Tehnologii de obţinere a compuşilor complecşi moleculari ai ciclodextrinelor cu unele substanţe chimioterapice
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StatusThe thesis was presented on the 18 December, 2008Approved by NCAA on the 26 February, 2009 Abstract – 1.32 Mb / in romanianThesisCZU 541.572.52 : 615.012.1+ 615.281
1.77 Mb /
in romanian121 pages |
Keywords
drug-cyclodextrin inclusion complex, sanguinarine, amantadine, rimantadine, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, polyvinylpyrrolidone, kneading, co-evaporation, lyophilizationSummary
The main aim of this study was to determine the most efficient technologies and optimal parameters for obtaining of the inclusion complexes of sanguinarine, amantadine and rimantadine, with cyclodextrins.
As a result of the studies performed the following binary and ternary systems were obtained and described: sanguinarine with β-cyclodextrin and hydroxypropyl-β-cyclodextrin, with and without addition of polyvynilpyrrolidone, amantadine and rimantadine with β-cyclodextrin and hydroxypropyl-β-cyclodextrin.
It has been found that the inclusion complexes are formed in the case of the case of the sanguinarine -β-cyclodextrin, sanguinarine-hydroxypropyl-β-cyclodextrin, amantadine-β- cyclodextrin, rimantadine-β-cyclodextrin.
The optimal technological parameters of the sanguinarine-β-cyclodextrin complex obtaining have been determined: pH of the reaction medium 8.0, addition of 0.1% polyvynilpyrrolidone to the reaction medium and use of lyophilization for the obtaining of the final product. It has been found that the addition of 0.1% polyvynilpyrrolidone to the reaction medium leads to the 2.4 fold increase in the yield of the process.
In vitro studies have shown that antiproliferative activity of the sanguinarine-hydroxypropyl-β-cyclodextrin complex is higher than that of the pure sanguinarine.
Four technologies for the obtaining of the amantadine and rimantadine inclusion complexes with β-cyclodextrin and hydroxypropyl-β-cyclodextrin have been studied. It has been found that:
- 1) the optimal technology for the amantadine-β-cyclodextrin complex obtaining is kneading; 2) the optimal technology for the rimantadine-β-cyclodextrin complex obtaining is lyophilization;
- 3)independently on the technology applied hydroxypropyl-β-cyclodextrin doesn’t form inclusion complexes neither with amantadine, nor with rimantadine.
Oficial Reviewers
- Nicon Ungur
doctor habilitat, associate professor (docent), Institute of Chemistry of the ASM - Iacob Guţu
doctor habilitat, professor, Moldova State University
Council's Members
- Mihail Colţa, president
doctor habilitat, professor - Valentina Ciobanu , secretary
doctor, associate professor (docent) - Valentin Bobeică, member
doctor habilitat, professor, Moldova State University - Pavel Chintea, member
doctor habilitat, professor, Institute of Genetics, Physiology and Plant Protection of the ASM - Victor Ghicavîi, member
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Theses
