Reconstitution parenteral preparations

The shelf life of reconstituted parenterals prepared in the hospital pharmacy is to be determined by the responsible pharmacist (see Sect. 22.6). When Ucensed injection fluids are reconstituted and prepared for individual patients the shelf life is determined by evaluation of the physico-chemical stability and risk of microbiological contamination. Shelf life depends from a microbiological viewpoint on the risks associated with aseptic preparation and the results of validation studies performed under the pharmacy s specified aseptic preparation cmiditions (see Sect. 31.3.6). 

For parenteral use, the antibiotic is packed in sterile vials as a powder (reconstituted before use) or suspension. For oral use it is prepared in any of the standard presentations, such as film-coated tablets. Searching tests are carried out on an appreciable number of random samples of the finished product to ensure that it satisfies the stringent quahty control requirements for potency, purity, freedom horn pyrogens and sterility. 

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). 

Parenteral 1 mg lyophilized powder to reconstitute for injection 1 See Table 41-4 for Insulin Preparations. 

The need for a multidose formulation may also dictate the use of a solid-state formulation. As the name implies, multidose products are intended to provide the patient with a product that contains several doses of the therapeutic within one container. Multidose formulations contain preservatives to kill any bacteria and prevent mold growth that may result from repeated entry into the drug product. Phenol and benzyl alcohol are two widely used preservatives in protein-based parenteral pharmaceuticals. Frequently, the addition of a preservative to the formulation compromises the long-term stability of the drug product, typically because the protein becomes physically unstable and/or exhibits oxidation. If the formulation scientist can obtain sufficient short-term stability (e.g., 2 weeks) for a formulation containing a preservative, then the use of a solid-state product may enable production of a multiuse formulation. In this case, the preservative is NOT added to the liquid bulk used to prepare the solid state. Instead, when the solid-state formulation is reconstituted prior to use, a preservative is included in the water for reconstitution. Thus the final product to be used is a multidose formulation that will experience only short-term exposure to the preservative. 

Polymeric micropsheres, particularly those prepared from the biodegradable polylactide/ polyglycolide polymers, have been widely investigated as a means to achieve sustained parenteral drug delivery. The advantage of formulating the polymeric matrix as microspheres is the ability to administer them via a conventional needle and syringe as a suspension formulation, rather than as an implant (see below). Lupron depot formulations are available which can provide therapeutic blood levels of leuprolide acetate for up to four months. These products are presented as lyophilized polylactic acid microspheres which are reconstituted to form a suspension prior to administration. 

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. 

Injections Infusions Parenterals Parenteral nutrition Administration Reconstitution Infusion systems RTA Formulation Preparation Phlebitis... 

The preparation activities that have been investigated covered 2 amounts of the active substance < 10 g and 10-100 g. So for working with either very small amounts (< say about 100 mg) or higher amounts > 100 g, this specific model may not offer the most suitable solutirm. Working with very small amounts occurs, for instance, within pharmacies, hospitals or nursing homes where employees crush tablets for patients with dysphagia (see Sect. 37.6.2) or reconstitute antibiotic mixtures or parenterals (see Sect. 26.5.3). 

Also in this situation a separate room is required for preliminary operations, e.g. disinfection of utensils and surfaces of materials. In the preparation room medicines are reconstituted, e.g. filling of syringes, infusion bags, medication cartridges, disposable infusion pumps and irrigations. In addition, parenteral nutrition fluids, antineoplastics, radiopharmaceuticals and eye preparations may be prepared in these premises. Radiopharmaceuticals and other very... 

Sterile medicines, and parenterals in particular, often require reconstitution (sometimes in excess of the SmPC) to make them ready to administer. Reconstitution of parenteral products requires aseptic handling (see Sect. 31.1). This handling can be simple (drawing up of a solution in a syringe for direct injection) or complex (preparation of a cassette reservoir with a number of substances for continuous... 

Freeze drying or lyophilization is a process that removes a solvent, typically water, from a frozen solution by sublimation. Studies in the 1930s and 1940s were done on blood serum and foods. More recently, research has focused on using freeze drying for pharmaceuticals, cosmetics, and chemicals. An increasing number of parenteral products have been prepared by freeze-drying techniques. The method reduces particulate contamination, improves product quality and stability, and enhances the dissolution rate on reconstitution. 

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