Skip to main content

Advertisement

Log in

Preparation and characterization of cyclodextrin complexes of doxycycline hyclate for improved photostability in aqueous solution

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Doxycycline hyclate is Biopharmaceutical Classification System, class I drug (high solubility and high permeability), but it is associated with poor photostability. It is in the class of tetracycline antibiotic, which is used to treat various infections, but its bioavailability is compromised due to its sensitivity to light and aqueous instability. In this paper, the influence of inclusion complexation with different cyclodextrins, i.e., αCD, γCD, HPβCD and RMβCD, on the photostability of doxycycline hyclate in aqueous media was investigated. Host–guest inclusion complexes were prepared by freeze- drying method. The prepared complexes were characterized for drug content, SEM, XRPD, in vitro permeation studies and photostability studies. XRPD showed diffused peaks for most of the complexes, while SEM showed irregularly shaped particles. The formulation D20 (Drug: γCD in 1:20 molar ratio) showed the highest % drug content (83.72 ± 1.2%), and the formulations D1 (Drug: αCD in 1: 2 molar ratio) showed the lowest % drug content among all the CD complexes. It was found that the photodegradation of the drug was reduced significantly upon complexation. For Drug: CD complexes, the photostability of the aqueous solution of drug/CD complexes was found to be in the order of γCD > RMβCD > HPβCD > αCD with maximum photostability shown by Drug: γCD (1:20 molar ratio) complex. The obtained results suggested that cyclodextrin complexation can be used as an alternative approach for increasing the photostability of doxycycline hyclate.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Semsarzadeh, M.A., Amiri, S.: Preparation and properties of polyrotaxane from α-cyclodextrin and poly(ethylene glycol) with poly(vinyl alcohol). Bull. Mater. Sci. 36, 989–996 (2013)

    Article  CAS  Google Scholar 

  2. Moore, D.E., Fallon, M.P., Burt, C.D.: Photo-oxidation of tetracycline—a differential pulse polarographic study. Int. J. Pharm. 14, 133–142 (1983)

    Article  CAS  Google Scholar 

  3. Randhawa, A., Ngu, I., Bilsland, D.: Doxycycline photosensitivity. QJM: An International Journal of Medicine 111, 259–260 (2018).

  4. Bani-Yaseen, A.D., Al-Rawashdeh, N.F., Al-Momani, I.: Influence of inclusion complexation with β-cyclodextrin on the photostability of selected imidazoline-derived drugs. J. Incl. Phenom. Macrocycl. Chem. 63, 109–115 (2009)

    Article  CAS  Google Scholar 

  5. Challa, R., Ahuja, A., Ali, J., Khar, R.K.: Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 6, E329–E357 (2005)

    Article  Google Scholar 

  6. Kogawa, A.C., Zoppi, A., Quevedo, M.A., Nunes Salgado, H.R., Longhi, M.R.: Increasing doxycycline hyclate photostability by complexation with β-cyclodextrin. AAPS PharmSciTech 15, 1209–1217 (2014)

    Article  CAS  Google Scholar 

  7. Kfoury, M., Lounès-Hadj Sahraoui, A., Bourdon, N., Laruelle, F., Fontaine, J., Auezova, L., et al.: Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins. Food Chem. 196, 518–525 (2016)

    Article  CAS  Google Scholar 

  8. Ilic-Stojanovic, S., Nikolic, V., Nikolic, L., Zdravkovic, A., Kapor, A., Popsavin, M., et al.: The improved photostability of naproxen in the inclusion complex with 2-hydroxypropyl-β-cyclodextrin. Hemijska industrija 69, 361–370 (2015)

    Article  Google Scholar 

  9. Bayomi, M.A., Abanumay, K.A., Al-Angary, A.A.: Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state. Int. J. Pharm. 243, 107–117 (2002)

    Article  CAS  Google Scholar 

  10. Rivas-Granizo, P.E., Giorgetti, L., Ferraz, H.G.: Photostability of loratadine inclusion complexes with natural cyclodextrins. Int. J. Photoenergy 2015, e583052 (2015).

  11. Mielcarek, J., Daczkowska, E.: Photodegradation of inclusion complexes of isradipine with methyl-β-cyclodextrin. J. Pharm. Biomed. Anal. 21, 393–398 (1999)

    Article  CAS  Google Scholar 

  12. Kogawa, A.C., Salgado, H.R.N.: Doxycycline hyclate: a review of properties, applications and analytical methods. Int. J. Life Sci. Pharma Res. 2, 15 (2012)

    Google Scholar 

  13. Khodaverdi, E., Eisvand, F., Nezami, M.S., Shiadeh, S.N.R., Kamali, H., Hadizadeh, F.: Injectable in-situ forming depot of doxycycline hyclate/α-cyclodextrin complex using PLGA for periodontitis treatment: preparation, charac-terization, and in-vitro evaluation. Curr. Drug Del. (2020).https://doi.org/10.2174/1567201817999201103195104

  14. Zhang, H., Chen, M., He, Z., Wang, Z., Zhang, M., He, Z., et al.: Molecular modeling-based inclusion mechanism and stability studies of doxycycline and hydroxypropyl-β-cyclodextrin complex for ophthalmic delivery. AAPS PharmSciTech 14, 10–18 (2013)

    Article  Google Scholar 

  15. Suárez, D.F., Consuegra, J., Trajano, V.C., Gontijo, S.M.L., Guimarães, P.P.G., Cortés, M.E., et al.: Structural and thermodynamic characterization of doxycycline/β-cyclodextrin supramolecular complex and its bacterial membrane interactions. Colloids Surf. B 118, 194–201 (2014)

    Article  Google Scholar 

  16. George, S., Vasudevan, D.: Studies on the preparation, characterization, and solubility of 2-hp-β-cyclodextrin-meclizine HCl inclusion complexes. J. Young Pharm. 4, 220–227 (2012)

    Article  CAS  Google Scholar 

  17. Fernandes, C., Encarnação, I., Gaspar, A., Garrido, J., Borges, F., Garrido, E.M.: Influence of hydroxypropyl- -cyclodextrin on the photostability of fungicide pyrimethanil. Int. J Photoenergy bs, e489873 (2014).

  18. Cheirsilp, B., Rakmai, J.: Inclusion complex formation of cyclodextrin with its guest and their applications. Biology Eng. Med. 2 (2017).

  19. Photostability of Drugs and Drug Formulations. CRC Press, Boca Raton (2019)

  20. Semsarzadeh, M.A., Amiri, S.: Preparation and characterization of inclusion complexes of poly(dimethylsiloxane)s with γ-cyclodextrin without utilizing sonic energy. SILICON 4, 151–156 (2012)

    Article  CAS  Google Scholar 

  21. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins: basic science and product development. J. Pharm. Pharmacol. 62, 1607–1621 (2010)

    Article  CAS  Google Scholar 

  22. Gibaud, S., Zirar, S.B., Mutzenhardt, P., Fries, I., Astier, A.: Melarsoprol-cyclodextrins inclusion complexes. Int. J. Pharm. 306, 107–121 (2005)

    Article  CAS  Google Scholar 

  23. Zhao, M., Wang, H., Yang, B., Tao, H.: Identification of cyclodextrin inclusion complex of chlorogenic acid and its antimicrobial activity. Food Chem. 120, 1138–1142 (2010)

    Article  CAS  Google Scholar 

  24. Semalty, A.: Cyclodextrin and phospholipid complexation in solubility and dissolution enhancement: a critical and meta-analysis. Expert Opin. Drug Deliv. 11, 1255–1272 (2014)

    Article  CAS  Google Scholar 

  25. Semalty, A., Tanwar, Y.S., Semalty, M.: Preparation and characterization of cyclodextrin inclusion complex of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution. J. Therm. Anal. Calorim. 115, 2471–2478 (2014)

    Article  CAS  Google Scholar 

  26. Maher, M., Pandey, M., Adhikari, L., Semalty, A., Semalty, M.: Effect of hydrophilic excipients on cyclodextrin complexes of acyclovir in improving solubility, dissolution and permeability. Lett. Drug Des. Disc. 13(8), 771–780 (2016)

    Article  CAS  Google Scholar 

  27. Jullian, C., Orosteguis, T., Pérez-Cruz, F., Sánchez, P., Mendizabal, F., Olea-Azar, C.: Complexation of Morin with three kinds of cyclodextrin: a thermodynamic and reactivity study. Spectrochim. Acta Part A 71, 269–275 (2008)

    Article  Google Scholar 

  28. Janga, K.Y., King, T., Ji, N., Sarabu, S., Shadambikar, G., Sawant, S., et al.: Photostability issues in pharmaceutical dosage forms and photostabilization. AAPS PharmSciTech 19, 48–59 (2018)

    Article  CAS  Google Scholar 

  29. Encyclopedia of Pharmaceutical Technology: Third Edition, vol. 2. CRC Press, New York (2006)

    Google Scholar 

Download references

Acknowledgements

Authors are thankful to UGC-DAE Consortium for Scientific Research, Indore and Kolkata, for providing the research grant, fellowship, and instrument facilities under CRS-310 and RC15. The authors are also thankful to Panacea Biotech LTD, Baddi, H.P. for providing the gift sample of doxycycline hyclate for the research work. Analytical facilities provided by the USIC, HNB Garhwal University Srinagar Garhwal are thankfully acknowledged.

Funding

Funding was provided by UGC-DAE Consortium for Scientific Research, University Grants Commission (Grant Number CRS 310 and RC15).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mona Semalty.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pandey, M., Rani, P., Adhikari, L. et al. Preparation and characterization of cyclodextrin complexes of doxycycline hyclate for improved photostability in aqueous solution. J Incl Phenom Macrocycl Chem 102, 271–278 (2022). https://doi.org/10.1007/s10847-021-01116-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-021-01116-z

Keywords

Navigation