UNSUCCESSFUL DELIVERY OF TETRANDRINE FROM COLON-TARGETED DOSAGE FORMS COMPRISING ALGINATE/HYDROXYPROPYL METHYLCELLULOSE AND ALGINATEâ€“CHITOSAN BEADS
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 (F1â€“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
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 (F1â€“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.
polysaccharides for encapsulation and delivery. Crit Rev Food Sci Nutr
2. Amidon S, Brown JE, Dave VS. Colon-targeted oral drug delivery
systems: Design trends and approaches. AAPS PharmSciTech
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
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
8. Iswandana R, Pham BT, van Haaften WT, Luangmonkong T, Oosterhuis
D, Mutsaers HA, et al. Organâ€‘and speciesâ€‘specifc biological activity of
rosmarinic acid. Toxicol In Vitro 2016;32:261â€‘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
11. Goh C, Heng P, Chan L. Alginates as a useful natural polymer for
microencapsulation and therapeutic applications. Carbohydr Polym
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
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
21. Siepmann J, Peppas N. Modeling of drug release from delivery systems
based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv
22. Takka S, GÃ¼rel A. Evaluation of chitosan/alginate beads using
experimental design: Formulation and in vitro characterization. AAPS
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
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.
The 2nd Physics and Technologies in Medicine and Dentistry Symposium (PTMDS), Universitas Indonesia. Depok, Indonesia 402
Int J App Pharm, Vol 10, Special Issue 1, 2018
Iswandana et al.
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
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
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
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
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.