title: Novel orally swallowable IntelliCap(®) device to quantify regional drug absorption in human GI tract using diltiazem as model drug.
abstract: Typically, colonic absorption of a drug is mandatory for a sustained release formulation to hold the drug's plasma level for more than 12 or 24 h above the minimum therapeutic plasma concentration (efficacy). According to Drugs@FDA, only 7.4% of the oral drugs are extended release forms probably showing colonic absorption. Therefore an early determination of a drug's colonic absorption using the IntelliCap® in animals or humans will provide the mandatory information to initiate or stop a SR form development. Diltiazem (60 mg) is used in the oral swallowable IntelliCap® and the marketed SR form from Mylan (coated beads). A human study with 14 healthy volunteers compared the Mylan formulation with the IntelliCap® device that releases the drug identical to the in-vitro dissolution of the Mylan product. The plasma profiles of IntelliCap® and Mylan formulation are highly similar. The mean AUC (bioequivalence fulfilled) and mean Cmax of IntelliCap® shows only a difference of +15% and -12%, respectively. But the PK profile of the Mylan formulation shows a broader peak around Cmax. About 81.8% diltiazem was absorbed in the colon (IntelliCap®) comparable to former publications. The Mylan is a SR diffusion coated beads form whereas the IntelliCap® is a monolithic capsule. The beads are transported in the gut and spread which results in a longer Tmax and a broader Cmax peak. The IntelliCap® device can quantitatively measure the colonic absorption of a drug in excellent accordance to a standard oral SR dosage form.
authors.affiliation: Vivo Drug Delivery GmbH, CH8832, Wollerau, Switzerland.
authors.forename: Dieter
authors.initials: D
authors.lastname: Becker
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Tycho
authors.initials: T
authors.lastname: Heimbach
authors.forename: Robert C
authors.initials: RC
authors.lastname: Penland
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanke
authors.forename: Jeff
authors.initials: J
authors.lastname: Shimizu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kulmatycki
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004867:Equipment Design; D005772:Gastrointestinal Transit; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D012995:Solubility; D014159:Transducers; D055815:Young Adult
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D004110:Diltiazem