Sulfonic Acid Derivative-Modified SBA-15, PHTS and MCM-41 Mesoporous Silicas as Carriers for a New Antiplatelet Drug: Ticagrelor Adsorption and Release Studies.

Michał Moritz,Małgorzata Geszke-Moritz

doi:10.3390/ma13132913

Michał Moritz, Małgorzata Geszke-Moritz

Open Access

https://doi.org/10.3390/ma13132913

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Abstract

Three mesoporous, siliceous materials, i.e., SBA-15 (Santa Barbara Amorphous), PHTS (Plugged Hexagonal Templated Silica) and MCM-41 (Mobil Composition of Matter), functionalized with a sulfonic acid derivative, were successfully prepared and applied as the carriers for the poorly water-soluble drug, ticagrelor. The siliceous carriers were characterized using nitrogen sorption analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM) and elemental analysis. The adsorption studies were conducted in acetonitrile. At the highest equilibrium concentrations, the amount of ticagrelor Qe that adsorbed onto the examined silicas was in the range of 83 to 220 mg/g, increasing in the following order: PHTS-(CH2)3-SO3H < SBA-15-(CH2)3-SO3H < MCM-41-(CH2)3-SO3H. The equilibrium adsorption data were analyzed using the Freundlich, Jovanovich, Langmuir, Temkin, Dubinin-Radushkevich, Dubinin-Astakhov and Redlich-Peterson models. In order to find the best-fit isotherm for each model, a nonlinear fitting analysis was carried out. Based on the minimized values of the ARE function, the fit of the isotherms to the experimental points for ticagrelor adsorption onto the modified silicas can be ordered as follows: SBA-15-(CH2)3-SO3H (Redlich-Peterson > Dubinin-Astakhov > Temkin), PHTS-(CH2)3-SO3H (Redlich-Peterson > Temkin > Dubinin-Astakhov), MCM-41-(CH2)3-SO3H (Redlich-Peterson > Dubinin-Astakhov > Langmuir). The values of adsorption energy (above 8 kJ/mol) indicate the chemical nature of ticagrelor adsorption onto propyl-sulfonic acid-modified silicas. The results of release studies indicated that at pH 4.5, modified SBA-15 and MCM-41 carriers accelerate the drug dissolution process, compared to the dissolution rate of free crystalline ticagrelor. Intriguingly, modified PHTS silica provides prolonged drug release kinetics compared to other siliceous adsorbents and to the dissolution rate of crystalline ticagrelor. A Weibull release model was employed to describe the release profiles of ticagrelor from the prepared carriers. The time necessary to dissolve 50% and 90% of ticagrelor from mesoporous adsorbents at pH 4.5 increased in the following order: SBA-15-(CH2)3-SO3H < MCM-41-(CH2)3-SO3H < PHTS-(CH2)3-SO3H.

Highlights

Ticagrelor is the first cyclopentyltriazolopyrimidine antiplatelet agent approved for use in the European Union (European Medicines Agency in 2010) and the USA (Food and DrugAdministration in 2011) [1].The use of antiplatelet agents is of great importance in the Materials 2020, 13, 2913; doi:10.3390/ma13132913 www.mdpi.com/journal/materials Materials FOR PEER REVIEWMaterials2020, 22ofof24 coronary syndromes
The results of the surface analysis for pure and sulfonic acid derivative-modified mesoporous silicas are presented in Tables 1 and 2, respectively
SBA-15, PHTS and MCM-41 materials modified with propyl-sulfonic acid groups exhibited good adsorption properties towards ticagrelor

Summary

Introduction

Ticagrelor is the first cyclopentyltriazolopyrimidine antiplatelet agent approved for use in the European Union (European Medicines Agency in 2010) and the USA (Food and DrugAdministration in 2011) [1].The use of antiplatelet agents is of great importance in the Materials 2020, 13, 2913; doi:10.3390/ma13132913 www.mdpi.com/journal/materials Materials FOR PEER REVIEWMaterials2020, 22ofof coronary syndromes. Ticagrelor is the first cyclopentyltriazolopyrimidine antiplatelet agent approved for use in the European Union (European Medicines Agency in 2010) and the USA Administration in 2011) [1]. The use of antiplatelet agents is of great importance in the Materials 2020, 13, 2913; doi:10.3390/ma13132913 www.mdpi.com/journal/materials Materials FOR PEER REVIEW. Therapy for patients with acute coronary syndromes. The chemical structure of ticagrelor difluorophenyl)cyclopropyl]amino}‐5‐(propylsulfanyl)‐3H‐[1,2,3]triazolo[4,5‐d]pyrimidin‐3‐yl]‐5‐(2‐. It is an oral antagonist of the P2Y12 receptor. Ticagrelor is a rapid, selective, noncompetitive and

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