Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug

Abstract

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.

Clay Nanotube Immobilization on Animal Hair for Sustained Anti-Lice Protection

“…When dissolved in the solvent, the drug can be easily absorbed by halloysite nanotubes with continuous stirring and vacuuming. Borrego-Sánchez et al studied its interaction with low aqueous soluble antiparasitic drugs with the other clay materials [ 2 , 25 ]. One hundred and fifty milligrams of permethrin (Sigma Aldrich, St. Louis, MO, USA) was dissolved in 3 mL of 95% ethanol (Sigma Aldrich) to obtain a saturated solution (50 mg/mL).…”

Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as a Way to Enhance Dissolution Rate and Permeability

“…Ana Borrego-Sánchez et al also studied a drug with low water solubility—praziquantel—for which the dissolution rate is a factor that limits bioavailability. The team obtained praziquantel–clay and praziquantel–calcium carbonate systems, successfully achieving accelerated release and increased solubility for the drug [ 37 , 38 ].…”

Melatonin/Nanoclay Hybrids for Skin Delivery

“…Nanoclays are good candidates to be used as vehicles of melatonin because of their widely known capabilities for the retention of organic molecules, and protecting the loaded actives from degradation and improving their release profiles once administered [26][27][28][29]. Nanoclays are well known ingredients of skin formulations [30] once they have accomplished safety and stability requirements [31].…”

“…The drug intercalated into montmorillonite interlayer and the hybrid was even more effective as antibacterial that the pristine drug. Montmorillonite, laminar mineral, can be used to modify the release of drugs [29,42], and to protect them from the degradation [43]. Moreover, it have been recently demonstrated that clays have a proliferative effect on fibroblasts [44], which can lead to a potential synergistic effect between melatonin and montmorillonite for wound heling and skin protection.…”