Solutions metered dose inhaler formulations

Warren SJ, Farr SJ. Formulation of solution metered dose inhalers and comparison with aerosols emitted from conventional suspension systems. Int J Pharma 1995 124 195-203. 

Since the introduction of metered-dose inhalers, nasal solutions have increasingly been formulated as nasal sprays. Initially, aerosol-based systems containing chloro-fluorocarbons were employed however, the Montreal Protocol put an end to this. Thereafter, mechanical pumps or actuators were employed to deliver nasal formulations as sprays. These devices, using actuators, can precisely deliver as little as 25 pL and as much as 200 pL of a formulation. However, various factors must be considered in formulating the spray these include viscosity, particle size, and surface tension, all of which may affect the accuracy of the dose administered. 

Smyth, H. D., Beck, V. P, Williams, D., and Hickey, A. J. (2004),The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers, AAPS PharmSciTech, 5, E7. 

Surfactants are found in both solution and suspension formulations of metered dose inhalers (MDIs). The most common surfactants found in pressurised aerosol preparations include sorbitan trioleate (Span 85),... 

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 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. 

Metered-dose inhaler (MDI) Canister held inverted Formulation (CFC, HFA, solution, suspension) Actuator cleanliness Addition of a spacer device Inspiratory flow (slow, deep) Breath-holding Coordinating actuation with inhalation Priming and shaking the device... 

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... 

In general, and with a few rare exceptions (see below), the inhaled route of administration is the most difficult that is commonly encountered. Metered dose inhalers and nebulizers are considered together here because they have many features in common. These formulations, in both cases, are administered as aerosols of drug solution. 

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