Inhalation lyophilization

With respect to the shellfish meat, asthma and contact urticaria were reported in a restaurant worker from the handling of scallops (Goetz and Whisman, 2000). Inhalation of lyophilized clam in a factory producing freeze-dried clam was reported as a cause of occupational asthma (Desjardins et al, 1995). Occupational asthma has also been linked... 

Virazole is a brand name for ribavirin, a synthetic nucleoside with antiviral activity. VIRAZOLE for inhalation solution is a sterile, lyophilized powder to be reconstituted for aerosol administration. Each 100-mL glass vial contains 6 g ribavirin, and when reconstituted to the recommended volume of 300 mL with sterile water for injection... 

Protein-based drugs have been formulated mainly as stable liquids or in cases where liquid stability is limiting as lyophilized dosage forms to be reconstituted with a suitable diluent prior to injection. This is because their delivery has been limited primarily to the parenteral routes of intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration. There are a few drugs that have been developed for pulmonary delivery, such as rhDNase (Pulmozyme ) and an inhalable formulation of insulin (e.g., Exubra ). However, even such drugs have been formulated as either liquid or lyophilized or spray-dried powders. This chapter will focus only on excipients that are applicable to liquid and lyophilized protein formulations. 

Lactose is widely used as a filler or diluent in tablets and capsules, and to a more limited extent in lyophilized products and infant formulas.Lactose is also used as a diluent in dry-powder inhalation. Various lactose grades are commercially available that have different physical properties such as particle size distribution and flow characteristics. This permits the selection of the most suitable material for a particular application for example, the particle size range selected for capsules is often dependent on the type of... 

Both the inhalant (aerosol) and parenteral dosage forms of pentamidine iselhionale arc sterile lyophilized powders that must be made up as sterile aqueous solutions prior to use. Sterile water fur injection must be used to reconstitute the aerosol, to avoid precipitation of the pentamidine salt. Adverse reactions to the drug ate common. These include cough and bmnehospasm (inhalation) and hypertension and hypoglycemia (injection). 

Cisplatin is only available for intravenous use. It is generally supplied in vials as a solution or as a lyophilized powder. The possibility exists for dermal, oral, or inhalation exposure during production, and during preparation of dosing formulations. 

The majority of medicines today are formulated as tablets [1], Tablets are formulated rapidly and economically, and they have high patience compliance. Also, many compounds, such as aspirin, degrade rapidly in solution and are formulated in solid dosages to increase stability [2]. Drug substances that are oils, liquids, and solids may be formulated into capsules, tablets, lyophiles, creams, or microsuspensions. Administration may be through ingestion, injection, topical application, inhalation, and other routes. The reader may consult other texts for discussion of formulation options [1,3]. Formulations are selected for stability and the ability to best deliver the active agent to the affected area of the patient or consumer. 

The manufacturing factors that may be affected by the choice of a particular polymorphic form include granulation, milling and compression, stability (particularly for semisolid forms), amount of dose delivered in metered inhalers, crystallization from different solvents at different speeds and temperature, precipitation, concentration or evaporation, crystallization from the melt, grinding and compression, lyophilization, and spray drying. In the manufacturing processing, crystallization is a major problem and it can be avoided by a careful study of polymorphic transition, particularly in supercritical fluids. 

A simple way of applying enzymes in a non-aqueous reaction is through addition of lyophilized enzyme powder. With a hydrophobic solvent, this will create an enzyme suspension and, if other conditions (substrate, temperature, etc.) are acceptable, it will probably work. For a quick screening of a range of enzymes it may even be the most optimal setup. It is, however, well known that many enzymes lose activity upon lyophilization (which to some degree can be prevented by the use of lyoprotectants). Another concern is that enzyme dust is potentially allergenic if inhaled. 

Direct contact with enzymes should be avoided. This is particularly important with respect to the inhalation of aerosols (from liquid formulations) or protein dust from lyophilized or spray-dried protein preparations. Depending on the person, the tendency to develop allergies (itching, red stains) can be very different. However, the development of serious health problems due to contact with cell-free protein formulations is extremely unlikely. 

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