Abstract
Purpose
To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process.
Materials and Methods
HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit® were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t 50) was quantified from 50% increase of pixels in the imaging area.
Results
In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t50) calculated for in vitro was 25±5 min and for in vivo was 13±5 min. In vivo also were determined mean values for GRT (55±19 min), SITT (185±82 min) and OCTT (240±88 min).
Conclusions
AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.
Similar content being viewed by others
References
L. Yang, J. S. Chu, and J. A. Fix. Colon-specific drug delivery: new approaches and in vitro/in vivo evaluation. Int. J. Pharm. 235:1–15 (2002).
M. A. Shareef, R. K. Khar, A. Ahuja, F. J. Ahmad, and S. Raghava. Colonic drug delivery: an updated review. AAPS Pharm. Sci. 5:1–26 (2003).
E. T. Cole, R. A. Scott, A. L. Connor, I. R. Wilding, H-U. Petereit, C. Schminke, T. Beckert, and D. Cadé. Enteric coated HPMC capsules designed to achieve intestinal targeting. Int. J. Pharm. 231:83–95 (2002).
O. Honkanen, J. Marvola, H. Kanerva, K. Lindevall, M. Lipponen, T. Kekki, A. Ahonen, and M. Marvola. Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract. Eur. J. Pharm. Sci. 21:671–678 (2004).
C. S. Leopold. Coated dosage forms for colon-specific drug delivery. Pharm. Sci. Technol. Today. 2:197–252 (1999).
C. D. Melia and S. S. Davis. Review article: mechanisms of drug release from tablets and capsules. I: disintegration. Aliment. Pharmacol. Ther. 3:223–232 (1989).
E. Lipka and G. L. Amidon. Setting bioequivalence requirements for drug development based on preclinical data: optimizing oral drug delivery systems. J. Control. Release. 62:41–49 (1999).
M. Zahirul and I. Khan. Dissolution testing for sustained or controlled release oral dosage forms and correlation with in vivo data: challenges and opportunities. Int. J. Pharm. 140:131–143 (1996).
N. Rouge, P. Buri, and E. Doelker. Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int. J. Pharm. 136:117–139 (1996).
M. Singh and V. Waluch. Physics and instrumentation for imaging in-vivo drug distribution. Adv. Drug Deliv. Rev. 4:7–20 (2000).
I. R. Wilding, A. J. Coupe, and S. S. Davis. The role of γ-scintigraphy in oral drug delivery. Adv. Drug Deliv. Rev. 46:103–124 (2001).
J. C. Richardson, R. W. Bowtell, K. Mäder, and C. D. Melia. Pharmaceutical applications of magnetic resonance imaging (MRI). Adv. Drug Deliv. Rev. 57:1191–1209 (2005).
A. Steingoetter, D. Weishaup, P. Kunz, K. Mäder, H. Lengsfeld, M. Thumshirn, P. Boesiger, M. Fried, and W. Schwizer. Magnetic resonance imaging for the in vivo evaluation of gastric-retentive tablets. Pharm. Res. 20:2001–2007 (2003).
A. Steingoetter, P. Kunz, D. Weishaupt, K. Mäder, H. Lengsfeld, M. Thumshirn, P. Boesiger, M. Fried, and W. Schwizer. Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging. Aliment. Pharmacol. Ther. 18:713–720 (2003).
W. Weitschies, O. Kosch, H. Mönnikes, and L. Trahms. Magnetic Marker Monitoring: an application of biomagnetic measurement instrumentation and principles for the determination of the gastrointestinal behavior of magnetically marked solid dosage forms. Adv. Drug Deliv. Rev. 57:1210–1222 (2005).
J. R. A. Miranda, O. Baffa, and R. B. Oliveira. An AC biosusceptometer to study gastric emptying. Med. Phys. 19:445–448 (1992).
L. A. Corá, M. F. Américo, R. B. Oliveira, O. Baffa, R. Moraes, F. G. Romeiro, and J. R. A. Miranda. Disintegration of magnetic tablets in human stomach evaluated by alternate current biosusceptometry. Eur. J. Pharm. Biopharm. 56:413–420 (2003).
L. A. Corá, F. G. Romeiro, M. Stelzer, M. F. Américo, R. B. Oliveira, O. Baffa, and J. R. A. Miranda. AC biosusceptometry in the study of drug delivery. Adv. Drug Deliv. Rev. 57:1223–1241 (2005).
O. Baffa, R. B. Oliveira, J. R. A. Miranda, and L. E. A. Troncon. Analysis and development of AC biosusceptometer for orocaecal transit time measurements. Med. Biol. Eng. Comput. 33:353–357 (1995).
R. B. Oliveira, O. Baffa, L. E. A. Troncon, J. R. A. Miranda, and C. R. Cambrea. Evaluation of a biomagnetic technique for measurement of orocaecal transit time. Eur. J. Gastroenterol. Hepatol. 8:491–495 (1996).
J. R. A. Miranda, R. B. Oliveira, P. L. Sousa, F. J. H. Braga, and O. Baffa. A novel biomagnetic method to study gastric antral contractions. Phys. Med. Biol. 42:1791–1799 (1997).
R. Moraes, L. A. Corá, M. F. Américo, R. B. Oliveira, O. Baffa, and J. R. A. Miranda. Measurement of gastric contraction activity in dogs by means of AC biosusceptometry. Physiol. Meas. 24:337–345 (2003).
M. Moreira, L. Murta, and O. Baffa. Imaging ferromagnetic tracers with an AC biosusceptometer. Rev. Sci.Instrum. 71:2532–2538 (2000).
L. A. Corá, U. Andreis, F. G. Romeiro, M. F. Américo, R. B. Oliveira, O. Baffa, and J. R. A. Miranda. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry. Phys. Med. Biol. 50:5523–5534 (2005).
L. A. Corá, F. G. Romeiro, M. F. Américo, R. B. Oliveira, O. Baffa, M. Stelzer, and J. R. A. Miranda. Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry. Eur. J. Pharm. Sci. 27:1–8 (2006).
E. H. Frei, E. Gunders, M. Pajewsky, W. J. Alkan, and J. Eshcher. Ferrites as contrast material for medical X-ray diagnosis. J. Appl. Phys. 39:99–1001 (1968).
V. G. Belikov and A. G. Kuregyan. Generation and medicobiological application of magnetic fields and carriers (review). Pharm. Chem. J. 35:88–95 (2001).
A. David, B. Yagen, A. Sintov, and A. Rubinstein. Acrylic polymers for colon-specific drug delivery. STP Pharma Sci. 7:546–554 (1997).
K. Lehman. Practical Course in Film Coating of Pharmaceutical Dosage Forms with Eudragit®, Pharma Polymers, Darmstadt, 2001.
D. F. Evans, G. Pye, R. Bramley, A. G. Clark, T. J. Dyson, and J. D. Hardcastle. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 29:1035–1041 (1988).
M. K. Chourasia and S. K. Jain. Pharmaceutical approaches to colon target drug delivery systems. J. Pharm. Pharmaceut. Sci. 6:33–66 (2003).
E. M. M. Quigley. Gastric and small motility in health and disease. Gastroenterol. Clin. North Am. 25:113–145 (1996).
A. J. Coupe, S. S. Davis, and I. R. Wilding. Variation in gastrointestinal transit of pharmaceutical dosage forms in healthy subjects. Pharm. Res. 8:360–364 (1991).
F. Kedzierewicz, P. Thouvenot, J. Lemut, A. Etienne, M. Hoffman, and P. Maincent. Evaluation of peroral silicone dosage forms in humans by gamma-scintigraphy. J. Control. Release. 58:195–205 (1999).
S. S. Davis, J. G. Hardy, and J. W. Fara. Transit of pharmaceutical dosage forms through the small intestine. Gut. 27:886–892 (1986).
D. Harris, J. T. Fell, H. L. Sharma, and D. C. Taylor. GI transit of potential bioadhesive formulations in man: a scintigraphy study. J. Control. Release. 12:45–53 (1990).
C. J. Kenyon, R. V. Nardi, D. Wong, G. Hooper, I. R. Wilding, and D. R. Friend. Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation. Aliment. Pharmacol. Ther. 11:205–213 (1997).
C. Tuleu, A. W. Basit, W. A. Waddington, P. J. Ell, and J. M. Newton. Colonic delivery of 4-aminosalicylic acid using amylase-ethylcellulose-coated hydroxypropylmethylcellulose capsules. Aliment. Pharmacol.Ther. 16:1771–1779 (2002).
K.-H. Lin, S.-Y. Lin, and M.-J. Li. Compression forces and amount of outer coating layer affecting the time-controlled disintegration of the compression-coated tablets prepared by direct compression with micronized ethylcellulose. J. Pharm. Sci. 90:2005–2009 (2001).
H. Zhou. Pharmacokinetic strategies in deciphering atypical drug absorption profiles. J. Clin. Pharmacol. 43:211–227 (2003).
Acknowledgments
The authors would like to thank the Brazilian agencies: FAPESP/PRONEX (03/10107-5) and CAPES for financial support. Eudragit® samples used in this study were supplied from Almapal S/A—Tecnologia Validada, Brazil. HPMC capsules (V-Caps®) were a gift from Capsugel—Divison of Pfizer, Brazil.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Corá, L.A., Romeiro, F.G., Paixão, F.C. et al. Enteric Coated Magnetic HPMC Capsules Evaluated in Human Gastrointestinal Tract by AC Biosusceptometry. Pharm Res 23, 1809–1816 (2006). https://doi.org/10.1007/s11095-006-9035-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-006-9035-0