The development of a tablet formulation of quercetin with the carrot extract with improved solubility for the atherosclerosis prevention

Abstract

The primary goal in the development of tablet dosage forms is to ensure their quality, safety, and therapeutic effectiveness. In addition to containing the required amount of the active pharmaceutical ingredient (API), a tablet must meet specific technological parameters that ensure stability, consistent dose uniformity, and ease of use for the patient. The determination of pharmacotechnological mass parameters during tableting is of particular importance as this factor directly affects the accuracy of the active substance dosing, formulation homogeneity and uniform distribution of the API, as well as the mechanical strength and resistance of tablets to fracture. In addition, these parameters significantly influence biopharmaceutical characteristics, including the disintegration time and drug release rate. In the development of tablets intended for the prevention and treatment of atherosclerosis, pharmacotechnological considerations become even more critical.

Aim. To study the pharmacotechnological parameters of tablet formulations, which is a fundamental task in pharmaceutical technology as it determines the success of the drug development and further clinical application of the medicine.

Materials and methods. A tableting blend and tablet samples previously designated as “Carocetin” were used as the study objects. The study employed methods regulated by the State Pharmacopoeia of Ukraine (SPhU). In addition, the coefficients of vibration compaction and heterogeneity, as well as the angle of collapse, were determined. The tablet quality was assessed based on the mechanical strength, friability, disintegration time, and the coefficients of compaction and compressibility.

Results. It has been found that the use of a solid dispersion of quercetin with polyvinylpyrrolidone K-30 improves its technological properties and creates prerequisites for enhanced bioavailability. The role of modifying the thick extract of roots by blending it with microcrystalline cellulose-102 in a ratio of 1:1 has been evaluated; this approach ensures reduced hygroscopicity and improved flowability of the mixture without the loss of the biological activity. The analysis of pharmacotechnological parameters has demonstrated that, according to the Carr classification, the tableting blend corresponds to flowability class I, which allows the use of the direct compression method without prior granulation. The relationships between compression pressure and the physicomechanical quality parameters of tablets have been characterized, and it has been found that optimal characteristics, namely the sufficient mechanical strength, low friability, and acceptable disintegration time are achieved at a compression pressure of 100 ± 1 kN.

Conclusions. It has been demonstrated that the pharmaceutical composition developed on the basis of a solid dispersion of quercetin and a thick extract of carrot roots is technologically justified for producing tablets by the direct compression method. The use of a moderate compression pressure (100 ± 1 kN) has been proven to be optimal, ensuring the proper tablet quality and compliance with the requirements of the SPhU for tablets previously designated as “Carocetin”. The approach proposed is considered to create favorable conditions for increasing the bioavailability of biologically active compounds and can be applied in the further development of combined solid dosage forms with anti-atherogenic properties in the tablet form.