Inhalation delivery methods

Relenza ) in 1999. The polar nature of Relenza precluded significant oral absorption, and therefore an infraoral inhalation drug delivery method was developed that delivered the drug to the primary site of infection. 

LiCalsi C, Christensen T, Bennett JV, Phillips E, Witham C (1999) Dry powder inhalation as a potential delivery method for vaccines. Vaccine 17 1796-1803. 

Among them are carbon monoxide, cyanide, benzopyrene, and tar, the same toxic chemicals present in cigarette smoke. (Some researchers feel that any beneficial effects that may be found in the medicinal use of marijuana are actually negated by the current lack of a suitable alternative delivery method.) Additionally, any pesticides sprayed on the plant by the grower are present in the smoke, and are inhaled along with the THC. 

Selection of the appropriate route of administration and delivery device is critical for the commercial success of a drug product. Although injections are the most efficient delivery method for proteins, they are not always the most suitable from the patient s perspective. Few routes of administration (IV, IM, SC, pulmonary, and topical for local delivery) have been successful to date with protein therapeutics because of the size and complexity of the protein structure. Consideration of the bioavailability via a given route must be made when determining the dose required. Use of a delivery device such as an implantable pump, needle-free injector, or dry-powder inhaler may yield a product with a commercial advantage over a competitor s product. 

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all pulmonary drug-delivery methods that existed before now, it delivered small molecule compounds (brochodilators or inhaled corticosteroids) to the airway (not necessarily to the deep lung) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems and their basic characteristics. 

Since the human respiratory tract is anatomically and physiologically a very heterogeneous system, the rate and extent of absorption of macromolecules as well as their potential adverse reactions depend on the regional doses. The most convenient method to deliver drugs to the respiratory tract is by inhalation. Other methods of delivery such as intratracheal instillation are used in experimental settings but are generally unsuitable for real-life therapeutic products. This section... 

This chapter presents an overview of formulation design, describes device function, and addresses product operation in relation to inhalation delivery system performance for nebulizers, MDIs, and DPIs. Methods of manufacture of... 

Apart from the seed zone method, a conventional seeding technique can also be used for preparing microcrystals for inhalation. This method involves the creation of seeds by suspending protein particles in a suitable buffer solution and centrifuging this suspension at about 10,000rpm for about lOmin. The supernatant can then be stored at 4°C, to be used as a seed solution. Protein particles can then be dissolved in another buffer solution but at a much lower pH to facilitate the dissolution of the protein. The amount of protein is then slowly increased to achieve supersaturation. The solution is then filtered and the initially prepared seed solution is added to the filtrate. The mixture is sealed and incubated at 37°C. The only issue with this conventional seeding method is that crystals above 5 pm could be formed, which are not suitable for pulmonary delivery (see Note 2). 

Boe J, Stiksa G, Svensson K, Asbrink E. New method of evaluating patient preference for different inhalation delivery systems. Ann Allergy 1992 68 255-260. 

Ricin is not an infectious agent but rather is a potent protein toxin produced from castor beans (Figure 3.5). Castor beans are common worldwide and the toxin is easy to produce. It makes a good bioweapon (better for assassination than for mass exposure) because it is stable and can be administered by several routes (inhalation, oral, or injection). Although ricin is not as deadly as some toxins, the ease of its production makes it attractive as a weapon. It has been especially attractive for small terrorist organizations that lack funds for obtaining more deadly weapons. Aerosol would be the most effective delivery method, but it is difficult to produce ricin particles in the 5-micron range so it is less useful for mass exposures. 

Following a biological attack in the form of an aerosol, signs of botulinum poisoning might appear much faster than in the food-borne form of illness. While the battlefield scenario includes inhaled particles, the use of projectiles such as flechettes contaminated with botulinum toxin is another possible delivery method. 

Kim CS, Hu SC, DeWitt P, Gerrity TR. Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. J Appl Physiol 1996 81 2203-2213. 

The data in Table 8.2 are taken from a study reported by Hindle et the purpose of which was to determine whether a new dry powder inhaler (DISK) was equivalent to a traditional metered-dose inhaler (MDI) in its ability to deliver doses of a bronchodilator to the lungs of volunteers. The data are the percentages of an inhaled dose of salbutamol recovered in a urine sample taken 30 min post-inhalation for each method of delivery in nine volunteers. Ameasure of treatment effect is the difference in percentages within volunteers, shown in the fourth column. Of these differences seven are negative and two are positive (fifth column) and the question we need to answer is how likely is it that if there is no difference between the inhalers, we would see this degree of imbalance between negatives and positives ... 

Compositions and methods for nucleic acid delivery to the lung. Inhale Therapeutic Systems Inc., San Carlos, CA. U.S. Patent No. 5994314, issued 11-30-1999. 

Depending on the particle morphology, several administration methods can be used aerosol, inhalation, and systemic- and subcutaneous injections. Typically, particles in the range of 5 to 100 pm are subcutaneously injectable, 1-5 pm particles are suitable for aerosol delivery and... 

Non-invasive insulin delivery is still experimental. The various methods (transdermal, nasal, lungs, oral) have been reviewed, with special attention to the various techniques and administration of inhaled insulin, which seems the most promising alternative to injection (266,267). 

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