Norma Lindsey Buchanan

Improving glyburide solubility and dissolution by complexation with hydroxybutenyl‐β‐cyclodextrin

Objectives Glyburide, an important drug for type 2 diabetes, has extremely poor aqueous solubility and resulting low bioavailability. This study describes the ability of hydroxybutenyl‐β‐cyclodextrin (HBenBCD) to form complexes with glyburide, with enhanced solubility and dissolution rate in vitro.

Pharmacokinetics of letrozole in male and female rats: influence of complexation with hydroxybutenyl-β-cyclodextrin

Cyclodextrins (CDs) are one of the most successful solutions to the problem of poor drug solubility. In this study, we examined the in‐vitro effects of three CDs on the solubility of letrozole, a breast cancer drug that is practically insoluble in water. The most promising, hydroxybutenyl‐β‐cyclodextrin (HBenβCD), was used for in‐vivo studies in male and female Sprague‐Dawley rats. Letrozole is a drug with dramatic gender‐based differences in pharmacokinetics. For example, the terminal half‐life (t1/2) of letrozole following intravenous administration in male rats was 11.5 ± 1.8 h (n = 3), while in female rats it was 42.3 ± 2.9 h (n = 3). HBenβCD increased the solubility and enhanced the dissolution rate of letrozole. Complexation of letrozole with HBenβCD improved oral absorption in male rats and maximized absorption in female rats. Regardless of gender, the presence of HBenβCD in the formulation increased the in‐vivo rate of absorption. When administered in a capsule formulation with letrozole, HBenβCD resulted in a higher Cmax (61% in male rats, 42% in female), shorter Tmax values (8.4 to 6.3 h in male, 16.4 h to 5.4 h in female) and increased absolute oral bioavailability (46 ± 2 vs 38 ± 3 in male, 101 ± 3 vs 95 ± 2 in female). Thus, solubility limits both rate and extent of letrozole absorption in male rats, but limits only the rate of absorption in female rats.

Molybdenum catalyzed ethylene carbonylation. II. Spectroscopic investigation of the reactions and equilibria of molybdenum hexacarbonyl and molybdenum halocarbonyls under reaction conditions

Abstract A surprisingly efficient carbonylation of ethylene to yield propionic anhydride and propionic acid using halide promoted Mo(CO)6 catalysts has been recently reported in the literature. Although the earlier report included detailed kinetics and a unique mechanistic interpretation involving a metalloradical process, the spectroscopic examination, which played an important role in clarifying the reaction mechanism, was only described qualitatively. This report describes the in situ infrared spectroscopic investigation of the chemistry of the molybdenum carbonyl catalysts in greater detail. Emphasis will be on the spectroscopic examinations of the equilibria of Mo(CO)6 and the molybdenum halocarbonyls, the oxidation of Mo(0) with alkyl halides, and in situ regeneration of the active catalyst under reaction conditions. As part of this investigation, a general method for the determination of equilibrium constants for reactions involving infrared active species using attenuated total reflectance technique, ATR, is described wherein neither the extinction coefficient nor the effective pathlength are known with certainty. The method is demonstrated using the equilibrium between Mo(CO)6 and Mo(CO)5I− as an example.