engleski

Milling and comilling Praziquantel at cryogenic and room temperatures: Assessment of the process- induced effects on drug properties

This study is a comprehensive evaluation of praziquantel (PZQ) behavior upon grinding considering theinfluence of milling temperature (cryogenic vs room temperature), frequency and time and presenceof polymers (milled raw PZQ vs comilled PZQ/povidone and PZQ/crospovidone at 50:50 w/w) on twoexperimental responses (residual crystallinity and PZQ recovery). To this aim a full factorial design wasset up and the responses of the experimental design were statistically assessed.The powder temperature, measured in different milling conditions, was found to increase with increas-ing milling frequency and time, up to a maximum recorded value of 46.9◦C (after 90 min at R.T.), for allthe three powder systems. When PZQ was ground in RT environment, the recovery was 100%, indepen-dently from frequency and time of milling. Its residual crystallinity remained pronounced (>70%) uponmilling, even if treated at the most severe conditions. Conversely, when the drug was milled in presenceof the polymers, it showed a higher tendency to degradation and amorphysation, independently fromthe choice of the polymer. The use of cryogenic conditions, operating at temperatures lower than PZQglass transition, permitted to dramatically reduce PZQ residual crystallinity when the drug was groundby itself. In the case of binary mixtures, the switch to a cryogenic environment did not affect significantlythe experimental responses, but permitted to obtain a more predictable trend of both drug recovery andresidual crystallinity when varying time and frequency of milling.

Praziquantel ; Cryo-milling ; Drug recovery ; Crystallinity ; Thermal analysis ; Factorial design

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