TY - JOUR

T1 - Polymeric composites of 1,2,4-thiadiazole

T2 - solubility, dissolution and permeability assay

AU - Volkova, Tatyana V.

AU - Domanina, Ekaterina N.

AU - Chislov, Mikhail V.

AU - Proshin, Alexey N.

AU - Terekhova, Irina V.

N1 - Funding Information: This investigation was performed within the State Program of Fundamental Scientific Research (No. 0092-2014-0005). The authors thank Prof. Annette Bauer-Brandl (Dept. of Physics Chemistry and Pharmacy, University of Southern Denmark) and Labtastic distributor ( https://labtastic.shop ) for donation of the Permeapad™ barrier. Authors thank the “The Upper Volga Region Centre of Physicochemical Research ” (Ivanovo, Russia) and St. Petersburg State University Center “Thermogravimetric and Calorimetric Research” for the provision of scientific equipment (DSC). Publisher Copyright: © 2019, Akadémiai Kiadó, Budapest, Hungary. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - The derivative of 1,2,4-thiadiazole (TDZ) can be considered as a perspective agent for the Alzheimer’s disease prevention. Due to a highly lipophilic character, the compound reveals good membrane permeability properties and poor solubility in aqueous media. In order to solve this problem, water-soluble biodegradable polymers: PEG 6000 (PEG), PVP K29-30 (PVP) and linear (A–B–A type) ethylene oxide-propylene oxide block copolymer Pluronic F127 (F127) were used in the present investigation to obtain binary and ternary TDZ composites (solid dispersions) with improved solubility and dissolution rate. Composites were prepared by a mechanical grinding procedure. Differential scanning calorimetry and FTIR spectroscopy were used to characterize the obtained samples. The interaction of TDZ with PVP after the grinding procedure was revealed. Shake-flask method was applied to measure the solubility of the composites. A dramatical increase in the solubility was shown for the solid dispersion with F127 above the critical micelle concentration. The dissolution behavior was studied with the help of the basket method at pH 1.2 and pH 6.8. The dissolution of TDZ/polymer solid dispersions was substantially accelerated as compared to pure TDZ and physical mixtures. The dissolution mechanism was estimated through the Korsmeyer–Peppas model equation. Franz diffusion cell and new Permeapad™ barrier were applied for the permeability assay. The permeability of TDZ in solid dispersions through the Permeapad™ barrier was shown to decrease in comparison with the pure TDZ. It was concluded that composites with PEG, PVP and F127 are an effective tool for increasing the solubility and dissolution of 1,2,4-thiadiazole derivative.

AB - The derivative of 1,2,4-thiadiazole (TDZ) can be considered as a perspective agent for the Alzheimer’s disease prevention. Due to a highly lipophilic character, the compound reveals good membrane permeability properties and poor solubility in aqueous media. In order to solve this problem, water-soluble biodegradable polymers: PEG 6000 (PEG), PVP K29-30 (PVP) and linear (A–B–A type) ethylene oxide-propylene oxide block copolymer Pluronic F127 (F127) were used in the present investigation to obtain binary and ternary TDZ composites (solid dispersions) with improved solubility and dissolution rate. Composites were prepared by a mechanical grinding procedure. Differential scanning calorimetry and FTIR spectroscopy were used to characterize the obtained samples. The interaction of TDZ with PVP after the grinding procedure was revealed. Shake-flask method was applied to measure the solubility of the composites. A dramatical increase in the solubility was shown for the solid dispersion with F127 above the critical micelle concentration. The dissolution behavior was studied with the help of the basket method at pH 1.2 and pH 6.8. The dissolution of TDZ/polymer solid dispersions was substantially accelerated as compared to pure TDZ and physical mixtures. The dissolution mechanism was estimated through the Korsmeyer–Peppas model equation. Franz diffusion cell and new Permeapad™ barrier were applied for the permeability assay. The permeability of TDZ in solid dispersions through the Permeapad™ barrier was shown to decrease in comparison with the pure TDZ. It was concluded that composites with PEG, PVP and F127 are an effective tool for increasing the solubility and dissolution of 1,2,4-thiadiazole derivative.

KW - 1,2,4-thiadiazole

KW - Dissolution

KW - Permeability

KW - Polymers

KW - Solubility

KW - INTERPLAY

KW - WATER-SOLUBLE DRUG

KW - PLURONIC F127

KW - BLOCK-COPOLYMERS

KW - INCLUSION COMPLEXES

KW - FORMULATION

KW - THERMAL-ANALYSIS

KW - DELIVERY

KW - 1

KW - 2

KW - SOLID DISPERSIONS

KW - ENHANCEMENT

KW - 4-thiadiazole

UR - http://www.scopus.com/inward/record.url?scp=85074824521&partnerID=8YFLogxK

U2 - 10.1007/s10973-019-08947-6

DO - 10.1007/s10973-019-08947-6

M3 - Article

AN - SCOPUS:85074824521

VL - 140

SP - 2305

EP - 2315

JO - Journal of Thermal Analysis and Calorimetry

JF - Journal of Thermal Analysis and Calorimetry

SN - 1388-6150

IS - 5

ER -