Advances in biotechnology and recombinant technologies have lead to the
production of several classes of new drugs such as peptide and protein drugs.
These compounds are mostly indicated for chronic use but their inherent
characteristics such as size, polarity and stability prevent them from
incorporation in novel dosage forms. The bioavailability of nearly all peptide
drugs is very low due to poor absorption from the administration site. Several
challenges confront the pharmaceutical scientist in developing effective and
innovative dosage forms for these classes of drugs. A lot of attention has
been given to the nasal route of drug administration for delivery of peptide
drugs. The availability of several promising classes of absorption enhancers
and new drug delivery technologies has also prompt scientists to develop new
delivery systems for nasal administration of peptide drugs.
It has been shown in recent years that N-trimethyl chitosan chloride (TMC), a
quaternary derivative of chitosan, is effective in enhancing the absorption of
several peptide drugs, both in the peroral route and in the nasal route of drug
administration. Early indications are that new drug delivery technologies such
as Pheroid technology will also be able to enhance peptide drug absorption in
the nasal route. The aim of this study was to evaluate and compare the
absorption enhancing abilities of TMC and Pheroid technology in the nasal
delivery of calcitonin, a peptide hormone with low bioavailability.
Pheroid vesicles and Pheroid microsponges were prepared and characterized
for their morphology and size distribution. Calcitonin was entrapped into these
vesicles and microsponges and TMC and TMO solutions (0.5 % w/v),
containing calcitonin, was also prepared. These formulations were
administered nasally to rats in a volume of 100 μl/kg body-weight to obtain a
final concentration of 10 IU/kg body-weight of calcitonin. Plasma calcitonin
and calcium levels were determined over a period of 3 hours.
The results of this study clearly indicated that both Pheroid formulations and
the TMC formulation increase the nasal absorption of calcitonin with a
resulting decrease in plasma calcium levels, indicating an increased
absorption of calcitonin. The highest increase in calcitonin absorption was
obtained with the TMC formulation and this was explained by the difference in
the mechanism of action in enhancing peptide absorption between TMC and
Pheroid technology. It was concluded that Pheroid technology is also a potent
system to enhance peptide drug delivery and that the exact mechanism of
action should be investigated further. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/888 |
| Date | January 2005 |
| Creators | Kotzé, Jeanéne Celesté |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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