Peroral delivery of calcitonin with pheroid technology

Abstract

Purpose: The purpose of this study was to evaluate the absorption enhancing potential of Pheroid technology and TMC (N-trimethyl chitosan chloride), a chitosan derivative, on the peroral administration of salmon calcitonin. Methods: The research strategy was to administer salmon calcitonin, a large polar peptide drug with a known stability profile and quantitive therapeutic effect, alone and in combinations with two different Pheroid formulations and two derivatives of chitosan namely TMC and TMO to the jejunum mucosal surface of laboratory rats. Entrapment of calcitonin in Pheroids were confirmed and analyzed with CLSM. In vivo studies were conducted on Sprague-Dawley rats. Rats were fasted for 24 hours. The carotis communis was cannulated for the collection of blood samples after 0, 5, 10, 15, 30, 60, 120 and 180 minutes. An incision was made to the abdomen of the rats to ligate the jejunum were the different formulations of Pheroid microsponges and vesicles and TMC and TMO with salmon calcitonin (500 IU/kg) were injected. Blood samples were collected immediately and centrifuged. Serum was stored at -40 OC until analysis. Analyses were done with a Radio Immuno Assay. Results: With both Pheroid technology and TMC greater concentrations of salmon calcitonin were observed as with salmon calcitonin in saline. Peak plasma concentration values were found just after 15 minutes. Conclusion: It was found that Pheroid technology shows definite potential for enhancing absorption of salmon calcitonin after peroral administration. Pheroid technology has a favourable release profile which results in a greater bioavailability of salmon calcitonin after oral administration. This study once again confirmed TMC is not an excipient that can be omitted in the peroral administration of peptide and protein drugs in the future.