Novel orally swallowable IntelliCap(®) device to quantify regional drug absorption in human GI tract using diltiazem as model drug

AAPS PharmSciTech. 2014 Dec;15(6):1490-7. doi: 10.1208/s12249-014-0172-1. Epub 2014 Jul 15.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Biological Availability
  • Capsules
  • Colon / metabolism*
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Diltiazem / administration & dosage*
  • Diltiazem / blood
  • Diltiazem / chemistry
  • Diltiazem / pharmacokinetics*
  • Equipment Design
  • Gastrointestinal Transit
  • Humans
  • Intestinal Absorption*
  • Male
  • Metabolic Clearance Rate
  • Solubility
  • Transducers
  • Young Adult

Substances

  • Capsules
  • Delayed-Action Preparations
  • Diltiazem

Associated data

  • ISRCTN/ISRCTN45336965