MELOXICAM-PECTIN-β-CYCLODEXTRIN TERNARY COMPLEX BY KNEADING FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE

Authors

  • RAJESH JAGTAP Department of Pharmaceutics, Annasaheb Dange College of B Pharmacy, Ashta, Sangli, Maharashtra, India.
  • SHRINIVAS MOHITE Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Sangli, Maharashtra, India.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i4.32126

Keywords:

meloxicam, beta-cyclodextrin, pectin, ternary complex, solubility enhancement

Abstract

Objective: The objective of the present investigation was to improve the solubility and dissolution rate of poorly soluble drug meloxicam by its ternary inclusion complexation with natural polymers and beta-cyclodextrin (β-CD) by kneading.

Methods: Equimolar physical mixture (1:1) was prepared by homogeneously kneading drug and β-CD using a solution of agar and pectin in water to get a paste, then paste was dried overnight to get inclusion complex. Inclusion complex was evaluated for drug content, the yield of the adsorption process, Fourier-transform infrared (FTIR), differential scanning calorimeter (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), dissolution, and stability studies.

Results: The phase solubility diagrams exhibit AL showing a linear increase of drug solubility and indicating the formation of soluble complexes. The FTIR and DSC show compatibility between meloxicam and β-CD, while slight broadening in the peak with a reduction in intensity and early onset indicates the reduction in drug crystallinity which confirms in PXRD pattern. The SEM of binary, as well as ternary, showed no aggregation, and there was a gap between the particles also indicating good redispersibility. The dissolution rate of the drug from the kneaded ternary complex with pectin was significantly rapid compared with the pure drug. The maximum drug release was observed at 85.21±1.84% at the end of 60 min. The ternary complex was found stable after 3 months stability studies.

Conclusion: The results indicated that ternary inclusion complexation with natural polymers and β-CD was most useful for enhancement of solubility and dissolution rate of a poorly soluble drug like meloxicam.

Downloads

Download data is not yet available.

References

Shah N, Seth AK, Balaraman R. Bioavailability enhancement of poorly soluble raloxifene by designing inclusion complex with Β–cyclodextrin. Int J Pharm Pharm Sci 2015;7:205-11.

Prabhakaran R, Janakiraman K, Harindran J. Improvement of bioavailability of cefuroxime axetil oral suspension by inclusion complexation method. Int J Pharm Pharm Sci 2016;8:361-4.

Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins 1. Drug solubilization and stabilization. J Pharm Sci 1996;85:1017-25.

Baboota S, Agarwal SP. Inclusion complexation of meloxicam with b-cyclodextrin. Indian J Pharm Sci 2002;64:408-11.

Loftsson T. Increasing the cyclodextrin complexation of drugs and drug biovailability through addition of water-soluble polymers. Pharmazie 1998;53:733-40.

Vijaya Kumar SG, Mishra DN. Preparation, characterization and in vitro dissolution studies of solid dispersion of meloxicam with PEG 6000. Yakugaku Zasshi 2006;126:657-64.

Uekama K, Hirayama F, Irie T. Application of cyclodextrins. Drug Target Deliv 1994;3:411-56.

Jagtap S, Magnum C, Jadge D, Jagtap R. Solubility enhancement technique: A review. J Pharm Sci Res 2018;10:2205-11.

Loftsson T, Brewster M. Cyclodextrins as pharmaceutical excipient. Pharm Tech Eur 1997;9:26-34.

Arora P, Singh J, Chadha R. Physicochemical characterization and evaluation of telmisartan: Hydroxypropyl-Β-cyclodextrin: Tween 80 inclusion complex. Int J Pharm Pharm Sci 2017;9:51-8.

Mura P, Faucci MT, Bettinetti GP. The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl-beta-cyclodextrin. Eur J Pharm Sci 2001;13:187-94.

Shaikh AA, Chaudhari PD, Holkar SS. A design of experiment approach for optimization and characterization of Etodolac ternary system using spray drying. Int J Pharm Pharm Sci 2017;9:233-40.

Brewster M, Loftsson T. Cyclodextrins as pharmaceutical solubilizer. Adv Drug Deliv Rev 2007;59:645-66.

Valero M, Carrillo C, Rodríguez LJ. Ternary naproxen: β-cyclodextrin: Polyethylene glycol complex formation. Int J Pharm 2003;265:141-9.

Pokharkar V, Khanna A, Venkatpurwar V, Dhar S, Mandpe L. Ternary complexation of carvedilol, beta-cyclodextrin and citric acid for mouth-dissolving tablet formulation. Acta Pharm 2009;59:121-32.

Rakkaew P, Suksiriworapong J, Chantasart D. Β-cyclodextrin-based ternary complexes of haloperidol and organic acids: The effect of organic acids on the drug solubility enhancement. Pharm Dev Technol 2018; 23:715-22.

Mura P, Maestrelli F, Cirri M. Ternary systems of naproxen with hydroxypropyl-beta-cyclodextrin and aminoacids. Int J Pharm 2003; 260:293-302.

Jagtap S, Magdum C. Enhanced dissolution and solubility of Epalrestat with β-cyclodextrin ternary complex using Arginine. J Drug Deliv Ther 2018; 8:62-7.

Ghorpade VS, Remeth D, Kailas M, Vijay H. Preparation and evaluation of domperidone/β-cyclodextrin/citric acid/mannitol quaternary inclusion complex: An in vitro study. Asian J Pharm 2016;10:375-85.

El-Maradny HA, Mortada SA, Kamel OA, Hikal AH. Characterization of ternary complexes of meloxicam-HPbetaCD and PVP or L-arginine prepared by the spray-drying technique. Acta Pharm 2008;58:455-66.

Jug M, Bećirević-Laćan M. Multicomponent complexes of piroxicam with cyclodextrins and hydroxypropyl methylcellulose. Drug Dev Ind Pharm 2004;30:1051-60.

de Miranda JC, Azevedo Martins TE. Cyclodextrins and ternary complexes: Technology to improve solubility of poorly soluble drugs. Braz J Pharm Sci 2011;47:665-82.

Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instrum 1965;4:117-212.

Bayomi MA, Abanumay KA, Al-Angary AA. Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state. Int J Pharm 2002;243:107-17.

Bhosale Ashok V, Hardikar Sharwaree R, Jagtap Rajesh S. Formulation of beta-cyclodextrin complexed controlled release matrix tablet of glipizide and its in vitro evaluation. Int J Pharm Tech Res 2009;1:773-8.

Sharma S, Sher P, Badve S, Pawar AP. Adsorption of meloxicam on porous calcium silicate: Characterization and tablet formulation. AAPS PharmSciTech 2005;6:E618-25.

Ramana MV, Himaja M, Dua K. A new approach: Enhancement of solubility of rofecoxib. Asian J Pharm 2008;2:96-101.

Streubel A, Siepmann J, Bodmeier R. Floating matrix tablets based on low density foam powder: Effects of formulation and processing parameters on drug release. Eur J Pharm Sci 2003;18:37-45.

Rajesh J, Rajendra D, Shrinivas M. Enhancement of solubility and dissolution rate of nifedipine by using novel solubilizer sepitrap 80 and sepitrap 4000. J Drug Deliv Ther 2018;8:293-300.

Tran HT, Park JB, Hong KH, Choi HG, Han HK, Lee J, et al. Preparation and characterization of pH-independent sustained release tablet containing solid dispersion granules of a poorly water-soluble drug. Int J Pharm 2011;415:83-8.

International Conference on Harmonization (ICH). Harmonized Tripartite Guideline for Stability Testing of New Drugs Substances and Products Q1A (R2) Aug-2003. Q1 (R2). International Conference on Harmonization; March, 2004.

Rhodes CT, Cartesan T. Drug Stability Principle and Procedure. 3rd ed. New York: Marcel Dekker; 2001.

Yi T, Wan J, Xu H, Yang X. A new solid self-microemulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water soluble drugs. Eur J Pharm Biopharm 2008;70:439-44.

Gohel MC, Patel MR, Patel KV. Studies in dissolution enhancement of nifedipine. Drug Dev Ind Pharm 1996;22:263-8.

Published

07-04-2019

How to Cite

RAJESH JAGTAP, and SHRINIVAS MOHITE. “MELOXICAM-PECTIN-β-CYCLODEXTRIN TERNARY COMPLEX BY KNEADING FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE”. Asian Journal of Pharmaceutical and Clinical Research, vol. 12, no. 4, Apr. 2019, pp. 189-94, doi:10.22159/ajpcr.2019.v12i4.32126.

Issue

Section

Original Article(s)