title: A scintigraphic investigation of the disintegration behaviour of capsules in fasting subjects: a comparison of hypromellose capsules containing carrageenan as a gelling agent and standard gelatin capsules.
abstract: Two-piece hard shell capsules made from hypromellose (or hydroxypropyl methylcellulose, HPMC) have been proposed as an alternative to conventional gelatin capsules for oral drug delivery; however, little is known about their in vivo behaviour. The aim of this study was to compare the disintegration of HPMC and gelatin capsules in fasted human subjects using the technique of gamma scintigraphy. HPMC capsules containing carrageenan as a gelling agent (QUALI-V(R), Qualicaps) and gelatin capsules (Qualicaps) of size 0 were filled with a lactose-based mixture. The capsules were separately radiolabelled with indium-111 and technetium-99m. Both capsules were administered simultaneously with 180ml water to eight healthy male subjects following an overnight fast. Each volunteer was positioned in front of the gamma camera and sequential 60s images were acquired in a continuous manner for 30min. No differences in the oesophageal transit of the two types of capsules were noted, with the capsules arriving in the stomach in a matter of seconds. All the capsules disintegrated in the stomach. The mean (+/-S.D.) disintegration time for the HPMC capsules was 9+/-2min (range 6-11min). The corresponding mean time for the gelatin capsules was 7+/-4min (range 3-13min). These disintegration times were not significantly different (P=0.108, paired t-test). In conclusion, HPMC and gelatin capsules show rapid and comparable in vivo disintegration times in the fasted state. HPMC capsules containing carrageenan as a gelling agent therefore offer a practical alternative to gelatin capsules as an oral drug delivery carrier.
authors.affiliation: Department of Pharmaceutics, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK. catherine.tuleu@pharmacy.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Tuleu
authors.forename: M K
authors.initials: MK
authors.lastname: Khela
authors.forename: D F
authors.initials: DF
authors.lastname: Evans
authors.forename: B E
authors.initials: BE
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Nagata
authors.forename: A W
authors.initials: AW
authors.lastname: Basit
mesh_terms: D000328:Adult; D002214:Capsules; D002351:Carrageenan / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005215:Fasting / Q000378:metabolism; D005720:Gamma Rays; D005780:Gelatin / Q000737:chemistry*; D005782:Gels; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012995:Solubility
chemical_list: D002214:Capsules; D005079:Excipients; D005782:Gels; D065347:Hypromellose Derivatives; D002351:Carrageenan; D005780:Gelatin; D008747:Methylcellulose