Pharmaceutical development of praziquantel nanocrystals and their potential application for paediatric patients
1: Andressa Daniele Artico Silva; 2: Michelle Alvares Sarcinelli; 3: Beatriz Ferreira de Carvalho Patricio; 4: Marcelo Henrique da Cunha Chaves; 5: Murilo Henrique Moreira Facure; 6: Daniel Souza Corrêa; 7: Livia Deris Prado; 8: Helvécio Vinícius Antunes Rocha
1: Postgraduate Program in Management, Research and Development in the Pharmaceutical Industry – Farmanguinhos, FIOCRUZ, Brazil and Laboratory of Micro and Nanotechnology – Farmanguinhos, FIOCRUZ, Brazil;
2: Laboratory of Micro and Nanotechnology – Farmanguinhos, FIOCRUZ, Brazil;
3: Laboratory of Micro and Nanotechnology – Farmanguinhos, FIOCRUZ, Brazil;
4: Laboratory of Micro and Nanotechnology – Farmanguinhos, FIOCRUZ, Brazil;
5: National Laboratory for Nanotechnology in Agribusiness (LNNA), Embrapa Instrumentation, Brazil;
6: Nanotechnology National Laboratory for Agriculture (LNNA), Embrapa Instrumentation, Brazil;
7: Laboratory of Analytical Development and Validation – Farmanguinhos, FIOCRUZ, Brazil;
8: Postgraduate Program in Management, Research and Development in the Pharmaceutical Industry – Farmanguinhos, FIOCRUZ, Brazil and Laboratory of Micro and Nanotechnology – Farmanguinhos, FIOCRUZ, Brazil
Praziquantel is still the drug of choice for schistosomiasis control, however, its use involves some challenges mainly because of the drug low aqueous solubility, which is a limiting step for its oral absorption. In this context, a particle size reduction approach can increase solubility and dissolution rate of drugs, enhancing their bioavailability. As a result, the produced tablets could be smaller and, therefore, easier to swallow. Additionally, the drug has a pronounced bitter taste that makes it difficult for children to adhere to the treatment. Also, there is an indication in the literature that the use of pure L-praziquantel (L-PZQ) isomer would result in advantages, such as improved palatability. Thus, the objective of this work was to decrease particle size to increase the dissolution profile of the praziquantel racemate (rac-PZQ) and L-PZQ. In this way, rac-PZQ and L-PZQ suspensions were prepared in a colloid and pearl mill (using sodium lauryl sulfate and poloxamer 407 as stabilizers), and then spray dried to obtain the nanocrystals (NCs). The suspensions were evaluated by laser diffraction (LD) and dynamic light scattering (DLS). The characterization of the dry powders was carried out by X-ray powder diffraction (XRPD), scanning electron microscopy (SEM) and powder dissolution. Finally, an electronic tongue based on impedance spectroscopy was used to study the palatability, which data was processed by using the principal component analysis (PCA). Samples presented average diameters of 346.2 nm and 720.2 nm, respectively. Even after processing, the crystalline structure of the drug was maintained. A considerable increase in the dissolution profile of samples was observed in comparison to raw racemate or isomer, with drug dissolved percentage of almost 100%. The electronic tongue results showed that the method was effective in discriminating the tested samples, indicating a possible difference in palatability between them.
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