Biopharmaceutical research and quality control parameters of a combined ointment for the herpes treatment

Abstract

Introduction. Considering the etiology and pathogenesis, for the treatment of diseases caused by herpes viruses, it is advisable to use combined drugs that have a comprehensive effect on various links of the pathological process and expand the spectrum of pharmacological action of the drug.For the treatment of mono‐ and mixed herpesvirus infections, we have proposed a combined drug in the form of an ointment with acyclovir and miramistin. Purpose: to substantiate the relevance of developing a combined ointment with acyclovir and miramistin, to determine the quality profile of the drug, the effect of excipients on rheology, and to evaluate the antiviral activity of the ointment. Materials and methods. The object of the study was an ointment with acyclovir and miramistin. Vaseline oil, Paraffin, Propylene glycol, and Cetostearyl alcohol were used as the base of the combined ointment. The rheological properties of the ointments were studied using a Rheolab QC rotational viscometer (Anton Paar, Austria). The effect of the CSA concentration on the rheological characteristics was investigated by constructing a hysteresis loop and determining the dependence of the effective viscosity on the shear rate. The quantitative content of the active substances acyclovir and miramistin was determined by high‐performance liquid chromatography. The in vivo antiviral activity of the ointment was studied in guinea pigs. Results. As a result of the analysis of the pharmaceutical market of Ukraine, it was determined that monopreparations with acyclovir mainly dominate, most of which are in the form of tablets. The target quality profile of the combined ointment containing acyclovir and miramistin was determined, and critical indicators of the quality of the drug were assessed. The study of the rheological parameters of the ointment proved the possibility of regulating the ultimate static shear stress and dynamic viscosity by changing the CSA concentration, which is rational within the concentration range of 1%–3.5%. Studies of antiviral activity in vivo showed that the ointment is more effective than Zovirax cream and allows significantly reducing the duration of the disease caused by the herpes virus type 2. Conclusions. For the treatment of mixed herpesvirus infections, the creation of a combined ointment with acyclovir and miramistin was justified, its antiviral effect was proven. The target quality profile, critical indicators were determined, and a method for quantitative analysis of acyclovir and miramistin was developed. The optimal composition of the ointment base was determined and its rheological properties were studied. In vivo studies showed that the use of the ointment 3 times a day significantly reduced the duration of the disease, and its effectiveness against HSV‐II was confirmed in comparison with Zovirax cream.