Affiliation:
1. Department of Pharmacy, Cangzhou Medical College, Cangzhou, Hebei Province 061000, China
2. Department of
Pharmacy, Abasyn University Islamabad, Islamabad, Pakistan
3. Department of Pharmacy, Faculty of Biological Sciences,
Quaid-i-Azam University, Islamabad, Pakistan
Abstract
Background:
Celecoxib is generally used for the treatment of rheumatoid arthritis, however
its poor bioavailability and cytotoxicity in pure form have reduced its therapeutic efficacy. This study
aims to develop celecoxib liquid suppositories with improved bioavailability and reduced toxicity.
Methods:
The celecoxib liquid suppositories were prepared by thoroughly mixing celecoxib, poloxamer
188 and poloxamer 407, and tween-20, respectively used as drug, polymers and surfactant, in triple
distilled water using cold technique. The developed liquid suppositories were characterized in terms of
their gelation temperature, gelation time, and gel strength. Moreover, the muco-adhesive force was
determined for the suppositories. The release behavior of the liquid suppositories was investigated in
distilled water and compared with drug suspension. Furthermore, pharmacokinetics and morphological
studies were carried out in rats after rectal administration of the celecoxib liquid suppository compared
with drug suspension.
Results:
Poloxamer 188 and Tween-20 concentrations have significantly reduced the gelation temperature
and time; however, the gel strength and bio-adhesive force were significantly enhanced. The concentration
of celecoxib has no significant effect on the properties of liquid suppositories. A significantly
enhanced and potentially sustained drug release was observed from the celecoxib liquid suppositories as
compared with the drug suspension. The optimized formulation was easy to administer rectally because
it quickly forms gel upon insertion into the body due to a suitable gelation temperature of about
31.7 °C. After rectal administration in rats, the celecoxib liquid suppository gave a significantly increased
pharmacokinetic profile including enhanced plasma concentration and 9.7 fold improved area
under the curve (AUC) compared to the drug suspension. Additionally, the morphology study exhibited
no toxicity to the rectal tissue, no signs of irritation, or injury after the application of suppository. However,
severe rectal tissue toxicity and irritation was observed in the suspension treated rectum.
Conclusions:
It can be concluded that the liquid suppository system may significantly enhance the solubilization
and bio-availability of sparingly water-soluble drugs as evident in the case of celecoxib with
no toxicity at the site of application.
Publisher
Bentham Science Publishers Ltd.
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