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AAPS PharmSciTech. 2005 September; 6(3): E464–E472.
Published online 2005 October 22. doi:  10.1208/pt060358
PMCID: PMC2750392

Diclofenac-β-cyclodextrin binary systems: Physicochemical characterization and in vitro dissolution and diffusion studies


The aim of this work was to study the influence of β-cyclodextrin (β-CD) on the biopharmaceutic properties of diclofenac (DCF). To this purpose the physicochemical characterization of diclofenac-β-cyclodextrin binary systems was performed both in solution and solid state. Solid phase characterization was performed using differential scanning calorimetry (DSC), powder x-ray diffractometry (XRD), and Fourier transform infrared spectroscopy (FTIR). Phase solubility analyses, and in vitro permeation experiments through a synthetic membrane were performed in solution. Moreover, DCF/β-CD interactions were studied in DMSO by1H nuclear magnetic resonance (NMR) spectroscopy. The effects of different preparation methods and drug-to-β-CD molar ratios were also evaluated. Phase solubility studies revealed 1[ratio]1 M complexation of DCF when the freeze-drying method was used for the preparation of the binary system. The true inclusion for the freeze-dried binary system was confirmed by1H NMR spectroscopy, DSC, powder XRD, and IR studies. The dissolution study revealed that the drug dissolution rate was improved by the presence of CDs and the highest and promptest release was obtained with the freeze-dried binary system. Diffusion experiments through a silicone membrane showed that DCF diffusion was higher from the saturated drug solution (control) than the freeze-dried inclusion complexes, prepared using different DCF-β-CD molar ratios. However, the presence of the inclusion complex was able to stabilize the system giving rise to a more regular diffusion profile.

Keywords: diclofenac-β-cyclodextrin inclusion complex, dissolution, permeation

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Selected References

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1. Duchene D. New trends in cyclodextrins and derivatives. Paris: Editions de Santè; 1992. pp. 351–407.
2. Frömming KH, Szejtli J. Cyclodextrins in Pharmacy, Topics in Inclusion Science. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1994.
3. Thompson DO. Cyclodextrins-enabling excipients: their present and future use in pharmaceuticals. Crit Rev Ther Drug Carrier Syst. 1997;14:1–104. [PubMed]
4. Masson M, Loftsson T, Masson G, Stefänsson ES. Cyclodextrins as permeation enhancer some theoretical evaluations and in vitro testing. J Control Release. 1999;59:107–118. doi: 10.1016/S0168-3659(98)00182-5. [PubMed] [Cross Ref]
5. Matsuda H, Arima H. Cyclodextrins in transdermal and rectal delivery. Adv Drug Deliv Rev. 1999;36:81–99. doi: 10.1016/S0169-409X(98)00056-8. [PubMed] [Cross Ref]
6. Loftsson T, Arima H. Cyclodextrins in ophthalmic drug delivery. Adv Drug Deliv Rev. 1999;36:59–79. doi: 10.1016/S0169-409X(98)00055-6. [PubMed] [Cross Ref]
7. Kristmundsdottir T, Loftsson T, Holbrook WP. Formulation and clinical evaluation of hydrocortisone solution for the treatment of oral disease. Int J Pharm Biopharm. 1996;139:63–68.
8. Merkus FWHM, Verhoef JC, Marttin E, Romeijn SG, Kuy WAJJ, Schipper NGM. Cyclodextrins in nasal drug delivery. Adv Drug Deliv Rev. 1999;36:41–57. doi: 10.1016/S0169-409X(98)00054-4. [PubMed] [Cross Ref]
9. Jarho K, Urtti A, Stella VJ, Jarvinen T. Modified β-cyclodextrin (SBE7-β-CyD) with viscous vehicle improves the ocular delivery and tolerability of pilocarpine prodrug in rabbits. Int J Pharm Pharmacol. 1996;48:264–270. [PubMed]
10. Lutterotti L, Ceccato R, Maschio R, Pagani E. Quantitative Analysis of Silicate Glass in Ceramic Materials by the Rietveld Method. Mater Sci Forum. 1998;281:87–92. doi: 10.4028/ [Cross Ref]
11. McCusker LB, Dreele RB, Cox DE, Löuer D, Scardi P. Rietveld refinement guidelines. J Appl Cryst. 1999;32:36–50. doi: 10.1107/S0021889898009856. [Cross Ref]
12. Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem Instrum. 1965;4:117–212.
13. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27:48–49. [PubMed]
14. Mukne AP, Nagarsenker MS. Triamterene-β-cyclodextrin Systems: Preparation, Characterization and In Vivo Evaluation. AAPS Pharm Sci Tech. 2004;5:E19–E19. doi: 10.1208/pt050119. [PMC free article] [PubMed] [Cross Ref]
15. Ottani S, Castellari C. Two Monocline Forms of Diclofenac Acid. Acta Crystallogr. 1997;53:794–797. doi: 10.1107/S0108270197002126. [Cross Ref]
16. Ficarra R, Ficarra P, Bella MR, et al. Study of beta-blockers/beta-cyclodextrins inclusion complex by NMR. DSC, X-ray and SEM investigation. J Pharm Biomed Anal. 2000;23:33–40. doi: 10.1016/S0731-7085(00)00261-2. [PubMed] [Cross Ref]
17. Barbato F, Cappello B, Rotonda MI, Miro A, Quaglia F. Diclofenac/β-cyclodextrin binary systems: a study in solution and in the solid state. J Incl Phenom Macro. 2003;46:179–185. doi: 10.1023/A:1026303516401. [Cross Ref]
18. Mura P, Maestrelli F, Cirri M, Furlanetto S, Pinzauti S. Differential scanning calorimetry as tools in the study of drug-cyclodextrin interactions. J Thermal Anal & Cal. 2003;74:769–777. doi: 10.1023/B:JTAN.0000011009.46113.01. [Cross Ref]
19. Dollo G, Corre P, Chevanne F, Verge R. Inclusion complexation of amide-typed local anaesthetics with β-cyclodextrin and its derivates. I. Physicochemical characterization. Int J Pharm. 1996;131:219–228. doi: 10.1016/0378-5173(95)04334-9. [Cross Ref]
20. Nozawa Y, Morioka Y, Sadzuka Y, Miyagishima A, Hirota S, Guillory JK. Mechano-chemical formation of indomethacin β-cyclodextrin inclusion compounds in power phase roll mixtures. Pharm Acta Helv. 1997;72:113–117. doi: 10.1016/S0031-6865(97)00003-4. [Cross Ref]
21. Pose-Vilarnovo B, Perdomo-Lòpez I, Echezarreta-Lopez M, Schroth-Pardo P, Estrada E, Torres-Labandeira JJ. Improvement of water solubility of sulfamethizole through it complexation with β and hydroxypropyl-β-cyclodextrin: characterization of the interaction in solution and in solid state. Eur J Pharm Sci. 2001;13:325–331. doi: 10.1016/S0928-0987(01)00131-2. [PubMed] [Cross Ref]
22. Fernandes CM, Carvalho RA, Pereira da Costa S, Veiga JB. Multimodal molecular encapsulation of nicardipine hydrochloride by β-cyclodextrin, hydroxypropyl-β-cyclodextrin and triacetyl-β-cyclodextrin in solution. Structural studies by1H NMR and ROESY experiments. Eur J Pharm Sci. 2003;18:285–296. doi: 10.1016/S0928-0987(03)00025-3. [PubMed] [Cross Ref]
23. Mucci A, Schenetti L, Vandelli MA, Ruozi B, Forni F. Evidence of the existence of 2[ratio]1 guest-host complexes between diclofenac and cyclodextrins in D2O solutions A1H and 13C NMR study on diclofenac/β-cyclodextrin and diclofenac/2-hydroxypropyl-β-cyclodextrin systems.J Chem Res. 1999;414–415.
24. Arancibia JA, Escandar GM. Complexation study of diclofenac with β-cyclodextrin and spectrofluorimetic determination. Analyst. 1999;124:1833–1838. doi: 10.1039/a906719a. [PubMed] [Cross Ref]
25. Mura P, Faucci MT, Parrini PL, Furlanetto S, Pinzauti S. Influence of the preparation method on the physicochemical properties of ketoprofencyclodextrin binary systems. Int J Pharm. 1999;179:117–128. doi: 10.1016/S0378-5173(98)00390-1. [PubMed] [Cross Ref]
26. Dias MMR, Raghavan SL, Pellett MA, Hadgraft J. The effect of β-cyclodextrins on the permeation of diclofenac from supersaturated solutions. Int J Pharm. 2003;263:173–181. doi: 10.1016/S0378-5173(03)00366-1. [PubMed] [Cross Ref]
27. Jervolino M, Raghavan SL, Hadgraft J. Membrane penetration enhancement of ibuprofen using supersaturation. Int J Pharm. 2000;198:229–238. doi: 10.1016/S0378-5173(00)00346-X. [PubMed] [Cross Ref]

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