title: The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets.
abstract: Four different hydrophilic matrix formulations based on hydroxypropyl methylcellulose (HPMC) were investigated for erosion properties in vivo. Three formulations contained a fixed amount of HPMC (40%) with varying proportions of two HPMC grades with different molecular weights (Methocel K100LV and K4M), and a fourth formulation contained a lower amount of the HPMC of lower molecular weight (20%). The effect of food on the in vivo erosion behavior was investigated on two formulations containing different contents of the same HPMC grade. The in vivo erosion behavior and gastrointestinal transit were investigated using magnetic marker monitoring (MMM). The in vitro and in vivo erosion-time profiles show that the erosion was strongly dependent on the composition of the formulation. The formulations containing a larger proportion of high molecular weight HPMC or higher content of HPMC exhibit relatively slower erosion rate and vice versa. In vivo erosion rates were significantly higher under postprandial administration as compared to fasted state administration. No rapid disintegration of any of the formulations (i.e. formulation failure that can potentially cause dose dumping) was observed.
authors.affiliation: Institute of Pharmacy, Ernst-Moritz-Arndt-University of Greifswald, 17487 Greifswald, Germany.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Jain
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Söderlind
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Viridén
authors.affiliation: SocraTec R&D GmbH, 61440 Oberursel, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schug
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Abrahamsson
authors.affiliation: SocraTec R&D GmbH, 61440 Oberursel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Knopke
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Farhad
authors.initials: F
authors.lastname: Tajarobi
authors.affiliation: SocraTec R&D GmbH, 61440 Oberursel, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Blume
authors.affiliation: SocraTec R&D GmbH, 61440 Oberursel, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Anschütz
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Welinder
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Richardson
authors.affiliation: Institute of Pharmacy, Ernst-Moritz-Arndt-University of Greifswald, 17487 Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nagel
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, 431 83 Mölndal, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Abrahmsén-Alami
authors.affiliation: Institute of Pharmacy, Ernst-Moritz-Arndt-University of Greifswald, 17487 Greifswald, Germany. Electronic address: werner.weitschies@uni-greifswald.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
mesh_terms: D000328:Adult; D059305:Diet, High-Fat; D005215:Fasting / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry; D018565:Food-Drug Interactions; D005753:Gastric Mucosa / Q000378:metabolism; D005772:Gastrointestinal Transit; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D007420:Intestine, Large / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D060328:Magnetic Phenomena; D008297:Male; D008970:Molecular Weight; D019518:Postprandial Period; D012995:Solubility; D013607:Tablets
chemical_list: D005290:Ferric Compounds; D013607:Tablets; C000499:ferric oxide; D065347:Hypromellose Derivatives
keywords: Hydrophilic matrix; Hydroxypropyl methylcellulose (HPMC); In vivo erosion; Magnetic marker monitoring (MMM)