Formulation of praziquantel binary and ternary solid dispersions into hard-gelatin capsules

ORLANDI S.; LEONARDI D.; SALOMON C.J.

Cordoba

Congreso; III Reunión Internacional de Ciencias Farmacéuticas RICIFA; 2014

Solid dispersions (SDs) are one of the most promising tools to improve the solubility, dissolution rate and oral bioavailability of drugs with low aqueous solubility. Even though this technique has been widely applied in the last decades, there is still limited knowledge about the successful design of SDs by mixing hydrophilic polymers and surfactants. The aim of the present study was to improve the dissolution rate of praziquantel (PZQ), as model drug, by binary SDs systems. Also, it was evaluated whether the addition of a surfactant to the SDs (ternary SDs) was an effective method to increase the drug dissolution rate. Selected mixtures were formulated into hard-gelatin capsules. PZQ is a drug of choice used for cysticercosis and neurocysticercosis and its solubility in water is 0,4 mg/ml. The SDs systems were prepared by the solvent method using as polymeric carriers polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) and poloxamer 237 as surfactant agent. Dissolution studies, differential scanning calorimeter (DSC), X-ray diffractometry and infrared spectroscopy were used to characterize the SDs of PZQ. Drug release rates from the binary SDs were evidently higher than the dissolution rate of drug alone. Corresponding physical mixtures (PMs) also demonstrated higher dissolution profiles than PZQ alone. Unexpectedly, it was observed a similar dissolution profiles between the SDs and the PMs. The dissolution rate of PZQ from the ternary SDs was very similar to the binary systems showing that the influence of the surfactant on the drug dissolution was negligible. Similar results were found when both PMs and SDs were formulated into capsules. By DSC, it was observed a remarkable difference between the thermograms of PZQ alone and the SDs. In conclusion, PZQ formulations with enhanced dissolution behaviour were successfully formulated through the preparation of binary PMs and SDs while the addition of surfactants did not greatly improved the drug dissolution.