Development and physicochemical characterization of solid dispersions containing praziquantel for the treatment of schistosomiasis

Abstract

Praziquantel (PZQ) is an anthelminthic agent active against parasitic flatworms of the Schistosoma type and the most important drug for the treatment and morbidity control of schistosomiasis. In this study, a highperformance liquid chromatography method was employed for quantification of PZQ in the physical mix (PM) and solid dispersion (SD) prepared by Fusion Method utilizing the carriers Gelucire Ò 50/13 and mannitol in ratio 3:1; 1:1; 1:3 PZQ/carrier. Furthermore, PM and SD were characterized by Thermogravimetry-Differential Thermal Analysis, Differential Scanning Calorimetry, Infrared Spectroscopy, X-Ray Diffraction, and Scanning Electron Microscopy. Solubility assay was made to evaluate the solubility of PZQ in purified water, in 0.1 mol L-1 HCl solution and 0.2 mol L-1 buffered phosphate solution. PZQ dissolution test was carried out in 0.1 mol L-1 HCl and 0.2 M buffered phosphate (pH 6.8). The interaction between PZQ and carriers in PMs and SDs was evidenced due to experimental enthalpy, which was different from expected enthalpy. However, this interaction did not affect the solubility of the drug. In PZQ dissolution test, the best result was for SD 1:1 PZQ/Gelucire, which presented higher dissolution rate and release extension than PM and PZQ. Thus, SD may be a strategy to enhance the solubility and dissolution, a crucial step in the development of a pharmaceutical dosage form containing PZQ for possible application in the treatment of schistosomiasis.

Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution

“…Praziquantel is a poorly water-soluble neutral compound [ 3 ], thus the solubility in gastric (0.1 M HCl) and small intestinal (50 mM phosphate buffer, pH 6.8 with no bile salts) conditions were not statistically different (297 ± 6 µg/mL and 282 ± 149 µg/mL, respectively, Table 1 ). Our findings appear slightly higher but probably not significantly different to those reported in the literature where the solubility of praziquantel in 0.1 M HCl and 200 mM phosphate buffer pH 6.8 was 164 µg/mL and 206 µg/mL, respectively [ 14 ], which could be due to differences in the sample incubation temperatures (23 °C vs. 37 °C in the current study) and the presence of surfactant excipients in the Biltricide ® tablets used in this study. In addition, as depicted in Figure 2 b, once praziquantel was dissolved in the low pH gastric condition, no drug precipitation occurred when the pH of the medium was adjusted to 6.8, suggesting that praziquantel could remain solubilised during gastrointestinal transit.…”

Praziquantel Fifty Years on: A Comprehensive Overview of Its Solid State

“…Several studies reported the possibility of amorphizing PZQ in the presence of a second compound through the formation of amorphous solid dispersions [ 17 , 29 , 30 , 31 , 32 , 33 , 34 , 36 , 37 , 50 , 51 , 56 , 57 , 98 , 99 ].…”

“…The literature provides little information about amorphous forms of PZQ. Several studies reported the possibility of amorphizing PZQ in the presence of a second compound through the formation of amorphous solid dispersions [17,[29][30][31][32][33][34]36,37,50,51,56,57,98,99].…”

“…Over 50 years of research on PZQ, several studies have been carried out to enhance its properties by preparing solid dispersions of the drug with povidone [ 17 , 29 , 30 , 31 ], sodium starch glycolate [ 32 ], mesoporous silica [ 33 ], calcium carbonate complexes [ 34 , 35 ], mannitol and Gelucire [ 36 ], and clay minerals [ 37 ], and by preparing PZQ-β-cyclodextrins systems [ 38 , 39 , 40 , 41 , 42 , 43 , 44 ], PZQ-liposomes systems [ 45 ], polymeric and solid lipid nanoparticles [ 46 , 47 , 48 , 49 ], coground systems [ 50 , 51 , 52 , 53 ], fast dispersible granules [ 54 ], melt granulation and ultrasonic spray congealing [ 55 ] and, more recently, micro and nanocrystals [ 56 , 57 ].…”

Physico-chemical characterisation of three-component co-amorphous systems generated by a melt-quench method

“…However, miscibility of the active ingredient in the polymer is one of the major issues in amorphous solid dispersions [10][11][12]. To overcome poor miscibility issues, the amount of polymer is increased, and this causes volume enlargement of the dosage form [13,14]. Furthermore, amorphous materials are more hygroscopic than crystalline materials and the glass-transition temperature of most amorphous drugs is lowered, even with only very small water content [15][16][17][18].…”