Liquid dosage forms parenteral formulations

The liquid formulation for parenteral administration requires additional physical and microbiological functionalities, such as syringeability, sterility, osmolarity, and pyrogen freedom. The particle size change can influence the syringeability of injection of a suspension formulation as well as the level of irritation at the site. Terminal sterilization such as autoclave or gamma irradiation may affect the physical stability of the dosage form. Both formulation and container systems should be evaluated [63]. 

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. 

Solid oral dosage forms, particularly tablets, are the preferred type of formulation worldwide. Not only are these products widely accepted by consumers, but they are also relatively cheaper to develop and manufacture than oral liquids or suspensions, parenterals, or suppositories. Figure 4 shows, quite clearly, that the elderly primarily make use of solid oral dosage forms (165). 

Given the complexity of some of the dosage forms mentioned earlier, this guidance was limited to solid oral dosage forms, liquid oral dosage forms, and parenterals (small and large volume). These products serve as models, and the principles applied can be used for all other dosage forms such as inhalation products, topical formulations, and transdermal systems. 

In practical terms, terminal sterilization of liquid parenteral products means sterilizaticMi by saturated steam. Production of free radicals in water prohibits the application of radiation sterilization to aqueous products, but radiation sterilization may be suitable for some solid dosage forms. Dry heat and ethylene oxide are unlikely to be of any value. In the first instance, therefore, saturated steam should be the process of first choice for sterilization of thermally stable drug substances dosage forms should not be formulated in ways that compromise thermal stability. 

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