Solid State of Tulobuterol : Characterization, Dissolution, Transformation

The objective of this work was to investigate the existence of new crystal forms of tulobuterol which is used to prevent morning asthma attacks by ${\beta}_2$ agonist and the transformation of crystal forms. Three crystal forms of tulobuterol have been isolated by recrystallization and Form 2 was transformed to Form 4 at 52% RH and 95% RH and these four crystal forms are characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). The DSC and PXRD patterns of four crystal forms of tulobuterol were different respectively. The dissolution patterns of these three crystal forms of tulobuterol were studied and they showed significant differences in the dissolution rate. After storage of 2 months at 0% RH (silica gel, $20^{\circ}C$), 52% RH (saturated solution of $Na_2Cr_2O_7{\cdot}2H_2O/20^{\circ}C$) and 95% RH (saturated solution of $Na_2HPO_4/20^{\circ}C$), Form 1 and Form 3 were not transformed. But Form 2 was transformed to Form 4 at 52% RH and 95% RH.