Development of Binary and Ternary complex of Cefuroxime Axetil with Cyclodextrin for Improving Pharmaceutical Characteristics
Binary and Ternary complex of Cefuroxime Axetil with Cyclodextrin
Objective: The objective of the current research is systematic development and characterization of binary and ternary inclusion complexes of Cefuroxime axetil with β-Cyclodextrin to improve its Pharmaceutical characteristics by using kneading method.
Method: Phase solubility study was carried out using Higuchi and Connors method. Based on its result, binary complexes of Cefuroxime axetil with different ratio of β-Cyclodextrin were developed and characterized using DSC, FT-IR and XRD. Then, binary complex were analyzed for in vitro dissolution testing. The ternary complex were developed using different ratio of PVP K-30 as ternary component and evaluated for in vitro dissolution testing and in vitro taste masking.
Results: Binary complex of Cefuroxime axetil with β-Cyclodextrin (1:1) showed better drug release in comparison to pure drug. During the development of ternary complex, β-Cyclodextrin (1:1) and 1% w/v PVP K-30 as ternary agent resulted in optimized ternary complex. The DSC, FT-IR and XRD studies clearly revealed the formation of binary and ternary complexes. The ternary complex showed better drug release of >85% drug release within 30 min. in comparison to binary complex. The in vitro taste masking study revealed the taste masking efficiency of ternary complex of cefuroxime with β-Cyclodextrin.
Conclusion: The developed binary and ternary complex of Cefuroxime axetil based on β-Cyclodextrin with PVP K-30 showed improved in vitro dissolution rate and taste masking in comparison to pure drug. The drug release was better in ternary complexes. The present research work successfully shows the utility of binary and ternary complexes for improving Pharmaceutical characteristics of Cefuroxime axetil.
2. Loh ZH, Samanta AK, Sia-Heng PW. Overview of milling techniques for improving the solubility of poorly water-soluble drugs. Asian J Pharm Sci 2014;10:255-74.
3. Patel BB, Patel JK, Chakraborty S, Shukla D. Revealing facts behind spray dried solid dispersion technology used for solubility enhancement. Saudi Pharm J 2015;23:23352-65.
4. Kalepu S, Nekkanti V. Improved delivery of poorly soluble compounds using nanoparticle technology: A review. Drug Deliv Transl Res 2016;6:319-32.
5. Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H et al. Pharmaceutical practical technology: An approach to improve drug solubility dissolution and bioavailability. Asian J Pharm Sci 2014;9:304-16.
6. Zawilska JB, Wojcieszak J, Olejniczak AB. Prodrugs: A challenge for the drug development. Pharmacol Reports 2013;65:1-14.
7. Jain S, Patel NK, Lin S. Solubility and dissolution enhancement strategies: Current understanding and recent trends. Drug Dev Ind Pharm 2014;41:875-87.
8. Kumar A, Sahoo SK, Padhee K. Review on solubility enhancement techniques for hydrophobic drugs. Int J Pharma 2011;3:1-7.
9. Valero M, Pérezrevuelta BI, Rodríguez LJ. Effect of PVPK-25 on the formation of the naproxen: ?-cyclodextrin complex. Int J Pharm 2003;253:97–10.
10. Aytac Z, Uyar T. Antioxidant activity and photostability of ?-tocopherol/?-cyclodextrin inclusion complex encapsulated electrospun polycaprolactone nanofibers. Eur Polymer J 2016;79:140-149.
11. Ribeiro T, Loftsson D, Ferreira D. Investigation and physicochemical characterization of vinpocetine-sulfobutylether ?-cyclodextrin binary and ternary complexes. Chem Pharm Bull 2003;51:914–22.
12. Mura P, Maestrelli F, Cirri M. Ternary systems of naproxen with hydro-xypropyl-?-cyclodextrin and amino acids. Int J Pharm 2003;260:293–02.
13. Gajare P, Patil C, Kalyane N. Effect of hydrophilic polymer on pioglitazone complexation with hydroxylpropyl ?-cyclodextrin. Dig J Nanomater Biostruct 2009;4 891–97.
14. Crini G. Review: A history of cyclodextrins. Chem Rev 2013;114:10940–75.
15. Sruti J, Patra CN, Swain S. Improvement in the dissolution rate and tableting properties of cefuroxime axetil by melt-granulated dispersion and surface adsorption. Acta Pharm Sin B 2013;3:113–22.
16. Parfitt K, Martindale D. The Extra Pharmacopoeia, Thirty-sixthed Pharmaceutical Press London 2009.
17. Dhumal RS, Biradar SV, Yamamura S. Preparation of amorphous cefuroxime axetil nanoparticles by sonoprecipitation for enhancement of bioavailability. Eur J Pharm Biopharm 2008;70:109–15.
18. Varshosaz J, Hassanzadeh F, Mahmoudzadeh M. Preparation of cefur- oxime axetil nanoparticles by rapid expansion of supercritical fluid technology. Powder Technol 2009; 189:97–02.
19. Shah M, Pore Y, Dhawale S. Physicochemical characterization of spray dried ternary micro-complexes of cefuroxime axetil with hydroxypropyl-?- cyclodextrin. J Incl Phenom Macrocycl Chem 2013;76:391–01.
20. Loftsson T, Hreinsdottir D, Masson M. Evaluation of cyclodextrin solubilization of drugs Int J Pharm 2005;302:18–28
21. Guedes FL, Alves GMC, Santos FLA, Lima LF, Rolim LA, Neto PJR. Cyclodextrinas: A review. Rev Bras Farm 2008;89:220–25.
22. Wang J, Cao Y, Sun B, Wang C. Physicochemical and release characterisation of garlic oil-?-cyclodextrin inclusion complexes. Food Chem 2011;127:1680–85.
23. Wang J, Cao Y, Sun B, Wang C. Characterisation of inclusion complex of transferulic acid and hydroxypropyl-?-cyclodextrin. Food Chem 2011;124:1069–75.
24. Aytac Z, Uyar T. Antioxidant activity and photostability of ?-tocopherol/?-cyclodextrin inclusion complex encapsulated electrospun polycaprolactone nanofibers. Eur Poly J 2016;79:140–49.
25. Byun Y, Rodriguez K, Han JH, Kim YT. Improved thermal stability of polylactic acid (PLA) composite film via PLA-?-cyclodextrin-inclusion complex systems. Int J Biol Macromol 2015;81:591-98.
26. Cheirsilp B, Rakmai J. Inclusion complex formation of cyclodextrin with its guest and their applications. Biol Engineering Med 2016;2:1-6.
27. Lis MJ, García ÓC, Maestá Bezerra F. Inclusion complexes of citronella oil with ?-cyclodextrin for controlled release in biofunctional textiles. Polymers (Basel) 2018; 10(12):21-25.
28. Marcolino AIP, Macedo LB, Nogueira-Librelotto DR, Fernandes JR, Bender CR, Wust KM et al. Preparation characterization and in vitro cytotoxicity study of dronedarone hydrochloride inclusion complexes. Mater Sci Eng C Mater Biol Appl 2019;100:48-61.
29. Mennini N, Maestrelli F, Cirri M, Mura P. Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated- ?-cyclodextrin and l-arginine aimed to improve the drug solubility. J Pharm Biomed Anal 2016;129:350-58.
30. Ammara HO, Salama HA, Ghorab M, Mahmoud A. Formulation and biological evaluation of glimepiride-cyclodextrin-polymer systems. Int J Pharm 2006;309:129-38.
31. Araujo EJ, Silva OA, Rezende-Junior LM, Sousa IJ, Araújo DY, Carvalho RB et al. Synthesis characterization and cytotoxic evaluation of inclusion complexes between Riparin A and ?-cyclodextrin. J Mol Structure 2017;1142:84-91.
32. Gao S, Bie C, Liu Y, Zhang T, Fu Y, Ye F. Functional supramolecular of inclusion complex of herbicide fluroxypyr with HP?CD. Polymers (Basel) 2018; 10(12):4-16.
33. Yang Y, Gao J, Ma X, Huang G. Inclusion complex of tamibarotene with hydroxypropyl-?-cyclodextrin: Preparation characterization in vitro and in vivo evaluation. Asian J Pharm Sci 2016;12:187-92.
34. Yoshikiyo K, Yoshioka Y, Narumiya Y, Oe S, Kawahara H, Kurata K et al. Thermal stability and bioavailability of inclusion complexes of perilla oil with ?-cyclodextrin. Food Chem 2019;294:56-59.
35. Cheirsilp B, Rakmai J. Inclusion complex formation of cyclodextrin with its guest and their applications. Bio Eng Med 2016;2:1-6.
36. Pandya V, Sheth H, Patel S, Pandya K, Aundhia C. Formulation development of fast dispersible tablet of cefuroxime axetil. Eur J Biomed Pharm Sci 2017;4(3):254-67.
37. Sapte S, Pore Y. Inclusion complexes of cefuroxime axetil with ?-cyclodextrin: Physicochemical characterization molecular modeling and effect of L-arginine on complexation. J Pharm Anal 2016;2:56- 62.
38. Sherje AP, Patel F, Murahari F, Suvarna V, Patel K. Study on effect of L-arginine on solubility and dissolution of Zaltoprofen: Preparation and characterization of binary and ternary cyclodextrin inclusion complexes. Chem Physics Letters 2018;694:120-28.
39. Valero M, Tejedor J, Rodriguez LJ. Encapsulation of nabumetone by means of drug: cyclodextrin:polyvinylpyrrolidone ternary complex formation. J Lumine Sci 2006;126:297-02.
40. Carolina A, Asbahr C, Franco L, Barison A, Silva WP. Binary and ternary inclusion complexes of finasteride in HP?CD and polymers: Preparation and characterization. Bioorganic Med Chem 2009;17:2718-23.
41. Albertini B, Cavallari C, Passerini N, Voinovich D, Gonzalez-Rodriguez ML, Magarotto L. Characterization and taste-masking evaluation of acetaminophen granules: comparison between different preparation methods in a high-shear mixer. Eur J Pharm Sci 2004;21:295-03.
42. Fini A, Bergamante V, Ceschel G, Ronchi C, Moraes CAF. Fast dispersible/slow releasing ibuprofen tablets. Eur J Pharm Biopharm 2008;69:335-41.
43. Mady FM, Abou-Taleb AE, Khaled KA, Yamasaki K, Iohara D, Taguchi K et al. Evaluation of carboxymethyl- ?-cyclodextrin with acid function: Improvement of chemical stability oral bioavailability and bitter taste of famotidine. Int J Pharm 2010; 99(10):4285–94.
44. Shah PP, Mashru RC. Influence of chitosan crosslinking on bitterness of mefloquine hydrochloride microparticles using central composite design. J Pharm Sci 2009;98:690-03.
45. Shahzad Y, Shah SN, Atique S, Ansari MT, Bashir F, Hussain T. The evaluation of coated granules to mask the bitter taste of dihydroartemisinin. Braz J Pharm Sci 2011;47:323-30.
46. Dumbare AS, Shelke PV, Gadhave MV, Banerjee SK. Preparation and evaluation of suspension of cefuroxime axetil. Int J Ind Pharm Biosci 2012;1(1):152-57.
47. Lee CW, Kim SJ, Youn YS, Widjojokusumo E, Lee YH, Kim J. Preparation of bitter taste masked cetirizine dihydrochloride ?-cyclodextrin inclusion complex by supercritical antisolvent (SAS) process. J Supercri Fluids 2010;55:348-57.
This work is licensed under a Creative Commons Attribution 4.0 International License.