Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
Metadatos
Afficher la notice complèteAuteur
Borrego Sánchez, Ana María; Sánchez Espejo, Rita María; García Villén, Fátima; Viseras Iborra, César Antonio; Sainz Díaz, Claro IgnacioEditorial
MDPI
Materia
Praziquantel Drugs Montmorillonite Montmorillonite Organic solvents In vitro dissolution tests Cytotoxicity
Date
2020Referencia bibliográfica
Borrego-Sánchez A, Sánchez-Espejo R, García-Villén F, Viseras C, Sainz-Díaz CI. Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug. Pharmaceutics. 2020; 12(10):914. [https://doi.org/10.3390/pharmaceutics12100914]
Patrocinador
Ministerio de Ciencia e Innovacion government PCIN-2017-098 FIS2016-77692-C2-2-P CGL2016-80833-R; Junta de Andalucia RNM1897 P18-RT-3786Résumé
Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis
disease. This drug has very low aqueous solubility, requiring high oral doses for its administration
which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the
parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible
and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to
encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between
the layers in the case of the montmorillonite. The interactions between the drug and clay minerals
are studied experimentally with the strategy for preparing interactions products in organic solvents
(ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be
enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products,
the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug
demonstrated by different techniques. This led to a significant increase in the dissolution rate of the
praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for
the praziquantel–montmorillonite product prepared in dichloromethane that presented a controlled
release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed
in the interaction products prepared with ethanol. The interaction product with sepiolite was
biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However,
interaction products with montmorillonite did not produce cell death, but they showed affectation
and damage of cells in the cell cycle study at the highest concentration tested (20–100 µM). Therefore,
the different organic solvents used are adequate for the improvement of the biopharmaceutical profile
of praziquantel. Drug–clay interaction products, specifically with sepiolite, showed very promising
results in which new accelerated oral release systems of the praziquantel were obtained.