Amitraz Solid Dosage Form

Abstract

This study considered the use of urea eutectics as fast release solid dosage carrier forms for the acaricide N-methylbis (2,4-xylyliminomethyl) methylamine (AmitrazTM). Wettol D2 and Arkopal N090 were chosen as the wetting agent and dispersants respectively. Their optimum levels were determined as the surfactant concentrations that yielded a minimum in the dispersion viscosity of a concentrated (30% m/m) Amitraz suspension. The optimum dosage levels were found to be ca. 2% Arkopal N090 and ca. 1% Wettol D2. Eutectic phase diagrams were obtained using the melting-cooling method. The components were ground together into a fine powder and heated in a glass tube immersed in a silicon oil bath. The liquid was allowed to cool down and solidify at ambient conditions. The time-dependant temperature change of the sample was tracked with a thermocouple. The data was captured in real time on a personal computer and analysed using an Excel spreadsheet programme. The melt-cast method was used to prepare eutectic mixtures. They were characterised using DSC, DTA, XRD and Light Microscopy. The XRD peaks showed the presence of the two separate crystal structures for the eutectic mixture constituents. The urea – CaBr2.2H2O combination was initially considered as carrier for Amitraz. However, this eutectic system was found to be too hygroscopic. Small additions of PEG 6000 improved the tablet strength but decreased the dissolution rate. Urea and acetamide formed a eutectic at ± 46oC with a composition of ca. 40 % m/m urea. Unfortunately acetamide is a suspected carcinogen. Therefore the urea - 1,3-dimethylurea was selected as Amitraz carrier system instead. The eutectic mixture comprised 40% m/m urea and 60% m/m 1,3-dimethylurea, which melt at ± 56oC. The melt-press method was used to prepare Amitraz containing pellets measuring 5 mm thick and 33 mm ö and weighing about 5,0 g. It was possible to suspend Amitraz powder in the eutectic melt mixture provided it remained in powder form. However, when liquefied (by melting), phase separation occurred. Thus the temperature of the eutectic mixture should be kept below the 80oC melting point of Amitraz. The dissolution tests were performed in a 10-liter Pyrex glass beaker with normal tap water (± 25oC). The time taken for complete dissolution was measured with a stopwatch. These results were confirmed with turbidity tests. Starch-based super disintegrants were used in an attempt to enhance the dissolution rate of the pellets. Explotab® improved the dissolution rate of 30% and 40% m/m Amitraz formulations slightly. The best formulation obtained in this study had the following composition (in m/m): 30% Amitraz; 8% CaCO3; 1 % Wettol D2; 2% Arkopal N090; 10% Explotab® and 49% urea – 1,3-dimethylurea eutectic. Such tablets disintegrated within 6,5 minutes when suspended in water.