TY - JOUR

T1 - Оценка влияния поливинилпирролидон-винилацетата на свойства кверцетина в составе бинарной твердой дисперсии, полученной методом экструзии горячего расплава

AU - Danilova, A. A.

AU - Gusev, K. A.

AU - Arkhipova, N. O.

AU - Danilov, L. G.

AU - Vishnyakov, E. V.

AU - Maimistov, D. N.

AU - Flisyuk, E. V.

PY - 2025/1/1

Y1 - 2025/1/1

N2 - Introduction. Flavonoids, despite their pronounced therapeutic benefits, are limitedly used in medicine as active pharmaceutical ingredients (API) owing to a complex of unsatisfactory physicochemical properties. In order to study the mentioned problem, we decided to use quercetin as model compound with extremely low water solubility and dissolution in gastrointestinal (GI) tract media. Therefore, the main idea appears to study the possibility and prospects of hot melt extrusion (HME) application for enhancement the solubility properties of quercetin in the composition of solid dispersion system (SDS) based on hydrophilic polymeric carrier (polyvinylpyrrolidone vinyl acetate, PVP/VA). Consequently, there is a necessity to select effective drug-to-polymer ratio in solid dispersion for providing better solubility and dissolution properties. Aim. Assessment of PVP/VA effect on quercetin solubility properties in binary solid dispersion prepared by HME. Materials and methods. Quercetin substance with purity 98 % was purchased from Molekula Limited, United Kingdom. PVP/VA (copolymer of polyvinylpyrrolidone with vinyl acetate in the ratio of 60: 40, VIVAPHARM® PVP/VA 64) as carrier was procured from JRS PHARMA (JRS PHARMA GmbH & Co. KG, Germany). Quercetin SDS were prepared using micro-conical twin screw compounder HAAKE™ MiniCTW (Thermo Fisher Scientific, Germany). The obtained samples were analyzed by phase-contrast microscopy, FTIR spectroscopy and differential scanning calorimetry (DSC). Quercetin quantitative content in SDS were determined by UV-spectrophotometry. Results and discussion. The improvement of water solubility and dissolution rates of quercetin SDS in comparison with pure substance was observed for all solid dispersion compositions irrespective to drug-to-polymer ratio. Notably, with reduction of quercetin content in SDS compositions the PVP/VA contribution was increased. We found partial or even complete amorphization of API in formulations with 1 % and 5 % quercetin content, resulting in the improvement of water solubility properties, stability of solutions and increased dissolution rates in GI tract media. Water solubility of 1 % SDS relative to pure substance was enhanced by 353-fold. At the same time, the complete release of quercetin from 1 % SDS was achieved in 40 minutes in the hydrochloric acid and citrate buffer, and also quercetin dissolution of 90 % in 60 minute was observed in phosphate buffer. Conclusion. 1 % quercetin SDS based on PVP/VA appears to be the most promising for solid dosage forms development.

AB - Introduction. Flavonoids, despite their pronounced therapeutic benefits, are limitedly used in medicine as active pharmaceutical ingredients (API) owing to a complex of unsatisfactory physicochemical properties. In order to study the mentioned problem, we decided to use quercetin as model compound with extremely low water solubility and dissolution in gastrointestinal (GI) tract media. Therefore, the main idea appears to study the possibility and prospects of hot melt extrusion (HME) application for enhancement the solubility properties of quercetin in the composition of solid dispersion system (SDS) based on hydrophilic polymeric carrier (polyvinylpyrrolidone vinyl acetate, PVP/VA). Consequently, there is a necessity to select effective drug-to-polymer ratio in solid dispersion for providing better solubility and dissolution properties. Aim. Assessment of PVP/VA effect on quercetin solubility properties in binary solid dispersion prepared by HME. Materials and methods. Quercetin substance with purity 98 % was purchased from Molekula Limited, United Kingdom. PVP/VA (copolymer of polyvinylpyrrolidone with vinyl acetate in the ratio of 60: 40, VIVAPHARM® PVP/VA 64) as carrier was procured from JRS PHARMA (JRS PHARMA GmbH & Co. KG, Germany). Quercetin SDS were prepared using micro-conical twin screw compounder HAAKE™ MiniCTW (Thermo Fisher Scientific, Germany). The obtained samples were analyzed by phase-contrast microscopy, FTIR spectroscopy and differential scanning calorimetry (DSC). Quercetin quantitative content in SDS were determined by UV-spectrophotometry. Results and discussion. The improvement of water solubility and dissolution rates of quercetin SDS in comparison with pure substance was observed for all solid dispersion compositions irrespective to drug-to-polymer ratio. Notably, with reduction of quercetin content in SDS compositions the PVP/VA contribution was increased. We found partial or even complete amorphization of API in formulations with 1 % and 5 % quercetin content, resulting in the improvement of water solubility properties, stability of solutions and increased dissolution rates in GI tract media. Water solubility of 1 % SDS relative to pure substance was enhanced by 353-fold. At the same time, the complete release of quercetin from 1 % SDS was achieved in 40 minutes in the hydrochloric acid and citrate buffer, and also quercetin dissolution of 90 % in 60 minute was observed in phosphate buffer. Conclusion. 1 % quercetin SDS based on PVP/VA appears to be the most promising for solid dosage forms development.

KW - antiplasticization

KW - dissolution

KW - hot melt extrusion

KW - quercetin

KW - solid dispersions

KW - solubility

UR - https://www.mendeley.com/catalogue/4bb6c551-6399-36e8-b007-f973ea9bd68e/

U2 - 10.33380/2305-2066-2025-14-1-1935

DO - 10.33380/2305-2066-2025-14-1-1935

M3 - статья

VL - 14

SP - 127

EP - 137

JO - Drug Development and Registration

JF - Drug Development and Registration

SN - 2305-2066

IS - 1

ER -