Parenteral preparations

Distilled water is often used in the formulahon of oral and topical pharmaceutical preparations and a low bacterial count is desirable. It is also used after distillation with a specially designed still, often made of glass, for the manufacture of parenteral preparations and a post-distillation heat sterilization stage is commonly included in the process. Water for such preparahons is often stored at 80°C in order to prevent bacterial growth and the production of pyrogenic substances which accompany such growth. 

Water for injection (WFI) is the most widely used solvent for parenteral preparations. The USP requirements for WFI and purified water have been recently updated to replace the traditional wet and colorimetric analytical methods with the more modern and cost-effective methods of conductivity and total organic carbon. Water for injection must be prepared and stored in a manner to ensure purity and freedom from pyrogens. The most common means of obtaining WFI is by the distillation of deionized water. This is the only method of preparation permitted by the European Pharmacopoeia (EP). In contrast, the USP and the Japanese Pharmacopeias also permit reverse osmosis to be used. The USP has also recently broadened its definition of source water to include not only the U.S. Environmental Protection Agency National Primary Drinking Water Standards, but also comparable regulations of the European Union or Japan. 

Instruments that measure scattered light, such as the Photo-Nephelometer (Coleman Instruments, Oak Brook, IL), are used to evaluate and set clarity standards for parenteral preparations. It is not possible to establish an overall standard value for all products (e.g., 30 ne-phelos) because the value itself is relative and influenced by many factors, including concentration, aging, stopper extracts, and the solubility characteristics of the raw materials. Nephelometer readings are insensitive to contamination by large (visible) particulates. 

The significance of particulate contamination in all parenteral preparations and devices has received much attention. Although it has not been established that particles can cause toxic effects, the pharmaceutical industry, the medical profession, hospital pharmacists, and FDA all realize the importance of reducing particulate levels in all parenteral products and devices. 

Pyrogens may be detected in parenteral preparations (or other substances) by a number of methods. Two such methods are widely employed in the pharmaceutical industry. 

Its major disadvantage is its selectivity it only detects endotoxin-based pyrogens. In practice, however, endotoxin represents the pyrogen that is by far the most likely to be present in pharmaceutical products. The LAL method is used extensively within the industry. It is used not only to detect endotoxin in finished parenteral preparations, but also in WFI and in biological fluids, such as serum or cerebrospinal fluid. 

Irritation. Tissue irritation upon injection, and the accompanying damage and pain, is a concern that must be addressed for the final formulation, which is to be either tested in humans or marketed, rather than for the active ingredient. This is because most irritation factors are either due to or influenced by aspects of formulation design (see Avis, 1985, for more information or parenteral preparations). These factors are not independent of the route (TV, IM, or SC) that will be used and, in fact (as discussed later), are part of the basis for selecting between the various routes. 

Avis, K.E. (1985). Parenteral preparations. In Remington s Pharmaceutical Sciences (Gennaro, A. R., Ed.). Mack Publishing Company, Easton, PA, pp. 1518-1541. 

Ciclosporin is a potent immunosuppressant, which is markedly nephrotoxic. It may cause gastrointestinal disturbances. Ciclosporin is available as capsules, oral solution and parenteral preparations. 

One of the main disadvantages of depot parenteral preparations is that administration of these preparations may not be acceptable to the patient. The depot preparation requires a lower dosing frequency when compared with other dosage forms. 

Q23 The use of a suspension as a parenteral preparation is contraindicated when the route of administration is ... 

Parenteral preparations in the form of a suspension cannot be administered through the intravenous route. Preparations intended for administration in this way must be soluble solutions to avoid occlusion of the veins. 

Age or body weight can affect the systemic availability of many antimicrobial agents. In the physically smaller animal (sheep and pig) the peak serum concentration of a drug is usually higher and is followed by a rapid decline compared with a lower peak and a slower decline of the antibiotic in seruon of the larger animal (cow and horse). The limited experimental data appear to indicate that the extent of systemic availability of IM-administored antibiotics can vary as widely between different sites as between IM and SC sites. A corollary to this observation is that the location of the extra-vascular injection site should be well-defined when determining the systemic availability of parenteral preparations (9). 

Gut oedema can reduce drug bioavailability, increasing Tmax and reducing Cmax- If the response to oral drug is less than would have been expected or absent altogether, consider this explanation and, if appropriate and necessary, change to a parenteral preparation. 

Halofantrine, a 9-phenanthrenemethanol derivative, is a blood schizonticide and is active against Plasmodium vivax and chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum. As no parenteral preparation is available it cannot be used for severely ill patients. Oral absorption is slow and incomplete and is increased by a fatty meal. 

The polymyxins are slowly excreted by glomerular filtration the slow elimination rate is due to binding in tissues. Elimination is decreased in patients with renal disease, and drug accumulation can lead to toxicity. Sodium coUstimethate, the parenteral preparation, binds less to tissue and is excreted faster than the free base. 

Iron complex, parenteral preparations iron-dextran... 

Iron trivalent, parenteral preparations iron-sorbitol-citric acid complex... 

Parenteral preparations Iron dextran (IMFERON) Iron-sorbitol citric acid complex (JECTOFER). 

Parenteral preparations containing fixed dose combination of streptomycin with penicillin. 

One of the most important processes involved in the scale-up of liquid parenteral preparations is mixing (1). For liquids, mixing can be defined as a... 

Iron dextran, iron sucrose complex, and sodium ferric gluconate complex Parenteral preparations can cause hypersensitivity reactions ... 

When it is necessary to maintain continuously elevated plasma corticosteroid levels to suppress ACTH, a slowly absorbed parenteral preparation or small oral doses at frequent intervals are required. The opposite situation exists with respect to the use of corticosteroids in the treatment of inflammatory and allergic disorders. The same total quantity given in a few doses may be more effective than that given in many smaller doses or in a slowly absorbed parenteral form. 

I Highly resistant borosilicate glass Parenteral preparations... 

II Treated soda-Ume glass Acidic or neutral parenteral preparations... 

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