Sj. Warren et Sj. Farr, FORMULATION OF SOLUTION METERED-DOSE INHALERS AND COMPARISON WITH AEROSOLS EMITTED FROM CONVENTIONAL SUSPENSION SYSTEMS, International journal of pharmaceutics, 124(2), 1995, pp. 195-203
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.