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

Autor: Zanolla D; Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy., Perissutti B; Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy. Electronic address: bperissutti@units.it., Passerini N; Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy., Invernizzi S; Società dei Naturalisti e Matematici di Modena, Via Università 4, 41121 Modena, Italy., Voinovich D; Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy., Bertoni S; Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy., Melegari C; Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy., Millotti G; Juraj Dobrila University of Pula, Zagrebačka ul. 30, 52100, Pula, Croatia., Albertini B; Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2018 May 10; Vol. 153, pp. 82-89. Date of Electronic Publication: 2018 Feb 13.
DOI: 10.1016/j.jpba.2018.02.018
Abstrakt: This study is a comprehensive evaluation of praziquantel (PZQ) behavior upon grinding considering the influence of milling temperature (cryogenic vs room temperature), frequency and time and presence of polymers (milled raw PZQ vs comilled PZQ/povidone and PZQ/crospovidone at 50:50 w/w) on two experimental responses (residual crystallinity and PZQ recovery). To this aim a full factorial design was set up and the responses of the experimental design were statistically assessed. The powder temperature, measured in different milling conditions, was found to increase with increasing milling frequency and time, up to a maximum recorded value of 46.9 °C (after 90 min at R.T.), for all the three powder systems. When PZQ was ground in RT environment, the recovery was 100%, independently from frequency and time of milling. Its residual crystallinity remained pronounced (>70%) upon milling, even if treated at the most severe conditions. Conversely, when the drug was milled in presence of the polymers, it showed a higher tendency to degradation and amorphysation, independently from the choice of the polymer. The use of cryogenic conditions, operating at temperatures lower than PZQ glass transition, permitted to dramatically reduce PZQ residual crystallinity when the drug was ground by itself. In the case of binary mixtures, the switch to a cryogenic environment did not affect significantly the experimental responses, but permitted to obtain a more predictable trend of both drug recovery and residual crystallinity when varying time and frequency of milling.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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