeable film “Kuprofan” in the Franz cell apparatus (producer PermeGear, Inc., USA). As a dialysis medium taking into account 2-mercaptobenzothiazole solubility we used solution containing methanol and water 1:1 and chinosolum releasing was carried out into water. Concentration of active pharmaceutical substances released from experimental ointments after 30 min was determined by spectrophotometric method. Results . The obtained results indicate significant advantage of the hydrophilic ointment bases, which provide an optimal level of release of 2-mercaptobenzothiazole and chinosolum from the experimental composite soft dosage forms for external use. Based on the obtained data, ointment compositions with 2-mercaptobenzothiazole and chinosolum on the basis of sodium carboxymethylcellulose (prescription №1) and methylcellulose (prescription №2) glycerogel were selected for further research. Conclusions. It was established that the sort of base significantly influences on 2-mercaptobenzothiazole and chinosolum releasing from the antimycotic formulations of semisolid dosage forms for external use. Variance analysis of results revealed that delivery vehicles on the base of sodium carboxymethylcellulose and methylcellulose glycerogel provide optimal 2-mercaptobenzothiazole and chinosolum releasing.