Application of molecular modeling to the study of cyproterone acetate stability in the presence of cyclodextrin derivatives

in Journal of Drug Delivery Science and Technology (2004), 14(5, SEP-OCT), 357-362

The ability of cyclodextrins (CDs) to increase the solubility of cyproterone acetate (CPA) was previously shown by phase-solubility and NMR studies [1]. In the present work, the influence of various CDs ... [more ▼]

The ability of cyclodextrins (CDs) to increase the solubility of cyproterone acetate (CPA) was previously shown by phase-solubility and NMR studies [1]. In the present work, the influence of various CDs on the stability of CPA was studied in pH 6 and pH 8 aqueous solutions at 25degreesC. Different CDs were tested: hydroxypropyl-beta-cyclodextrin (HPbetaCD), randomly methylated beta-cyclodextrin (RAMEB), hydroxypropyl-gamma-cyclodextrin (HPgammaCD) and gamma-cyclodextrin (gammaCD). At pH 6, the presence of these CDs reduces the degradation of CPA. Nevertheless, at pH 8, the gamma-CD derivatives are ineffective against the degradation of CPA, whereas the beta-CD derivatives (HPbetaCD and RAMEB) allow decreasing CPA hydrolysis. Molecular modeling was performed to theoretically calculate some of the most energetically favorable conformations for gamma-CD and RAMEB complexes with CPA. The position of the ester group in the CD caivity seems to be the most important factor influencing the hydrolysis of CPA. Other factors, such as the size of the cavity, the substitution of the CD hydroxyls and the stability constant also have a strong incidence on CPA stability. [less ▲]

Development of a hydrogel containing GM-CSF to improve the dendritic cells colonisation of HPV+ epithelium

in Proceedings of Eur conference on drug delivery and pharmaceutical technology (2004)

Skin compatibility of cyclodextrins and their derivatives: a comparative assessment using a corneoxenometry bioassay.

in European Journal of Pharmaceutics & Biopharmaceutics (2004), 57(3), 479-82

Few studies have been performed to assess the risk of skin damage by cyclodextrins (CD) and they have yielded contradictory results. The present study was conducted using the corneoxenometry bioassay on ... [more ▼]

Few studies have been performed to assess the risk of skin damage by cyclodextrins (CD) and they have yielded contradictory results. The present study was conducted using the corneoxenometry bioassay on human stratum corneum to compare the skin compatibility of CD currently used in pharmaceutical preparations (betaCD, gammaCD, Rameb, Dimeb, Trimeb, HP-betaCD and HP-gammaCD) and that of new amphiphilic CD derivatives, namely, the phospholipidyl-CD (DMPE-Dimeb and DMPE-Trimeb). All the tested CD were well tolerated by the stratum corneum at a concentration of 5%. However, inter-individual reactivity was larger for DMPE-Dimeb, suggesting a more aggressive trend for this compound. Cutaneous Index of Mildness values obtained confirm that Dimeb is able to extract some skin components and shows that DMPE-Dimeb performs similarly. [less ▲]

Cyclodextrins as a potential carrier in drug nebulization

in Journal of Controlled Release (2004), 96(3), 403-410

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the ... [more ▼]

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

Cyclodextrins as a potential carrier in drug nebulization.

in Journal of Controlled Release (2004), 96(3), 403-10

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the ... [more ▼]

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations. [less ▲]

The skin compatibility of new cyclodextrin derivatives: the phospholipidyl-cyclodextrins

Poster (2003, October)

Hydrosoluble mixtures of cyproterone and/or an ester of it, processes to obtain them and uses thereof

Patent (2003)

Effect of inhaled cyclodextrins on the pulmonary inflammation and bronchial hyperresponsiveness in mice

Conference (2003, May)

Influence of cyclodextrins on the solubility and the stability of cyproterone acetate

Conference (2003, May)

Etude de l'inclusion du miconazole dans les cyclodextrines par le CO2 supercritique: caracterisation des complexes par HPLC, CP-MAS-NMR et FT-IR

Conference (2003, January)