ABSTRACT
The aim of the present study was to formulate stabilized suspension-type metered-dose inhalation aerosols, and to examine the connection between the stabilizing additives and the optimal particle size. For the stabilization of the suspended particles, hydrophilic- and hydrophobic-type additives were applied. Oleil oleate was selected as a hydrophilic anionic surfactant, and the hydrophobizing agent was dimethyl siloxane polymer. The effect of the amount of the applied hydrophilic and hydrophobic additives on the optimal particle size was modeled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design. We found that if the proper type and amount of additives are selected, it is possible to acquire the therapeutically best composition.
Subject(s)
Nebulizers and Vaporizers , Surface-Active Agents/analysis , Water/chemistry , Dose-Response Relationship, Drug , Evaluation Studies as Topic , Nonlinear Dynamics , Particle Size , SolubilityABSTRACT
The aim of this study was to examine the influence of the concentrations of surfactant and suspending agent on the quantity of effective particles (size < 10 microm) delivered by metered-dose inhalers. A 2-factor, 3-level, face-centred central composite design was used to construct a second-order polynomial model which describes the effect of formulation factors (suspending agent, surface-active ingredient) on the therapeutically important characteristic (effective particle size) delivered by metered-dose inhalers. Oleic acid was selected as the surface-active ingredient, and the suspending agent was anhydrous alcohol. A non-linear model demonstrated with good correlation the effect of the amounts of surfactant and suspending agent on the quantity of particles of effective size. The results obtained enable determination of the correct amount of surface-active ingredient and the optimum quantity of the suspending agent, thus enabling formulation of a therapeutically effective formulation.
