The pharmaceutical development of combined oral dosage forms taking into account possible risks to quality

Abstract

At the current stage of the pharmaceutical sector development, the development and introduction of new combined medicines in the form of oral solutions is relevant. Compared to other dosage forms, oral medications require the addition of excipients, which are used not only to ensure the necessary technological properties of the dosage form, but also to improve its organoleptic properties (flavor correctors).

Aim. To conduct the pharmaceutical development of a new original combined medicinal product based on meldonium with DL-malic acid in single-dose polymer ampoules; to determine potential risk factors related to the quality and compatibility of active pharmaceutical substances and excipients, the impact of primary packaging, production conditions, and the quality control of the finished product.

Materials and methods. The following research methods were used: description – visually, transparency, color – physicochemical, pH – potentiometric, related impurities, the quantitative content – liquid chromatography, potentiometric. The study objects were active pharmaceutical ingredients, such as meldonium manufactured by Chemrio International Limited, China, and DL-malic acid manufactured by Bartek Ingredients Inc., Canada, as well as excipients and polyethylene ampoules of the Purell PE 3020D brand with a relative density of 0.926 g/cm³.

Results and discussion. At the stage of the pharmaceutical development of a new combined medicinal product containing meldonium and DL-malic acid as active pharmaceutical ingredients, the optimal doses of active substances, and the dosage form were determined. The composition and manufacturing technology of the drug were scientifically justified. The physical and chemical properties of active substances and excipients, their compatibility in solution, the effect of polyethylene primary packaging on the quality of the finished product during the expected shelf life were studied. Critical control points were identified to prevent or eliminate hazards or reduce them to an acceptable level. The risks of the technological process of manufacturing a combined oral solution were assessed.

Conclusions. As a result of the pharmaceutical development of a combined medicinal product in the form of an oral solution in single-dose containers based on meldonium and DL-malic acid, the quality and quantity of active substances and excipients with the optimal pH values of the solution have been determined. It has allowed obtaining a medicinal product with pleasant organoleptic characteristics, stable during the expected shelf life in polyethylene ampoules.