Skip to main content

Advertisement

SpringerLink
Log in

Advanced Technologies for Oral Controlled Release: Cyclodextrins for Oral Controlled Release

  • Mini-Review
  • Theme: Advanced Technologies for Oral Controlled Release
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability, and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug–drug or drug–additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water-soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g., as osmotic pumps) and/or hydrophobic CDs. New controlled delivery systems based on nanotechnology carriers (nanoparticles and conjugates) have also been reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

REFERENCES

  1. Vyas A, Saraf S, Saraf S. Cyclodextrin based novel drug delivery systems. J Incl Phenom Macrocycl Chem. 2008;62:23–42.

    Article  CAS  Google Scholar 

  2. Hoffman AS. The origins and evolution of “controlled” drug delivery systems. J Control Release. 2008;132:153–63.

    Article  PubMed  CAS  Google Scholar 

  3. Rupp C, Steckel H, Müller BW. Solubilization of poorly water-soluble drugs by mixed micelles based on hydrogenated phosphatidylcholine. Int J Pharm. 2010;395:272–80.

    Article  PubMed  CAS  Google Scholar 

  4. Szejtli S. Introduction and general overview of cyclodextrin chemistry. Chem Rev. 1998;98:1743–53.

    Article  PubMed  CAS  Google Scholar 

  5. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12:1068–75.

    Article  PubMed  CAS  Google Scholar 

  6. Xiong J, Guo J, Huang L, Meng B, Ping Q. The use of lipid-based formulations to increase the oral bioavailability of Panax notoginseng saponins following a single oral gavage to rats. Drug Dev Ind Pharm. 2008;34:65–72.

    Article  PubMed  CAS  Google Scholar 

  7. Liu Y, Sun C, Hao Y, Liang T, Zheng L, Wang S. Mechanism of dissolution enhancement and bioavailability of poorly water soluble celecoxib by preparing stable amorphous nanoparticles. J Pharm Pharmaceut Sci. 2010;13:589–606.

    CAS  Google Scholar 

  8. Carrier RL, Miller LA, Ahmed I. The utility of cyclodextrins for enhancing oral bioavailability. J Control Release. 2007;123:78–99.

    Article  PubMed  CAS  Google Scholar 

  9. Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl-β-cyclodextrin. Eur J Pharm Biopharm. 2008;68:303–9.

    Article  PubMed  CAS  Google Scholar 

  10. Králová J, Kejík Z, Břísa T, Poučkova, Král A, Martásek P, et al. Porphyrin–cyclodextrin conjugates as a nanosystem for versatile drug delivery and multimodal cancer therapy. J Med Chem. 2010;53:128–38.

    Article  PubMed  CAS  Google Scholar 

  11. Kim EY, Gao ZG, Park JS, Lee H, Han K. rhEGF/HP-β-CD complex in poloxamer gel for ophthalmic delivery. Int J Pharm. 2002;233:159–67.

    Article  PubMed  CAS  Google Scholar 

  12. Haeberlin B, Gengenbacher T, Meinzer A, Fricker G. Cyclodextrins—useful excipients for oral peptide administration? Int J Pharm. 1996;137:103–10.

    Article  CAS  Google Scholar 

  13. Uekama K, Hirayama F, Irie T. Cyclodextrin drug carrier systems. Chem Rev. 1998;98:2045–76.

    Article  PubMed  CAS  Google Scholar 

  14. Loftsson T, Järvinen T. Cyclodextrins in ophthalmic drug delivery. Adv Drug Deliv Rev. 1999;36:59–79.

    Article  Google Scholar 

  15. Matsuda H, Arima H. Cyclodextrins in transdermal and rectal delivery. Adv Drug Deliv Rev. 1999;36:81–99.

    Article  PubMed  CAS  Google Scholar 

  16. Loftsson T, Másson M, Sigurdsson HH. Cyclodextrins and drug permeability through semi-permeable cellophane membranes. Int J Pharm. 2002;232:35–43.

    Article  PubMed  CAS  Google Scholar 

  17. Zerrouk N, Corti G, Ancillotti S, Maestrelli F, Cirri M, Mura P. Influence of cyclodextrins and chitosan, separately or in combination, on glyburide solubility and permeability. Eur J Pharm Biopharm. 2006;62:241–6.

    Article  PubMed  CAS  Google Scholar 

  18. Ling W, Xuehua J, Weijuan X, Chenrui L. Complexation of tanshinone IIA with 2-hydroxypropyl-β-cyclodextrin: effect on aqueous solubility, dissolution rate, and intestinal absorption behavior in rats. Int J Pharm. 2007;341:58–67.

    Article  CAS  Google Scholar 

  19. Pescitelli G, Bilia AR, Bergonzi MC, Vincieri FF, Di Bari L. Cyclodextrins as carriers for kavalactones in aqueous media: spectroscopic characterization of (S)-7,8-dihydrokavain and β-cyclodextrin inclusion complex. J Pharm Biomed Anal. 2010;52:479–83.

    Article  PubMed  CAS  Google Scholar 

  20. Nakanishi K, Masukawa T, Nadai T, Yoshii K, Okada S, Miyajima K. Prolonged release of drug from triacetyl-β-CD complex for oral and rectal administration. J Incl Phenom Macrocycl Chem. 1996;25:181–4.

    Article  CAS  Google Scholar 

  21. Péroche S, Degobert G, Putauxc J-L, Blanchin M-G, Fessi H, Parrot-Lopez H. Synthesis and characterisation of novel nanospheres made from amphiphilic perfluoroalkylthio-β-cyclodextrins. Eur J Pharm Biopharm. 2005;60:123–31.

    Article  PubMed  CAS  Google Scholar 

  22. Ganapathy HS, Lee MY, Park C, Lim KT. Sustained release applications of a fluoroalkyl ester-functionalized amphiphilic cyclodextrin by inclusion complex formation with water-soluble drugs in supercritical carbon dioxide. J Fluorine Chem. 2008;129:1162–6.

    Article  CAS  Google Scholar 

  23. Wang Z, Horikawa T, Hirayama F, Uekama K. Design and in-vitro evaluation of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-beta-cyclodextrin and hydroxypropylcellulose. J Pharm Pharmacol. 1993;45:942–6.

    Article  PubMed  CAS  Google Scholar 

  24. Hirayama F, Uekama K. Cyclodextrin-based controlled drug release system. Adv Drug Deliv Rev. 1999;36:125–41.

    Article  PubMed  CAS  Google Scholar 

  25. Fernandes CM, Ramos P, Falcão AC, Veiga FJ. Hydrophilic and hydrophobic cyclodextrins in a new sustained release oral formulation of nicardipine: in vitro evaluation and bioavailability studies in rabbits. J Control Release. 2003;88:127–34.

    Article  PubMed  CAS  Google Scholar 

  26. Woldum HS, Larsen KL, Madsen F. Cyclodextrin controlled release of poorly water-soluble drugs from hydrogels. Drug Deliv. 2008;15:69–80.

    Article  PubMed  CAS  Google Scholar 

  27. Irie T, Uekama K. Pharmaceutical applications of cyclodextrins 3. Toxicological issues and safety evaluation. J Pharm Sci. 1997;86:147–61.

    Article  PubMed  CAS  Google Scholar 

  28. Namazi H, Bahrami S, Entezami AA. Synthesis and controlled release of biocompatible prodrugs of β-cyclodextrin linked with PEG containing ibuprofen or indomethacin. Iran Polym J. 2005;14:921–7.

    CAS  Google Scholar 

  29. Duchêne D, Wouessidjewe D, Ponchel G. Cyclodextrins and carrier systems. J Control Release. 1999;62:263–8.

    Article  PubMed  Google Scholar 

  30. Kamada M, Hirayama F, Udo K, Yano H, Arima H, Uekama K. Cyclodextrin conjugate-based controlled release system: repeated- and prolonged-releases of ketoprofen after oral administration in rats. J Control Release. 2002;82:407–16.

    Article  PubMed  CAS  Google Scholar 

  31. Szejtli J. Cyclodextrin technology. Dordrecht: Kluwer Academic; 1988. p. 450.

    Google Scholar 

  32. Wenz G, Han B-H, Müller A. Cyclodextrin rotaxanes and polyrotaxanes. Chem Rev. 2006;106:782–817.

    Article  PubMed  CAS  Google Scholar 

  33. Endo T, Ueda H. Large ring cyclodextrins—recent progress. FABAD J Pharm Sci. 2004;29:27–38.

    CAS  Google Scholar 

  34. Taira H, Nagase H, Endo T, Ueda H. Isolation, purification and characterization of large-ring cyclodextrins (CD36 CD39). J Incl Phenom Macrocycl Chem. 2006;56:23–8.

    Article  CAS  Google Scholar 

  35. Szejtli J. The properties and potential uses of cyclodextrin derivatives. J Incl Phenom Mol Recog Chem. 1992;14:25–36.

    Article  CAS  Google Scholar 

  36. Szente L, Szejtli J. Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development. Adv Drug Deliv Rev. 1999;36:17–28.

    Article  PubMed  CAS  Google Scholar 

  37. Challa R, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech. 2005;6:E329–57.

    Article  PubMed  Google Scholar 

  38. Mura P, Furlanetto S, Cirri M, Maestrelli F, Corti G, Pinzauti S. Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the solid state. J Pharm Biom Anal. 2005;37:987–94.

    Article  CAS  Google Scholar 

  39. Buchanan CM, Buchanan NL, Edgar KJ, Little JL, Ramsey MG, Ruble KM, et al. Pharmacokinetics of saquinavir after intravenous and oral dosing of saquinavir: hydroxybutenyl-β-cyclodextrin formulations. Biomacromolecules. 2008;9:305–13.

    Article  PubMed  CAS  Google Scholar 

  40. Roux M, Perly B, Djedaїni-Pilard F. Self-assemblies of amphiphilic cyclodextrins. Eur Biophys J. 2007;36:861–7.

    Article  PubMed  CAS  Google Scholar 

  41. Frӧmming K-H, Szejtli J. Cyclodextrins in pharmacy. Dordrecht: Kluwer Academic; 1994.

    Google Scholar 

  42. Al-Omar A, Abdou S, De Robertis L, Marsura A, Finance C. Complexation study and anticellular activity enhancement by doxorubicin–cyclodextrin complexes on a multidrug-resistant adenocarcinoma cell line. Bioorg Med Chem Lett. 1999;9:1115–20.

    Article  PubMed  CAS  Google Scholar 

  43. García-Rodriguez JJ, Torrado J, Bolás F. Improving bioavailability and anthelmintic activity of albendazole by preparing albendazole–cyclodextrin complexes. Parasite. 2001;8:S188–90.

    PubMed  Google Scholar 

  44. Uekama K. Design and evaluation of cyclodextrin-based drug formulation. Chem Pharm Bull. 2004;52:900–15.

    Article  PubMed  CAS  Google Scholar 

  45. Loftsson T, Vogensen SB, Desbos C, Jansook P. Carvedilol: solubilization and cyclodextrin complexation: a technical note. AAPS PharmSciTech. 2008;9:425–30.

    Article  PubMed  CAS  Google Scholar 

  46. Uekama K, Hirayama F, Arima H. Recent aspect of cyclodextrin-based drug delivery system. J Incl Phenom Macrocycl Chem. 2006;56:3–8.

    Article  CAS  Google Scholar 

  47. Dua K, Ramana MV, Sara UV, Himaja M, Agrawal A, Garg V, et al. Investigation of enhancement of solubility of norfloxacin β-cyclodextrin in presence of acidic solubilizing additives. Curr Drug Deliv. 2007;4:21–5.

    Article  PubMed  CAS  Google Scholar 

  48. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20.

    Article  PubMed  CAS  Google Scholar 

  49. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry: Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). August 2000 BP; http://www.fda.gov/cder/guidance/index.htm. Accessed Jun 2010.

  50. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry SUPAC-MR: Modified release solid oral dosage forms scale-up and postapproval changes: chemistry, manufacturing, and controls; in vitro dissolution testing and in vivo bioequivalence documentation. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), September 1997 CMC 8; http://www.fda.gov/cder/guidance/index.htm. Accessed Jun 2010.

  51. Council of Europe. Dosage forms. In: European Pharmacopoeia, supplement 6.0, Council of Europe, Strasbourg; 2007. p. 717–53

  52. Khan MZI. Dissolution testing for sustained or controlled release oral dosage forms and correlation with in vivo data: challenges and opportunities. Int J Pharm. 1996;140:131–43.

    Article  CAS  Google Scholar 

  53. Lemesle-Lamache V, Wouessidjewe D, Chéron M, Duchéne D. Study of β-cyclodextrin and ethylated β-cyclodextrin salbutamol complexes, in vitro evaluation of sustained-release behaviour of salbutamol. Int J Pharm. 1996;141:117–24.

    Article  CAS  Google Scholar 

  54. Ikeda Y, Kimura K, Hirayama F, Arima H, Uekama K. Controlled release of a water soluble drug, captopril, by a combination of hydrophilic and hydrophobic cyclodextrin derivatives. J Control Release. 2000;66:271–80.

    Article  PubMed  CAS  Google Scholar 

  55. Ikeda Y, Motoune S, Marumoto A, Sonoda Y, Hirayama F, Arima H, et al. Effect of 2-hydroxypropyl-β-cyclodextrin on release rate of metoprolol from ternary metoprolol/2-hydroxypropyl-β-cyclodextrin/ethylcellulose tablets. J Incl Phenom Macrocycl Chem. 2002;44:141–4.

    Article  CAS  Google Scholar 

  56. Jug M, Bécirevi-Laan M. Influence of hydroxypropyl-β-cyclodextrin complexation on piroxicam release from buccoadhesive tablets. Eur J Pharm Sci. 2004;21:251–60.

    Article  PubMed  CAS  Google Scholar 

  57. Pose-Vilarnovo B, Rodríguez-Tenreiro C, Santos JF Rosa dos, Vázquez-Doval J, Concheiro A, Alvarez-Lorenzo C, et al. Modulating drug release with cyclodextrins in hydroxypropyl methylcellulose gels and tablets. J Control Release. 2004;94:351–63.

    Article  PubMed  CAS  Google Scholar 

  58. Miro A, Rondinone A, Nappi A, Ungaro F, Quaglia F, La Rotonda MI. Modulation of release rate and barrier transport of Diclofenac incorporated in hydrophilic matrices: role of cyclodextrins and implications in oral drug delivery. Eur J Pharm Biopharm. 2009;72:76–82.

    Article  PubMed  CAS  Google Scholar 

  59. Ribeiro L, Ferreira DC, Veiga FJB. In vitro controlled release of vinpocetine-cyclodextrin-tartaric acid multicomponent complexes from HPMC swellable tablets. J Control Release. 2005;103:325–39.

    Article  PubMed  CAS  Google Scholar 

  60. Rodriguez-Tenreiro C, Alvarez-Lorenzo C, Rodriguez-Perez A, Concheiro A, Torres-Labandeira JJ. Estradiol sustained release from high affinity cyclodextrin hydrogels. Eur J Pharm Biopharm. 2007;66:55–62.

    Article  PubMed  CAS  Google Scholar 

  61. Nielsen AL, Madsen F, Larsen KL. Cyclodextrin modified hydrogels of PVP/PEG for sustained drug release. Drug Deliv. 2009;16:92–101.

    Article  PubMed  CAS  Google Scholar 

  62. Frézard F, Martins PS, Bahia AP, Le Moyec L, Melo AL, Pimenta AM, et al. Enhanced oral delivery of antimony from meglumine antimoniate/β-cyclodextrin nanoassemblies. Int J Pharm. 2008;347:102–8.

    Article  PubMed  CAS  Google Scholar 

  63. Özdemir N, Ordu S, Özkan Y. Studies of floating dosage forms of furosemide: in vitro and in vivo evaluations of bilayer tablet formulations. Drug Dev Ind Pharm. 2000;26:857–66.

    Article  PubMed  Google Scholar 

  64. Shishu, Gupta N, Aggarwal N. Bioavailability enhancement and targeting of stomach tumors using gastro-retentive floating drug delivery system of curcumin—“a technical note”. AAPS PharmSciTech. 2008;9:810–3.

    Article  PubMed  CAS  Google Scholar 

  65. Garg R, Gupta GD. Preparation and evaluation of gastroretentive floating tablets of silymarin. Chem Pharm Bull. 2009;57:545–9.

    Article  PubMed  CAS  Google Scholar 

  66. Sigurdsson HH, Knudsen E, Loftsson T, Leeves N, Sigurjonsdotir JF, Másson M. Mucoadhesive sustained drug delivery system based on cationic polymer and anionic cyclodextrin/triclosan complex. J Incl Phenom Macrocycl Chem. 2002;44:169–72.

    Article  CAS  Google Scholar 

  67. Venter JP, Kotzé AF, Auzély-Velty R, Rinaudo M. Synthesis and evaluation of the mucoadhesivity of a CD chitosan derivative. Int J Pharm. 2006;313:36–42.

    Article  PubMed  CAS  Google Scholar 

  68. Prabaharan M, Gong S. Novel thiolated carboxymethyl chitosan-g-β-cyclodextrin as mucoadhesive hydrophobic drug delivery carriers. Carbohydr Polym. 2008;73:117–25.

    Article  CAS  Google Scholar 

  69. Jug M, Maestrelli F, Bragagnib M, Mura P. Preparation and solid-state characterization of bupivacaine hydrochloride cyclodextrin complexes aimed for buccal delivery. J Pharm Biom Anal. 2010;52:9–18.

    Article  CAS  Google Scholar 

  70. Mura P, Corti G, Cirri M, Maestrelli F, Mennini N, Bragagni M. Development of mucoadhesive films for buccal administration of flufenamic acid: effect of cyclodextrin complexation. J Pharm Sci. 2010;99:3019–29.

    PubMed  CAS  Google Scholar 

  71. Okimoto K, Rajewski RA, Stella VJ. Release of testosterone from an osmotic pump tablet utilizing (SBE)7m-β-cyclodextrin as both a solubilizing and an osmotic pump agent. J Control Release. 1999;58:29–38.

    Article  PubMed  CAS  Google Scholar 

  72. Okimoto K, Ohike A, Ibuki R, Aoki O, Ohnishi N, Rajewski RA, et al. Factors affecting membrane-controlled drug release for an osmotic pump tablet (OPT) utilizing (SBE)7m -β-CD as both a solubilizer and osmotic agent. J Control Release. 1999;60:311–9.

    Article  PubMed  CAS  Google Scholar 

  73. Zannou EA, Streng WH, Stella VJ. Osmotic properties of sulfobutylether and hydroxypropyl cyclodextrins. Pharm Research. 2001;18:1226–31.

    Article  CAS  Google Scholar 

  74. Okimoto K, Tokunaga Y, Ibuki R, Irie T, Uekama K, Rajewski RA, et al. Applicability of (SBE)7m-β-CD in controlled-porosity osmotic pump tablets (OPTs). Int J Pharm. 2004;286:81–8.

    Article  PubMed  CAS  Google Scholar 

  75. Sotthivirat S, Haslam JL, Stella VJ. Controlled porosity-osmotic pump pellets of a poorly water-soluble drug using sulfobutylether-β-cyclodextrin, (SBE)7m-β-CD, as a solubilizing and osmotic agent. J Pharm Sci. 2007;96:2364–74.

    Article  PubMed  CAS  Google Scholar 

  76. Sotthivirat S, Haslam JL, Lee PI, Rao VM, Stella VJ. Release mechanisms of a sparingly water-soluble drug from controlled porosity-osmotic pump pellets using sulfobutylether-β-cyclodextrin as both a solubilizing and osmotic agent. J Pharm Sci. 2009;98:1992–2000.

    Article  PubMed  CAS  Google Scholar 

  77. Rao VM, Haslam JL, Stella VJ. Controlled and complete release of a model poorly water-soluble drug, prednisolone, from hydroxypropyl methylcellulose matrix tablets using (SBE)7m-β-cyclodextrin as a solubilizing agent. J Pharm Sci. 2001;90:807–16.

    Article  PubMed  CAS  Google Scholar 

  78. Trapani G, Lopedota A, Boghetich G, Latrofa A, Franco M, Sanna E, et al. Encapsulation and release of the hypnotic agent zolpidem from biodegradable polymer microparticles containing hydroxypropyl-β-cyclodextrin. Int J Pharm. 2003;268:47–57.

    Article  PubMed  CAS  Google Scholar 

  79. Smith JS, Macrae RJ, Snowden MJ. Effect of SBE7-β-cyclodextrin complexation on carbamazepine release from sustained release beads. Eur J Pharm Biopharm. 2005;60:73–80.

    Article  PubMed  CAS  Google Scholar 

  80. Cavalli R, Trotta F, Trotta M, Pastero L, Aquilano D. Effect of alkylcarbonates of γ-cyclodextrins with different chain lengths on drug complexation and release characteristics. Int J Pharm. 2007;339:197–204.

    Article  PubMed  CAS  Google Scholar 

  81. Trichard L, Fattal E, Besnard M, Bochot A. α-Cyclodextrin/oil beads as a new carrier for improving the oral bioavailability of lipophilic drugs. J Control Release. 2007;122:47–53.

    Article  PubMed  CAS  Google Scholar 

  82. Yoshinari M, Matsuza K, Hashimoto S, Ishihara K, Inoue T, Oda Y, et al. Controlled release of simvastatin acid using cyclodextrin inclusion system. Dent Mater J. 2007;26:451–6.

    Article  PubMed  CAS  Google Scholar 

  83. Blode H, Schürmann R, Benda N. Novel ethinyl estradiol-beta-cyclodextrin clathrate formulation does not influence the relative bioavailability of ethinyl estradiol or coadministered drospirenone. Contraception. 2008;77:171–6.

    Article  PubMed  CAS  Google Scholar 

  84. Zhou Y, Guo Z, Zhang Y, Huang W, Zhou Y, Yan D. Hyperbranched polyamidoamines containing β-cyclodextrin for controlled release of chlorambucil. Macromol Biosci. 2009;9:1090–7.

    Article  PubMed  CAS  Google Scholar 

  85. Temtem M, Pompeu D, Jaraquemada G, Cabrita EJ, Casimiro T, Aguiar-Ricardo A. Development of PMMA membranes functionalized with hydroxypropyl-β-cyclodextrins for controlled drug delivery using a supercritical CO2-assisted technology. Int J Pharm. 2009;376:110–5.

    Article  PubMed  CAS  Google Scholar 

  86. Yano H, Hirayama F, Kamada M, Arima H, Uekama K. Colon-specific delivery of prednisolone-appended α-cyclodextrin conjugate: alleviation of systemic side effect after oral administration. J Control Release. 2002;79:103–12.

    Article  PubMed  CAS  Google Scholar 

  87. Zou M-J, Cheng G, Okamoto H, Hao X-H, An F, Cui F-D, et al. Colon-specific drug delivery systems based on cyclodextrin prodrugs: in vivo evaluation of five aminosalicylic acid from its cyclodextrin conjugates. World J Gastroenterol. 2005;11:7457–60.

    PubMed  CAS  Google Scholar 

  88. Udo K, Hokonohara K, Motoyama K, Arima H, Hirayama F, Uekama K. 5-Fluorouracil acetic acid/β-cyclodextrin conjugates: drug release behaviour in enzymatic and rat cecal media. Int J Pharm. 2010;388:95–100.

    Article  PubMed  CAS  Google Scholar 

  89. Minami K, Hirayama F, Uekama K. Colon-specific drug delivery based on a cyclodextrin prodrug: release behavior of biphenylylacetic acid from its cyclodextrin conjugates in rat intestinal tracts after oral administration. J Pharm Sci. 1998;87:715–20.

    Article  PubMed  CAS  Google Scholar 

  90. Liu X-M, Lee H-T, Reinhardt RA, Marky LA, Wang D. Novel biomineral-binding cyclodextrins for controlled drug delivery in the oral cavity. J Control Release. 2007;122:54–62.

    Article  PubMed  CAS  Google Scholar 

  91. Zugasti ME, Zornoza A, Goñi MM, Isasi JR, Vélaz I, Martín C, et al. Influence of soluble and insoluble cyclodextrin polymers on drug release from hydroxypropyl methylcellulose tablets. Drug Dev Ind Pharm. 2009;35:1264–70.

    Article  PubMed  CAS  Google Scholar 

  92. Stancanelli R, Crupi V, De Luca L, Ficarra P, Ficarra R, Gitto R, et al. Improvement of water solubility of non-competitive AMPA receptor antagonists by complexation with β-cyclodextrin. Bioorg Med Chem. 2008;16:8706–12.

    Article  PubMed  CAS  Google Scholar 

  93. Trapani A, Garcia-Fuentes M, Alonso MJ. Novel drug nanocarriers combining hydrophilic cyclodextrins and chitosan. Nanotechnology. 2008;19:1–10.

    Article  CAS  Google Scholar 

  94. Cheng J, Khin KT, Jensen GS, Liu A, Davis ME. Synthesis of linear, β-cyclodextrin-based polymers and their camptothecin conjugates. Bioconjug Chem. 2003;14:1007–17.

    Article  PubMed  CAS  Google Scholar 

  95. Cavalli R, Peira E, Caputo O, Gasco MR. Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with β-cyclodextrins. Int J Pharm. 1999;182:59–69.

    Article  PubMed  CAS  Google Scholar 

  96. Duchêne D, Ponchela G, Wouessidjewen D. Cyclodextrins in targeting: application to nanoparticles. Adv Drug Deliv Rev. 1999;36:29–40.

    Article  PubMed  Google Scholar 

  97. Tozuka Y, Wongmekiat A, Sakata K, Moribe K, Oguchi T, Yamamoto K. Co-grinding with cyclodextrin as a nanoparticle preparation method of a poorly water soluble drug. J Incl Phenom Macrocycl Chem. 2004;50:67–71.

    CAS  Google Scholar 

  98. Mourtzis N, Eliadou K, Aggelidou C, Sophianopoulou V, Mavridis IM, Yannakopoulou K. Per(6guanidino-6-deoxy)cyclodextrins: synthesis, characterization and binding behaviour toward selected small molecules and DNA. Org Biomol Chem. 2007;5:125–31.

    Article  PubMed  CAS  Google Scholar 

  99. Du Y-Z, Xu J-G, Wang L, Yuan H, Hu F-Q. Preparation and characteristics of hydroxypropyl-β-cyclodextrin polymeric nanocapsules loading nimodipine. Eur Polym J. 2009;45:1397–402.

    Article  CAS  Google Scholar 

  100. Sajeesh S, Sharma CP. Cyclodextrin–insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery. Int J Pharm. 2006;325:147–54.

    Article  PubMed  CAS  Google Scholar 

  101. Zhang N, Li J, Jiang W, Ren C, Li J, Xin J, et al. Effective protection and controlled release of insulin by cationic β-cyclodextrin polymers from alginate/chitosan nanoparticles. Int J Pharm. 2010;393:212–8.

    Article  PubMed  CAS  Google Scholar 

  102. Agüeros M, Areses P, Campanero MA, Salman H, Quincoces G, Peñuelas I, et al. Bioadhesive properties and biodistribution of cyclodextrin–poly(anhydride) nanoparticles. Eur J Pharm Sci. 2009;37:231–40.

    Article  PubMed  CAS  Google Scholar 

  103. Agüeros M, Zabaleta V, Espuelas S, Campanero MA, Irache JM. Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride) nanoparticles. J Control Release. 2010;145:2–8.

    Article  PubMed  CAS  Google Scholar 

  104. Jansook P, Kurkov SV, Loftsson T. Cyclodextrins as solubilizers: formation of complex aggregates. J Pharm Sci. 2010;99:719–29.

    PubMed  CAS  Google Scholar 

  105. Yamanoi T, Yoshida N, Oda Y, Akaike E, Tsutsumida M, Kobayashi N, et al. Synthesis of mono-glucose branched cyclodextrins with a high inclusion ability for doxorubicin and their efficient glycosylation using Mucor hiemalis endo-β-N-acetylglucosaminidase. Bioorg Med Chem Lett. 2005;15:1009–13.

    Article  PubMed  CAS  Google Scholar 

  106. Burckbuchler V, Wintgens V, Leborgne C, Lecomte S, Leygue N, Scherman D, et al. Development and characterization of new cyclodextrin polymer-based DNA delivery systems. Bioconjug Chem. 2008;19:2311–20.

    Article  PubMed  CAS  Google Scholar 

  107. Lu X, Ping Y, Xu FJ, Li ZH, Wang QQ, Chen JH, et al. Bifunctional conjugates comprising β-cyclodextrin, polyethylenimine, and 5-fluoro-2′-deoxyuridine for drug delivery and gene transfer. Bioconjug Chem. 2010;21:1855–63.

    Article  PubMed  CAS  Google Scholar 

  108. Upadhyay AK, Singh S, Chhipa RR, Vijayakumar MV, Ajay AK, Bhat MK. Methyl-β-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: involvement of Akt, NF-κB and Bcl-2. Toxicol Appl Pharmacol. 2006;216:177–85.

    Article  PubMed  CAS  Google Scholar 

  109. Higashi T, Hirayama F, Misumi S, Arima H, Uekama K. Design and evaluation of polypseudorotaxanes of pegylated insulin with cyclodextrins as sustained release system. Biomaterials. 2008;29:3866–71.

    Article  PubMed  CAS  Google Scholar 

  110. Higashi T, Hirayama F, Yamashita S, Misumi S, Arima H, Uekama K. Slow-release system of pegylated lysozyme utilizing formation of polypseudorotaxanes with cyclodextrins. Int J Pharm. 2009;374:26–32.

    Article  PubMed  CAS  Google Scholar 

  111. Cannavà C, Crupi V, Ficarra P, Guardo M, Majolino D, Mazzaglia A, et al. Physico-chemical characterization of an amphiphilic cyclodextrin/genistein complex. J Pharm Biomed Anal. 2010;51:1064–8.

    Article  PubMed  CAS  Google Scholar 

  112. Sajomsang W, Gonil P, Ruktanonchai UR, Pimpha N, Sramala I, Nuchuchua O, et al. Self-aggregates formation and mucoadhesive property of water-soluble β-cyclodextrin grafted with chitosan. Int J Biol Macromol. 2011;48:589–95.

    Article  PubMed  CAS  Google Scholar 

  113. Chen C-Y, Chen F-A, Wu A-B, Hsu H-C, Kang J-J, Cheng H-W. Effect of hydroxypropyl-β-cyclodextrin on the solubility, photostability and in-vitro permeability of alkannin/shikonin enantiomers. Int J Pharm. 1996;141:171–8.

    Article  CAS  Google Scholar 

  114. Tommasini S, Calabrò ML, Raneri D, Ficarra P, Ficarra R. Combined effect of pH and polysorbates with cyclodextrins on solubilization of naringenin. J Pharm Biom Anal. 2004;36:327–33.

    Article  CAS  Google Scholar 

  115. Terao K, Nakata D, Fukumi H, Schmid G, Arima H, Hirayama F, et al. Enhancement of oral bioavailability of coenzyme Q10 by complexation with γ-cyclodextrin in healthy adults. Nutrition Res. 2006;26:503–8.

    Article  CAS  Google Scholar 

  116. Lu Z, Cheng B, Hub Y, Zhang Y, Guolin Zou G. Complexation of resveratrol with cyclodextrins: solubility and antioxidant activity. Food Chem. 2009;113:17–20.

    Article  CAS  Google Scholar 

  117. Motoyama K, Nagamoto K, Abd Elazim SO, Hirayama F, Uekama K, Arima H. Potential use of 2-hydroxypropyl-β-cyclodextrin for preparation of orally disintegrating tablets containing dl-alpha-tocopheryl acetate, an oily drug. Chem Pharm Bull. 2009;57:1206–12.

    Article  PubMed  CAS  Google Scholar 

  118. Mura P, Bettinetti G, Melani F, Manderioli A. Interaction between naproxen and chemically modified β-cyclodextrins in the liquid and solid state. Eur J Pharm Sci. 1995;3:347–55.

    Article  CAS  Google Scholar 

  119. Mura P, Bettinetti GP, Manderioli A, Faucci MT, Bramanti G, Sorrenti M. Interactions of ketoprofen and ibuprofen with β-cyclodextrins in solution and in the solid state. Int J Pharm. 1998;166:189–203.

    Article  CAS  Google Scholar 

  120. Charoenchaitrakool M, Dehghani F, Foster NR. Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-β-cyclodextrin. Int J Pharm. 2002;239:103–12.

    Article  PubMed  CAS  Google Scholar 

  121. Naidu BN, Chowdary KP, Murthy KV, Satyanarayana V, Hayman AR, Becket G. Physicochemical characterization and dissolution properties of meloxicam–cyclodextrin binary systems. J Pharm Biom Anal. 2004;35:75–86.

    Article  CAS  Google Scholar 

  122. Türk M, Upper G, Steurenthaler M, Hussein Kh, Wahl MA. Complex formation of ibuprofen and β-cyclodextrin by controlled particle deposition (CPD) using SC-CO2. J Supercrit Fluids. 2007;39:435–43.

    Article  CAS  Google Scholar 

  123. Fukuda M, Miller DA, Peppas NA, McGinity JW. Influence of sulfobutyl ether β-cyclodextrin (Captisol®) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion. Int J Pharm. 2008;350:188–96.

    Article  PubMed  CAS  Google Scholar 

  124. Cirri M, Maestrelli F, Mennini N, Mura P. Physical–chemical characterization of binary and ternary systems of ketoprofen with cyclodextrins and phospholipids. J Pharm Biom Anal. 2009;50:683–9.

    Article  CAS  Google Scholar 

  125. Sauceau M, Rodier E, Fages J. Preparation of inclusion complex of piroxicam with cyclodextrin by using supercritical carbon dioxide. J Supercrit Fluids. 2008;47:326–32.

    Article  CAS  Google Scholar 

  126. Salústio PJ, Feio G, Figueirinhas JL, Pinto JF, Cabral Marques HM. The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity. Eur J Pharm Biopharm. 2009;71:377–86.

    Article  PubMed  CAS  Google Scholar 

  127. Lu Y, Zhang X, Lai J, Yin Z, Wu W. Physical characterization of meloxicam-β-cyclodextrin inclusion complex pellets prepared by a fluid-bed coating method. Particuology. 2009;7:1–8.

    Article  CAS  Google Scholar 

  128. Esclusa-Díaz MT, Gayo-Otero M, Pérez-Marcos MB, Vila-Jato JL, Torres-Labandeira JJ. Preparation and evaluation of ketoconazole–β-cyclodextrin multicomponent complexes. Int J Pharm. 1996;142:183–7.

    Article  Google Scholar 

  129. Mura P, Faucci MT, Manderioli A, Bramanti G. Influence of the preparation method on the physicochemical properties of binary systems of econazole with cyclodextrins. Int J Pharm. 1999;193:85–95.

    Article  PubMed  CAS  Google Scholar 

  130. Lee S-Y, Jung I-I, Kim J-K, Lim G-B, Ryu J-H. Preparation of itraconazole/HP-β-CD inclusion complexes using supercritical aerosol solvent extraction system and their dissolution characteristics. J Supercrit Fluids. 2008;44:400–8.

    Article  CAS  Google Scholar 

  131. Moyano JR, Ginés JM, Arias MJ, Rabasco AM. Study of the dissolution characteristics of oxazepam via complexation with β-cyclodextrin. Int J Pharm. 1995;114:95–102.

    Article  CAS  Google Scholar 

  132. Archontaki HA, Vertzoni MV, Athanassiou-Malaki MH. Study on the inclusion complexes of bromazepam with β- and β-hydroxypropyl-cyclodextrins. J Pharm Biom Anal. 2002;28:761–9.

    Article  CAS  Google Scholar 

  133. Jain AC, Adeyeye MC. Hygroscopicity, phase solubility and dissolution of various substituted sulfobutylether β-cyclodextrins (SBE) and danazol–SBE inclusion complexes. Int J Pharm. 2001;212:177–86.

    Article  PubMed  CAS  Google Scholar 

  134. Savolainen J, Järvinen K, Matilainen L, Järvinen T. Improved dissolution and bioavailability of phenytoin by sulfobutylether-β-cyclodextrin ((SBE)7m-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) complexation. Int J Pharm. 1998;165:69–78.

    Article  CAS  Google Scholar 

  135. Latrofa A, Trapani G, Franco M, Serra M, Muggironi M, Fanizzi FP, et al. Complexation of phenytoin with some hydrophilic cyclodextrins: effect on aqueous solubility, dissolution rate, and anticonvulsant activity in mice. Eur J Pharm Biopharm. 2001;52:65–73.

    Article  PubMed  CAS  Google Scholar 

  136. Echezarreta-López M, Torres-Labandeira JJ, Castiñeiras-Seijo L, Santana-Penín L, Vila-Jato JL. Complexation of the interferon inducer, bropirimine, with hydroxypropyl-β-cyclodextrin. Eur J Pharm Sci. 2000;9:381–6.

    Article  PubMed  Google Scholar 

  137. Ficarra R, Ficarra P, Di Bella MR, Raneri D, Tommasini S, Calabrò ML, et al. Study of the inclusion complex of atenolol with β-cyclodextrins. J Pharm Biom Anal. 2000;23:231–6.

    Article  CAS  Google Scholar 

  138. Patel N, Chotai N, Patel J, Soni T, Desai J, Patel R. Comparison of dissolution profiles of oxcarbazepine-HP-β-CD tablet formulations with marketed oxcarbazepine tablets. Dissolution Tech. 2008;15:28–34.

    CAS  Google Scholar 

  139. Hamada H, Ishihara K, Masuoka N, Mikuni K, Nakajima N. Enhancement of water-solubility and bioactivity of paclitaxel using modified cyclodextrins. J Biosci Bioeng. 2006;102:369–71.

    Article  PubMed  CAS  Google Scholar 

  140. Wong JW, Yuen KH. Improved oral bioavailability of artemisinin through inclusion complexation with β- and γ-cyclodextrins. Int J Pharm. 2001;227:177–85.

    Article  PubMed  CAS  Google Scholar 

  141. Usuda M, Endo T, Nagase H, Tomono K, Ueda H. Interaction of antimalarial agent artemisinin with cyclodextrins. Drug Dev Ind Pharm. 2000;26:613–9.

    Article  PubMed  CAS  Google Scholar 

  142. Wen X, Tan F, Jing Z, Liu Z. Preparation and study the 1:2 inclusion complex of carvedilol with β-cyclodextrin. J Pharm Biom Anal. 2004;34:517–23.

    Article  CAS  Google Scholar 

  143. Zingone G, Rubessa F. Preformulation study of the inclusion complex warfarin–β-cyclodextrin. Int J Pharm. 2005;291:3–10.

    Article  PubMed  CAS  Google Scholar 

  144. Terekhova IV, Volkova TV, Perlovich GL. Interactions of theophylline with cyclodextrins in water. Mendeleev Commun. 2007;17:244–6.

    Article  CAS  Google Scholar 

  145. Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion complexes of tadalafil with natural and chemically modified beta-cyclodextrins. I: Preparation and in-vitro evaluation. Eur J Pharm Biopharm. 2008;70:819–27.

    Article  PubMed  CAS  Google Scholar 

  146. Liu Y, Chen G-S, Chen Y, Lin J. Inclusion complexes of azadirachtin with native and methylated cyclodextrins: solubilization and binding ability. Bioorg Med Chem. 2005;13:4037–42.

    Article  PubMed  CAS  Google Scholar 

  147. Petralito S, Zanardi I, Memoli A, Annesini MC, Travagli V. Solubility, spectroscopic properties and photostability of Rhein/cyclodextrin inclusion complex. Spectrochim Acta Part A. 2009;74:1254–9.

    Article  CAS  Google Scholar 

  148. Chowdary KP, Srinivas SV. Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl-β-cyclodextrin. AAPS PharmSciTech. 2006;7:E184–9.

    Article  Google Scholar 

  149. He Y, Tabibi E, Yalkowsky SH. Solubilization of two structurally related anticancer drugs: XK-469 and PPA. J Pharm Sci. 2006;95:97–107.

    Article  PubMed  CAS  Google Scholar 

  150. Gladys G, Claudia G, Marcela L. The effect of pH and triethanolamine on sulfisoxazole complexation with hydroxypropyl-β-cyclodextrin. Eur J Pharm Sci. 2003;20:285–93.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

    Paulo José Salústio, Patrícia Pontes, Claúdia Conduto, Inês Sanches, Catarina Carvalho, João Arrais & Helena M. Cabral Marques

Authors
  1. Paulo José Salústio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrícia Pontes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claúdia Conduto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inês Sanches
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Catarina Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. João Arrais
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Helena M. Cabral Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helena M. Cabral Marques.

Additional information

Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salústio, P.J., Pontes, P., Conduto, C. et al. Advanced Technologies for Oral Controlled Release: Cyclodextrins for Oral Controlled Release. AAPS PharmSciTech 12, 1276–1292 (2011). https://doi.org/10.1208/s12249-011-9690-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-011-9690-2

Key words

Search

Navigation