Steroids inhaler preparations

In cases of severe acute asthmatic attacks, bronchodilators and steroids for direct dehveiy to the lungs may be needed in large doses. This is achieved by direct inhalation via a nebulizer device this converts a liquid into a mist or fine spray. The dmg is diluted in small volumes of Water for Injections BP before loading into the reservoir of the machine. This vehicle must be sterile and preservative-fiee and is therefore prepared as a terminally sterilized unit dose in polyethylene nebules. 

Glucocorticoids are available in a wide range of preparations, so that they can be administered parenterally, orally, topically, or by inhalation. Obviously the oral route is preferred for prolonged therapy. However, parenteral administration is required in certain circumstances. Intramuscular injection of a water-soluble ester (phosphate or succinate) formed by esterification of the C21 steroid alcohol produces peak plasma steroid levels within 1 hour. Such preparations are useful in emergencies. By contrast, acetate and tertiary butylacetate esters must be injected locally as suspensions and are slowly absorbed from the injection site, which prolongs their effectiveness to approximately 8 hours. 

Inhaled glucocorticoid preparations, such as be-clomethasone dipropionate and betamethasone valerate, provide an effective alternative to systemic steroids in the treatment of chronic asthma, with lesser side effects than oral or parenteral glucocorticoids (see Chapter 39). In fact, inhaled glucocorticoids have become a mainstay of asthma therapy. Inhalation delivers the agent directly to the target site in relatively low doses, with the potential for more frequent administration. Moreover, inhaled glucocorticoids are metabolized in the lung before they are absorbed, which reduces their systemic effects. However, even modest doses of... 

Local therapy, such as topical preparations for skin disease, ophthalmic forms for eye disease, intra-articular injections for joint disease, inhaled steroids for asthma, and hydrocortisone enemas for ulcerative colitis, provides a means of delivering large amounts of steroid to the diseased tissue with reduced systemic effects. 

Williamson IJ, Matusiewicz SP, Brovm PH, Greening AP, Crompton GK. Frequency of voice problems and cough in patients using pressurized aerosol inhaled steroid preparations. Eur Respir J 1995 8(4) 590-2. 

The soup method is of course not suitable for drug suspensions, such as the steroid preparations for use with nebulizers, since the drug may not be uniformly distributed in either the suspension or the droplets generated by the nebulizer. However, radioactive particles whose characteristics are similar to the drug particle may be useful surrogates for suspension aerosols inhaled from nebulizers (67). 

Currently, suspensions prepared from micronised active substances are the only marketed dehvery system for nebulisation of poorly water soluble substances such as steroids and cyclosporine [53]. Several problems are inherent in nebulising micro-suspensions and they vary from non-optimised lung deposition for the active substance to heterodispersity of the active substance concentration in the aerosol droplets and poor compatibility with different types of nebulisers, particularly ultrasonic devices. Suspensions may also have poor stability and the two components (solid and liquid) tend to separate with time within the formulation by sedimentation or flocculation, depending on the particle density relative to that of the liquid. Several jet nebulisers can deliver suspensions quite effectively, even independently of the primary particle size [54], but ultrasonic devices may convert primarily the continuous phase into aerosol whereas vibrating mesh inhalers can be blocked by particles being larger than the pore diameter of the membrane. 

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