TY - JOUR

T1 - Исследование динамики высвобождения дифлунизала из полимерной матрицы

AU - Михайлова, П.А.

AU - Адамова, Александра Александровна

AU - Генералова, Ю.Э.

AU - Снетков, П. П.

AU - Морозкина, Светлана Николаевна

PY - 2024/1/29

Y1 - 2024/1/29

N2 - Introduction. The effectiveness of diflunisal in the treatment of cardiac amyloidosis has been clinically proven. Currently, only tablet forms of diflunisal are registered in the world, however, long-term use of NSAIDs leads to characteristic side effects. Therefore, delivery systems for diflunisal (including a form for external use) are now being actively developed to reduce side effects and improve its bioavailability. Aim. Research of the dynamics of release of the active substance diflunisal from the polymer matrix of hyaluronic acid. Materials and methods. The objects of the study are diflunisal gels in hyaluronic acid with a concentration of the main substance of 0.093, 0.14, 0.19 and 0.25 %. Quantitative determination was carried out by reverse-phase HPLC using a Prontosil C18, 120-5, 75 × 2 mm chromatographic column, thermostatically controlled at 40 °C. Eluent: phosphate buffer solution (PBS) with pH 3.0 and acetonitrile (30: 70), flow rate 0.1 ml/min. Eluates were detected at wavelengths of 230, 270, 310 nm. Results and discussion. During the work, a method (HPLC) was selected and a method for determining diflunisal in a HA matrix was developed. The delivery system under study significantly increases the solubility of diflunisal in an aqueous solution compared to the dissolution of the substance. The release of the active substance from the matrices was carried out in a phosphate buffer solution with pH 7.6. The release rate for all samples exceeded 90 % after 3 hours after the start of the experiment, with most of the active substance released within an hour. Conclusion. The data obtained suggest that the release profile is characteristic of biodegradable matrices and diffusion-controlled delivery systems. Complete extraction of diflunisal from HA was achieved using PBS with pH 7.6 as a dissolution medium.

AB - Introduction. The effectiveness of diflunisal in the treatment of cardiac amyloidosis has been clinically proven. Currently, only tablet forms of diflunisal are registered in the world, however, long-term use of NSAIDs leads to characteristic side effects. Therefore, delivery systems for diflunisal (including a form for external use) are now being actively developed to reduce side effects and improve its bioavailability. Aim. Research of the dynamics of release of the active substance diflunisal from the polymer matrix of hyaluronic acid. Materials and methods. The objects of the study are diflunisal gels in hyaluronic acid with a concentration of the main substance of 0.093, 0.14, 0.19 and 0.25 %. Quantitative determination was carried out by reverse-phase HPLC using a Prontosil C18, 120-5, 75 × 2 mm chromatographic column, thermostatically controlled at 40 °C. Eluent: phosphate buffer solution (PBS) with pH 3.0 and acetonitrile (30: 70), flow rate 0.1 ml/min. Eluates were detected at wavelengths of 230, 270, 310 nm. Results and discussion. During the work, a method (HPLC) was selected and a method for determining diflunisal in a HA matrix was developed. The delivery system under study significantly increases the solubility of diflunisal in an aqueous solution compared to the dissolution of the substance. The release of the active substance from the matrices was carried out in a phosphate buffer solution with pH 7.6. The release rate for all samples exceeded 90 % after 3 hours after the start of the experiment, with most of the active substance released within an hour. Conclusion. The data obtained suggest that the release profile is characteristic of biodegradable matrices and diffusion-controlled delivery systems. Complete extraction of diflunisal from HA was achieved using PBS with pH 7.6 as a dissolution medium.

KW - delivery system

KW - diflunisal

KW - high performance liquid chromatography

KW - hyaluronic acid

KW - polymer matrix

KW - release

UR - https://www.mendeley.com/catalogue/aec443a2-e116-38a3-bb6b-bd31d82e1cfc/

U2 - 10.33380/2305-2066-2024-13-1-1538

DO - 10.33380/2305-2066-2024-13-1-1538

M3 - статья

VL - 13

SP - 75

EP - 80

JO - Drug Development and Registration

JF - Drug Development and Registration

SN - 2305-2066

IS - 1

ER -