S T Dogru1, S Calis, F Oner. 1. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Abstract
BACKGROUND: Salmon calcitonin (sCT) is a polypeptide hormone consisting of 32 amino acid residues (MW approx. 3400 Da), which can be used successfully for the treatment of osteoporosis, Paget's disease and hypercalcaemia. Only nasal and parenteral preparations of sCT are currently available, and as injections are poorly accepted by patients, nonparenteral preparations for oral, rectal and nasal administration are highly desirable. However, oral sCT is poorly bioavailable, being susceptible to enzymatic degradation in the gastrointestinal tract. OBJECTIVES: To design a formulation of sCT suitable for oral use. METHOD: A water/oil/water (w/o/w) type multiple emulsion formulation was designed for oral application of sCT. sCT was placed in the inner water phase, and a protease inhibitor, aprotinin, was included in the outer water phase of this system to investigate the influence of protease inhibitors in the presence of sCT. The effectiveness of the formulation was evaluated in vitro by placing emulsion samples in a dialysis medium and in vivo by using a rat model. RESULTS: Incorporating sCT in the inner aqueous phase of a w/o/w emulsion appears to protect the peptide from enzymatic degradation. sCT was further protected by incorporating the protease inhibitor, aprotinin, in the outer aqueous phase. CONCLUSION: w/o/w emulsion formulations appear to be promising carrier systems for peptide-protein drugs.
BACKGROUND: Salmon calcitonin (sCT) is a polypeptide hormone consisting of 32 amino acid residues (MW approx. 3400 Da), which can be used successfully for the treatment of osteoporosis, Paget's disease and hypercalcaemia. Only nasal and parenteral preparations of sCT are currently available, and as injections are poorly accepted by patients, nonparenteral preparations for oral, rectal and nasal administration are highly desirable. However, oral sCT is poorly bioavailable, being susceptible to enzymatic degradation in the gastrointestinal tract. OBJECTIVES: To design a formulation of sCT suitable for oral use. METHOD: A water/oil/water (w/o/w) type multiple emulsion formulation was designed for oral application of sCT. sCT was placed in the inner water phase, and a protease inhibitor, aprotinin, was included in the outer water phase of this system to investigate the influence of protease inhibitors in the presence of sCT. The effectiveness of the formulation was evaluated in vitro by placing emulsion samples in a dialysis medium and in vivo by using a rat model. RESULTS: Incorporating sCT in the inner aqueous phase of a w/o/w emulsion appears to protect the peptide from enzymatic degradation. sCT was further protected by incorporating the protease inhibitor, aprotinin, in the outer aqueous phase. CONCLUSION: w/o/w emulsion formulations appear to be promising carrier systems for peptide-protein drugs.