Analysis of the use of excipients in medicines of biological origin

Abstract

Annotation. The development of protein products has a number of difficulties and uncertainties regarding the use of excipients due to the high instability of the active pharmaceutical ingredient. The aim of the study was to analyze the nomenclature of excipients in original medicines of biological origin and evidence-based information on general trends in their use in protein products. Based on the content analysis of scientific sources of pharmaceutical information using data from PubMed, Elsevier and Compendium scientific databases, the State Register of Medicines of Ukraine, the most common excipients in biological medicines available on the Ukrainian market were identified. It was found that the main categories of substances were: buffering agents, pH regulators, surfactants and lyoprotectants that ensure the stability of biological drugs, which are mostly represented by parenteral dosage forms. In these drugs, sodium phosphate, sodium hydroxide, hydrochloric acid are often used to stabilize pH, and histidine is used in monoclonal antibodies. To protect protein compositions from mechanical stresses, surfactants such as polysorbate 80 and polysorbate 20 were used in a larger percentage of preparations. Sugars such as sucrose, trehalose, lactose, sorbitol, mannitol, and glycine played an important role in protecting the protein from destabilizing conditions during the lyophilization process. Excipients that are typical only for protein products were found. In particular, phenol in polypeptide hormone formulations and methacresol in cytokine and growth factor formulations as antimicrobial preservatives; zinc and protamine sulfate in insulin formulations as stabilizers. Albumin as a stabilizer and solubilizer is present in preparations with cytokines and growth factors, toxins and some enzymes. Excipients, in addition to ensuring stability during transportation and use of biological drugs in various environmental conditions, affect their safety profiles and therefore require serious clinical consideration to improve the safety of these drugs.