Hydrofluoroalkanes propellant

CFC, chlorofluorocarbon propellant HFA, hydrofluoroalkane propellant MDI, metered-dose inhaler. 

With respect to the formulations used in MDIs, the development over recent years has focused on the replacement of chlorofluorocarbon (CFC) propellants by hydrofluoroalkane propellants. Recently, new developments have been reviewed in a number of papers [50-52]. 

More patients using the hydrofluoroalkane (18%) withdrew from the study than patients using the chlorofluorocarbon (4.8%). Most of the withdrawals in both groups were unrelated to safety (9 and 3.2% respectively). The reasons for withdrawal included intercurrent illness, loss to followup, and inadvertent prescription errors. More patients using the hydrofluoroalkane withdrew because of an adverse event or because of the taste of the inhaler, 3.8 versus 0.9% and 3.1 versus 0.2% respectively. The authors concluded that the data supported the evidence already obtained in clinical trials that reformulation of salbutamol in a hydrofluoroalkane propellant does not result in changes in safety compared with a chlorofluorocarbon formulation. 

Table 5 Physicochemical Properties of Chlorofluorocarbon and Alternative Hydrofluoroalkane Propellants such as Hydrofluorocarbons...

William RO III, Rodgers TL, Liu J. Study of solubility of steroids in hydrofluoroalkane propellants. Drug Dev Ind Pharm 1999 25 1227-1234. 

Propellants may be of a number of different types CFCs, hydrofluoroalkanes (HFAs), or alkanes. The composition impacts upon performance. A numerical system is employed to identify fluorinated propellants. The rules governing this numbering system allow the molecular structure to be derived from the numerical descriptor. The rules may be listed as follows ... 

DeStefano G, Kelash-Cannavo LJ, inventors Boehringer Ingelheim Pharmaceuticals, Inc., U.S., assignee. Formulation for a Metered Dose Inhaler Using Hydrofluoroalkanes as Propellants. US Patent 2004184994, 2004. 

Propane, butane, and isobutane are hydrocarbons (HC). They are used as aerosol propellants alone, in combination with each other, and in combination with a hydrofluoroalkane (HFA) propellant. They are used primarily in topical pharmaceutical aerosols (particularly aqueous foam and some spray products). 

Raoult s law is important because it allows the calculation of vapour pressure from a knowledge of the composition of the solution. The requirement of the Montreal Protocol in 1989 for the replacement of chlorofluorocarbon (CFG) propellants in pressurised metered-dose inhalers with hydrofluoroalkanes (HFAs), because of the ozone-depleting... 

Binary mixtures of hydrofluoroalkanes show behaviour which approaches ideality. Figure 2.3(a) shows the vapour pressure-composition plots for a mixture of the propellants HFA 134a (tetrafluoroethane) and HFA 227 (heptafluoropropane) the linearity of the plots indicates that Raoult s law is obeyed over the temperature range examined. It is frequently necessary to include a cosolvent such as alcohol in the aerosol formulation to... 

Changes to manufacturing processes of propellant-based metered-dose inhalers (pMDIs) due to the transition to hydrofluoroalkane- (HFA-) based formu lations from chlorofluorocarbon- (CFC-) based systems are under way. These changes are proceeding concurrently with reformulation efforts of the pMDI systems themselves. In some cases, this may result in changes to the formulation [1],... 

The most significant developments in metered-dose inhaler technology to occur since the early 1990s have been the introduction of hydrofluoroalkane (HFA) systems as alternatives to chlorofluorocarbon (CFC) systems [174]. This has largely been caused by the link between the use of CFC systems and ozone depletion in the upper atmosphere [152,175]. Albuterol and beclomethasone have been reformulated in HFA products, but as yet the CFC products are still subject to an annually renewable medical exemption. The Food and Drug Administration has recently published its position on alternative propellant formulations, which should initiate the phase-out of CFCs [176]. In the meantime, a number of generic CFC products of albuterol have been manufactured. The opportunity for reformulation of products as they come of patent is likely to increase research and development in this area in the near future. New formulation opportunities will also arise from these developments, including solutions [177], micellar [178,179], and microemulsion [180]. 

The original pMDIs employed CFC propellants 11, 114, and 12 [e.g., beclo-methasone dipropionate (BDP) products Vanceril and Beclovent.]15 In recent years, these propellants have been replaced with hydrofluoroalkane (HFA) propellants 134a... 

The pressurized metered dose inhalers in the use of environmentally friendly propellants means the choice of hydrofluoroalkanes, wherein the dosage form can be a suspension of the solution form. The problems of formulating suspensions, as discussed earlier, apply here as well, but particularly with respect to interactions with the formulation components specific to pressurized inhaler systems. 

Information about the true density of a powder can be used to predict whether a compound will cream or sediment in a metered dose inhaler (MDI) formulation. The densities of the hydrofluoroalkane (HFA) propellants, 227 and 134a, which are replacing chlorofluoro-carbons (CFCs) in MDI formulations, are 1.415 and 1.217 g/cm , respectively. Therefore, suspensions of compounds that have a true density less than these figures will cream (rise to the surface), and those that are denser will sediment. Those that match the density of the propellant will stay in suspension for a longer period (Williams III et al. 1998). It should be noted, however, that the physical stability of a suspension is not merely a function of the true density of the material. 

In pressurised metered dose inhaler (pMDI) technology, CFC propellants are being replaced with the ozone-friendly hydrofluoroalkanes (HFA)-134a and -227. In pMDI drug delivery systems, the drugs are formulated as a suspension or as a solution, depending on the solubility of... 

Enviroiunentally-Safe Propellants Hydrofluoroalkanes (HFAs) are replacing chlorofluorocarbons in hand-held asthma inhalers, because of CFC damage to the ozone layer. Draw the structures of the HFAs listed below. 

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