Parenteral products types

Oral Staphylococcal enterocolitis and antibiotic-associated pseudomembranous colitis produced by C. difficile. The parenteral product may also be given orally for these infections. Oral vancomycin is not effective for other types of infection. 

It is important to understand the various types of waters used in parenteral products. The most frequently used solvent in parenteral products is Water for Injection, USP, which is not required to be sterile... 

The results of endotoxin tests for in-process solutions, bulk materials, and finished parenteral products should be reported in the same units as those assigned to the product. Two factors determine the sensitivity of a BET. For infusion solutions and device extracts, the gel-clot sensitivity or the lowest point on the standard curve (lambda for kinetic LAL) and the amount of dilution determine test sensitivity.For products that have an endotoxin limit in EU/mg, the choice of lambda and the concentration of the test material determine sensitivity. The formula for product-specific sensitivity (PSS) is a convenient way to calculate the sensitivity of a BET for this type of product, where ... 

The principles behind the sterilization processes are described in Chapter 20. The choice of method is determined largely by the ability of the formulation and container to withstand the physical stresses applied during the sterilization process. All products intended for sterilization should be manufactured under clean conditions and therefore will be of low microbial content (bioburden) prior to sterilization. Under these conditions, the sterilization process will not be overtaxed and will generally be within the safety limits needed to provide the required level of sterility assurance (Chapter 20). The next section emphasizes parenteral products, but the practices described apply to many other types of sterile product. 

The uses of parenteral products for animals and the development process of these ate nearly identical to those products used for humans. The sterile dosage form types include solutions, suspensions, emulsions, and lyophilized powders. Any dosage form must be chemically, physically, and microbiologically stable, sterile, easy to inject, cause minimal pain and irritation upon injection, and packaged in appropriate vial sizes. Multiple-use vials are more common in animal health to treat herds/flocks). 

Development of a solution formulation requires a number of key pieces of preformulation information. Of these, solubility (and any pH dependence) and stability are probably the most important. Since parenteral products probably represent the most common solution formulation type, these are discussed in more detail. The principles and practices governing the formulation development of parenteral products have been reviewed by Sweetana and Akers (1996) and are discussed in detail in Chapter 9 on Parenteral Dosage Forms. Rowe et al. (1995) have described an expert system for the development of parenteral products. 

There are, arguably, a greater variety of formulations administered by the parenteral route than by any other. These include emulsions, suspensions, liposomes, particulate systems and solid implants as well as the ubiquitous simple solution. What sets parenteral products apart from most other dosage forms, (with the exception of ocular products), is the absolute requirement for sterility, regardless of the formulation type. This requirement must be uppermost in the pharmaceutical scientist s mind from the first stages of formulation conception, so that the formulation and manufacturing process can be developed in tandem to produce an optimised sterile product. 

Today parenteral products are divided into two types, namely large and small volume parenterals. Large volume solutions in containers of 100 ml or more are essentially for intravenous use, usually over an extended period of time. Such solutions are also for irrigation and dialysis. Small volume parenterals are for immediate injection by various routes, such as subcutaneous, intramuscular and intravenous. 

The pharmacopoeias deal with ingredient water of two types. Purified Water and Water for Injection. The principal difference in biological quality between the two types of water is that Water for Injection is specified to be pyrogen-free (less than 0.25 Eu of bacterial endotoxin per mL). Only water of Water for Injection quality may be used to dissolve, dilute, or compound parenteral products, because endotoxins may pass through 0.22 pm sterilizing filters. Control of bacterial endotoxins is achieved in the first instance through control of microbiological contamination. 

Some or all of the principles of aseptic manufacture are used in the manufacture of terminally sterilized products. There are two main reasons for this. The first is micTobiological. The numbers and types of microorganisms present in or on a product item prior to sterilization make up a major determinant of sterility and merit serious consideration. The second reason is the avoidance of large non viable particles in parenteral products. 

The United States Phannacopoeia (USP) has three general specifications for water quality that are apphcable to medical and pharmaceutical uses, namely, USP Water for Injection (WFI), USP Purified Water and Drinking Water [81]. The primary difference between WFI and PW is the tolerance of microorganismas and endotoxins. Sterile WFI is the most demanding and expensive to produce. It is used for the final purification steps of parenteral products or where water is expected to have direct contact with human blood. Standard USP water specifications for pharmaceuticals manufacturing are conductivity =0.2—1.0 pS/cm at 25°C pH 5.0—7.0 TOC level <500 ppb and bacteria count <100 cfu/100 ml. WFI also requires bacteria count <10 cfu/100 ml and endotoxin level <0.25 EU/ml [74]. The types of water recommended for pharmaceutical applications and operations are given in Table 3.9 [82]. 

As an example after working hours a parenteral product has to be prepared, urgently, in the safety cabinet. If the safety cabinet has been switched off at that moment, it takes approximately 30 minutes (depending on which machine and type) before the preparation can be started. If the preparation was to be started too soon, the product quality and the protection of the preparing pharmacist could not be guaranteed. 

USP Type II can be used for products that remain below pH 7.0 for their shelf life. The suitability of Type II for small volume parenterals should be evaluated for unbuffered solutions on a case-by-case basis. Type II containers are frequently found to be suitable for a variety of large-volume parenterals due to the less stringent requirements imposed by their lower surface-to-volume ratios. 

An elastomeric closure is a packaging component that is, or may be, in direct contact with a drug product. Elastomer selection for parenteral packaging principally involves consideration of chemical, physical, and biological properties, with emphasis on the stability profile of the drug/container system. Typical elastomeric closure compositions are listed in Tables 1 1. Although certain packaging applications frequently call to mind certain elastomer types, it is not feasible to prescribe specific... 

In this table, it can be recognized that there are problems inherent in these types of formulations from both the patient s and the manufacturer s point of view. This is why most pharmaceutical companies make attempts to avoid these types of dosage forms, if at all possible. However, with the advent of biotechnological products, which often do not lend them, selves to conventional dosage formulations, parenteral and invasive measures may be the only answer. 

Virtually all therapeutic proteins must enter the blood in order to promote a therapeutic effect. Such products must usually be administered parenterally. However, research continues on the development of non-parenteral routes which may prove more convenient, less costly and obtain improved patient compliance. Alternative potential delivery routes include transdermal, nasal, oral and bucal approaches, although most progress to date has been recorded with pulmonary-based delivery systems (Chapter 4). An inhaled insulin product ( Exubera , Chapters 4 and 11) was approved in 2006 for the treatment of type I and II diabetes. 

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