Ground Calcium Carbonate as a Low Cost and Biosafety Excipient for Solubility and Dissolution Improvement of Praziquantel
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Borrego Sánchez, Ana María; Sánchez Espejo, Rita María; Albertini, Beatrice; Passerini, Nadia; Cerezo González, María Pilar; Viseras Iborra, César Antonio; Sainz Díaz, Claro IgnacioEditorial
MDPI
Materia
Praziquantel Calcium carbonate Schistosomiasis Bioavailability Solubility Cytotoxicity
Date
2019-10-14Referencia bibliográfica
Borrego-Sánchez, A., Sánchez-Espejo, R., Albertini, B., Passerini, N., Cerezo, P., Viseras, C., & Sainz-Díaz, C. I. (2019). Ground Calcium Carbonate as a Low Cost and Biosafety Excipient for Solubility and Dissolution Improvement of Praziquantel. Pharmaceutics, 11(10), 533.
Sponsorship
We also acknowledge for financial support the MINECO, for projects FIS2016-77692-C2-2-P and CGL2016-80833-R, and the Andalusian government, for project RNM1897.Abstract
Calcium carbonate is an abundant mineral with several advantages to be a successful carrier
to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an
antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence
characterized by high-permeability and low-solubility. Therefore, the dissolution rate is the
limiting factor for the gastrointestinal absorption that contributes to the low bioavailability.
Consequently, the therapeutic dose of the praziquantel must be high and big tablets and capsules are
required, which are difficult to swallow, especially for pediatric and elderly patients. Mixtures of
praziquantel and calcium carbonate using solid-solid physical mixtures and solid dispersions
were prepared and characterized using several techniques (X-ray diffraction differential scanning
calorimetry, thermogravimetric analysis, scanning electron microscopy, laser diffraction, Fourier
transform infrared and Raman spectroscopies). Solubility of these formulations evidenced that the
solubility of praziquantel-calcium carbonate interaction product increased in physiological media.
In vitro dissolution tests showed that the interaction product increased the dissolution rate of the
drug in acidic medium. Theoretical models were studied to understand this experimental behavior.
Cytotoxicity and cell cycle studies were performed, showing that praziquantel-calcium carbonate
physical mixture and interaction product were biocompatible with the HTC116 cells, because it did
not produce a decrease in cell viability or alterations in the cell cycle.