Injectable products intravenous infusions

Most injections are formulated as aqueous solutions, with Water for Injections BP as the vehicle. The formulation of injections depends upon several factors, namely the aqueous solubility of the active ingredient, the dose to be employed, thermal stability of the solution, the route of injection and whether the product is to be prepared as a multidose one (i.e. with a dose or doses removed on different occasions) or in a singledose form (as the term suggests, only one dose is contained in the injection). Nowadays, most injections are prepared as single-dose forms and this is mandatory for certain routes, e.g. spinal injections such as the intrathecal route and large-volume intravenous infusions (section 2.2). Multidose injections may require the inclusion of a suitable... 

Route of administration The reconstituted product must be administered intravenously by either direct syringe injection or drip infusion. Kogenate and Kogenate FS must be administered within 3 hours after reconstitution. 

In several cases the special nature of a formulation will preclude dilution by an aqueous infusion fluid. Injectable products containing phenytoin, digoxin and diazepam may come into this category if they are formulated in a nonaqueous but water-miscible solvent (such as an alcohol-water mixture) or as a solubilised (e.g. micellar) preparation. Addition of the formulation to water may result in precipitation of the dmg, depending on the final concentration of the dmg and solvent. It has been suggested that precipitation of the relatively insoluble diazepam may account for the high (3.5%) incidence of thrombophlebitis which occurs when diazepam is given intravenously. 

The belladonna alkaloids are absorbed rapidly after oral administration (75). They enter the circulation when applied locally to the mucosal surfaces of the body. Atropine absorbed from inhaled smoke of medicated cigarettes can abolish the effects of intravenous infusion of methacholine in humans. The transconjunctival absorption of atropine is considerable. About 95% of radioactive atropine is absorbed and excreted followingsubconjunctival injection in the rabbit. The total absorption of quaternary ammonium derivatives (Section 3.5) of the alkaloids after an oral dose is only about 25%. The liver, kidney, lung, and pancreas are the most important organs that take up the labeled atropine. The liver probably excretes metabolic products of atropine by way of bile into the intestine (in mice and rats). 

Toxicity from local anesthetics (other than cocaine) is usually caused by therapeutic overdosage (ie, excessive doses for local nerve blocks), inadvertent acceleration of intravenous infusions (lidocaine), or accidental injection of products meant for dilution (eg, 20% lidocaine) instead of those formulated for direct administration (2% solution). Acute injection of lidocaine has also been used as a method of homicide. 

Due to the lack of activity after oral administration for most peptides and proteins, administration by injection or infusion - that is, by intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration - is frequently the preferred route of delivery for these drug products. In addition, other non-oral administration pathways have been utilized, including nasal, buccal, rectal, vaginal, transder-mal, ocular, or pulmonary drug delivery. Some of these delivery pathways will be discussed in the following sections in the order of the increasing biopharmaceutic challenges to obtain adequate systemic exposure. 

Formulation studies are performed to develop a suitable vehicle to solubilize the drug for administration to patients, generally by intravenous injection or infusion in the case of cancer. The low solubility of many natural products in water poses considerable problems, but these can be overcome by use of co-solvents or emulsifying agents (surfactants) such as Cremophore EL (polyoxyethylated castor oil). 

Injectable formulations are normally administered by intravenous (IV) bolus, IV infusion, intramuscular bolus, or subcutaneous bolus, but also occasionally as subcutaneously implanted osmotically driven pumps, or as dental products via subgingival local administration. The injectable formulations are either ready-to-use solutions, concentrated solutions for dilution, or lyophilized powders that are reconstituted prior to injection. 

The most important requirement is that the salt possesses sufficient solubility at physiologically compatible pH values to permit incorporation into the dosage form. Buffering the solution to an appropriate pH can often enhance solubility. Salts may also be prepared in situ in the formulation. This is particularly useful when the main route of administration utilizes the parent drug form. Where the aqueous solubility of the salt is not sufficiently high, co-solvents may need to be added to enhance solubility (e.g. propylene glycol is used as the vehicle in phe-nobarbitone sodium injection). Parenteral solutions based on co-solvent vehicles normally cannot be directly injected intravenously because there is the risk of precipitation at the injection site. Therefore, such products are diluted with isotonic saline or 5%w/v dextrose solution to produce a lower concentration that remains soluble and can be safely administered by infusion. Alternative delivery routes are by subcutaneous or intramuscular administration by which, in... 

The formulation of parenteral products involves careful consideration of the proposed route of administration and the volume of the injection. Injections are administered to the body by many routes into various layers of the skin, the subcutaneous and muscle tissue, into arteries or veins, into or around the spinal cord, or directly into various organs (e.g., the heart or the eye). The volume to be injected can range from microliters, typically diagnostic agents administered intradermally or insulin administered subcutaneously, to several liters administered intravenously as infusions. The route of administration and the volume to be injected affect the composition of the formulation. 

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