Intravenous injection formulation

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

Figure 7 Observed concentration—time data for ISMN from the test extended-release formulations included in the four PK studies. The profile for the reference formulation (a) is represented as an intravenous injection with the same AUC as the reference extended-release formulation (IMDUR) and the literature elimination half-life of 3.77 hr. IVIVC development included the two fast ( ) and one medium (o) batch from Study 194.573 and two slow batches ( ) from Study 372.05/196.638 and external validation included the two medium batches ( ) in Studies 196.581 and 372.02.

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

The synthetic route should aim at incorporating the label as late as possible in the sequence. This requires the development of rapid syntheses (generally not more than 3 h for compounds) including HPLC purification and formulation of the radiopharmaceutical for intravenous injection. The large amounts of reagents compared to those of the labelled substrate [20] usually lead to rapid reactions. However, unexpected labelled compounds can also arise from side reactions of reagents in excess or from reactive impurities present in the reaction medium [21]. 

Dosage form ReFacto is a sterile lyophifized powder for injection available in nominal dosage strengths of 250, 500, and 1000 international units (lU) per vial. Recombinate is formulated as a sterile lyophifized powder preparation of concentrated recombinant AHF for intravenous injection and is available in single-dose bottles which contain nominally 250, 500, and 1000 lU per bottle. The final product contains an insufficient quantity of von Willebrand Factor to have any clinically effect in patients with von Willebrand s disease. 

Cyclizine has antimuscarinic properties and is a potent anti-emetic, effective for the control of postoperative and drug-induced nausea and vomiting. It has been used to prevent motion sickness, although diphenhydramine and promethazine are more effective. It is available in oral and parenteral formulations. In contrast to many other first-generation antihistamines sedation is not marked. It is available in tablet form as the hydrochloride and in injectable form as the lactate. Because of its anticholinergic action, blurred vision and dry mouth are associated with clinical doses. When given by rapid intravenous injection tachycardia may be a problem. Meclozine is a related drug which, like cyclizine, is used primarily for motion sickness. 

Amphotericin is an amphoteric polyene macrolide (polyene = containing many double bonds macrolide = containing a large lactone ring of 12 or more atoms). It is nearly insoluble in water and is therefore prepared as a colloidal suspension of amphotericin and sodium desoxycholate for intravenous injection. Several new formulations have been developed in which amphotericin is packaged in a lipid-associated delivery system (Table 48-1 and Liposomal Amphotericin B). 

The clinical usefulness of somatostatin is limited by its short half-life in the circulation (3 minutes) when it is administered by intravenous injection. Octreotide is a synthetic octapeptide with actions similar to somatostatin. When administered intravenously, it has a serum half-life of 1.5 hours. It also may be administered by subcutaneous injection, resulting in a 6- to 12-hour duration of action. A longer-acting formulation is available for once-monthly depot intramuscular injection. 

Intravenous injection is the most common route although subcutaneous injection may also be used. A concentrated nasal spray formulation has been proved to be efficient for home treatment of patients with bleeding episodes or even minor surgical procedures and has also been used prophylacticly (4). The nasal spray used to treat diabetes insipidus (Desmospray) is too dilute for use in disorders of hemostasis. Similarly, desmopressin in tablet form (Desmotabs) is intended for treatment of nocturnal enuresis in children and is of no use in the treatment of hemostatic disorders. 

Moschwitzer, J., Achleitner, G., Pomper, H., and Muller, R. H. (2004) Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology, Eur. J. Pharm. Biopharm., 58 615-619. 

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