Influence of homolog composition and hydration states of magnesium stearate on carrier-based dry powder formulations for inhalation

Magnesium stearate (MgSt) has been used as a force control agent (FCA) to enhance the aerosol performance of carrier-based dry-powder inhalers (DPIs). MgSt is a mixture of magnesium salts of fatty acids—primarily stearic acid (SA) and palmitic acid (PA)—and the SA:PA ratio can vary depending on the natural source. In addition, different processing routes can yield variation in both chemical and solid form composition of commercial grade MgSt. This study investigated whether variations in fatty acid composition and hydration state (hydrate form) of MgSt affect the aerosol performance of carrier-based DPIs. Samples of MgSt with different SA/PA molar ratios and hydration states were obtained and micronized, then blended with coarse lactose (carrier) and tratinterol hydrochloride (TH), a new long-acting bronchodilator used as a model drug, to prepare DPI formulations (TH-DPIs). After physicochemical characterization, the aerosol performance of the TH-DPI formulations was assessed using a Next Generation Impactor (NGI). NGI results showed that the fine particle fraction (FPF) of TH-DPIs increased with increasing MgSt content, irrespective of fatty acid composition or hydration state. Changes in the SA/PA ratio had little effect on aerosol performance. In contrast, formulations containing trihydrate MgSt generally exhibited higher FPFs than those containing dihydrate or low-hydration MgSt. In conclusion, changes in the hydration state of MgSt exert a greater impact on DPI aerosol performance than variations in its fatty-acid composition.