Progress in the Formulation and Delivery of Somatostatin Analogues for Acromegaly

A 14-amino acid cystin bridge-containing neuropeptide was discovered in 1973 and designated as "growth hormone-inhibiting hormone (GHIH)," i.e. somatostatin. Its discovery led to the synthesis of three analogues which were licenced for the treatment of acromegaly: octreotide, lanreotide, and pasireotide. Somatostatin analogues are currently approved only as either subcutaneous (s.c.) or intramuscular (i.m.) long-acting injections. We examine the challenges that must be overcome to create oral formulations of somatostatin analogues and examine selected clinical trial data. While octreotide has low intestinal permeability, similar to almost all other peptides, it has an advantage of being more stable against intestinal peptidases. The development of new oral formulation strategies may eventually allow for the successful oral administration of potent somatostatin analogues with high therapeutic indices.