Applications parenteral administration

Drugs are administered to animals by parenteral or enteral administration, and topical application. Parenteral administration bypasses the alimentary tract and can be effected by a variety of routes including intravenous, intramuscular, subcutaneous, intraperitoneal, or intrapleural injections inhalation and percuta-neously. In intravenous injections, entry of dmgs into the system depends only upon the rate of injection and not on absorption into the bloodstream. As a result, water-soluble poorly absorbed drugs may be readily administered. 

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

As has been pointed out earlier in this chapter, the dietary consumption and historical medicinal use of carotenoids has been well documented. In the modern age, in addition to crocin, 3.7, and norbixin, 3.8, several carotenoids have become extremely important commercially. These include, in particular, astaxanthin, 3.6 (fish, swine, and poultry feed, and recently human nutritional supplements) lutein, 3.4, and zeaxanthin, 3.3 (animal feed and poultry egg production, human nutritional supplements) and lycopene, 3.2 (human nutritional supplements). The inherent lipophilicity of these compounds has limited their potential applications as hydrophilic additives without significant formulation efforts in the diet, the lipid content of the meal increases the absorption of these nutrients, however, parenteral administration to potentially effective therapeutic levels requires separate formulation that is sometimes ineffective or toxic (Lockwood et al. 2003). 

Fat-emulgated preparations for parenteral administration have been elaborated for clinical applications. Since these are administered to the patients intravenously, the size of fat emulsion particles should not exceed the size of the largest naturally occurring lipoproteins-chylomicrons, i.e. about I fiin. Fat emulsions on the basis of com oil (preparation lipomaize), cottonseed oil (lipofundin, lipomol). 

Parenteral administration This route is applicable for drugs which are inactivated by gastrointestinal tract or absorption is poor when given orally or there is a urgency for fast response in small dose. Intramuscular, intravenous, or subcutaneous routes are commonly used. The intravenous injection (in aqueous solution) is introduced directly into the vein by which a rapid response is produced. The subcutaneous injection are given through the layer of skin, while intramuscular injection, introduced through the skin layer deep into the muscle. The nature of intramuscular injection may be in aqueous or oily solution/suspension form. The aqueous solution will be rapidly absorbed as compared to oily solution or suspension. So, the rate of absorption is dependent on the nature of the preparation. 

Nystatin is a polyene macrolide much like amphotericin B. It is too toxic for parenteral administration and is only used topically. Nystatin is currently available in creams, ointments, suppositories, and other forms for application to skin and mucous membranes. It is not absorbed to a significant degree from skin, mucous membranes, or the gastrointestinal tract. As a result, nystatin has little toxicity, although oral use is often limited by the unpleasant taste. 

Nystatin is available as an ointment for topical applications and as a suspension or tablet for oral administration. It is approved for oral administration at 100,000 lU/day for 7 days in chickens and turkeys by the Food and Drug Administration (FDA), but it is also used in cattle for treatment of genital mycoses. Nystatin is remarkably low in toxicity when given orally, but it is much more toxic after parenteral administration. 

Side-effects Morphine induces a variety of centrally- and peripherally-mediated side-effects. The most important of which is respiratory depression following parenteral administration, especially in the postoperative situation. Chronic oral application induces constipation and chronic treatment with oral morphine must be supplemented with laxatives. Other frequent side-effects are nausea, vomiting, dizziness and sedation. 

Historically, the administration of crystalline APIs has mainly found use in parenteral applications associated with intramuscular and subcutaneous injections as well as topical applications of suspensions containing micronized APIs. Commercially marketed pharmaceuticals categorized as suspensions for parenteral administration are illustrated in Table 17.3. Many of these products utilize drug substance size reduction in order to promote dissolution following administration. The degree... 

Polylactic acid has been studied extensively for controlled release applications ranging from the oral delivery of simple drugs such as indomethacin9 to the parental administration of complex proteins such as insulin.10 Polylactic acid of different molecular weights has been studied as matrix material for parenteral administration. Seki et al.11 used polylactic acid 6000 and Smith and Hunneyball8 used polylactic acid 100,000 for the controlled delivery of drugs by the parenteral route. Several polylactic acid systems have been studied for the controlled... 

Sulfated polysaccharides are very poorly absorbed following oral administration, and efficacy upon parenteral administration has not been demonstrated. Their greatest potential may well reside in their topical application, i.e., as a gel formulation in the prevention of sexual HIV, and HSV, transmission. 

Nanoparticles have numerous applications in the chemical, food, pharmaceutical, biomedical and semiconductor industries. For example, nanoparticles as drug carriers can increase drug efficacy, and can reduce toxicity and side effect after parenteral administration (Feng et al., 2002). Nanoparticles used for industrial applications should have desirable physical properties, including appropriate size, surface charge, surface area, porosity and mechanical strength. The functionality of... 

Nasal administration. Apart from parenteral administration, controlled release dosage forms based upon the microsphere concept should have application to other routes of administration. Microspheres in the form of pellets have been used to deliver drugs to the gastrointestinal tract and other examples include the administration of microspheres to the eye and topically to the lungs. In recent studies Ilium (20) has employed microspheres as possible controlled release formulations for nasal application. Such studies have relevance to the delivery of novel macromolecular compounds such as peptides and proteins. 

Abstract Nucleic acid molecules have emerged as versatile tools with promising utility in a variety of biochemical, diagnostic, and therapeutic applications. A parenteral administration of a nucleic acid is inconvenient because of pain, fear, and risks being associated with this type of application. The intestinal epithelium is considered to be an attractive site for oral delivery of therapeutic genes. 

Administration The highly polar, polycationic structure of the aminoglycosides prevents adequate absorption after oral administration. Therefore, all aminoglycosides (except neomycin [nee oh MYE sin]) must be given parenterally to achieve adequate serum levels. [Note The severe nephrotoxicity associated with neomycin precludes parenteral administration, and its current use is limited to topical application or oral treatment in hepatic coma to reduce the intestinal bacterial population.]... 

Percutaneous absorption can be determined by applying a known amount of chemical to a specified surface area and then measuring the level of the chemical in the urine and/or feces. To correct for incomplete excretion of the material in urine/feces levels are measured following parenteral administration of the chemical. Radioactive-labeled chemicals, usually carbon 14 or tritium, are widely used for analytic convenience. Ingestion of the test material by the animal must be prevented, and this may require restraint of the animal or design of specialized protective apparatus for the site of application. Because urine and feces are collected for analysis, specialized cages are also required. 

Early development of nucleic acid therapy was aimed at genetic deficiency diseases which were amenable to replacement therapy, or correction by administration of the protein products of the defective genes, as described in Chapter 3. The introduction of the normal counterpart of a defective gene into cells of the patient, resulting in the long-term production of the missing protein, appeared as a desirable alternative to the repeated parenteral administration of purified protein (Verma, 1990 Caskey, 1992). However, the current span of nucleic acid-based therapies far exceeds this limited application conceived initially (Riordan and Martin, 1991 Crooke, 1992a). 

Carboxymethylcellulose sodium is widely used in oral and topical pharmaceutical formulations, primarily for its viscosity-increasing properties. Viscous aqueous solutions are used to suspend powders intended for either topical application or oral and parenteral administration. Carboxymethylcellulose sodium may also be used as a tablet binder and disin-tegrant, and to stabilize emulsions. ... 

In topical preparations, propylene glycol is regarded as minimally irritant, although it is more irritant than glycerin. Some local irritation is produced upon application to mucous membranes or when it is used under occlusive conditions. Parenteral administration may cause pain or irritation when used in high concentration. 

Trehalose is used for the lyoprotection of therapeutic proteins, particularly for parenteral administration. Other pharmaceutically relevant applications include use as an excipient for diagnostic assay tablets for stabilization during the freeze-thaw and lyophilization of liposomes and for stabilization of blood cells,cosmetics, and monoclonal antibodies. Trehalose may also be used in formulations for topical application. ... 

Very few chronic toxicity studies have been reported. After repeated local applications in animals, sensitization dermatitis may develop. Chronic parenteral administration increases the white blood cell count by 30%. 

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