Development and optimization of quantitative composition of rectal suppositories with diosmin and hesperidin by the method of mathematical planning of the experiment

Abstract

In the development of suppositories biphasic media are rarely used. It is due to the occurrence of possible instabilities within the system «dispersed phase and a dispersing medium». To solve such problems, it is rational to use the methods of mathematical planning of the experiment. The method of mathematical planning of the experiment feature is the diversity of approaches to model construction. This means that these methods are theoretically predict the results of a future experiment, analyze the data obtained, prevent the repetition of experiments and optimize the technology of medicine.
 The aim of the present research was to develop and optimize of quantitative composition of rectal suppositories with diosmin and hesperidin by the method of mathematical planning of experiment.
 Objects of the study were samples of suppositories of the biphasic type with diosmin and hesperidin. The dispersing medium of these samples consisted of hydrophobic (Witepsol W35 and emulsifiers) and hydrophilic parts (sodium alginate gel with the addition of Ca2+ as a complexing cation). Preliminary results of determining the percentage limits of the hydrophobic part of the dispersed medium were carried out by studying the indicators of the release of active substances from the dosage form and the laser diffraction method. As responses of experiments was used such indicator as: disintegration time, hardness and mucoadhesion.
 As a result of the studies, the functional dependence of the indicators on the amount of components of the suppository dispersed medium was established. It was found that acceptable values of the responses should conform to the following conditions: hardness and mucoadhesion should be close to the maximum, and the disintegration time – to the minimum.
 According to the results of the study it was found that the optimal content of the mixture of emulsifiers – 6.29%, solid fat – 39.51%, the hydrophilic part of the biphasic medium – 29.58%. Responses that will provide the system with the necessary structural-mechanical and pharmaco-technological properties are within: y1 (2.713); y2 (22.639); y3 (439.283). The obtained data will be used in further studies to optimize the composition and technology of rectal suppositories with diosmin and hesperidin.