Aerosol formulation stability

In a metered dose inhaler, where fine drug particles are suspended in a propellent, stability and aggregation of the suspension are crucial for the performance of the inhaler. In an investigation into the aerosol formulation stability. Span 80 was added to a suspension of lactose to study the effect on deaggregation under shear.f An increase in shear stress was found to decrease aggregate size and boundary fractal dimension (Fig. 9), which was interpreted as a more compact aggregate. 

One of the most important direct uses for nitromethane is in the stabilization of halo-genated hydrocarbons. For example, small amounts of nitromethane are widely used in industry to form stable non-corrosive mixtures with 1,1,1-trichloroethane for vapour degreasing, dry cleaning and for cleaning semiconductors and lenses. It is also used to stabilize the halogenated propellants for aerosols and to inhibit corrosion on the interiors of tin-plated steel cans containing water-based aerosol formulations (Markofsky, 1991 Angus Chemical Co., 1998). 

Poor Formulation Stability for Macromolecules existing aerosol systems are not designed to protect the formulations of delicate macromolecules. 

Sprays are liquid dosage forms aerosolized into the oral cavity for transmucosal drug delivery. Due to the formation of small droplets upon aerosolization of the liquid, sprays can achieve shorter lag times and a faster onset of action than other liquid formulations. Oral-lyn is a micellar system utilizing a blend of surfactants as permeation enhancers and formulation stabilizers. The product is one application of the RapidMist system patented by Generex Biotechnology Corporation that has also been used to develop products for vaccine delivery, pain management, and weight loss. 

Uses Vise, modifier, foam stabilizer, lubricant, conditioner, emulsifier, wetting agent, thickener, penetrant, dye dispersant, scouring aid, antistat for cosmetics and toiletries industrial foam booster/stabilizer metal processing textile surfactant aerosol formulations charge soap in dry cleaning Properties Paste sol. in water, oil, alcohol, perc, Stod., kerosene, CFC sp.gr. 0.99 Witcamide 6310 [Witco ]... 

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

Specific formulation strategies need to be employed for macromolecule compounds. An excellent review of protein stability in aqueous solutions has been published by Chi et al. (92). In addition to solution stability of proteins and peptides, aerosolization may result in significant surface interfacial destabilization of these compounds if no additional stabilization excipients are added. This is due to the fact that protein molecules are also surface active and adsorb at interfaces. The surface tension forces at interfaces perturb protein structure and often result in aggregation (92). Surfactants inhibit interface-induced aggregation by limiting the extent of protein adsorption (92). 

Another concern to formulators is the ingress of moisture into HFA-formulated MDIs [143], HFA propellants have a higher moisture affinity compared to the CFC propellants, especially HFA 134a. In addition, the inclusion of ethanol in some formulations increases its hydrophilicity. Moisture entering the canister can have several effects it may alter the physical or chemical stability of the formulation and aerosolization performance of HFA MDIs. Due to its lower volatility compared to... 

Andya, J.D. Maa, Y.F. Constantino, H.R. Nguyen, P.A. Dosovich, N. Sweeny, T.D. Hsu, C.C. Shire, S.J. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of recombinant humanized anti-IgE monoclonal antibody. Pharm. Res. 1999, 16, 350-358. 

Lo Y-I. Tsai J-C. Kuo J-H. Liposomes and disaccharides as carriers in spray-dried powder-formulations of superoxide dismutase J Control Release 2004 94 259-72. Lcchuga-Ballcstcros D, Charan C, Stults CLM. etal. Triteucine improves aerosol performance and stability of spray-dried powders for inhalation. J Pharm Sci 2007 96(5) 1258-69. Faldt P, Bergenstiihl B. The surface composition of spray-dried protein-lactose powders, niysiochcm Eng Aspects 1993 183-90. 

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