Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract.
The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150-200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.
Honkanen
Outi
O
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, PO Box 56, FI-00014 Helsinki, Finland. outi.honkanen@helsinki.fi
Marvola
Janne
J
Kanerva
Hanna
H
Lindevall
Kai
K
Lipponen
Maija
M
Kekki
Tommi
T
Ahonen
Aapo
A
Marvola
Martti
M
D000328:Adult; D002214:Capsules; D004341:Drug Evaluation / Q000379:methods; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005772:Gastrointestinal Transit / Q000502:physiology; D006801:Humans; D065347:Hypromellose Derivatives; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D018709:Statistics, Nonparametric
D002214:Capsules; D065347:Hypromellose Derivatives; D008747:Methylcellulose