Controlled release systems aim at achieving a predictable and reproducible drug release
profile over a desired time period. These controlled release formulations offer many
advantages over conventional dosage forms. These advantages include: reduced dosing
intervals, constant drug levels in the blood, increased patient compliance and decreased
adverse effects. Complex controlled release formulations such as those with sustained
release properties, often require additional steps during the production phase. The cost
and economic impact associated with these complex controlled release dosage
formulations often outweigh the short term benefits. Thus the development of an
economic method to produce controlled release particles is of great importance especially
in third world countries.
In controlled release formulations the drug is often equally dispersed throughout a
polymer matrix. In the presence of a thermodynamically compatible solvent, swelling
occurs and the polymer releases its content to the surrounding medium. The rate of drug
release can be controlled by interfering with the amount of swelling and rate of diffusion
by manipulating the viscosity of the polymer matrix.
Chitosan is an ideal candidate for controlled drug delivery through matrix release
systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because
beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce
fluctuation in peak plasma, and minimize potential side effects without lowering drug
bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug.
Chitosan beads and excipient containing chitosan beads were prepared by ionotropic
gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing
pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced.
The excipients were added individually and in combinations to the
chitosadpyrazinamide dispersion and the beads were characterized on the basis of their
morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well
as drug release (dissolution properties).
The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was
noted that the inclusion of excipients in the beads resulted in an increase in drug loading
with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of
67.09 ± 0.22%.
It was expected that the addition of the pharmaceutical excipients would lead to a
sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst
release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15
minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion
of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide
over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug
(approximately 40%) in the beads to be released over the extended period. Other
polymers can also be investigated to control the release of pyrazinamide. Further studies
are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nwu/oai:dspace.nwu.ac.za:10394/1354 |
| Date | January 2006 |
| Creators | Havenga, John Botha |
| Publisher | North-West University |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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