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The use of formulation technology to assess regional gastrointestinal drug absorption in humans.
Eur J Pharm Sci. 2004 Feb; 21(2-3):179-89.EJ

Abstract

The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract.

Authors+Show Affiliations

Department of Pharmaceutics, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK. abdul.basit@ulsop.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14757489

Citation

Basit, Abdul W., et al. "The Use of Formulation Technology to Assess Regional Gastrointestinal Drug Absorption in Humans." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 21, no. 2-3, 2004, pp. 179-89.
Basit AW, Podczeck F, Newton JM, et al. The use of formulation technology to assess regional gastrointestinal drug absorption in humans. Eur J Pharm Sci. 2004;21(2-3):179-89.
Basit, A. W., Podczeck, F., Newton, J. M., Waddington, W. A., Ell, P. J., & Lacey, L. F. (2004). The use of formulation technology to assess regional gastrointestinal drug absorption in humans. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 21(2-3), 179-89.
Basit AW, et al. The Use of Formulation Technology to Assess Regional Gastrointestinal Drug Absorption in Humans. Eur J Pharm Sci. 2004;21(2-3):179-89. PubMed PMID: 14757489.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The use of formulation technology to assess regional gastrointestinal drug absorption in humans. AU - Basit,Abdul W, AU - Podczeck,Fridrun, AU - Newton,J Michael, AU - Waddington,Wendy A, AU - Ell,Peter J, AU - Lacey,Larry F, PY - 2004/2/6/pubmed PY - 2004/12/16/medline PY - 2004/2/6/entrez SP - 179 EP - 89 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 21 IS - 2-3 N2 - The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract. SN - 0928-0987 UR - https://www.unboundmedicine.com/medline/citation/14757489/The_use_of_formulation_technology_to_assess_regional_gastrointestinal_drug_absorption_in_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928098703002756 DB - PRIME DP - Unbound Medicine ER -