title: In vitro evaluation of the dissolution behaviour of itraconazole in bio-relevant media.
abstract: Drugs in the gastrointestinal tract are exposed to a medium of partially digested food, comprising mixtures of fat, protein and carbohydrate. The dissolution behaviour of itraconazole was evaluated in bio-relevant media which were developed to take this into account. Media containing milk with different fat contents, protein (albumin, casein, gluten and gelatin), carbohydrates (glucose, lactose and starch) and amino acids (lysine, glycine, alanine and aspartic acid) to mimic a digested meal and bile components (sodium taurocholate and lecithin) to represent a key endogenous digestive material were investigated. The effect of medium composition on the intrinsic dissolution rate of itraconazole was evaluated as this drug has extremely poor solubility and its bioavailability is affected by food. Dissolution tests were carried out in simple compendial media based on dilute solutions of hydrochloric acid or neutral solutions of phosphate buffer and in more complex media containing the dietary components. The data obtained showed that most of the dietary components enhanced the solubility compared to simulated gastric fluid (SGF) but to differing extents. The greatest increase in dissolution was observed with the addition of milk and albumin although an increase was also seen with other proteins, amino acids and simulated gastrointestinal fluids.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, UK.
authors.forename: Heba S
authors.initials: HS
authors.lastname: Ghazal
authors.forename: A Mark
authors.initials: AM
authors.lastname: Dyas
authors.forename: James L
authors.initials: JL
authors.lastname: Ford
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hutcheon
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001646:Bile / Q000737:chemistry; D001682:Biological Availability; D004040:Dietary Carbohydrates / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D004044:Dietary Proteins / Q000378:metabolism; D018565:Food-Drug Interactions; D005750:Gastric Juice / Q000378:metabolism; D007419:Intestinal Secretions / Q000378:metabolism; D017964:Itraconazole / Q000737:chemistry* / Q000493:pharmacokinetics; D008892:Milk / Q000378:metabolism; D012995:Solubility
chemical_list: D000596:Amino Acids; D000935:Antifungal Agents; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D017964:Itraconazole