Paediatric drug development: reformulation, in vitro, genomic and in vivo evaluation

摘要: Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 the potassium-sparing diuretic spironolactone was NHS specials list for November 2011 drug tariff with view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, chosen their interaction transporter proteins in small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril formulated without extensive development excipients water soluble. Ramipril are both insoluble strategies combating this employed. successfully solubilised using low concentrations of acetic acid a co-solvent system also via complexation hydroxypropyl-β-cyclodextrin. A suspension produced take formulation third direction. Spironolactone dosages too high solubilisation techniques be effective so suspensions developed. buffer controlled sensitive whilst precisely balanced surfactant suspending agent mix provided excellent physical stability. Characterisation, stability profiling permeability assessment performed following development. The process highlighted current shortcomings taste pharmaceutical preparations resulting early stage research into novel vitro cell based assay. developed initial phase used model investigating microarray application an vitro-in vivo correlation carrier mediated absorption. Caco-2 cells assessed transport studies changes genetic expression ATP-binding cassette solute superfamilies. Findings which compared findings. It not possible ascertain between absorption individual genes even gene families, however there (R2 = 0.9934) total number significantly changed levels predicted human