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AAPS PharmSciTech. 2002 February; 3(4): 59.
Published online 2002 December 2. doi:  10.1208/pt030433
PMCID: PMC2751341

In vitro evaluation of dissolution behavior for a colon-specific drug delivery system (CODES) in multi-pH media using United States Pharmacopeia apparatus II and III


United States Pharmacopeia dissolution apparatus II (paddle) and III (reciprocating cylinder) coupled with automatic sampling devices and software were used to develop a testing procedure for acquiring release profiles of colon-specific drug delivery system (CODES) drug formulations in multi-pH media using acetaminophen (APAP) as a model drug. System suitability was examined. Several important instrument parameters and formulation variables were evaluated. Release profiles in artificial gastric fluid (pH 1.2), intestinal fluid (pH 6.8), and pH 5.0 buffer were determined. As expected, the percent release of APAP from coated core tablets was highly pH dependent. A release profile exhibiting a negligible release in pH 1.2 and 6.8 buffers followed by a rapid release in pH 5.0 buffer was established. The drug release in pH 5.0 buffer increased significantly with the increase in the dip or paddle speed but was inversely related to the screen mesh observed at lower dip speeds. It was interesting to note that there was a close similarity (f2=80.6) between the release profiles at dip speed 5 dpm and paddle speed 100 rpm. In addition, the release rate was reduced significantly with the increase in acid-soluble Eudragit E coating levels, but lactulose loading showed only a negligible effect. In conclusion, the established reciprocating cylinder method at lower agitation rates can give release profiles equivalent to those for the paddle procedure for CODES drug pH-gradient release testing. Apparatus III was demonstrated to be more convenient and efficient than apparatus II by providing various programmable options in sampling times, agitation rates, and medium changes, which suggested that the apparatus II approach has better potential for in vitro evaluation of colon-specific drug delivery systems.

Keywords: colon-specific drug delivery, acetaminophen (APAP), USP apparatus II (paddle), USP apparatus III (reciprocating cylinder), dissolution automation

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Selected References

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1. Yoshikawa Y, Hu Z, Kimura G, Murakami M, Yoshikawa H, Takada K. A dissolution test for a pressure-controlled colon delivery capsule: rotating beads method. J Pharm Pharmacol. 1999;51:979–989. doi: 10.1211/0022357991773447. [PubMed] [Cross Ref]
2. Rubinstein A. Approaches and opportunities in colon-specific drug delivery. Crit Rev Ther Drug Carrier Syst. 1995;12:101–149. [PubMed]
3. Kinget R, Kalala W, Vervoort L, Lan Den Mooter G. Colonic drug targeting. J Drug Target. 1998;6:129–149. doi: 10.3109/10611869808997888. [PubMed] [Cross Ref]
4. Watanabe S, Kawai H, Katsuma M, Fukui M. Colon-specific drug release system. US patent 6 368 629. April 9, 2002.
5. Takemura S, Watanabe S, Katsuma M, Fukui M. Human gastrointestinal transit study of a novel colon delivery system (CODES) using gamma scintigraphy. Proceed Int Symp Control Rel Bioact Mater. 2000;27:445–446.
6. Yang LB, Chu JS, Fix JA. Colon-specific drug delivery: new approaches and in vitro/in vivo evaluation. Int J Pharm. 2002;235:1–15. doi: 10.1016/S0378-5173(02)00004-2. [PubMed] [Cross Ref]
7. Rubinstein A, Radai R, Ezra M, Pathak S, Rokem JS. In vitro evaluation of calcium pectinate: a potential colon-specific drug delivery carrier. Pharm Res. 1993;10:258–263. doi: 10.1023/A:1018995029167. [PubMed] [Cross Ref]
8. Molly K, Woestyne V, Verstraete W. Development of a 5-step multichamber reactor as a simulation of the human intestinal microbial ecosystem. Appl Microbiol Biotechnol. 1993;39:254–258. doi: 10.1007/BF00228615. [PubMed] [Cross Ref]
9. Schacht E, Gevaert A, Kenawy ER, Molly K, Verstraete W, Adriaensens P, Carleer R, Gelan J. Polymers for colon specific drug delivery. J Control Release. 1996;39:327–338. doi: 10.1016/0168-3659(95)00184-0. [Cross Ref]
10. Prasad YVR, Krishnaiah YSR, Satyanarayana S. In vitro evaluation of guar gum as a carrier for colon-specific drug delivery. J Control Release. 1998;58:281–287. doi: 10.1016/S0168-3659(97)00181-8. [PubMed] [Cross Ref]
11. Khan MZI, Prebeg Z, Kurjakovic N. A pH-dependent colon targeted oral drug delivery system using methacrylic acid copolymers, I: manipulation of drug release using Eudragit L100-55 and Eudragit S100 combinations. J Control Release. 1999;58:215–222. doi: 10.1016/S0168-3659(98)00151-5. [PubMed] [Cross Ref]
12. Fukui E, Miyamura N, Uemura K, Kobayashi M. Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting. Int J Pharm. 2000;204:7–15. doi: 10.1016/S0378-5173(00)00454-3. [PubMed] [Cross Ref]
13. Wong D, Larrabee S, Clifford K, Tremblay J, Friend DR. USP dissolution apparatus III (reciprocating cylinder) for screening of guarbased colonic delivery formulations. J Control Release. 1997;47:173–179. doi: 10.1016/S0168-3659(97)01633-7. [Cross Ref]
14. Takeuchi H, Yasuji T, Yamamoto H, Kawashima Y. Spray-dried lactose composite particles containing an ion complex of alginatechitosan for designing a dry-coated tablet having a time-controlled releasing function. Pharm Res. 2000;17:94–99. doi: 10.1023/A:1007530927887. [PubMed] [Cross Ref]
15. U.S. Pharmacopeial Convention . United State Pharmacopeia XXII/National Formulary XVII. Suppl 4. Rockville, MD: USP; 1991. pp. 2510–2514.
16. Society of Japanese Pharmacopoeia . The Japanese Pharmacopoeia (JP) XIV. Tokyo, Japan: Society of Japanese Pharmacopoeia; 2001. pp. 31–33.
17. Rohrs BR. Calibration of the USP 3 (reciprocating cylinder) dissolution apparatus. Dissolut Technol. 4(2):11–14, 18.
18. Ashford M, Fell T. Targeting drugs to the colon: delivery systems for oral administration. J Drug Target. 1994;2:241–258. doi: 10.3109/10611869408996806. [PubMed] [Cross Ref]
19. Borst I, Ugwu S, Beckett AH. New and extended applications for USP drug release apparatus 3. Dissolut Technol. 4(1):11–15, 18.
20. Pillay V, Fassihi R. Unconventional dissolution methodologies. J Pharm Sci. 1999;88:843–851. doi: 10.1021/js990139b. [PubMed] [Cross Ref]
21. Schauble T. A comparison of various sampling methods for tablet release tests using the stirrer methods (USP Apparatus 1 & 2). Dissolut Technol. 3(2):11–15.
22. Rohrs BR, Burch-Clark DL, Witt MJ, Stelzer DJ. USP dissolution apparatus 3 (reciprocating cylinder): instrument parameter effects on drug release from sustained release formulations. J Pharm Sci. 1995;84:922–926. doi: 10.1002/jps.2600840804. [PubMed] [Cross Ref]
23. Esbelin B, Beyssac E, Aiache JM, Shiu GK, Skelly JP. A new method of dissolution in vitro, the Bio-Dis apparatus: comparison with the rotating bottle method and in vitro: in vivo correlations. J Pharm Sci. 1991;80:991–994. doi: 10.1002/jps.2600801017. [PubMed] [Cross Ref]
24. Khougaz K, Wong WM, Kwong E, Clas SD. Effect of excipients on the solubilization of a hydrophobic compound in aqueous SDS solutions. AAPS Contributed Paper 2205, Oct 29–Nov 2, 2000. Indianapolis, IN.
25. Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison-statistics and analysis of the similarity factor f2. Pharm Res. 1998;15:889–896. doi: 10.1023/A:1011976615750. [PubMed] [Cross Ref]
26. Food and Drug Administration . Guidance for industry: dissolution testing of immediate release solid oral dosage forms. Rockville, MD: FDA; 1997.
27. Yu LX, Wang JT, Hussain AS. Evaluation of USP apparatus 3 for dissolution testing of immediate-release products. AAPS PharmSci. 2002;4(1);article 1. [PMC free article] [PubMed]
28. Bown RL, Gibson JA, Sladen GE, Hicks B, Dawson AM. Effect of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device. Gut. 1975;15:999–1004. doi: 10.1136/gut.15.12.999. [PMC free article] [PubMed] [Cross Ref]
29. Yang LB, Watanabe S, Li J, et al. Effect of colonic lactulose availability on the timing of drug release onset in vivo from a unique colon-specific drug delivery system (CODES). Pharm Res. In press. [PubMed]

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