Parenteral preparations preparation method

The Ph. Eur. states requirements to the extractable volume of parenterals The volume of the injection in the container is sufficient to permit the withdrawal and administratirai of the nominal dose using a normal technique . In Ph. Eur. chapter 2.9.17 Test for extractable volume of parenteral preparations the method of analysis is described. 

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. 

An example of the second method of parenteral suspension preparation is testosterone suspension. Here, the vehicle is prepared and sterile-filtered. The testosterone is dissolved separately in acetone and sterile-filtered. The testosterone-acetone solution is aseptically added to the sterile vehicle, causing the testosterone to crystallize. The resulting suspension is then diluted with sterile vehicle, mixed, the crystals allowed to settle, and the supernatant solution siphoned off. This procedure is repeated several times until all the acetone has been removed. The suspension is then brought to volume and filled in the normal manner. 

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. 

The extent of absorption (systemic availability) of a drug is estimated by the method of corresponding areas. Comparison of total AUC following the intramuscular injection of a parenteral preparation (solution or suspension) with that following the intravenous injection of a bolus dose of the drug (parenteral solution) provides an estimation of absolute bioavailability, while comparison of AUCs following intramuscular injection of different parenteral preparations (one of which must be a reference formulation) at the same injection site or of the same parenteral preparation at different injection sites estimates the relative bioavailability. A crossover design with an appropriate washout period between the phases of the bioavailability study should be used whenever feasible. 

Liquid formulations for parenteral use require preparation methods and composition that make the formulation stable and sterile. Other requirements for parenteral formulations are given by the European Pharmacopoeia such as tonicity, efficacy of the antimicrobial... 

Method testing for application in local tap water, bi-distilled water, deionized water, and parenteral preparation... 

VI. Dosage and method of administration (adults and children). Note The parenteral preparation is no longer available in the United States. The oral form may be substituted, but is of unknown efficacy. 

For irrigatiOTis steam sterilisation in its final container for 15 min at 121 °C (see Sect. 30.5.1) is preferred. These are the same requirements as for parenteral solutions. An aseptic preparation method with bacterial filtration through a 0.2 pm filter, followed by heating at 100 C for 30 min (or another proper combination of temperature and time or validated aseptic conditimis) is an alternative when one of the substances is sensitive to a higher temperature. If an active substance is not heat resistant at all, only an aseptic preparation with bacterial filtration over a 0.2 pm filter is possible. In such cases the starting materials should be sterile or have a low bioburden and the irrigation should be prepared asep-tically. See also Sect. 30.6. 

Two basic methods are used to prepare parenteral suspensions (a) sterile vehicle and powder are combined aseptically, or (b) sterile solutions are combined and the crystals formed in situ. Examples of these procedures may be illustrated using Penicillin G Procaine Injectable Suspension USP and Sterile Testosterone Injectable Suspension USP. 

The basic principles employed in the preparation of parenteral products do not vary from those widely used in other sterile and non-sterile liquid preparations. However, it is imperative that all calculations are made in an accurate and most precise manner. Therefore, an issue of a parenteral solution scale-up essentially becomes a liquid scale-up task, which requires a high degree of accuracy. A practical yet scientifically sound means of performing this scale-up analysis of liquid parenteral systems is presented below. The approach is based on the scale of agitation method. For singlephase liquid systems, the primary scale-up criterion is equal liquid motion when comparing pilot-size batches to a larger production-size batches. 

For parenteral uses, the sizes of MLVs prepared by the above methods need to be small enough t pass through the aseptic Liter. Three methods that are used in reducing the particles sizes will bi discussed as follows sonication, high-pressure homogenization, and extrusion. 

---