Formulation of solution metered dose inhalers and comparison with aerosols emitted from conventional suspension systems

Warren, Simon; Farr, Stephen J.

doi:10.1016/0378-5173(95)00076-u

Cited by 20 publications

(5 citation statements)

References 9 publications

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“…Micellar solubilization was used to enhance the solubility of albuterol and triamcinolone actonide in CFC-solution formulations using an isotropic solution of soya phosphatidylcholine (63). The solubility of the drugs increased proportionally with the addition of the surfactant but decreased with the addition of increased water relative to the surfactant.…”

Section: Novel Solubilization Aidsmentioning

confidence: 99%

Advances in Metered Dose Inhaler Technology: Formulation Development

2014

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Pressurized metered dose inhalers (MDIs) are a long-standing method to treat diseases of the lung, such as asthma and chronic obstructive pulmonary disease. MDIs rely on the driving force of the propellant, which comprises the bulk of the MDI formulation, to atomize droplets containing drug and excipients, which ideally should deposit in the lungs. During the phase out of chlorofluorocarbon propellants and the introduction of more environmentally friendly hydrofluoroalkane propellants, many improvements were made to the methods of formulating for MDI drug delivery along with a greater understanding of formulation variables on product performance. This review presents a survey of challenges associated with formulating MDIs as solution or suspension products with one or more drugs, while considering the physicochemical properties of various excipients and how the addition of these excipients may impact overall product performance of the MDI. Propellants, volatile and nonvolatile cosolvents, surfactants, polymers, suspension stabilizers, and bulking agents are among the variety of excipients discussed in this review article. Furthermore, other formulation approaches, such as engineered excipient and drug-excipient particles, to deliver multiple drugs from a single MDI are also evaluated.

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Section: Novel Solubilization Aidsmentioning

confidence: 99%

Advances in Metered Dose Inhaler Technology: Formulation Development

2014

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“…The pressurised metered dose inhaler (pMDI) is the most commonly used form of respiratory therapeutic world‐wide [1,2] . pMDIs can be suspension‐ or solution‐based systems [3] . In a suspension, the solid phase, active pharmaceutical ingredient (API) is dispersed throughout the pressurised liquid phase (hydrofluoroalkane (HFA)‐134a (norflurane) or HFA 227, propellant) through mechanical agitation, with the use of certain excipients or suspending agents.…”

Section: Introductionmentioning

confidence: 99%

Co-deposition of a triple therapy drug formulation for the treatment of chronic obstructive pulmonary disease using solution-based pressurised metered dose inhalers

Adi

Young

Traini

2011

Journal of Pharmacy and Pharmacology

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“…Solution systems offer the advantages of improved performance and uniformity because of drug homogeneity and physical stability but have increased potential for physical degradation. 5 Corresponding Author: Hugh D.C. Smyth, 1311 Kerr Hall, CB 7360, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 966-0484; Fax: (919) 966-0197; Email: hsmyth@email.unc.edu Significant particle size changes have also been noted in the transition from CFC-based systems to HFAbased formulations.…”

Section: Introductionmentioning

confidence: 99%

Multimodal particle size distributions emitted from HFA-134a solution pressurized metered-dose inhalers

Smyth

2003

AAPS PharmSciTech

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The purpose of this research was to investigate the measurement and in vitro delivery implications of multimodal distributions, occurring near or in the respirable range, emitted from pressurized metered-dose inhalers (pMDIs). Particle size distributions of solution pMDIs containing hydrofluoroalkane-134a (HFA-134a) and ethanol were evaluated using 2 complementary particle-sizing methods: laser diffraction (LD) and cascade impaction (CI). Solution pMDIs were formulated from mixtures of HFA-134a (50%-97.5% wt/wt) and ethanol. A range of propellant concentrations was selected for a range of vapor pressures. The fluorescent probe, Rhodamine B, was included for chemical analysis. The complementary nature of LD and CI allowed identification of 2 dominant particle size modes at 1 and 10 micro m or greater. Increasing propellant concentrations resulted in increases in the proportion of the size distributions at the 1- micro m mode and also reduced the particle size of the larger droplet population. Despite significant spatial differences and time scales of measurement between the particle-sizing techniques, the fine particle fractions obtained from LD and CI were practically identical. This was consistent with LD experiments, which showed that particle sizes did not decrease with increasing measurement distance, and may be explained by the absence of significant evaporation/disintegration of larger droplets. The fine particle fractions (FPFs) emitted from HFA-134a/ethanol solution pMDI can be predicted on the basis of formulation parameters and is independent of measurement technique. These results highlight the importance of presenting particle size distribution data from complementary particle size techniques.

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Formulation of solution metered dose inhalers and comparison with aerosols emitted from conventional suspension systems

Cited by 20 publications

References 9 publications

Advances in Metered Dose Inhaler Technology: Formulation Development

Advances in Metered Dose Inhaler Technology: Formulation Development

Co-deposition of a triple therapy drug formulation for the treatment of chronic obstructive pulmonary disease using solution-based pressurised metered dose inhalers

Multimodal particle size distributions emitted from HFA-134a solution pressurized metered-dose inhalers

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