Aerosols pressurised

Annex 10 Manufacture of Pressurised Metered Dose Aerosol Preparations for Inhalation Annex 11 Computerised Systems... 

Liquid instillation and nebulised aerosols are the most common methods for pulmonary administration to experimental animals [22, 54, 109, 134], The use of pressurised metered dose inhaler (pMDIs) and dry powder inhaler (DPIs) in preclinical studies is limited by the need for formulation development, which often cannot be performed in early drug discovery due to short supply of test materials. A number of alternative techniques for intra-tracheal administration of coarse sprays and powder formulations have been described [9, 15, 21, 36, 71, 80, 99, 138],... 

Farr, S.J., Rowe, A.M., Rubsamen, R., and Taylor, G., Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler. Thorax, 50 639-644 (1995). 

Salbutamol is a selective (32 agonist that may be administered by inhalation from either a pressurised aerosol delivering 100 pg per puff (standard dose 1-2 puffs) or a powder inhaler (metered dose 500 pg). The duration of action is 4-6 hours. In patients unable to use a pressurised aerosol, salbutamol-containing solution may be nebulised in a stream of oxygen using a specially designed face mask. Similarly, salbutamol-containing solution can be nebulised and introduced into the inspiratory limb of a mechanical ventilation system. 

This steroid is widely used and is administered by pressurised aerosol (200 pg per puff) given up to three to four times a day as prophylaxis. It is often prescribed in combination with a selective 32-adrenoceptor agonist, such as salbutamol. There are few steroid-related side effects when the inhaled route is employed at recommended dosages. 

Annex 10 Manufacture of pressurised metered-dose aerosol preparations for inhalation Annex 11 Computerized systems... 

Manufacture of immunological veterinary medical products Manufacture of medicinal gases Manufacture of herbal medicinal products Sampling of starting and packaging materials Manufacture of liquids, creams, and ointments Manufacture of pressurised metered-dose aerosol preparations for inhalation... 

Patients who have difficulty in coordination with inhalers can use a spacer device. These remove the need for coordination between actuation of a pressurised metered dose inhaler and inhalation. The spacer device reduces the velocity of the aerosol and subsequent impaction on the oropharynx. In addition, the device allows more time for evaporation of the propellant so that a larger proportion of the particles can be inhaled and deposited in the lungs. The size of the spacer is important, the larger spacers with a one-way valve (Nebuhaler, Volumatic) being most effective. Spacer devices are particularly useful for patients with poor inhalation technique, for children, for patients requiring higher doses, for nocturnal asthma, and for patients who have poor coordination. 

Newman, S. P., Weisz, A. W., Talaee, N., and Clarke, S. W. (1991), Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique, Thorax, 46, 712-716. 

Newman, S. R, Millar, A. B., Lennard-Jones, T. R., Moren, F., and Clarke, S. W. (1984), Improvement of pressurised aerosol deposition with nebuhaler spacer device, Thorax, 39, 935-941. 

Disadvantages are that special apparatus is needed (some patients find pressurised aerosols difficult to use to best effect) and a drug must be nonirritant if the patient is conscious. Obstructed bronchi (mucus plugs in asthma) may cause therapy to fail. 

Pressurised aerosol. Drug is dissolved in a low boiling point liquid in a canister under pressure. Opening the valve releases a metered dose of liquid that is ejected into the atmosphere, carrier liquid... 

Newman, S.P. Miller, A.B. Lennard-Jones, T.R. Moren, E. Clarke, S.W. Improvement of pressurised aerosol deposition with nebuhaler space device. Thorax 1984, 59, 935-941. 

Crompton, G.K. Problems patients have using pressurised aerosol inhalers. Eur. J. Respir. Dis. 1982, 63, 101-104. 

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),... 

Emulsification is used in aerosol products to produce foams which are generally formulated as o/w emulsions. The liquified propellant forms the disperse phase of the emulsion, and the medication is usually in the aqueous continuous phase. On discharge from the pressurised container, the propellant vaporizes to form bubbles which remain trapped within the aqueous phase giving rise to a foam. These are referred to as stable foam products. Nonaqueous stable foams may also be formulated, where the water is replaced by various glycols such as polyethylene glycol. Quick breaking foams result when the propellant is in the external phase. The product is emitted as a foam and collapses into a liquid. 

The product of fast pyrolysis is vapours, aerosols and gases from decomposition of holocellulose and lignin with any carrier gases from fluidisation or transport. Aerosols consist of sub-micron liquid droplets and they present a severe problem in tbe successful recovery of the pyrolysis oils. These aerosols appear visually as smoke. The aerosols are probably formed directly from pyrolysing biomass, especially from submicron biomass particles that are rapidly depolymerised. The liquid product can then be entrained out of the reactor before it is vaporised. Another mechanism proposed for the formation of aerosols in the pyrolysis reactor involves the ejection of liquid droplets from internally pressurised cell capillaries of a pyrolysing particle (33). 

How is the book arranged In the first few chapters we examine the properties of dmgs and excipients in the solid state and in solution. Gases also are treated because of their importance in the design and use of therapeutic pressurised aerosols, which until recently have been derived from chlorinated fluorocarbons (CFCs), but now are based on volatile fluorinated hydrocarbons (HFAs). 

Typical pressurised aerosol systems are discussed in Chapter 7. In two-phase systems the... 

The Autohaler has been devised as a breath-activated pressurised inhaler system because of the difficulty experienced by some patients in coordinating manual operation of an aerosol with inhalation. The Autohaler is activated by the negative pressure created during the inhalation phase of respiration and is specifically designed to respond to shallow inhalation in those with restricted pulmonary capacity. 

BS 4172 1993. Hand-iteld Pressurised Aerosol Dispensers Against Houseflies- Han I. S >eeitiealion for insecticidal efficiency, Part Tl. Method for determination of insecli-eidal efficiency, British Standards Institution, London. 

Chemical Specialities Manufacturers Association (CSMA) (1971). Aerosol and pressurised space sprav insecticide test method for flying insects. Soap Chem. Spec. Blue fitwt. p. 158. 

There are increasing pressures on the pharmaceutical industry to use environmentally friendly materials in products, which are biodegradable or recyclable and do no harm to the environment. Examples are the replacement of CFCs in pressurised metered dose aerosols and the replacement of polyvinyl chloride (PVC) for alternative packaging materials in some countries. Any special restrictions on the use of materials in the product need to be identified at the product design stage. The choice of appropriate materials to suit product, customer and environment may also have cost implications. 

Unlike most other drug delivery systems, those in the respiratory area can have a major influence on physician/patient acceptance. A wide range of devices are available in the three main categories of dry powder inhalers (DPIs) and metered dose inhalers (MDIs), i.e., pressurised aerosols and nebulisers. The preferred type of inhaler varies considerably between countries (e.g., DPIs in Scandinavia and MDIs in the United States), and between patient groups (e.g., nebulisers for paediatrics). 

Here the formulation is made up to between a 500 and 1000 L scale in pressurised vessels and then filled into cans through the aerosol valve, precrimped onto the can. Naturally, appropriate safety precautions have to be made for working with large-scale pressurised systems. With increasing scale, there is the move to increasing automation of the filling process. 

Brambilla, G., D. Ganderton, R. Garzia, D. Lewis, B. Meakin, and P. Ventura. 1999. Modulation of aerosol clouds produced by pressurised inhalation aerosols. Ini. J. Pharmaceut. 186 53-61. 

Gases may be liquefied, pressurised, volatile, inert, i.e. vapours, inhalations, aerosols. 

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