title: CombiCap: A novel drug formulation for the basel phenotyping cocktail.
abstract: Phenotyping of cytochrome P450 isoenzymes is used for metabolic profiling. Phenotyping cocktails are usually administered as individual marketed products, which are not designed for diagnostic applications. Therefore, a formulation strategy was developed, which can be applied to any phenotyping cocktail. The formulation was validated in vitro and in vivo in human volunteers using caffeine, efavirenz, flurbiprofen, metoprolol, midazolam, and omeprazole (Basel Cocktail). Spray dried di-calcium phosphate particles (Fujicalin) were used as an inert drug carrier for probe drugs. All drugs were successfully loaded into Fujicalin by a solvent evaporation method. Mini-tablets were produced and demonstrated good physical characteristics, expected drug content and immediate release profiles for all drug formulations. Mini-tablets were introduced into a capsule (CombiCap) and used for a pilot study in human volunteers. Plasma samples were collected and analyzed by liquid chromatography and mass spectrometry. Plasma concentration ratios between the parent drugs and the respective metabolites were equivalent for the novel CombiCap formulation and individually dosed Basel Cocktail drugs. We conclude that the CombiCap formulation platform can be easily adopted for different types of phenotyping cocktails due to its scalable and modular design, which allows a simple and convenient combination of variable doses of different probe drugs.
authors: Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors: Marine
authors: M
authors: Camblin
authors: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors: Benjamin
authors: B
authors: Berger
authors: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors: Manuel
authors: M
authors: Haschke
authors: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors: Stephan
authors: S
authors: Krähenbühl
authors: Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.
authors: Jörg
authors: J
authors: Huwyler
authors: Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors: Maxim
authors: M
authors: Puchkov
mesh_terms: D002130:Calcium Phosphates / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004338:Drug Combinations; D004339:Drug Compounding; D065546:Drug Liberation; D064368:Healthy Volunteers; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D010641:Phenotype; D010865:Pilot Projects; D013607:Tablets
chemical_list: D002130:Calcium Phosphates; D004338:Drug Combinations; D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D013607:Tablets; C452280:fujicalin; D003577:Cytochrome P-450 Enzyme System
keywords: Basel Cocktail; CYP450 phenotyping; Drug formulation; Drug loading; Fujicalin; Mini tablets