DEVELOPMENT OF BINARY AND TERNARY COMPLEX OF CEFUROXIME AXETIL WITH CYCLODEXTRIN FOR IMPROVING PHARMACEUTICAL CHARACTERISTICS
Objective: The current research objective is systematic development and characterization of binary and ternary inclusion complexes of cefuroxime axetil with β-cyclodextrin to improve its pharmaceutical characteristics by using the kneading method.
Methods: 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 differential scanning calorimeter (DSC), fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffractometry (XRD). Then, binary complexes were analyzed for in vitro dissolution testing. The ternary complexes were developed using different ratio of PVP K-30 as a 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 than pure drug. During the development of the ternary complex, β-cyclodextrin (1:1) and 1% w/v PVP K-30 as a ternary agent resulted in an 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% within 30 min. in comparison to binary complex. The in vitro taste-masking study revealed the taste masking efficiency of the 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. Devara R, Habibuddin M, Aukunuru J. Enhancement of dissolution rate of poorly soluble drug itraconazole by nanosuspension technology: its preparation and evaluation studies. Asian J Pharm Clin Res 2018;11:414-21.
3. Sopyan I, Fudholi A, Muchtaridi M, Puspitasari I. A simple effort to enhance solubility and dissolution rate of simvastatin using co-crystallization. Int J Pharm Pharm Sci 2016;8:342-6.
4. Kalepu S, Nekkanti V. Improved delivery of poorly soluble compounds using nanoparticle technology: a review. Drug Delivery Transl Res 2016;6:319-32.
5. Navdeep, Verma R, Kaushik D. Recent developments in self-micro emulsifying drug delivery system: an overview. Asian J Pharm 2019;13:59-72.
6. Kaushik R, Budhwar V, Kaushik D. An overview on recent patents and technologies on solid dispersion. Recent Pat Drug Delivery Formul 2020;14:63-74.
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 Pharm 2011;3:1-7.
9. Sogali BS, Murthy KVR. Comparative studies with different cyclodextrin derivatives in improving the solubility and dissolution of saquinavir. Asian J Pharm Clin Res 2018;11:509-16.
10. Nuss RA, Zein H. Enhancement of candesartan cilexetil dissolution rate by using different methods. Asian J Pharm Clin Res 2015;8:320-36.
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 hydroxypropyl-?-cyclodextrin and amino acids. Int J Pharm 2003;260:293–302.
13. Gajare P, Patil C, Kalyane N. Effect of hydrophilic polymer on pioglitazone complexation with hydroxyl propyl ?-cyclodextrin. Dig J Nanomater Biostruct 2009;4:891–7.
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 cefuroxime axetil nanoparticles by rapid expansion of supercritical fluid technology. Powder Technol 2009;189:97–102.
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;76:391–401.
20. Loftsson T, Hreinsdottir D, Masson M. Evaluation of cyclodextrin solubilization of drugs Int J Pharm 2005;302:18–28.
21. Mendhe AA, Kharwade RS, Mahajan UN. Dissolution enhancement of poorly water-soluble drug by cyclodextrins inclsion complexation. Int J Appl Pharm 2016;8:60-5.
22. Wang J, Cao Y, Sun B, Wang C. Physicochemical and release characterization of garlic oil-?-cyclodextrin inclusion complexes. Food Chem 2011;127:1680–5.
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;79:140–9.
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;81:591-8.
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, Garcia OC, Maesta Bezerra F. Inclusion complexes of citronella oil with ?-cyclodextrin for controlled release in biofunctional textiles. Polymers (Basel) 2018;10:21-5.
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;129:350-8.
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, Araujo 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. Earle RR, Jammu R, Usha L, Lingam RK. Comparison and characterization of inclusion complexes and solid dispersions in enhancement of dissolution rate of poorly water-soluble drug. Int J Appl Pharm 2018;10:173-7.
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. Verma R, Kaushik D. Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential. Drug Delivery 2020;1:756-71.
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;4:254-67.
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 Lett 2018;694:120-8.
39. Valero M, Tejedor J, Rodriguez LJ. Encapsulation of nabumetone by means of drug: cyclodextrin: polyvinylpyrrolidone ternary complex formation. J Lumine Sci 2006;126:297-302.
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. Ain S, Singh R, Ain Q. Characterization and intrinsic dissolution rate study of microwave-assisted cyclodextrin inclusion complexes of gemfibrozil. Int J Pharm Pharm Sci 2016;8:160-73.
42. Shaikh AA, Chaudhari PD, Holkar SS. A design of experiment approach for optimization and characterization of etodolac ternary system using spray drying. Int J Pharma Pharm Sci 2017;9:233-40.
43. Kaushik D, Dureja H. Central composite designed taste masked ion-exchange resinates for development of azithromycin dispersible tablets. J Pharm Res 2015;14:7-14.
44. Fini A, Bergamante V, Ceschel G, Ronchi C, Moraes CAF. Fast dispersible/slow releasing ibuprofen tablets. Eur J Pharm Biopharm 2008;69:335-41.
45. 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;99:4285–94.
46. Kaushik D. Development of taste masked levofloxacin oral suspension using ion exchange resonates. J Chem Pharm Res 2016;8:385-94.
47. 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.
48. Dumbare AS, Shelke PV, Gadhave MV, Banerjee SK. Preparation and evaluation of suspension of cefuroxime axetil. Int J Ind Pharm Biosci 2012;1:152-7.
49. Du Y, Zhai Y, Zhang J, Wu C, Sun J, He Z. Development and evaluation of taste-masked dry suspension of cefuroxime axetil for enhancement of oral bioavailability. Asian J Pharm Sci 2013;8:287-94.
50. Jagtap R, Mohite S. Meloxicam-pectin-?-cyclodextrin ternary complex by kneading for enhancement of solubility and dissolution rate. Asian J Pharm Clin Res 2019;12:189-94.
51. 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;6:300-6.
52. Prabhakaran RKJ, Harindran J. Improvement of bioavailability of cefuroxime axetil oral suspension by inclusion complexation method. Int J Pharm Pharm 2016;8:361-4.
53. Ding Y, Pang Y, Vara Prasad CVNS, Wang B. Formation of inclusion complex of enrofloxacin with 2-hydroxypropyl-?-cyclodextrin. Drug Delivery 2020;27:334-43.
54. Prabhakaran R, Janakiraman K, Harindran J. Formulation and evaluation of taste-masked oral suspension of cefuroxime axetil using hydroxypropyl-beta-cyclodextrin. Asian J Pharm Clin Res 2016;9:90-102.
This work is licensed under a Creative Commons Attribution 4.0 International License.