RESUMO
(-)-Alpha-bisabolol was found to form an inclusion complex with beta-cyclodextrin (beta-CD) in solution as well as in the solid state. To investigate molecular associations of beta-CD with pure (-)-alpha-bisabolol or (-)-alpha-bisabolol as a component of camomile essential oil, phase solubility studies were undertaken. A B(s) type solubility with an apparent complex constant of 273 M(-1) for the pure (-)-alpha-bisabolol and 304 M(-1) for (-)-alpha-bisabolol as a constituent of the essential oil were obtained. The two curves in the phase solubility diagram reach their plateau at different concentrations of (-)-alpha-bisabolol, 7.04 x 10(-4) M for the pure substance and 2.88 x 10(-4) M for the substance as a component of the essential oil. Although the shapes of the curves are almost similar, the intrinsic solubility's of pure (-)-alpha-bisabolol (4.85 x 10(-4) M) and (-)-alpha-bisabolol as a component of the essential oil (1.82 x 10(-4) M) differ significantly. An inclusion complex having a stoichiometric composition of 2:1 (beta-CD: drug) was obtained. A mechanism of complexation has been proposed on the basis of the stability constant calculated from phase solubility data and the stoichiometric ratio of the solid state complexation.
Assuntos
Camomila/química , Ciclodextrinas/química , Óleos Voláteis/química , Sesquiterpenos/química , beta-Ciclodextrinas , Química Farmacêutica , Cromatografia Gasosa , Estabilidade de Medicamentos , Etanol , Modelos Moleculares , Sesquiterpenos Monocíclicos , Solubilidade , Tensão Superficial , Fatores de Tempo , ÁguaRESUMO
Particle size analysis of drug and excipient is of particular interest for dry powder inhalation (DPI) formulations development and quality control. In this work, the deposition in the upper, the medium and the lower (i.e. the respirable fraction) Twin Impinger compartments of sodium cromoglycate (SCG), lactose (as excipient) and a 1:1 mixture thereof was determined by chemical analysis using a DPI device--the Micro-hale--and compared with the results obtained by laser diffractometry for the same fractions. The analytical method for the SCG determination consisted of ultraviolet spectrophotometry and, for the lactose, high performance liquid chromatography with refractive index detection was used. Laser diffractometry as a quickly operating routine method can substitute the chemical analysis in order to evaluate the respirable fraction, under the conditions of the present work and therefore making formulation development easier and quicker.