UNSUCCESSFUL DELIVERY OF TETRANDRINE FROM COLON-TARGETED DOSAGE FORMS COMPRISING ALGINATE/HYDROXYPROPYL METHYLCELLULOSE AND ALGINATE–CHITOSAN BEADS

  • Raditya Iswandana Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia
  • Metah Putri Mutia Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia
  • Farahia Khairina Widyaningrum Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia

Abstract

Objective: The objective of this study was to optimize the formulations of antifibrotic tetrandrine beads using alginate and various concentrations of
hydroxypropyl methylcellulose (HPMC) and chitosan.
Methods: Beads were formulated with six (F1–F6) concentrations of polymer and were then characterized using scanning electron microscopy,
differential scanning calorimetry, and X-ray diffraction; these beads were used for measurements of moisture contents, swelling, and in vitro drug
release.
Results: Beads with the highest concentrations of HPMC and chitosan produced the highest entrapment efficiencies of 49.83% and 50.71%,
respectively. Moreover, drug release under stomach conditions (HCl pH 1.2 medium) was restricted to 75.01%, 61.01%, 51.86%, 74.84%, 66.00%,
and 41.63% with increasing HPMC and chitosan concentrations (F1–F6, respectively).
Conclusion: Beads of all formulations showed inadequate retention of tetrandrine under pH conditions of the upper gastrointestinal tract and would
likely be unsuccessful as colon-targeted dosage forms.

Keywords: Alginate, Antifibrotic tetrandrine beads, Chitosan, Hydroxypropyl methylcellulose, Ionic gelation.

References

1. Kosaraju SL. Colon targeted delivery systems: Review of
polysaccharides for encapsulation and delivery. Crit Rev Food Sci Nutr
2005;45:251-8.
2. Amidon S, Brown JE, Dave VS. Colon-targeted oral drug delivery
systems: Design trends and approaches. AAPS PharmSciTech
2015;16:731-41.
3. Wilson CG, Crowley PJ. Controlled Release in Oral Drug Delivery.
New York: Springer; 2011.
4. Pinto JF. Site-specific drug delivery systems within the gastro-intestinal
tract: From the mouth to the colon. Int J Pharm 2010;395:44-52.
5. Wang QS, Wang GF, Zhou J, Gao LN, Cui YL. Colon targeted oral
drug delivery system based on alginate-chitosan microspheres
loaded with icariin in the treatment of ulcerative colitis. Int J Pharm
2016;515:176-85.
6. Nussinovitch A. Polymer Macro-and Micro-Gel Beads: Fundamentals
and Applications. New York: Springer Science Business Media; 2010.
7. Rieder F, Fiocchi C. Intestinal fibrosis in inflammatory bowel
disease-current knowledge and future perspectives. J Crohns Colitis
2008;2:279-90.
8. Iswandana R, Pham BT, van Haaften WT, Luangmonkong T, Oosterhuis
D, Mutsaers HA, et al. Organ‑and species‑specifc biological activity of
rosmarinic acid. Toxicol In Vitro 2016;32:261‑8.
9. Rieder F, Bettenworth D, Imai J, Inagaki Y. Intestinal fibrosis and
liver fibrosis: Consequences of chronic inflammation or independent
pathophysiology? Inflamm Intest Dis 2016;1:41-9.
10. Jin H, Li L, Zhong D, Liu J, Chen X, Zheng J, et al. Pulmonary toxicity
and metabolic activation of tetrandrine in CD-1 mice. Chem Res
Toxicol 2011;24:2142-52.
11. Goh C, Heng P, Chan L. Alginates as a useful natural polymer for
microencapsulation and therapeutic applications. Carbohydr Polym
2012;88:1-12.
12. Iswandana R, Putri KS, Wulandari FR, Najuda G, Sari SP, Djajadisastra
J. Preparation of calcium alginate-tetrandrine beads using ionic gelation
method as colon-targeted dosage form. J Appl Pharm Sci 2018;8:68-74.
13. Patel N, Lalwani D, Gollmer S, Injeti E, Sari Y, Nesamony J, et al.
Development and evaluation of a calcium alginate based oral
ceftriaxone sodium formulation. Prog Biomater 2016;5:117-33.
14. Tahtat D, Mahlous M, Benamer S, Khodja AN, Oussedik-Oumehdi H,
Laraba-Djebari F, et al. Oral delivery of insulin from alginate/chitosan
crosslinked by glutaraldehyde. Int J Biol Macromol 2013;58:160-8.
15. Timmins P, Pygall SR, Melia CD. AAPS advances in the pharmaceutical
sciences series. In: Hydrophilic Matrix Tablets for Oral Controlled
Release. New York: Springer; 2014.
16. Abdalla KF, Kamoun EA, El Maghraby GM. Optimization of the
entrapment efficiency and release of ambroxol hydrochloride alginate
beads. J Appl Pharm Sci 2015;5:13-9.
17. Iswandana R, Putri KS, Dwiputra R, Yanuari T, Sari SP, Djajadisastra J.
Formulation of chitosan tripolyphosphate-tetrandrine beads using
ionic gelation method: In vitro and in vivo evaluation. Int J App Pharm
2017;9:109-15.
18. Pandey S, Mishra A, Raval P, Patel H, Gupta A, Shah D, et al. Chitosanpectin
polyelectrolyte complex as a carrier for colon targeted drug
delivery. J Young Pharm 2013;5:160-6.
19. Iswandana R, Putri KS, Sandiata CE, Triani S, Sari SP, Djajadisastra
J. Formulation of tetrandrine beads using ionic gelation method capectinate
coated PH-sensitive polymers as colon-targeted dosage form.
Asian J Pharm Clin Res 2017;10:90-5.
20. Raval MK, Prajapati DU, Varma SM, Khodifad MA, Patel JM,
Sheth NR. Influence of some hydrophilic polymers on dissolution
characteristics of furosemide through solid dispersion: An unsatisfied
attempt for immediate release formulation. J Pharm Negat Results
2010;1:29-34.
21. Siepmann J, Peppas N. Modeling of drug release from delivery systems
based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv
Rev 2012;64:163-74.
22. Takka S, Gürel A. Evaluation of chitosan/alginate beads using
experimental design: Formulation and in vitro characterization. AAPS
PharmSciTech 2010;11:460-6.
23. Verma A, Sharma M, Verma N, Pandit JK. Floating alginate beads:
Studies on formulation factors for improved drug entrapment efficiency
and in vitro release. Farmacia 2013;61:143-61.
24. Rajendran A, Basu SK. Alginate-chitosan particulate system for
sustained release of nimodipine. Trop J Pharm Res 2009;5:433-40.
25. Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery
systems for colon targeted drug delivery in inflammatory bowel disease:
Selective targeting to diseased versus healthy tissue. Nanomedicine
2015;11:1117-32.
26. Damian F, Blaton N, Naesens L, Balzarini J, Kinget R, Augustijns
P, et al. Physicochemical characterization of solid dispersions of the
antiviral agent UC-781 with polyethylene glycol 6000 and gelucire
44/14. Eur J Pharm Sci 2000;10:311-22.
27. Sankalia MG, Mashru RC, Sankalia JM, Sutariya VB. Reversed
chitosan-alginate polyelectrolyte complex for stability improvement
of alpha-amylase: Optimization and physicochemical characterization.
Eur J Pharm Biopharm 2007;65:215-32.
28. Jiang XH, Yang JQ, Li N, Wang H, Zhou QX. The pharmacokinetical
study of plant alkaloid tetrandrine with a simple HPLC method in
rabbits. Fitoterapia 2011;82:878-82.
29. Yang L, Chu JS, Fix JA. Colon-specific drug delivery: New approaches
and in vitro/in vivo evaluation. Int J Pharm 2002;235:1-5.
30. Voo W, Ooi C, Islam A, Tey B, Chan E. Calcium alginate hydrogel
beads with high stiffness and extended dissolution behaviour. Eur Poly
J 2016;75:343-53.
31. Mujtaba A, Ali M, Kohli K. Formulation of extended release
cefpodoxime proxetil chitosan-alginate beads using quality by design
approach. Int J Biol Macromol 2014;69:420-9.
32. Shaji J, Shaikh M. Formulation, optimization, and characterization
of biocompatible inhalable D-cycloserine-loaded alginate-chitosan
nanoparticles for pulmonary drug delivery. Asian J Pharm Clin Res
2016;9:82-95.
33. Lavanya N, Muzib I, Jithan A, Umamahesh B. Novel nanoparticles for
the oral delivery og low molecular weight heparin: In vitro and in vivo
assessment. Asian J Pharm Clin Res 2017;10:254-61.
34. Nair SC, Kumar BS, Krishna R, Lakshmi PS, Vasudev DT. Formulation
and evaluation of niosomal suspension of cefixime. Asian J Pharm Clin
Res 2017;10:194-201.
35. Atyabi F, Majzoob S, Iman M, Salehi M, Dorkoosh F. In vitro
evaluation and modification of pectinate gel beads containing
trimethyl chitosan, as a multi-particulate system for delivery
of water-soluble macromolecules to colon. Carbohydr Polym
2005;61:39-51.
36. Liu Z, Li J, Nie S, Liu H, Ding P, Pan W, et al. Study of an alginate/
HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin.
Int J Pharm 2006;315:12-7.
Statistics
75 Views | 63 Downloads
How to Cite
Iswandana, R., Mutia, M. P., & Widyaningrum, F. K. (2018). UNSUCCESSFUL DELIVERY OF TETRANDRINE FROM COLON-TARGETED DOSAGE FORMS COMPRISING ALGINATE/HYDROXYPROPYL METHYLCELLULOSE AND ALGINATE–CHITOSAN BEADS. International Journal of Applied Pharmaceutics, 10(1), 396-402. https://doi.org/10.22159/ijap.2018.v10s1.88
Section
Original Article(s)