Preparation and Evaluation of Pectin-based Colon-specific Pulsatile Capsule In Vitro and In Vivo = Jing Liu

다국어 초록 (Multilingual Abstract)

The purpose of this study was to develop and evaluate a colon-specific, pulsatile drug delivery system, which consists of an impermeable capsule body filled with a 5-aminosalicylic acid rapid-disintegrating tablet and a pectin-based erodible plug placed in the opening of the capsule body. To obtain an appropriate gel-forming ability and suitable lag time for the colon-specific drug delivery, high-methoxy pectin (HM-pectin) was formulated with lactose and lowmethoxy pectin (LM-pectin) with HPMC to prepare the plug tablet. In order to evaluate the lag time, prior to the rapid drug release, both the formulation of the plug tablet and in vitro release medium were studied. The lag time prior to the rapid drug release was mainly determined by the HM-pectin/lactose or LM-pectin/HPMC ratio. The addition of pectinase or rat cecal content into the release medium shortened the lag time significantly, which predicted the probable enzyme sensitivity of pectin plug tablet. In vivo studies showed that the plasma concentration of drug can only be detected 6 h after oral administration of the pulsatile capsule, which indirectly proved the colon-specific characteristics. These results show that the pulsatile capsule may have the therapeutic action for colon-specific drug delivery.

참고문헌 (Reference)

1 Peerapattana, J., "Time-controlled pulse-drug release from dry-coated wax matrix tablets for colon drug delivery" 14 : 293-301, 2004

2 Gazzaniga, A., "Time-controlled oral delivery systems for colon targeting" 358 : 3-3597, 2006

3 Kaus, L. C., "The intestinal transit of a single non-disintegrating object" 14 : 143-148, 1984

4 He, W., "Selective drug delivery to the colon using pectin-coated pellets" 62 : 264-272, 2008

5 Krogel, I., "Pulsatile drug release from an insoluble capsule body controlled by an erodible plug" 15 : 474-481, 1998

6 Jones, S. P., "Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs" 347 : 7-3478, 1996

7 Gliko-Kabir, I., "Phosphated crosslinked guar for colon-specific drug delivery. II. In vitro and in vivo evaluation in the rat" 63 : 129-134, 2000

8 Bigucci, F., "Pectin-based microspheres for colon-specific delivery of vancomycin" 61 : 41-46, 2009

9 Wong, T. W., "Pectin matrix as oral drug delivery vehicle for colon cancer treatment" 12 : 201-214, 2011

10 Friend, D. R., "New oral delivery systems for treatment of inflammatory bowel disease" 57 : 247-265, 2005

11 Freire, C., "Influence of the coating formulation on enzymatic digestibility and drug release from 5-aminosalicylic acid pellets coated with mixtures of high-amylose starch and Surelease intended for colon-specific drug delivery" 36 : 161-172, 2010

12 Yehia, S. A., "In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonic contents" 23 : 2761-2766, 2002

13 Krogel, I., "Evaluation of an enzyme-containing capsular shaped pulsatile drug delivery system" 16 : 1424-1429, 1999

14 Krogel, I., "Development of a multifunctional matrix drug delivery system surrounded by an impermeable cylinder" 61 : 43-50, 1999

15 Tozaki, H., "Degradation of insulin and calcitonin and their protection by various protease inhibitors in rat caecal contents : implications in peptide delivery to the colon" 49 : 164-168, 1997

16 McConnell, E. L., "Colonic treatments and targets : issues and opportunities" 17 : 335-363, 2009

17 Kumar, P., "Colon targeted drug delivery systems--an overview" 5 : 186-198, 2008

18 Fan, L. F., "Biphasic drug release : permeability and swelling of pectin/ethylcellulose films, and in vitro and in vivo correlation of film-coated pellets in dogs" 56 : 1118-1125, 2008

19 Sriamornsak, P., "Application of pectin in oral drug delivery" 8 : 1009-1023, 2011

20 Khan, M. Z., "A pH-dependent colon-targeted oral drug delivery system using methacrylic acid copolymers. II. Manipulation of drug release using Eudragit L100 and Eudragit S100 combinations" 26 : 549-554, 2000

21 Gupta, V. K., "A novel pH-and time-based multi-unit potential colonic drug delivery system" 213 : 83-91, 2001

22 Hinton, J. M., "A new method for studying gut transit times using radioopaque markers" 10 : 842-847, 1969

23 Pertuit, D., "5-amino salicylic acid bound nanoparticles for the therapy of inflammatory bowel disease" 123 : 211-218, 2007