Warren Kenyon Miller

Thin-film polymeric sensors for detection and quantification of multivalent metal ions

Abstract Chemical sensors that reversibly respond to multivalent metal ions are described. These sensors consist of a thin polymeric sensing element that changes size upon reversibly binding analyte ions, particularly heavy-metal ions. The polymeric sensing elements have been bonded to thin metal-foil strain gauges to form sensors. In laboratory evaluations these sensors exhibit high sensitivity to Ba(II), Cd(II), Pb(II), Cr(III), and Cr(VI). Sensor response time is fast, ranging from several seconds to a few minutes. The selectivity and repsonse characteristics of these sensors depend on the composition of the polymeric sensing element. This paper describes the sensitivity and selectivity demonstrated by sensors containing three chemically different polymeric sensing elements. Potential applications of these sensors include in situ real-time monitoring of the heavy-metal content of ground and surface water, municipal water supplies, and household tap water.

Lipophilic salts of poorly soluble compounds to enable high-dose lipidic SEDDS formulations in drug discovery

Graphical abstract Figure. No caption available. ABSTRACT Self‐emulsifying drug delivery systems (SEDDS) have been used to solubilize poorly water‐soluble drugs to improve exposure in high‐dose pharmacokinetic (PK) and toxicokinetic (TK) studies. However, the absorbable dose is often limited by drug solubility in the lipidic SEDDS vehicle. This study focuses on increasing solubility and drug loading of ionizable drugs in SEDDS vehicles using lipophilic counterions to prepare lipophilic salts of drugs. SEDDS formulations of two lipophilic salts—atazanavir‐2‐naphthalene sulfonic acid (ATV‐2‐NSA) and atazanavir‐dioctyl sulfosuccinic acid (ATV‐Doc)—were characterized and their performance compared to atazanavir (ATV) free base formulated as an aqueous crystalline suspension, an organic solution, and a SEDDS suspension, using in vitro, in vivo, and in silico methods. ATV‐2‐NSA exhibited ˜6‐fold increased solubility in a SEDDS vehicle, allowing emulsion dosing at 12 mg/mL. In rat PK studies at 60 mg/kg, the ATV‐2‐NSA SEDDS emulsion had comparable exposure to the free‐base solution, but with less variability, and had better exposure at high dose than aqueous suspensions of ATV free base. Trends in dose‐dependent exposure for various formulations were consistent with GastroPlus™ modeling. Results suggest use of lipophilic salts is a valuable approach for delivering poorly soluble compounds at high doses in Discovery.