Strategies for Solubility Enhancement of Anthelmintics (Review)
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Pharmaceutical Chemistry Journal, Vol. 54, No. 5, August, 2020 (Russian Original Vol. 54, No. 5, May, 2020)
DRUG SYNTHESIS METHODS AND MANUFACTURING TECHNOLOGY STRATEGIES FOR SOLUBILITY ENHANCEMENT OF ANTHELMINTICS (REVIEW) S. S. Khalikov1,* and A. V. Dushkin2 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 5, pp. 33 – 37, May, 2020.
Original article submitted November 9, 2019. Most drug substances are poorly soluble in water so that their efficacies must be improved by increasing the dosage, which not only creates economic problems but also increases the toxicity of the future medicine. These problems can be solved by developing various dosage forms, which involves additional financial costs, complicates the technology, increases development times to introduce the future medicine, etc. Another approach to improving the solubility of such drug substances is the development of methods and technologies for producing solid dispersions of these drug substances with excipients (polymers, dispersants, surfactants, etc.). The present review covers the development and application of mechanochemical technology to modify sparingly soluble anthelmintic drugs. The technology consists essentially of joint mechanical treatment of a drug substance and polymer in grinder-activators of controlled energy. This technology uses one stage and avoids the use of solvents, heating, evaporation, etc. The resulting solid dispersions include supramolecular systems with increased solubility and better bioavailability and are also highly active with reduced consumption of the active ingredients. Keywords: anthelmintics, solubility, mechanochemistry, dose, properties.
else the following adverse consequences could occur [3]. Low drug absorption in combination with its rapid degradation (especially if the drug includes labile structures such as peptides, proteins, etc.) could lead to an insufficient in vivo drug concentration, meaning that the therapeutic dose and; therefore, the desired pharmacological effect is not attained. Prolonged dissolution can distribute a toxic drug into other tissues (e.g., for antitumor preparations). Low solubility can cause drug plasma levels to oscillate and lead to unpredictable bioavailability levels. Solving the problem by increasing the dose and indications for drug substances to reach the required therapeutic action can lead to [4]: increased costs of the preparation; incomplete in vivo absorption of the drug substance and elimination into the environment; toxic action on the host organism because almost all drug substances are potentially hazardous compounds.
The solubility of drug substances plays an important role in the action of medicines designed primarily for peroral administration because the maximum rate of their passive transport through biological membranes, i.e., the main absorption pathway of drugs, depends on the membrane permeability and solution concentration [1]. Considering that about 40% of manufactured drug substances are classified as practically insoluble and greater
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