Development of the composition of hard capsules with antihelmintic activity based on praziquantel

Abstract

Introduction. Helminthiasis is one of the most common forms of parasitosis. To date, the pharmaceutical market still does not offer drugs of the ATX group P02BA01 based on the substance praziquantel, although it is recommended by current clinical protocols for the treatment of schistosomiasis and other parasitic invasions caused by trematodes and some types of cestodes. The aim of our study is to develop the composition of a solid dosage form, in particular, hard gelatin capsules, based on the active pharmaceutical ingredient praziquantel. Materials and methods of study. The objects of study were samples of the substance praziquantel and model samples of hard capsules with praziquantel and a variable composition of excipients. The studies used methods of microscopic analysis, determination of bulk density and density after shrinkage, and fluidity. Results of the study. It was found that praziquantel has very poor fluidity in terms of bulk density, density after shrinkage, compressibility after shrinkage, Gaussner coefficient, angle of repose and flow rate through the nozzle. According to the values of the angle of repose, praziquantel samples have satisfactory fluidity, which is typical for bound materials. The dose of praziquantel per 1 capsule was selected based on the analysis of clinical protocols for the treatment of helminthiasis of the digestive system. Thus, a single therapeutic dose of praziquantel is 5-20 mg/kg. We selected a dose of 350 mg per 1 capsule, which corresponds to 5 mg per 70 kg of body weight. Conclusions. Based on the study of the fluidity of five model samples of capsule mass in terms of the angle of repose and flow rate through the nozzle, the most rational composition of excipients was determined: lactose 9.5 wt.  %, aerosil 5.0 wt. %, wt. 2.0 wt. %, magnesium stearate 0.5 wt. %.