Ground Calcium Carbonate as a Low Cost and Biosafety Excipient for Solubility and Dissolution Improvement of Praziquantel.

Ana Borrego-Sánchez,Beatrice Albertini,Pilar Cerezo,C Ignacio Sainz-Díaz,Rita Sánchez-Espejo,Nadia Passerini,César Viseras

doi:10.3390/pharmaceutics11100533

Ana Borrego-Sánchez, Beatrice Albertini + Show 5 more

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https://doi.org/10.3390/pharmaceutics11100533

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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.

Highlights

Calcium carbonate, CaCO3, being a low cost material, with high surface area, excellent safety, biocompatibility and biodegradability, is a well-documented excipient in pharmaceutical solid dosage forms, mainly used as diluent [1]
A solid state characterization of the samples studied was performed by X-ray diffraction (Figure S1), differential scanning calorimetric analysis (Figure S2), thermogravimetric analysis (Figure S3), scanning electron microscope (Figure S4), Fourier Transform Infrared and Raman Spectroscopies (Figure S5) and particle size analysis
The results demonstrated that PZQ-ground calcium carbonate (GCC) physical mixture did not show any chemical-physical change with respect to the pure drug

Summary

Introduction

CaCO3, being a low cost material, with high surface area, excellent safety, biocompatibility and biodegradability, is a well-documented excipient in pharmaceutical solid dosage forms, mainly used as diluent [1]. It has been demonstrated that calcium carbonate can successfully act as hydrophilic porous carrier to improve the oral bioavailability of low water soluble drugs [2,3,4,5]. Most of the successfully designed calcium carbonate carriers have been prepared by emulsion techniques or chemical precipitation of the carbonate micro/nanoparticles [14]. Precipitation of calcium carbonate micro/nanoparticles is difficult to reproduce and scale up of the procedure is most of times challenging, avoiding the clinical use of these carriers. An interesting alternative is to overcome these challenges by using normalized pharmaceutical excipients grades of calcium carbonate as drug delivery carriers [1]

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