Dosage form aerosols

In aerosol dosage forms, the micronized active ingredient, suspending agent, CFC, and HFA propellants are usually the most crucial raw materials. Other additives such as antioxidants or flavors may also be crucial. 

Moren, F. Aerosol dosage forms and formulation. In Aerosols in Medicine, Principle, Diagnosis and Therapy, Moren, F., Dolovich, M.B., Newhouse, M.T., Newman, S.P., Eds. Elsevier Science Publisher Amsterdam, 1993 321-350. 

Lee SW, Sciarra JJ. Development of an aerosol dosage form containing insulin. / Pharm Sci 1976 65 567-572. 

Many therapeutically active ingredients are administered or applied to the body by means of the aerosol dosage form, including agents such as epinephrine, isoproterenol, antibiotics, antiseptics, steroids, and ergotamine. Oral aerosols have been used for the symptomatic treatment of asthma as well as for the treatment of migraine headaches, whereas topical aerosols find use in numerous dermatological manifestations. 

Particle size analysis of pharmaceutical aerosols has a strong foundation based on other disciplines. Most of the analytical techniques used were in existence before the development of the modem pharmaceutical aerosol dosage form. However, some significant challenges have to be overcome in the use of these techniques for assessing pharmaceutical systems. 

The aerosol dosage form provides several distinct advantages including ... 

Moran F. Aerosol dosage forms and formulations. In Moran F, Dolovitch MB, Newhouse MT, Newman SP, eds. Aerosols in Medicine, Principles, Diagnosis and Therapy, 2d ed. Amsterdam Elsevier Science, 1993 321-350. 

An aerosol dosage form developed by suspending zinc insulin crystals in a propellant together with oleyl alcohol to improve the wetting of the crystals was stated to be chemically stable (Lee and Sciarra, 1976), but as this conclusion was based on immunoassay results, it does not necessarily reflect reality. When insulin is formulated for pulmonary delivery by dry-powder generators (Byron, 1990), it is important to remember that insulin in the dry state, in an amorphous as well as a crystalline form, is hygroscopic, even when it contains 10-20% water, depending on the relative humidity. 

Yoshida, H., Okumura, K., Hori, R., Anmo, T., and Yamaguchi, H., 1979, Absorption ofinsulin delivered to rabbit trachea using aerosol dosage form, y. Pharm. Sci 68 670-671. 

Aerosols. Pressurized containers to deHver aerosolized dmg products through appropriate systems of valves and actuators have been available since the 1950s (see Aerosols). Such dosage forms are used as external appHcations of lotions and creams, for oral inhalation, or for treatment of the vaginal cavity, eg, contraceptive foams. Aerosols contain two- or three-phase systems, wherein a volatile Hquid or admixture of Hquids is sealed in a... 

An interface is defined as a boundary between two phases. The solid/liquid and the liquid/liquid interfaces are of primary interest in suspensions and emulsion, respectively. Other types of interfaces such as liquid/gas (foams) or solid/gas interfaces also play a major role in certain pharmaceutical dosage forms, e.g., aerosols. 

Aeromonas, DNA-based biosensor, 3 807 AeroSizer, 78 150—151 Aerosol containers, 7 781-782 Aerosol dispersions, 7 774-775 Aerosol drug dosage forms, 78 717 Aerosol emulsions, 7 773, 774 Aerosol flow reactors, 77 211-212 Aerosol foams, 7 773, 774 Aerosol packaging, 7 771 Aerosol pastes, 7 775 Aerosols, 7 769-787 8 697 economic aspects, 7 786 filling, 7 785-786 formulation, 7 771-780 product concentrate, 7 772-775 propellants, 7 775-781 U.S. production, 1985-2000, 7 770t Aerosol solutions, 7 772-773 Aerosol solvent extraction system (ASES), 24 17, 18... 

Drug development, proteins in, 20 839 Drug discovery, yeasts in, 26 488 Drug dosage forms, 15 702-718 aerosols, IS 717 biotechnology and, IS 717-718 capsules, 15 708 granules, 15 702-705 liquid, 15 712-713 lyophilization, 15 716 ophthalmic, 15 716 parenteral, IS 713-716 prolonged action/controlled release solid, 15 708-712... 

Rate of mucociliary clearance - Concentration of active ingredient - Type of dosage form (liquid, aerosol, powder)... 

The first section is focused on orally administered solid dosage forms, whereas within the second section, approaches for pulmonary administered aerosols are highlighted. 

Several dosage forms carry an increased risk of degradation or adjunct formation. Products such as injections and aerosols are more likely to interact with volatiles or extractables from packaging and closure systems. Tablets have the potential to form adjuncts with excipients (specifically, lactose has been shown to form adjuncts in tablets). Non-CFC propellants in aerosols have a large number of impurities that typically do not interact with drug substances, but the potential for these interactions does still exist. Creams, ointments, lotions, and other such products will each have specific interactions that should be considered while evaluating the impurity profile of a drug product. 

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

Aerosolized DNase (dornase) is a therapeutic protein designed for alveoli delivery to achieve local effects in the deep lung. Aerosolized DNase is formulated as a pulmonary dosage form, targeted for deep-lung delivery to reduce opportunistic infections due to the increased viscosity of mucus in the lung that affects respiratory function in patients with cystic fibrosis. 

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

Inhalation aerosols have been used for the delivery of drugs to the respiratory system since the mid-1950s. The most common dosage form for inhalation is the metered-dose inhaler (MDI), by which the drug is delivered from a pressurized container using a liquefied gas propellant. Medication delivered via this dosage form has allowed for a quick therapeutic response to the symptoms of asthma, emphysema, and chronic obstructive pulmonary disease (COPD), and has resulted in an improvement in the quality of life for millions of asthma sufferers. 

The process validation protocol of a new aerosol product should be written by a qualified manufacturing or validation specialist familiar with aerosols. Others experienced in oral dosage forms such as suspensions or solutions would also be helpful. These technical specialists may be within the research, validation, or technical support departments, since this work will be done prior to approval of a new product. Approval of the protocol should be given by quality assurance, quality control, production management, and research. 

Wu-Pong and Byron [15] have contributed a review of the issues associated with pulmonary delivery of ASOs. Since ASOs are freely soluble and highly hygroscopic, it would be reasonable to assume that initial dosage forms will rely upon the aerosolization of simple aqueous solutions. Our data indicate that commercially available nebulization devices will generate suitable aerosolizations of ASO solutions at concentrations up to 180 mg/mL [3]. Ultrasonic and jet nebulizations were found to have essentially no effect on the phosphorothioate stability of the ASO over 40 min, which is longer than typical treatment times. 

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