Stabilization and intestinal absorption of human calcitonin

The effect of different excipients and/or surface active compounds on the stability of human calcitonin in aqueous solution was studied. Calcitonin solution was partially stabilized with dilute acetic acid (0.01% (w/v) or higher), and among many tested surfactants, only lauryl sulfate proved to be a very efficient long-term stabilizer (1 year or more). Concentration dependency studies indicated that lauryl sulfate micelles were necessary to achieve long-term stabilization of human calcitonin in solution. Another liquid formulation was developed that also stabilized human calcitonin over a long period of time (3 months or more). Calcitonin was dissolved in polar, nontoxic, nonaqueous solvents, such as propylene glycol or polyethylene glycol 200 and this solution was emulsified in an oil phase composed of medium-chain glycerides. Medium and long-term stabilized formulations of human calcitonin were then studied for intestinal absorption via the duodenum and colon in rats. Using aqueous formulations containing 1% sodium dodecyl sulfate or 6.6% dodecyl maltoside as the enhancer, bioavailability values greater than 10% were achieved by intracolonic route of administration, demonstrating that the colon is better suited for calcitonin delivery and absorption. Pharmacodynamic responses and time profiles obtained were significant and comparable to those observed for intramuscular injection of human calcitonin.