FORMULATION OF SOLUTION METERED-DOSE INHALERS AND COMPARISON WITH AEROSOLS EMITTED FROM CONVENTIONAL SUSPENSION SYSTEMS

Micellar solubilisation was used to enhance the solubility of salbutam ol (SB) and triamcinolone acetonide (TAA) in chlorofluorocarbon solven ts with the aim of formulating solution metered dose inhaler (MDI) pro ducts of these drugs. Stable, isotropic solutions of soya phosphatidyl choline (SPC) were obtained in trichlorotrifluoroethane (P113) and a 3 0:70 mixture of trichlorofluoromethane (P11) and dichlorodifluorometha ne (P12) containing water at a maximum level of R(mol water/mol SPC) = 4. The solubility of SB and TAA in both the non-pressurised solvent ( P113) and the pressurised mixture (P11/P12) increased proportionately with SPC concentration but was reduced on increasing values of R. The incorporation of a charged lipid, dicetyl phosphate, into the micellar structure promoted the solubilisation of SB in both solvent systems. In SPC solutions, the optimal solubility of either drug was achieved a t R value of 0.9. Solution MDI formulations of SB and TAA gave reprodu cible shot potency throughout the pack-life, comparable to the perform ance of commercially available suspension products (SB, Ventolin; TAA, Azmacort). In contrast to suspension systems, however, there was no l oss of potency in the first spray actuated after storage with SB solut ion MDIs. The respirable fraction (RF) of drug emitted from solution M DIs was significantly increased by altering the orifice diameter of th e actuator. These studies confirmed that the highest RF values (in exc ess of those achieved with suspension products) were achieved when the MDIs were fired through an actuator with the smallest (0.25 mm) orifi ce.