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AAPS PharmSciTech. 2006 September; 7(3): E184–E189.
Published online 2006 September 29. doi:  10.1208/pt070379
PMCID: PMC2750521

Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl β-cyclodextrin

Abstract

Complexation of celecoxib with hydroxypropyl β-cyclodextrin (HPβCD) in the presence and absence of 3 hydrophilic polymers—polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)—was investigated with an objective of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPβCD and on the dissolution rate of celecoxib from the HPβCD complexes. The phase solubility studies indicated the formation of celecoxib-HPβCD inclusion complexes at a 1[ratio]1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were quite stable. Addition of hydrophilic polymers markedly enhanced the complexation and solubilizing efficiencies of HPβCD. Solid inclusion complexes of celecoxib-HPβCD were prepared in 1[ratio]1 and 1[ratio]2 ratios by the kneading method, with and without the addition of hydrophilic polymers. The solubility and dissolution rate of celecoxib were significantly improved by complexation with HPβCD. The celecoxib-HPβCD (1[ratio]2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of celecoxib. The addition of hydrophilic polymers also markedly enhanced the dissolution rate of celecoxib from HPβCD complexes: a 72.60-, 61.25-, and 39.15-fold increase was observed with PVP, HPMC, and PEG, respectively. Differential scanning calorimetry and X-ray diffractometry indicated stronger drug amorphization and entrapment in HPβCD because of the combined action of HPβCD and the hydrophilic polymers.

Keywords: Celecoxib, complexation, hydroxypropyl β-cyclodextrin, hydrophilic polymers, dissolution rate

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Fromming KH, Szejtli J. CDs in Pharmacy. Dordrecht, The Netherlands: Kluwer Academic; 1994.
2. Duchene D, Wouessidjewe D. Pharmaceutical and medicinal applications of cyclodextrins. In: Dumitriu S, editor. Polysaccharides in Medical Applications. New York, NY: Marcel Dekker; 1996. pp. 575–602.
3. Uekama K, Hirayama F, Irie T. Cyclodextrin drug carrier systems. Chem Rev. 1998;98:2045–2076. doi: 10.1021/cr970025p. [PubMed] [Cross Ref]
4. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins, I: drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–1025. doi: 10.1021/js950534b. [PubMed] [Cross Ref]
5. Rajewski RA, Stella VJ. Pharmaceutical applications of cyclodextrins, II:in vivo drug delivery. J Pharm Sci. 1996;85:1142–1169. doi: 10.1021/js960075u. [PubMed] [Cross Ref]
6. Martin Del Valle EM. Cyclodextrins and their uses: a review. Process Biochem. 2004;39:1033–1046. doi: 10.1016/S0032-9592(03)00258-9. [Cross Ref]
7. Thompson DO. Cyclodextrins—enabling excipients: their present and future use in pharmaceuticals. Crit Rev Ther Drug Carrier Syst. 1997;14:1–104. [PubMed]
8. Hedges AR. Industrial applications of cyclodextrins. Chem Rev. 1998;98:2035–2044. doi: 10.1021/cr970014w. [PubMed] [Cross Ref]
9. Mura P, Faucci MT, Bettinetti GP. The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl β-cyclodextrin. Eur J Pharm Sci. 2001;13:187–194. doi: 10.1016/S0928-0987(01)00093-8. [PubMed] [Cross Ref]
10. Geis GS. Update on clinical development with celecoxib, a new specific COX-2 inhibitor: what can we expect? Scand J Rheumatol Suppl. 1999;28:31–37. doi: 10.1080/030097499750042407. [PubMed] [Cross Ref]
11. Fort J. Celecoxib, a COX-2-specific inhibitor: the clinical data. Am J Orthop. 1999;28:13–18. [PubMed]
12. Davies NM, Gudde TW, Leeuw HA. Celecoxib, a new option in the treatment of arthropathies and familial adenomatous polyposis. Expert Opin Pharmacother. 2001;2:139–152. doi: 10.1517/14656566.2.1.139. [PubMed] [Cross Ref]
13. Moore PA, Hersh EV. Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice. J Am Dent Assoc. 2001;132:451–456. [PubMed]
14. Tindall E. Celecoxib for the treatment of pain and inflammation: the preclinical and clinical results. J Am Osteopath Assoc. 1999;99:S13–S17. [PubMed]
15. Dougados M, Beier JM, Joichine I, et al. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Arthritis Rheum. 2001;44:180–185. doi: 10.1002/1529-0131(200101)44:1<180::AID-ANR24>3.0.CO;2-K. [PubMed] [Cross Ref]
16. Reddy MN, Rehana T, Ramakrishna S, Chowdhary KP, Diwan PV. β-Cyclodextrin complexes of celecoxib: molecular modeling, characterization and dissolution studies. AAPS PharmSci. 2004;6:E7–E7. doi: 10.1208/ps060107. [PMC free article] [PubMed] [Cross Ref]
17. Higuchi T, Connors KA. Phase-solubility techniques. In: Reilly CN, editor. Advances in Analytical Chemistry and Instrumentation. New York, NY: Wiley-Interscience; 1965. pp. 117–212.
18. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27:48–49. [PubMed]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists