[The influence of viscosity-increasing pharmaceutic aids on the liberation of the peptide gonadotropin releasing hormone (GnRH) in solution].
The in vitro liberation of the peptide hormone GnRH from polymer solutions was studied as a function of the viscosity of the polymer solutions. The liberation experiments were performed with a flow through dialysis apparatus. From solutions of dextran, carboxymethylcellulose, hydroxyethylcellulose, and polyvinylpyrrolidone the release of GnRH is prolonged whereas the release of GnRH from highly viscous solutions of methylcellulose and polyacrylic acid is not. The delivery process was found to be diffusion-controlled in solutions of dextran, carboxymethylcellulose, and hydroxyethylcellulose. In solutions of polyvinylpyrrolidone the diffusion-controlled prolongation of the GnRH release is additionally influenced by binding of the peptide to the polymer. The results imply that in these polymer solutions the diffusion coefficient of GnRH does not obey the classical relation D approximately 1/eta which is often used to predict liberation from viscous solutions. Thus, the measured macroscopic viscosity of the polymer solutions is not relevant for the diffusion-controlled prolongation of the in vitro release of GnRH. This phenomenon can be explained by the obstruction effect and the microviscosity of the polymer solutions. The described rapid and simple method can be applied for the quantitative determination of the prolonged release in polymer solutions based on diffusion-controlled processes and is useful in the comparison of the efficacy of various polymeric additives. Furthermore the method allows the quantitative proof of the decrease of diffusion in viscous low-molecular solutions and the proof of prolongations of delivery due to the binding of the investigated drug to the polymer.
D004058:Diffusion; D005079:Excipients; D010455:Peptides / Q000032:analysis*; D010906:Pituitary Hormone-Releasing Hormones / Q000032:analysis*; D012996:Solutions; D014783:Viscosity
D005079:Excipients; D010455:Peptides; D010906:Pituitary Hormone-Releasing Hormones; D012996:Solutions
Untersuchungen über den Einfluss viskositätserhöhender pharmazeutischer Hilfsstoffe auf die Liberation des Peptids Gonadotropin Releasing Hormon (GnRH) in Lösung.