Preparation, Characterization, and Dissolution Kinetics of Two Novel Albuterol Salts

Abstract

The possibility of producing slowly dissolving albuterol salts was investigated as a potential means of extending the duration of action of the drug following aerosol delivery to the lung. Albuterol adipate and stearate were precipitated from alcoholic solutions of albuterol and adipic or stearic acids, respectively. Differential scanning calorimetry and hot stage microscopy showed that albuterol adipate and stearate produced single melting endotherms at 182 and 116 °C, respectively, which were distinct from those of albuterol (158 °C), adipic acid (152 °C), and stearic acid (70 °C). The aqueous solubilities of albuterol free base, sulfate, adipate, and stearate were 15.7,250,353, and 0.6 mg ⋅ mL-1, respectively, at room temperature. Only the solubilities of the adipate and the stearate increased significantly when the temperature was elevated to 37 °C (452.5 and 1.4 mg ⋅ mL-1, respectively). With a rotating disk dissolution method, albuterol free base, sulfate, and adipate were found to have intrinsic dissolution rates of 1.1, 20.4, and 24.0 mg-min-1 ⋅ cm-2, respectively, in pH 7.4 phosphate buffer at 37 °C. Albuterol stearate dissolved much more slowly and in a nonlinear fashion; this was explained by the deposition of a stearate-rich layer on the dissolving surface of the compacted salt.