Inhalation preparations

The discovery of the utility of the bis-chromone carboxylic acid derivative cromolyn sodium in the treatment of asthma and related allergies has led to an intensive, and thus far not very fruitful, effort to discover analogues which would show oral activity in contrast to the lead which must be administered by inhalation. Preparation of a typical analogue, proxicromil (63), starts with the O-allylated phenol 57. Claisen rearrangement leads to the corresponding C-allylated product 58. 

Inhalation preparations— These can be solutions, suspensions, orpowders intended to be inhaled as aerosols for administration to the lung. 

Ophthalmic, nasal, and oral inhalation preparations Appearance, color, consistency, pH, clarity (solutions), particle size and resuspendibility (suspensions, ointments), strength, and sterility... 

Paradoxical bronchospasm Occasionally patients have developed severe paradoxical airway resistance with repeated, excessive use of inhalation preparations the cause is unknown. Discontinue the drug immediately and institute alternative therapy. 

Based on the concept that asthma is an inflammatory disease that leads to airway obstruction, inhaled glucocorticoids are the first-line treatment for moderate to severe asthma. Inhaled preparations are particularly effective when used to prevent recurrent attacks. This therapy is often combined with an inhaled bron-chodUator such as a p-adrenergic agonist. The use of p-adrenergic agonists or theophylline enables use of a lower dose of glucocorticoid, especially in patients relatively resistant to therapy (see Chapter 39). 

Cetylpyridinium chloride is a quaternary ammonium cationic surfactant, used in pharmaceutical and cosmetic formulations as an antimicrobial preservative see Section 10. It is used therapeutically as an antiseptic agent used alone or in combination with other drugs for oral and throat care used in nonparenteral formulations licensed in the UK and used in oral and inhalation preparations at concentrations of 0.02-1.5 mg (see Section 16). 

It is also used in hot-melt extruded films for topical use. When it is produced with chlorpheniramine maleate, the matrix is stabilized, allowing film processing at lower temperatures. Mucoadhesive hydroxypropyl cellulose microspheres have been prepared for powder inhalation preparations. A specification for hydroxypropyl cellulose is included in the Food Ghemicals Godex (EGG). 

Included in the FDA Inactive Ingredients Guide (IM, IV, and SC injections oral capsules and tablets inhalation preparations ... 

Included in the EDA Inactive Ingredients Guide (IM, IV, and SC injections oral capsules and tablets inhalation preparations rectal, transdermal, and vaginal preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 

Leucine is used in pharmaceutical formulations as a flavoring agent. It has been used experimentally as an antiadherent to improve the deagglomeration of disodium cromoglycate microparticles in inhalation preparations and as a tablet lubricant. Leucine copolymers have been shown to successfully produce stable drug nanocrystals in water. 

Albuterol (e.g., Ventolin, Proventil) P2 adrenergic receptor agonist - causes bronchodilation. Drug of choice for treatment of acute asthma symptoms and to prevent exertion-induced asthma. Though promoted as a fte- selective agonists, side effects parallel nonspecific agonists (vasodilation, tachycardia, CNS stimulation, metabolic alterations. Table 2.1). Inhalation preparations have fewer side effects. 

In some cases, however, this approach is not possible. For example, with inhaled preparations for treating asthma, 90% of the preparation may be swallowed rather than inhaled, but it is the inhaled fraction which is important. Under such circumstances it becomes important to compare the pharmacodynamic response of reference and test formulations. 

Corticosteroid therapy, oral or parenteral (by inhalation) may offer dramatic relief from asthma when other less dangerous measures have failed. At least one of the inhalant preparations (beclomethasone dipropionate) seems to compete favourably with other anti-asthmatics as far as the risks involved are concerned. Recent data on the corticosteroids in all their forms can be found in Chapter 37. 

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