CARVEDILOL SOLUBILITY ENHANCEMENT BY INCLUSION COMPLEXATION AND SOLID DISPERSION: REVIEW
Carvedilol is an antihypertensive drug characterized by itslow aqueous solubility, a major obstacle in drug formulation development to improve its bioavailability. To overcome problem of poor aqueous solubility of Carvedilol, various approaches have been investigated including physical and chemical modifications of the drug. Most of these investigations focused onmodifying the drug structurefrom crystalline insoluble form to amorphous soluble form, reducing drug particle size to provide high surface area subjected to solvent, enhancing porosity degree, and improving wettability. A wide variety of polymers was used in order to achieve these goals. Carvedilol inclusion complex with Cyclodextrin (CD) and derivatives, solid dispersion with water-soluble carriers such as Polyvinylpyrrolidone K-30 (PVP K-30), Gelucire 50/13, porous silica (Sylysia 350), and SoluprusÂ® (polyvinyl caprolactamâ€“polyvinyl acetateâ€“polyethylene glycol graft copolymer) were previously investigated using different preparation methods such asSolvent evaporation method, fusion method, kneading method, and spray drying method. Analytical tests wereconducted to characterize these preparations. FTIR, SEM, DSC, XRD are among the most commonly used. The present paper summarizes different drug-carrier combinations used for solubility, dissolution rate and/or bioavailability enhancement of Carvedilol, with emphases on the preparation methods of Carvedilol inclusion complex and solid dispersions, and different tests used for their characterization.KEYWORDS: Carvedilol, solubility enhancement, inclusion complex, solid dispersion, bioavailability.
2. Goodman, L.S., Goodman and Gilman's the pharmacological basis of therapeutics. Vol. 1549. 1996: McGraw-Hill New York.
3. Amidon, G.L., et al., A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical research, 1995. 12(3): p. 413-420.
4. Vieth, M., et al., Characteristic physical properties and structural fragments of marketed oral drugs. Journal of medicinal chemistry, 2004. 47(1): p. 224-232.
5. Davis, M.E. and M.E. Brewster, Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov, 2004. 3(12): p. 1023-35.
6. Shityakov, S., J. Broscheit, and C. Forster, alpha-Cyclodextrin dimer complexes of dopamine and levodopa derivatives to assess drug delivery to the central nervous system: ADME and molecular docking studies. Int J Nanomedicine, 2012. 7: p. 3211-9.
7. Shityakov, S., et al., Ionization states, cellular toxicity and molecular modeling studies of midazolam complexed with trimethyl-beta-cyclodextrin. Molecules, 2014. 19(10): p. 16861-76.
8. Vandelli, M., et al., 2-Hydroxypropyl-Î²-cyclodextrin complexation with ursodeoxycholic acid. International journal of pharmaceutics, 1995. 118(1): p. 77-83.
9. Archontaki, H., M. Vertzoni, and M. Athanassiou-Malaki, Study on the inclusion complexes of bromazepam with Î²-and Î²-hydroxypropyl-cyclodextrins. Journal of pharmaceutical and biomedical analysis, 2002. 28(3): p. 761-769.
10. Dandawate, P.R., et al., Inclusion complex of novel curcumin analogue CDF and Î²-cyclodextrin (1: 2) and its enhanced in vivo anticancer activity against pancreatic cancer. Pharmaceutical research, 2012. 29(7): p. 1775-1786.
11. Wang, J., et al., Characterisation of inclusion complex of trans-ferulic acid and hydroxypropyl-Î²-cyclodextrin. Food Chemistry, 2011. 124(3): p. 1069-1075.
12. Nguyen, T.A., et al., An investigation into the supramolecular structure, solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex. Food chemistry, 2013. 136(1): p. 186-192.
13. Xu, C., et al., Investigation of inclusion complex of honokiol with sulfobutyl ether-Î²-cyclodextrin. Carbohydrate polymers, 2014. 113: p. 9-15.
14. Sekiguchi, O., Studies on Absorption of Eutectic Mixture. I. A Comparison of the Behavior of Eutectic Mixture of Sulfathiazole and that of Ordinary Sulfathiazole in Man. Chemical & pharmaceutical bulletin, 1961. 9(11): p. 866-872.
15. Leuner, C. and J. Dressman, Improving drug solubility for oral delivery using solid dispersions. European Journal of Pharmaceutics and Biopharmaceutics, 2000. 50(1): p. 47-60.
16. Serajuddin, A., Solid dispersion of poorly waterâ€soluble drugs: early promises, subsequent problems, and recent breakthroughs. Journal of pharmaceutical sciences, 1999. 88(10): p. 1058-1066.
17. Pouton, C.W., Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and â€˜self-microemulsifyingâ€™drug delivery systems. European Journal of Pharmaceutical Sciences, 2000. 11: p. S93-S98.
18. Humberstone, A.J. and W.N. Charman, Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Advanced drug delivery reviews, 1997. 25(1): p. 103-128.
19. Leuner, C. and J. Dressman, Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm, 2000. 50(1): p. 47-60.
20. Yu, L., Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv Drug Deliv Rev, 2001. 48(1): p. 27-42.
21. Hancock, B.C. and G. Zografi, Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci, 1997. 86(1): p. 1-12.
22. Saffoon, N., et al., Enhancement of oral bioavailability and solid dispersion: A review. 2011.
23. Goldberg, A.H., et al., Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures. IV. Chloramphenicol--urea system. J Pharm Sci, 1966. 55(6): p. 581-3.
24. Dubois, J.L. and J.L. Ford, Similarities in the release rates of different drugs from polyethylene glycol 6000 solid dispersions. J Pharm Pharmacol, 1985. 37(7): p. 494-5.
25. Jung, J.-Y., et al., Enhanced solubility and dissolution rate of itraconazole by a solid dispersion technique. International Journal of Pharmaceutics, 1999. 187(2): p. 209-218.
26. Loftsson, T., et al., Carvedilol: solubilization and cyclodextrin complexation: a technical note. AAPs PharmSciTech, 2008. 9(2): p. 425-430.
27. Loftsson, T. and M.E. Brewster, Cyclodextrins as functional excipients: methods to enhance complexation efficiency. Journal of pharmaceutical sciences, 2012. 101(9): p. 3019-3032.
28. Wen, X., et al., Preparation and study the 1: 2 inclusion complex of carvedilol with Î²-cyclodextrin. Journal of pharmaceutical and biomedical analysis, 2004. 34(3): p. 517-523.
29. Wilkinson, A.D.M.a.A., IUPAC. Compendium of Chemical Terminology, 2nd Ed. (the "Gold Book")1997, Blackwell Scientific Publications, Oxford.
30. Qian, F., J. Huang, and M.A. Hussain, Drug-polymer solubility and miscibility: Stability consideration and practical challenges in amorphous solid dispersion development. J Pharm Sci, 2010. 99(7): p. 2941-7.
31. T. Higuchi, K.A.C., phase solubility techniques. advances in analytical chemistry and instrumentation, 1965. 4: p. 117.
32. Yuvaraja, K. and J. Khanam, Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid. J Pharm Biomed Anal, 2014. 96: p. 10-20.
33. Chakraborty, S., et al., Assessment of solubilization characteristics of different surfactants for carvedilol phosphate as a function of pH. J Colloid Interface Sci, 2009. 335(2): p. 242-9.
34. Shewale, B.D., et al., Effect of hydroxylpropyl-beta-cyclodextrin on Solubility of Carvedilol. Indian J Pharm Sci, 2008. 70(2): p. 255-7.
35. Loftsson, T., et al., Carvedilol: solubilization and cyclodextrin complexation: a technical note. AAPS PharmSciTech, 2008. 9(2): p. 425-30.
36. Pokharkar, V., et al., Ternary complexation of carvedilol, beta-cyclodextrin and citric acid for mouth-dissolving tablet formulation. Acta Pharm, 2009. 59(2): p. 121-32.
37. Sharma, A. and C.P. Jain, Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci, 2010. 5(1): p. 49-56.
38. Jung Bo Shim, M.J.K., Seul Ji Kim, Su Ji Kang, Ji Hye Lee, Hyeong Seok Kim, Dongwon Lee, Gilson Khang, Dissolution properties of control released solid dispersion of carvedilol with HPMC and Eudragit RS. Journal of Pharmaceutical Investigation, 2012. 42:285 - 291.
39. Potluri, R.H., et al., Solubility enhancement and physicochemical characterization of carvedilol solid dispersion with Gelucire 50/13. Arch Pharm Res, 2011. 34(1): p. 51-7.
40. Planinsek, O., B. Kovacic, and F. Vrecer, Carvedilol dissolution improvement by preparation of solid dispersions with porous silica. Int J Pharm, 2011. 406(1-2): p. 41-8.
41. Shamma, R.N. and M. Basha, SoluplusÂ®: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation. Powder Technology, 2013. 237(0): p. 406-414.
42. Sharma, A. and C. Jain, Carvedilol-Î²-cyclodextrin Systems: Preparation, Characterization and in vitro Evaluation. Dhaka University Journal of Pharmaceutical Sciences, 2013. 12(1): p. 51-58.
43. PAMUDJI, J.S., R. MAULUDIN, and V.A. LESTARI, IMPROVEMENT OF CARVEDILOL DISSOLUTION RATE THROUGH FORMATION OF INCLUSION COMPLEX WITH Î’-CYCLODEXTRIN. 2014.
44. Tachibana, T. and A. Nakamura, A methode for preparing an aqueous colloidal dispersion of organic materials by using water-soluble polymers: Dispersion ofÎ’-carotene by polyvinylpyrrolidone. Kolloid-Zeitschrift und Zeitschrift fÃ¼r Polymere, 1965. 203(2): p. 130-133.
45. Hirlekar, R. and V. Kadam, Preparation and characterization of inclusion complexes of carvedilol with methyl-Î²-cyclodextrin. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2009. 63(3-4): p. 219-224.
46. Cao, F., J. Guo, and Q. Ping, The physicochemical characteristics of freeze-dried scutellarin-cyclodextrin tetracomponent complexes. Drug development and industrial pharmacy, 2005. 31(8): p. 747-756.
47. Oguchi, T., et al., Freeze-drying of drug-additive binary systems. I. Effects of freezing condition on the crystallinity. CHEMICAL & PHARMACEUTICAL BULLETIN, 1989. 37(7): p. 1881-1885.
48. ; Available from: http://www.wisegeek.com/what-is-coprecipitation.htm.
49. Semcheddine, F., et al., Effects of the Preparation Method on the Formation of True Nimodipine SBE-beta-CD/HP-beta-CD Inclusion Complexes and Their Dissolution Rates Enhancement. AAPS PharmSciTech, 2014.
50. Savjani, K.T., A.K. Gajjar, and J.K. Savjani, Drug solubility: importance and enhancement techniques. ISRN pharmaceutics, 2012. 2012.
51. Bhyan, S.J., et al., Formulation and evaluation of mouth dissolving tablets containing carvedilol solid dispersion.
52. Kovacic, B., F. Vrecer, and O. Planinsek, Solid dispersions of carvedilol with porous silica. Chem Pharm Bull (Tokyo), 2011. 59(4): p. 427-33.
53. Shamma, R.N. and M. Basha, SoluplusÂ®: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation. Powder Technology, 2013. 237: p. 406-414.
54. Wairkar, S. and R. Gaud, Solid dispersions: Solubility enhancement technique for poorly soluble drugs. International Journal of Research in Pharmaceutical and Biomedical Sciences, 2013. 4(3): p. 847.
55. Monkhouse, D.C. and J.L. Lach, Use of adsorbents in enhancement of drug dissolution. II. J Pharm Sci, 1972. 61(9): p. 1435-41.
56. Nagy, Z.K., et al., Comparison of electrospun and extruded soluplusÂ®â€based solid dosage forms of improved dissolution. Journal of pharmaceutical sciences, 2012. 101(1): p. 322-332.
57. Kim, E.-J., et al., Preparation of a solid dispersion of felodipine using a solvent wetting method. European journal of pharmaceutics and biopharmaceutics, 2006. 64(2): p. 200-205.
58. Craig, D.Q., The mechanisms of drug release from solid dispersions in water-soluble polymers. International journal of pharmaceutics, 2002. 231(2): p. 131-144.
59. Habib, M.J., Pharmaceutical solid dispersion technology2000: CRC Press.
60. Sharma, A., C.P. Jain, and Y.S. Tanwar, Preparation and characterization of solid dispersions of carvedilol with poloxamer 188. Journal of the Chilean Chemical Society, 2013. 58(1): p. 1553-1557.
61. Shim, J.B., et al., Dissolution properties of control released solid dispersion of carvedilol with HPMC and Eudragit RS. Journal of Pharmaceutical Investigation, 2012. 42(5): p. 285-291.
62. Kim BS, Y.J., Kim JY, Kim MS, Khang G, Lee HB, Application of HPMC (Hydroxypropyl Methycellulose) as drug delivery carrier system. Polym Sci Technol, 2007. 18(6): p. 549-533.
63. Griffiths, P.R. and J.A. De Haseth, Fourier transform infrared spectrometry. Vol. 171. 2007: John Wiley &Sons.
64. Lipson, H., Elements of X-ray diffraction. Contemporary Physics, 1979. 20(1): p. 87-88.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).