Layered double hydroxides of CaAl: A promising drug delivery system for increased dissolution rate and thermal stability of praziquantel

• Published in: Applied clay science Vol. 180; p. 105197
• Main Authors: Timóteo, Taysa Renata Ribeiro, Melo, Camila Gomes de, Danda, Lucas José de Alencar, Silva, Laysa Creusa Paes Barreto Barros, Fontes, Danilo Augusto Ferreira, Silva, Paulo César Dantas, Aguilera, Cindy Siqueira Britto, Siqueira, Lidiany da Paixão, Rolim, Larissa Araújo, Rolim Neto, Pedro José
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-11-2019
• Subjects: Clay minerals; Inorganic compounds; Kinetic solubility; Layered double hydroxides; Poorly soluble drugs; Praziquantel; Poorly soluble drugs; Kinetic solubility; Clay minerals; Inorganic compounds; Praziquantel; Layered double hydroxides
• ISSN: 0169-1317; 1872-9053
• DOI: 10.1016/j.clay.2019.105197

Layered double hydroxide (LDH) are promising drug delivery systems (DDS) for the transport of biologically active substances, with special attention to those with poor aqueous solubility. Praziquantel (PZQ) is an anthelmintic BCS class II drug, presenting low solubility and high permeability. Due to these qualities, its absorption becomes compromised, generating the need for relatively high doses. In this context, the synthesis and characterization of calcium and aluminum LDH (CaAl-LDH) was performed, as well as its application to PZQ release in order to obtain an increased solubility. Blends and physical mixtures (PMs) were initially formed in different CaAl-LDH:PZQ molar ratios (1:1, 2:1, 4:1), by the technique of co-solubilization and homogenization using mortar and pestle, respectively. The obtained materials were characterized by x-ray diffraction (XRD), thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), elemental analysis, particle size, surface area and degradation kinetics. An in vitro release test was also performed at both sink and non-sink conditions. XRD analysis showed that the CaAl-LDH-PZQ blends containing 10.87% (Blend 4) of the PZQ turned the drug into a material with amorphous characteristics, showing a decrease of its crystalline planes and also of its melting point in the DSC. It was possible to observe through the study of the degradation kinetics that CaAl-LDH promoted increased thermal stability to PZQ. For the kinetic parameters obtained in the non-isothermal condition, the activation energy values (Ea) of Blend 4 were higher when compared to crystalline PZQ. Dissolution tests under sink conditionsrevealed that Blends 2, 4 and the PMs were highlighted in the increase of solubility, presenting rapid release when compared to crystalline PZQ. Under non-sink conditions, the dissolution profile revealed the carrier's ability to maintain the drug in a supersaturated solution, retarding its nucleation and recrystallization events, which possibly leads to better bioavailability. Thus, stable and suitable DDS were obtained, capable of overcoming the solubility limitations of PZQ.
•CaAl-LDH and PZQ blends were formed by co-precipitation at various drug loading.•In-vitro dissolution demonstrated enhanced dissolution rate and kinetic solubility.•Thermal analysis revealed improved stability when PZQ was blended with LDH.