EC Paediatrics

For the first time, a soluble injectable dosage form of an inhibitor of the function of the adrenal cortex - o,p’-DDD - 1-,2-Chlorophenyl-1-(4’-Chlorophenyl)-2,2-Dichloroethane) (mitotane, chloditan), namely - a 5% solution of o,p’-DDD in a mixture of solvents of propylene glycol, ethyl alcohol, N,N-dimethylacetamide in a ratio of 7:2:1 for intravenous administration, was created. In vitro experiments on adrenal homogenates established the inhibitory effect of the drug on the synthesis of corticosteroids, and in vivo the influence of the specified dosage form on the morphofunctional state of the adrenal cortex was studied. The effect of o,p-DDD (mitotane, chloditan) on the cultured human adrenal cortex, inhibition of the synthesis of corticosteroid, has been established. It has been shown that when administered intravenously, the solution of chloditan inhibits the function of the adrenal cortex in experimental animals (dogs). Preclinical studies of the new dosage form of the drug o,p’-DDD were conducted and its acute and chronic toxicity were determined. According to the classification of compounds by toxicity, the solution of chloditan for injection belongs to class IV of low- toxic compounds, and the solvent to class VI of non-toxic substances. The chemical and pharmaceutical properties of the 5% solution for injection of o,p’ DDD were studied, which include the following indicators regulated by the State Pharmaceutical Federal Service for the Control of Pharmaceuticals and Biotechnology: description, identification, transparency, color, mechanical inclusions, accompanying impurities, extractable volume, sterility, bacterial endotoxins, abnormal toxicity, quantitative determination, storage conditions and shelf life. The results obtained indicate that, according to its parameters, the tested chloditan solution can be used for further research in the treatment of adrenal tumors and Cushing's disease.

 Keywords: Drug Form; Solution For Injection; Chloditan; Mitotane; Toxicity; Adrenal Cortex; Adrenocortical Activity

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