International Journal of Drug Delivery Technology
Volume 14, Issue 1

Solubility and Dissolution Enhancement of Candesartan Cilexetil by Complexation with Cyclodextrin

Ghaith M Aziz1*, Eman B H Al-Khedairy2

1Wassit Health Directorate, Ministry of Health, Baghdad, Iraq.

2Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq. 

Received: 08th November, 2023; Revised: 12th December, 2023; Accepted: 22th December, 2023; Available Online: 25th March, 2024

ABSTRACT

At present, numerous novel chemical compounds face challenges related to their limited solubility in aqueous environments. These compounds are classified under the Biopharmaceutical Classification System (BCS) as either class II or class IV substances. Different carriers were used to increase their solubility. Candesartan cilexetil (CC) is one of the most widely used antihypertensive drugs, which belongs to class II drugs.

The aim of this research was to enhance the solubility and dissolution rate of CC through a complexation approach involving β-cyclodextrin and its derivatives, specifically hydroxypropyl beta cyclodextrin (HP-β-CD), methyl beta cyclodextrin (M-β-CD), and sulfonyl ether beta-cyclodextrin (SBE-β-CD), serving as complexing agents. This complexation process was investigated both with and without the inclusion of poloxamer 407 (PX407) as a hydrophilic polymer. The complex was prepared through a combination of grinding, kneading, and co-evaporation techniques. The resulting complex underwent characterization, including assessments of its percentage yield, drug content, solubility, and dissolution properties, as well as analyses using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and fourier transforms infrared spectroscopy (FTIR). The results revealed that, the complex prepared using 1:1 molar ratio of M -β-CD:CC in the presence of 5% w/w PX407 by co-evaporation method had the highest percentage yield (97%) with drug content of 98.5%, the highest solubility (0.052 mg/mL) and fastest release of drug within 45 minutes compared to the other methods. The FTIR, DSC, and XRD confirmed the development of a partial inclusion complex of an amorphous nature.

Keywords: Solubility, Dissolution, Candesartan cilexetil, Complexation,

International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.1.37

How to cite this article: Aziz GM, Al-Khedairy EBH. Solubility and Dissolution Enhancement of Candesartan Cilexetil by Complexation with Cyclodextrin. International Journal of Drug Delivery Technology. 2024;14(1):257-264.

REFERENCES

  1. Moffat AC, Osselton B. Widdop (eds), Clarke’s Analysis of Drugs and Poisons. Pharmaceutical Press, London; 2011.
  2. Mekhilef SF, Hussein AA. Novel Combination for Self- Nanoemulsifying Drug Delivery System of Candesartan Iraqi J Pharm Sci (P-ISSN 1683-3597, E-ISSN 2521- 3512). 2018;123–34.
  3. Detroja C, Chavhan S, Sawant K. Enhanced antihypertensive activity of candesartan cilexetil nanosuspension: formulation, characterization and pharmacodynamic study. Sci Pharm. 2011;79(3):635–52.
  4. Saokham P, Muankaew C, Jansook P, Loftsson Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules. 2018;23(5):1161.
  5. Jansook P, Kulsirachote P, Asasutjarit R, Loftsson Development of celecoxib eye drop solution and microsuspension: A comparative investigation of binary and ternary cyclodextrin complexes. Carbohydr Polym. 2019;225:115209.
  6. Beale JM, Block J, Hill Organic medicinal and pharmaceuticalchemistry. 2010;
  7. de Freitas MR, Rolim LA, Soares MF de LR, Rolim-Neto PJ, de Albuquerque MM, Soares-Sobrinho JL. Inclusion complex of methyl-β-cyclodextrin and olanzapine as potential drug delivery system for schizophrenia. Carbohydr Polym. 2012;89(4):1095
  8. Higuchi T, Connors KA. Advances in analytical chemistry and instrumentation. Phase Solubility Stud. 1965;117–212.
  9. Jagtap S, Magdum C. Influence of Water-soluble polymers on Epalrestat ternary complexation by kneading. Res J Pharm Technol. 2019;12(8):3602–8.
  10. Sravya M, Deveswaran R, Bharath S, Basavaraj BV, Madhavan
  11. Development of orodispersible tablets of candesartan cilexetil- β-cyclodextrin complex. J Pharm. 2013;2013.
  12. Inoue Y, Watanabe S, Suzuki R, Murata I, Kanamoto I. Evaluation of actarit/γ-cyclodextrin complex prepared by different J Incl Phenom Macrocycl Chem. 2015;81(1):161–8.
  13. Mohammed IA, Ghareeb MM. Investigation of Solubility Enhancement Approaches of Iraqi J Pharm Sci (P-ISSN 1683-3597, E-ISSN 2521-3512). 2018;27(1):8–19.
  14. Sunkara SP, Suryadevara V, Bathula SL, Doppalapudi S, Padarthi PK, Kunam V. Formulation and Evaluation of Candesartan Cilexetil Fast Dissolving Tablets using Inclusion Complexes. Res J Pharm Technol. 2020;13(2):751–7.
  15. Jouyban A. Handbook of solubility data for pharmaceuticals. Crc Press; 2009.
  16. Shekh I, Gupta V, Jain A, Gupta Preparation and characterisation of beta cyclodextrin Aspirin Inclusion complex. Int J Pharm life Sci. 2011;
  17. Salih OS, Hamoddi ZM, Taher Development and Characterization of Controlled Release Tablets of Candesartan Cilexetil/β-Cyclodextrin Inclusion Complex.
  18. United States Pharmacopeial U.S. Pharmacopeial guidelines Dissolution. <711> Dissolution. 2011;1:1–8.
  19. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123–33.
  20. Hadian Z, Maleki M, Abdi K, Atyabi F, Mohammadi A, Khaksar Preparation and characterization of nanoparticle β-cyclodextrin: Geraniol inclusion complexes. Iran J Pharm Res IJPR. 2018;17(1):39.
  21. Sulaiman HT, Kassab HJ. Preparation and characterization of econazole nitrate inclusion complex for ocular delivery system. Int J App Pharm. 2018;10(3):175–81.
  22. Mura P, Maestrelli F, Cirri M, Nerli G, Di Cesare Mannelli L, Ghelardini C, et al. Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex. Pharmaceutics. 2021;13(6):872.
  23. Charoenchaitrakool M, Dehghani F, Foster NR. Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-β-cyclodextrin. Int J 2002;239(1–2):103–12.
  24. Kamboj VK, Verma Poloxamers based nanocarriers for drug delivery system. Der Pharm Lett. 2015;7(2):264–9.
  25. Kovvasu SP, Chowdary KPR. Formulation development and in vivo evaluation of pioglitazone inclusion complexes: A factorial study. Int J Appl Pharm. 2018;10(3):49–55.
  26. Elkordy AA, Ashoore A, Essa COMPLEXATION OF NAPROXEN WITH BETA-CYCLODEXTRIN WITH AND WITHOUT POLOXAMER 407 TO ENHANCE DRUG DISSOLUTION. J Appl Pharm. 2012;4(3).
  27. Kalia A, Poddar M. Solid dispersions: an approach towards enhancing dissolution Int J Pharm Pharm Sci. 2011;3(4):9–19.
  28. Fayed ND, Osman MA, Maghraby EL. Enhancement of dissolution rate and intestinal stability of candesartan cilexitil. J Appl Pharm Sci. 2016;6(05):102–11.
  29. Lu N, Xu H, Liu Y. Characterization and antimicrobial activity of a 2-O-methyl-β-cyclodextrin inclusion complex containing hexahydro-β-acids. J Mater Sci. 2019;54(5):4287–96.
  30. Alwan RM, Rajab NA. Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Iraqi J Pharm Sci (P-ISSN 1683-3597, E-ISSN 2521-3512). 2021;30(1):144–53.
  31. Raghad A-N, Hind E-Z. Enhancement of candesartan cilexetil dissolution rate by using different methods. Asian J Pharm Clin Res. 2015;8(1):320–6.
  32. Sweetman Martindale: the complete drug reference. 2005.
  33. Zoppi A, Delrivo A, Aiassa V, Longhi MR. Binding of sulfamethazine to β-cyclodextrin and methyl-β-cyclodextrin. AAPS PharmSciTech. 2013;14(2):727–35.
  34. Krishna HPS, Srinivasan B, Rajamanickam D, Veerabhadraiah BB, Varadharajan Solubility and dissolution enhancement of candesartan cilexetil by liquisolid compacts. Pharm Drug Deliv Res. 2015;2013.