Vehicles subcutaneous administration

Male Sprague Dawley or spontaneously hypertensive stroke prone Wistar or Lewis rats with adjuvant induced arthritis weighing 150-300 g or New Zealand rabbits with arteriosclerosis induced by cholesterol feeding for 3 months are used. The animals receive the test compound by oral, intravenous, intraperitoneal, or subcutaneous administration. Control animals are treated with vehicle alone. Prior to thrombus induction, the animals are pretreated by s.c. injection of... 

The solids content of parenteral suspensions is usually between 0.5 and 5.0%, except for insoluble forms of penicillin, in which concentrations of the antibiotic may exceed 30%. These sterile preparations are designed for intramuscular, intradermal, intra-lesional, intra-articular, or subcutaneous administration. The viscosity of a parenteral suspension should be low enough to facilitate injection. Common vehicles for parenteral suspensions include preserved 0.9% saline... 

Figure 4 Effect of DAPT administration on Afi in PDAPP mice. (a) Brain concentrations of DAPT and percentage reduction in cortical total A/ levels after subcutaneous administration of DAPT (100 mg/kg). Afi levels were significantly reduced compared with baseline from 1 to 18 h after administration, and a peak reduction of 40% occurred after 3 h. Af> levels closely reflected DAPT concentrations. (b) Total cortical levels of Af> and A/142 (expressed as a percentage of levels in vehicle-treated controls) 3 h after oral administration of DAPT (10, 30, or 100 mg/kg) to PDAPP mice. p < 0.05 versus vehicle-treated control. Reproduced with permission from Reference 107.

One somewhat different, but critical, parameter in animal health sterile products compared with human health care products is the irritation and residue at the injection site. For companion animals, the pain upon injection should be minimal, and any lasting reactions that cause either pain or visual lumps to a pet will not be tolerated by many owners. For food-producing animals such as cattle, pigs, and poultry, the added challenge is that of ensuring the residue levels at the injection site have been depleted adequately by the time the animal is harvested. The formulation scientist thus may need to carefully observe the viscosity and polarity of the vehicle as they can affect residue times. Volumes injected and the route can also have an impact. Oftentimes subcutaneous administration is used instead of intramuscular administration to minimize residues in the tissue and potential damage to meat (i.e., muscle). 

The methods of production of archeosomes are by lipid hydration method, detergent dialysis method, reverse phase evaporation method, sonication, membrane extrusion, freeze and thaw method (Weiner and Cannon, 1989 Relini et al, 1994 Watwe and Bellare, 1995). As carrier vehicles in vaccine formulations, as delivery systems for drugs, genes, or cancer screening agents (Allen, 1997). Primary work on mouse has been carried out which consists of intravenous, oral and subcutaneous administration of these archaeosomes and it has reported to be non-toxic and safe (Patel et al., 2004). 

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, e.g., vehicle and other excipient selection, as well as choice of route of administration, can prolong therapeutic activity and increase onset times, Thus, oily solutions, suspensions, or emulsions can be administered by subcutaneous or intramuscular routes to create prolonged effect, i.e., depot injection. 

Several types of CDD systems have been designed based on various mechanisms of drug release (Table I). These mechanisms are dependent on the required site of drug delivery, the physicochemical properties of the drug and also of the delivery vehicle (13), Modes of administration can be oral, sublingual, transdermal, rectal, intrauterine, ocular, or parenteral (intramuscular, peritoneal, and subcutaneous routes of injection). 

FIGURE 7.1 Characterization of cell division inhibitor PC190723. (A) Chemical structure of PC190723. (B) In vivo efficacy of PC190723 in a murine model of infection. Mice were injected intraperitoneally (IP) with a lethal inoculum of S. aureus ATCC 19636 at time 0. One hour after infection the animals received 3 mg/kg (uneven dashed line), 10 mg/kg (dotted line), or 30 mg/kg (dark line) of PC190723 negative control (vehicle only, dashed black line) or 3 mg/kg of the vancomycin control antibiotic (thick dark line) by subcutaneous (SC, top) or intravenous (IV, bottom) administration. Mortality was recorded daily for 7 days. (Source From Haydon, DJ. et al. 2008. Science 321, 1673, 2008. Reprinted with permission from AAAS.)... 

Test Species Test Article Dose Levels Frequency Administration Beagle dog Protein therapeutic 300, 100, 30 and 10 (ig/kg plus vehicle control Every other day (EOD), 14 doses total Subcutaneous, bolus injection duplicate aliquots of each formulation collected predose and postdose for the F , 7th, and 13lh dose to be analyzed for test article concentration... 

The U.S. Pharmacopoeia (USP) classifies injections into five different types. The dosage form selected for a particular drug product is dependent upon the characteristics of the drug molecule (e.g., stability in solution, solubility, and injectability), the desired therapeutic effect of the product (e.g., immediate vs. sustained release), and the desired route of administration. Solutions and some emulsions (e.g., miscible with blood) can be injected via most parenteral routes of administration. Suspensions and solutions that are not miscible with blood (e.g., injections employing oleaginous vehicles) can be administered via intramuscular or subcutaneous injection but should not be given intravenously. 

The most important requirement is that the salt possesses sufficient solubility at physiologically compatible pH values to permit incorporation into the dosage form. Buffering the solution to an appropriate pH can often enhance solubility. Salts may also be prepared in situ in the formulation. This is particularly useful when the main route of administration utilizes the parent drug form. Where the aqueous solubility of the salt is not sufficiently high, co-solvents may need to be added to enhance solubility (e.g. propylene glycol is used as the vehicle in phe-nobarbitone sodium injection). Parenteral solutions based on co-solvent vehicles normally cannot be directly injected intravenously because there is the risk of precipitation at the injection site. Therefore, such products are diluted with isotonic saline or 5%w/v dextrose solution to produce a lower concentration that remains soluble and can be safely administered by infusion. Alternative delivery routes are by subcutaneous or intramuscular administration by which, in... 

For the intramuscular and subcutaneous routes, the use of non-aqueous vehicles may be considered as a method of avoiding hydrolysis. For IV administration, the use of an oil-in-water emulsion is a possible, although little used, option. These approaches are discussed in the section Strategies for Formulating Poorly Soluble Drugs . 

Radiolabelled metabolites were identified in the urine, carcass and intestines of mice after the administration of a single subcutaneous 10 mg dose of S-labelled diethyl disulfide (approximately 400 mg/kg bw) in an aqueous vehicle. Ethyl methyl sulfone was detected in the urine, carcass and intestines of mice after a single oral dose of 160 mg diethyl disulfide/kg bw. This product forms via reduction of diethyl disulfide to ethyl thiol, which is subsequently methylated to methyl ethyl sulfide. The sulfide is then oxidized to the corresponding sulfone. Sulfate accounted for 80-90% of the radioactivity in urine. Ethyl methyl sulfone was also detected in the urine of rabbits and guinea-pigs after single oral doses of 200 and 185 mg diethyl disulfide/ kg bw, respeotively (Snow, 1957). 

In these tests, the form and area of the material, the thickness, and the surface area to extraction vehicle volume are critical considerations in the testing protocol. Appropriate extraction vehicles, that is, solvents, should be chosen to yield a maximum extraction of leachable materials to conduct the testing. Mice, rats, or rabbits are the usual animals of choice for the conduct of these tests and depending on the intended application of the biomaterial, oral, dermal, inhalation, intravenous, intraperitoneal, or subcutaneous application of the test substance may be used. Acute toxicity is considered to be the adverse effects that occur after administration of a single dose or multiple doses of a test sample given within 24 h. Subacute toxicity (repeat dose toxicity) focuses on adverse effects occurring after administration of a single dose or multiple doses of a... 

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