Unexpected solvent impact in the crystallinity of praziquantel / poly(vinylpyrrolidone) formulations. A solubility, DSC and solid-state NMR study

Abstract

The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The presence of PVP improves the solubility of PZQ (0.31±0.01mg/mL). A maximum of 1.29±0.03mg/mL of PZQ in solution was achieved for the 3:1 SD (E/E). The amount of PZQ in solution depends on the amount of polymer and on the preparation method. Solid-state NMR (ssNMR) and DSC were used to understand this behavior. Results show that PMs are a mixture of crystalline PZQ with the polymer, while SDs show different degrees of drug amorphization depending on the solvent used. For E/W SDs, PZQ exists in amorphous and crystalline states, with no clear correlation between the amount of crystalline PZQ and the amount of PVP. For E/E SDs, formulations with a higher percentage of PZQ are amorphous with the components miscible in domains larger than 3nm ((1)H ssNMR relaxation measurements). Albeit its higher saturation solubility, the 3:1 E/E PVP:PZQ sample has a significant crystalline content, probably due to the water introduced by the polymer. High PVP content and small crystal size account for this result.

A new soluble and bioactive polymorph of praziquantel

“…Since children are the main target of treatment, research is needed to enhance the solubility and the bioavailability of PZQ, in order to reduce the high therapeutic doses and therefore the dimension of tablets, which are difficult to swallow particularly for pediatric patients [5]. Several studies aimed to enhance PZQ properties such as the preparation of solid dispersion of the drug with Povidone [6][7][8] ,…”

In situ encapsulation of praziquantel through methyl methacrylate/diethylaminoethyl methacrylate and MMA/DMAEMA miniemulsion copolymerizations in presence of distinct ionic surfactants

“…Different strategies have been proposed for improvement of PZQ delivery in human bodies, including solid dispersion of PZQ in polyvinylpyrrolidone (PVP) [ 6,9 ] and other excipients, such as cyclodextrins [ 10,11 ] and solid lipid nanoparticles (SLN). [ 12,13 ] Encapsulation of PZQ in polymer nanoparticles and microparticles also constitutes a promising alternative for enhancement of PZQ dissolution rates in body fluids and masking of the inherent bitter taste.…”

Combining Mechanochemistry and Spray Congealing for New Praziquantel Pediatric Formulations in Schistosomiasis Treatment

“…Comparing the PZQ:PVP PM with the CC, the difference between the dissolution profiles was borderline significant ( f 2 = 49.7). Although the PVP was present in both systems, in the physical mixture, the drug and excipient were simply blended and, thus, did not interact with each other [24]; unlike in the CC system, the milling process led to the formation of bigger aggregates, decreasing the dissolution rate.…”