Parenteral delivery routes drug inhalation

Parenteral delivery routes are those that do not give rise to drug absorption into the splanchnic circulation. Thus, they avoid the possibility of hepatic first-pass metabolism. It should be noted that some parenteral routes do not avoid other first-pass metabolism effects (e.g., pleural metabolism for some inhaled drugs). Some major parenteral drug delivery routes are intraarterial, intrathecal, intravenous, intramuscular, trans-dermal, intranasal, buccal, inhalation, intraperitoneal, vaginal, and rectal. 

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. 

Although routine oral delivery of proteins has not been realized, some protein formulations have been developed for pulmonary delivery. Pulmonary delivery can result in either parenteral or local administration of the drug and, like oral delivery, is considered non-invasive. As with other routes of delivery, the size of the protein may limit its ability to be delivered systemi-cally via the pulmonary route of administration. Pulmozyme , a DNase-based formulation approved for the treatment of cystic fibrosis (CF), is delivered to the lungs by a nebulizer to clear blockage of the airways in the CF patient.Formulations for insulin to be administered by inhalation for systemic delivery of... 

Since the ideal attributes of drug substances differ markedly for different dosage forms, properties appropriate to one dosage form may be inappropriate for another. For this reason, the drug substance attributes should suit the primary mode of delivery (i.e. oral, parenteral, inhalation, or other routes, if appropriate) and the dose (or dose range) required. If other dosage forms are developed, such as line extensions, at a future date, it may be necessary to counteract any adverse properties of the selected salt using suitable formulation techniques. 

The delivery of freeze-dried preparations can be performed by different routes oral, nasal, anal, pulmonary, transdermal and parenteral. Of these routes, some do not require any treatment of the drug before it is administered, e.g. in the form of powders or tablets or in inhaling devices. For parenteral administration, however, whether by injection or infusion, the freeze-dried cake must be returned to a liquid state, a process referred to as reconstitution . The main vehicle will normally consist of water for injection or a solution, the concentration of which will establish isotonicity. The time required for the complete dissolution of the cake may in some cases be critical and should therefore be known. 

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