FORMULATION OF SOLUTION METERED-DOSE INHALERS AND COMPARISON WITH AEROSOLS EMITTED FROM CONVENTIONAL SUSPENSION SYSTEMS | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

2788955

Reference Type

Journal Article

Title

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

Author(s)

Warren, SJ; Farr, SJ

Year

1995

Is Peer Reviewed?

Yes

Journal

International Journal of Pharmaceutics
ISSN: 0378-5173
EISSN: 1873-3476

Volume

124

Issue

Page Numbers

195-203

Language

English

DOI

10.1016/0378-5173(95)00076-U

Web of Science Id

WOS:A1995RU06600005

Abstract

Micellar solubilisation was used to enhance the solubility of salbutamol (SB) and triamcinolone acetonide (TAA) in chlorofluorocarbon solvents with the aim of formulating solution metered dose inhaler (MDI) products of these drugs. Stable, isotropic solutions of soya phosphatidylcholine (SPC) were obtained in trichlorotrifluoroethane (P113) and a 30:70 mixture of trichlorofluoromethane (P11) and dichlorodifluoromethane (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 at R value of 0.9. Solution MDI formulations of SB and TAA gave reproducible shot potency throughout the pack-life, comparable to the performance of commercially available suspension products (SB, Ventolin; TAA, Azmacort). In contrast to suspension systems, however, there was no loss of potency in the first spray actuated after storage with SB solution MDIs. The respirable fraction (RF) of drug emitted from solution MDIs was significantly increased by altering the orifice diameter of the actuator. These studies confirmed that the highest RF values (in excess of those achieved with suspension products) were achieved when the MDIs were fired through an actuator with the smallest (0.25 mm) orifice.

Keywords

METERED DOSE INHALER; FORMULATION; MICELLAR SOLUBILIZATION; AEROSOL; SOLUTION; SUSPENSION