No abstract

The solubility of miconazole in water increased in the presence of cyclodextrins (CDs). The apparent K1:1 values calculated from the phase solubility diagrams of gamma-CD, hydroxypropyl-beta-CD, alpha-CD, hydroxyethyl-beta-CD, hydroxypropyl-gamma-CD, and beta-CD were 695 +/- 39.6, 363 +/- 34.1, 333 +/- 18.5, 312 +/- 31.0, 305 +/- 27.6, and 293 +/- 17.6 M(-1), respectively. Solid 1:1 molar complexes were prepared by freeze-drying and kneading and characterized by UV spectroscopy, differential scanning calorimetry, and electron microscopy. The dissolution rate increased to 28-255-fold and the solubility to 9-55-fold. Oral bioavailability in rats increased to 2.3-fold by complexation with hydroxypropyl-beta-CD. Human cadaver skin retained 2.6-fold more drug from the miconazole/alpha-CD complex and hairless mice skin retained 8.4-fold more drug from the HP-beta-CD complex than from miconazole solution alone in 24 h.

No abstract

Andrographis paniculata, a medicinal plant in Thailand national list of essential medicines, has been proposed for treatment of patients with mild to moderate coronavirus disease 2019. This study aims to develop a highly selective and sensitive liquid chromatography triple quadrupole tandem mass spectrometry method for quantitative determination of major diterpenoids in plasma and urine with application in pharmacokinetics. Chromatographic separation was performed on C18 column using a gradient mobile phase of water and acetonitrile. Mass spectrometry was analyzed using multiple reaction monitoring with negative ionization mode. This validated analytical method was very sensitive, less time consuming in analysis, and allowed the reliability and reproducibility on its application. The clinical pharmacokinetics was evaluated after single oral administration of A. paniculata extract (calculated as 60 mg of andrographolide). The disposition kinetics demonstrated that major diterpenoids could enter into systemic circulation, but they are mostly biotransformed (phase II) into conjugated glucuronide and sulfate metabolites. These metabolites are predominantly found in plasma and then extremely eliminated, in part through urinary excretion. The successful application of this analytical method supports its suitable uses in further clinical benefits after oral administration of A. paniculata.