Solubilization of ovine growth hormone with 2-hydroxypropyl-beta-cyclodextrin

Studies were undertaken to determine the effects of 2-hydroxypropyl-beta-cyclodextrin (HPCD) on the solubility of ovine-Growth Hormone (o-GH) in aqueous solution. HPCD, which is believed to form inclusion complexes with hydrophobic amino acid residues of peptides, markedly increased o-GH solubility at all o-GH and all HPCD concentrations tested. In HPCD solutions, o-GH was completely solubilized between pH 7.5 and 8.5, while in water, o-GH was not solubilized until a pH of 11.5 was reached. Temperature and repeated freeze-thaw cycles had little effect on o-GH solubility in HPCD. Vigorous shaking of solution of o-GH in HPCD did not result in precipitation of the peptide. These studies document that HPCD enhances o-GH solubility in aqueous solutions. Preparations of GH in HPCD may eliminate solubility problems observed in current human GH preparations intended for parenteral use.