Design and in vivo evaluation of solid-in-oil suspension for oral delivery of human growth hormone

Solid-in-oil (S/O) suspension containing human growth hormone (hGH), in which hGH was complexed with an edible surfactant, was designed and validated for oral administration of hGH. To optimize the formulation procedures, protein release behavior from the S/O suspensions under physiological conditions was first investigated with horseradish peroxidase (HRP) as a model protein. Evaluation of functional integrity of HRP released from the HRP-surfactant complex suggested that the solubilization process partly impaired the specific activity of HRP, however, the addition of trehalose in the formulation process regained up to about 50% of the biological activity. On the basis of the data collected with HRP, a surfactant-hGH complex prepared under optimized conditions was suspended in soybean oil to formulate S/O suspensions. After oral administration of the S/O suspension to male New Zealand rabbits, we detected hGH in the serum with 3.3% bioavailability, suggesting that hGH can be orally delivered to the systemic circulation by the present formulation.