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The aim of this study is to develop milk-based formulations for ionized and unionized lipophilic drugs. Solubility studies of the following non-steroidal anti-inflammatory drugs (NSAIDs): mefenamic acid, tolfenamic acid, ketoprofen, meloxicam, tenoxicam and nimesulide in phosphate– and glycine–NaOH buffers at nominal pH 8–12, were performed. The solubilities of cyclosporine and danazol in water–ethanol solutions were studied. NSAIDs–, cyclosporine–, danazol–, aspirin–milk oral liquid formulations were prepared by adding the appropriate volume of (i) NSAIDs–alkaline buffer solutions, (ii) water–ethanol solutions of cyclosporine and danazol and (iii) aspirin aqueous solution to 150–200 ml of milk. All the non-steroidal anti-inflammatory drugs exhibited increased solubility in the alkaline buffers. The actual pH values (range 6.7–7.7) of the final NSAIDs–milk formulations were very close to milk pH. The higher ethanol content in ethanol–water mixtures increased the solubility of danazol and cyclosporine. A 15 mg meloxicam–, a 100 mg cyclosporine– and a 500 mg aspirin–milk formulation was administered orally to healthy volunteers. All these formulations showed a satisfactory in vivo performance. The strong buffering capacity of milk that was observed and the high solubility of unionized drugs in ethanol allow the preparation of drug–milk formulations with enhanced pharmacokinetic properties.