Stability of the non-ionic surfactant polysorbate 80 investigated by HPLC-MS and charged aerosol detector.

An analytical method using HPLC coupled with a charged aerosol detector (CAD) and a mass selective detector (MSD) was developed to characterize the non-ionic surfactant polysorbate 80 (PS 80). The molecular structure and heterogeneous composition due to isomers and various lengths of PEG-chains make it difficult to develop sensitive and specific analytical methods. Hence, there is only limited knowledge about the stability and purity of this compound. Polysorbate 80 does not possess any chromophore, thus UV detection is not applicable. Therefore, CAD and MSD have been used for determination. The aim of this study was to characterize polysorbate 80 and to examine its stability at pH 1.0 and 37 degrees C simulating harsh gastric conditions. It was shown that this surfactant is liable to degradation under these conditions. Within 8 h monoesters of PS 80 were hydrolyzed to an extent of 9.5% (+/- 3.0%), whereas incubation in water did not result in any detectable degradation. Furthermore, we demonstrated that HPLC-MS is a suitable technique to investigate ethoxylated compounds like polysorbates.

Stability of extruded 17 beta-estradiol solid dispersions.

Recrystallization is one of the main problems concerning the stability of solid dispersions. Different analytical methods were applied showing that no recrystallization occurred after treating melt extruded solid dispersions with 17 beta-Estradiol as the model drug with heat or water vapor. A skillful choice of excipients--a combination of polymers and additives--could be the reason for improving the stability. The requirements of the USP 23 for Estradiol tablets of 75% dissolved drug after 60 min were fulfilled after storing the tablets for 6 months at 40 degrees C/75% RH. By observing the change in glass transition temperature, DSC analysis showed that the solid dispersions were stable against thermal stress. Isothermal microcalorimetry as well as moisture absorption gravimetry were methods to prove the stability of the solid dispersions against water vapor.

Melt extrusion--an alternative method for enhancing the dissolution rate of 17beta-estradiol hemihydrate.

17Beta-estradiol hemihydrate (17beta-E2) is a poorly water-soluble drug. Physical methods for improving the solubility and dissolution rate, e.g. micronization, have certain inherent disadvantages. The method of choice in this study, melt extrusion, proved to overcome many of the shortcomings of conventional methods. Different compositions of excipients such as PEG 6000, PVP (Kollidon 30) or a vinylpyrrolidone-vinylacetate-copolymer (Kollidon VA64) were used as polymers and Sucroester WE15 or Gelucire 44/14 as additives during melt extrusion. The solid dispersions resulted in a significant increase in dissolution rate when compared to the pure drug or to the physical mixtures. For example, a 30-fold increase in dissolution rate was obtained for a formulation containing 10% 17beta-E2, 50% PVP and 40% Gelucire 44/14. The solid dispersions were then processed into tablets. The improvement in the dissolution behavior was also maintained with the tablets. The USP XXIII requirement for estradiol tablets reaching greater than 75% drug dissolved after 60 min was obtained in this investigation.

Interaction of prostaglandin E1 with alpha-cyclodextrin in aqueous systems: stability of the inclusion complex.

Prostavasin, an inclusion complex of prostaglandin E1 (PGE1) with alpha-cyclodextrin (alpha-CD), is used in the therapy of thrombosis. Nuclear magnetic resonance measurements have been made to study the interaction of PGE1 with alpha-CD. The observed interaction (chemical shift) and the derived dissociation constant prove that only weak interaction forces are operative and that complete dissociation occurs upon dilution.

Effect of cyclodextrin derivatives on indomethacin stability in aqueous solution.

The effect of various cyclodextrins (CD) and cyclodextrin derivatives on indomethacin stability in phosphate buffer, pH 7.4, was investigated. The influence of CD-ring size, type of substituent, degree of substitution, substitution pattern, and influence of CD concentration were monitored. The indomethacin complex in solution was studied by 1H-NMR spectroscopy to develop a molecular inclusion model. The most favorable ring size for the stabilization of indomethacin was the beta-CD. The beta-CD derivatives inhibited the hydrolysis of indomethacin more effectively than the parent CD. Among the studied CD derivatives, those with lipophilic substituents, such as ethyl or methyl, were superior to those with hydrophilic substitutents. The more hydroxyl groups of the glucose moiety are substituted, the better is the stabilizing effect. Further, the p-chlorobenzoic part of the indomethacin molecule is included in the CD channel.