FORMULATION OF CHITOSAN TRIPOLYPHOSPHATE-TETRANDRINE BEADS USING IONIC GELATION METHOD: IN VITRO AND IN VIVO EVALUATION
Objective: Drug delivery to the colon via oral route can be directly treated a variety of diseases in the colon, such as fibrosis. Tetrandrine is a drug that has anti-fibrosis effects. In this study, chitosan-tripolyphosphate (TPP) beads containing tetrandrine was made and evaluated for in vitro release profile and in vivo targeted test.
Methods: Chitosan-TPP tetrandrine beads were prepared by ionic gelation method with variation in sodium tripolyphosphate concentration: 3% (Formula 1), 4% (Formula 2), and 5% (Formula 3). All formulae were characterized for its morphology, particle size, moisture content, process efficiency, entrapment efficiency, thermal character, crystallinity, and swelling. Then, the best formula was coated with HPMCP HP-55, CAP, Eudragit L100-55, or Eudragit L100 prior to drug release profile in vitro and in vivo test.
Results: Beads from all formulae had an average size: 920.50Â±0.04 Âµm, 942.21Â±0.08 Âµm, and 1085.95Â±0.03 Âµm; Water content: 7.28Â±0.003%, 5.64Â±0.005%, and 6.84Â±0.004%; Process efficiency: 29.70%, 28.96%, and 29.70%; Entrapment efficiency: 16.20Â±0.63%, 17.02Â±0.37%, and 20.42Â±0.70% for Formula 1, 2, and 3, respectively. In addition, the results of in vitro cumulative drug release were 67.36%, 76.04%, 83.12%, 83.21%, 40.16%, 37.98%, 45.86%, 41.71% for Formula 3A-3H, respectively.
Conclusion: It can be concluded that Formula 3D (CAP 15%) was chosen as a formulation with the best in vitro profile. Moreover, the in vivo targeted test showed that Formula 3D was able to deliver the beads to the intestine compared to the control beads.
2. Adhyatmika A, Putri KSS, Beljaars L, Melgert BN. The elusive anti-fibrotic macrophage. Frontiers Med 2015;2:1-11.
3. Speca S, Giusti I, Rieder F, Latella G. Celullar and molecular mechanisms of intestinal fibrosis. World J Gastroenterol 2012;18:3635-61.
4. Luangmonkong T, Suriguga S, Bigaeva E, Oosterhuis D, de Jong KP, Schuppan D, et al. Antifibrotic efficacy of a TGF-Î² kinase inhibitor on early-onset and end-stage of fibrosis in precision-cut human liver slices. AASLD Liver LearningÂ® 2015;110678.
5. Iswandana R, Pham BT, Van Haaften WT, Luangmonkong T, Oosterhuis D, Mutsaers HAM, et al. Organ-and species-specific biological activity of rosmarinic acid. Toxicol In Vitro 2016;32:261-8.
6. Westra IM, Oosterhuis D, Groothuis GMM, Olinga P. Precision-cut liver slices as a model for the early onset of liver fibrosis to test anti-fibrotic drugs. Toxicol Appl Pharmacol 2014;274:328â€“38.
7. Khazaeli P, Pardakhty A, Hassanzadeh F. Formulation of ibuprofen bead by ionotropic gelation. Iran J Pharm Res 2008;7:163-70.
8. Sanli O, Ay N, Isiklan N. Release characteristics of diclofenac sodium from poly(vinyl alcohol)/sodium alginate and poly(vinyl alcohol)-grafted poly(acrylamide)/sodium alginate blend beads. Eur J Pharm Biopharm 2007;65:204-14.
9. Patil JS, Kamalapur MV, Marapur SC, Kadam DV. Ionotropic gelation and polyelectrolyte complexation: the novel techniques to design hydrogel particulate sustained, modulated drug delivery system: a review. Digest J Nanomater Biostructures 2010;5:241-8.
10. Snejdrova E, Dittrich M. Pharmaceutical applications of plasticized polymers. In: Recent advances in plasticizers. Croatia: InTech Europe 2012. p. 69-90.
11. Prajapati SK, Tripathi P, Ubaidulla U, Anand V. Design and development of gliclazide mucoadhesive microcapsules: in vitro and in vivo evaluation. AAPS PharmSciTech 2008;9:224-30.
12. Srinatha A, Pandit JK, Singh S. Ionic cross-linked chitosan beads for extended release of ciprofloxacin: in vitro characterization. Indian J Pharm Sci 2008;70:16-21.
13. Tripathi GK, Singh S. Formulation and in vitro evaluation of pH-sensitive oil-entrapped buoyant beads of clarithromycin. Trop J Pharm Res 2010;9:533-9.
14. Mohanty S, Panigrahi AK. Multiparticulate drug delivery system for colon targeting. Int J Pharm Pharm Sci 2015;7:433-6.
15. El-Menshawe SF, Abdeltwab AM, Mohamed AI. Novel gastro-retentive polymeric microspheres: an approach for increased bioavailability and anonce daily dosing ofter butaline sulfate. Int J Pharm Pharm Sci 2016;8:320-9.
16. Bhumkar DR, Pokharkar VB. Studies on effect of pH on crosslinking of chitosan with sodium tripolyphosphate: a technical note. AAPS PharmSciTech 2006;7:E50.