Complexes between Progesterone (P) and β-cyclodextrin (BCD) to obtain water soluble formulations are widely known; since hydroxypropyl β-cyclodextrin (HPBCD) displays higher water solubility (48% p/v), we started experiments to achieve a better solubilization of the hormone, to obtain up to 50 mg/ml progesterone concentration in physiological solution, to formulate a suitable dosage form for progesterone therapy. We developed a production process in which the residual BCD (commercial HPBCD contains up to 0.8 % of unreacted material) is preliminarly separated by the formation of a poorly soluble complex. The stoichiometry and stability constant of the desired soluble complex were calculated by phase/solubility study. DSC and X-Ray analysis confirmed the absence of crystalline P in the final freeze-dried powder. The structural evaluation by spectroscopic analysis (Raman, FTIR and NMR) confirms the presence of an inclusion complex with a stoichiometry guest/host 1:2. The Raman spectrum of P shows tree sharp signals at 1616, 1664 and 1669 cm-1 due to the two carbonyls in position 3 and 20 of the steroid structure. HPBCD alone does not show signals in the considered area. P/HPBCD complex show a broad main signal at 1657 cm-1with a minor signal at 1691 cm-1 This change in the spectrum indicates the inclusion of the progesterone involving both rings A and D of the steroid structure. This idea was also confirmed by FT-IR spectroscopy (right). NMR experiment shows shifts of signals attributed to P protons 4, 18,19 and 21 indicating again a involvement of rings A and D in the inclusion complex (left).
1:2 Inclusion complex progesterone/HPBCD studied by Raman and NMR spectroscopy
FINI, ADAMO;
2006
Abstract
Complexes between Progesterone (P) and β-cyclodextrin (BCD) to obtain water soluble formulations are widely known; since hydroxypropyl β-cyclodextrin (HPBCD) displays higher water solubility (48% p/v), we started experiments to achieve a better solubilization of the hormone, to obtain up to 50 mg/ml progesterone concentration in physiological solution, to formulate a suitable dosage form for progesterone therapy. We developed a production process in which the residual BCD (commercial HPBCD contains up to 0.8 % of unreacted material) is preliminarly separated by the formation of a poorly soluble complex. The stoichiometry and stability constant of the desired soluble complex were calculated by phase/solubility study. DSC and X-Ray analysis confirmed the absence of crystalline P in the final freeze-dried powder. The structural evaluation by spectroscopic analysis (Raman, FTIR and NMR) confirms the presence of an inclusion complex with a stoichiometry guest/host 1:2. The Raman spectrum of P shows tree sharp signals at 1616, 1664 and 1669 cm-1 due to the two carbonyls in position 3 and 20 of the steroid structure. HPBCD alone does not show signals in the considered area. P/HPBCD complex show a broad main signal at 1657 cm-1with a minor signal at 1691 cm-1 This change in the spectrum indicates the inclusion of the progesterone involving both rings A and D of the steroid structure. This idea was also confirmed by FT-IR spectroscopy (right). NMR experiment shows shifts of signals attributed to P protons 4, 18,19 and 21 indicating again a involvement of rings A and D in the inclusion complex (left).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
