Inhalation products

The products are available as tablets, capsules, liquids (in the form of solutions, suspensions, emulsions, gels, or injectables), creams (usually oil-in-water emulsions), ointments (usually water-in-oil emulsions), and aerosols, which contain inhalable products or products suitable for external use. Propellants used in aerosols include chlorofluorocarbons (CFCs), which are being phased out. Recently, butane has been used as a propellant in externally applied products. The major manufactured groups include ... 

Figure 5 shows examples of two dry powder inhalers, the Turbuhaler and the Diskus, currently marketed in the United States for the delivery of the steroids, budesonide and fluticosone, respectively. Table 6 shows the major elements of a number of passive dry powder inhalers. In addition to the commercially available passive inhalation products, a number of active dispersion systems are under development the key characteristics of selected devices are shown in Table 7. 

The development pharmaceutics section should also include consideration of possible overdosing of the active ingredient that might arise from normal use of the dosage form—e.g., deposition of drug substance from a metered dose inhalation product in the mouth. 

Newton, P.E. (2000). Techniques for Evaluating Hazards of Inhaled Products. In Product Safely Evaluation Handbook, 2nd ed. Marcel Dekker, New York, pp. 243-298. 

According to an estimate in early 2000s, 12% of the pharmaceutical market comprises DDSs. This share will definitely increase in the future as it is evident from some of the considerations made above. Among the market share of various DDSs, oral dosage forms account for approximately 60%, inhalation products for 20%, transdermal about 10%, and injectables around 9%.119... 

Studies have shown that in order to clear the oropharyngeal impaction barrier (comprising the mouth, throat, and pharynx), particles with aerodynamic diameters smaller than 5 pm are required [3,4]. Only particles with aerodynamic diameters less than 3 pm reach the terminal bronchi and the alveoli in significant numbers [5]. Therefore, the particle diameter required to be produced by the delivery system depends to a great extent on the intended target lung tissue. Lung deposition is also affected substantially by the specific inhalation dynamics of the patient, which in turn are influenced by the delivery device. This article addresses various attributes of the dry powder inhalation product, from intrinsic material properties to final product performance. 

Formulation of dry powders for inhalation must rely on a very short list of excipients to fulfill the customary roles of diluent, stabilizer, solubilizer, processing aid, and property modifier (e.g., flow enhancer). In the United States, only a few materials are approved for use in inhalation products, and of those (e.g., propellants, surfactants) many are of little help in dry powder formulation. 

To measure lung deposition by imaging, the aerosol must be first labelled or tagged with a suitable radionuclide. Radiolabelling techniques have been developed for current inhalation products including nebulizers, propellant-driven metered dose inhalers, and dry powder inhalers. 

Numerous other peptides and proteins have been, or are still in development as inhalation products with the objective of systemic absorption. Examples of these are calcitonin, LH-RH antagonists, recombinant human granulocyte colony-stimulating factor and growth hormone. 

Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation, for example, fillers, disintegrants, binders, lubricants and glidants. An added complexity is the fact that certain excipients can have different functional roles in different formulation types. Thus, lactose is widely used as a filler or diluent in solid oral dosage forms, for example, tablets and capsules [2] and as a carrier for inhalation products [3]. 

The financial costs are also considerable. To complete the toxicology programme, an inhalation product would cost over 5 000 000 and with the most expeditious planning, would take 5 years to complete. 

Adverse reactions from inhalational products may include back or chest pain, bronchitis, cough, changes to COPD exacerbation, dizziness, dry mouth, dyspepsia, dyspnea, epistaxis, Gl distress, headache, influenza-like symptoms, nausea, nervousness, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, urinary tract infection. 

Hoye, W. L., Mogalian, E. M., and Myrdal, P. B. (2005), The effects of extreme temperatures on drug delivery of albuterol sulfate hydrofluoroalkane inhalation products, Am. J. Health-Syst. Pharm., 62(21), 2271-2277. 

Jinks, P., and Marsden, S. (1999),The development and performance of a fluoropolymer lined can for suspension metered dose inhaler product, in Fradley, G., Ed., Proceedings of Drug Delivery to the Lungsa X, The Aerosol Society, Portshead, United Kingdom, pp. 177-180. 

Although the use of Raman mapping has clear benefits to the analysis of inhaled product, the approach has a number of limitations. These include... 

Ultimately chemical images have the ability to show API adhering to other formulation excipients which is not possible by other sizing methods. Statistically, laser diffraction methods have less errors in the measurement as they measure millions of particle compared to the hundreds by Raman chemical imaging, but their lack of specificity means the whole sample is measured and not just the API. Ultimately the Raman method is still under development but provides the formulators of inhaled products an additional tool in understanding formulation properties and product. 

Epinephrine (Adrenalin, Bronkaid Mist, Primatene Mist, others). Epinephrine appears to directly stimulate all adrenergic receptor subtypes and is administered for a variety of reasons. Epinephrine is found in many antiasthmatic inhalation products because of its ability to stimulate beta-2 receptors on the bronchi. Because it stimulates vascular alpha-1 receptors, epinephrine may be applied topically to produce local vasoconstriction and control bleeding during minor surgical procedures (e.g., suturing superficial wounds). Likewise, epinephrine may be mixed with a local anes-... 

Figure 8.1 Mutually interdependent determining factors in development of a dry-powder inhalation product (Courtesy of SkyePharma.)...

The asthma market is thought to be worth some 6 billion worldwide, and consists mainly of inhaled products—bronchodilators and corticosteroids. It is a growing market because the incidence of asthma is increasing, especially in developed countries. It has been postulated that this increase is partly related to overuse of inhaled bronchodilators, which can mask progression of the underlying inflammatory disease process. Current recommendations specify the routine use of anti-inflammatory therapy (e g. inhaled steroids) for mild asthma, with bronchodilators used to relieve acute attacks in more serious cases. 

Sterile Injectable Pellet Implant Solution or Ointment for Ophthalmic Administration Inhalation Products Oral Dosage Forms... 

---