Isotonic solutions, injectable

Sterility, freedom from pyrogens, and acceptably low level of extraneous particulate matter are critical quality attributes of all injectable products. Additional critical quality attributes depend on the clinical use of the product. For example, for IV, IM, and SC routes, isotonicity and physiological pH (7.4) are always desirable in order to minimize potential irritation upon injection. Other factors may preclude this, however. If the required dose of drug must be administered in a small volume, it may not be feasible to formulate an isotonic solution. Likewise, solubility or stability considerations may preclude formulation at physiological pH. This explains why formulation pH for injectable drugs varies from about pH 2 to about pH 11. 

IV injection 5 to 10 mg, 15 to 30 minutes before induction of anesthesia, or to control acute symptoms during or after surgery. Repeat once if necessary. Prochlorperazine may be administered either undiluted or diluted in isotonic solution, but do not exceed 10 mg in a single dose of the drug. Do not exceed 5 mg/ml /min. Do not use bolus injection. 

Dosage form Campath is a sterile isotonic solution for injection. Each single use ampoule of Campath contains alem-tuzumab 30 mg. 

Ideally, a solution for injection should be an isotonic solution with a neutral (physiological) pH. However, the pH of a radiopharmaceutical is very important for its stability, and for labelled compounds, the pH for optimal stability is not always equivalent to physiological pH. For iodide solutions, the pH should be alkaline to prevent loss of radioiodine. Reducing agents, such as thiosulfate, are often added to radioiodide solutions to help this situation. A preservative can act as a stabilizer, an antioxidant, or a bactericidal agent. 

It has been also observed that hypertonic and hypotonic salt solutions tend to irritate sensitive tissue and cause pain when applied to mucous membranes of the eye, ear, and nose, etc., whereas isotonic solution causes no tissue irritation when it comes in contact with the tissue. Obviously, the tonicity of formulations that come in to direct contact with blood, muscle, eye, nose, and delicate tissues is critical. Therefore, the issue of tonicity is important in small- and large-volume injectables, ophthalmic products, and products intended for tissue irrigation. The degree of tissue irritation or hemolysis or crenation observed depends on the degree of deviation from isotonicity, the volume injected, the speed of injection, the concentration of the solutes in the injection, and the nature of the membrane. The parenteral and ophthalmic formulations are therefore adjusted to isotonicity if possible. 

Parenteral preparations are regularly prepared aseptically a short time or immediately prior to administration. Compounds susceptible to hydrolysis or oxidative decomposition in solution are preferentially stored as dry powders, concentrates under an inert atmosphere, or in combination with stabilizers. Concentrates for injections or infusions (European Pharmacopoeia, 2002) are diluted prior to administration, usually with sterilized Water for injection (European Pharmacopoeia, 2002) or sterile, isotonic solutions of sodium chloride, glucose, dextran, or buffer (see Table 14.3). Powders for injections or infusions (European Pharmacopoeia, 2002) are dissolved or suspended in the same media. Vitamins are aseptically added ex tempore to TPN preparations due to poor stability and the risk of precipitation (Hutchinson, 1998), as are trace metals that may influence the stability of the TPN formulation. A limited number of drugs may also be dissolved in the TPN infusion prior to administration (Hutchinson, 1998). 

In order to gain an antiserum for ferritin studies, Wohler and Schonlau (W7) injected rabbits with a 0.05 % isotonic solution of ferritin (20 % iron) at pH 7.2. Injections were made every fourth day, and 0.5, 1.0, 2.0, and (twice) 2.0 mg were given subcutaneously. The titer which was thus obtained was 1 500. If this antiserum was used in ImEl against separate sera with a content of at least 100 ng % ferritin, lines of precipitation could be stained with Berlin blue reaction. Ferritin shows a line which comes near Pi-globulin. A positive Ouchterlony test was obtained with most patients suffering from hepatitis epidemica or from liver cirrhosis. 

Tc chemistry is primarily the chemistry of anionic pertechnetate. This Tc species is eluted from the Mo/ Tc generator with high specific activity as an isotonic solution. Accordingly, Tc chemistry is aqueous solution chemistry in saline suitable to be injected intravenously. Also, Tc chemistry is an NCA chemistry because Tc activity is present in the radiopharmaceutical kit at 10 to 10 M. 

Patients with intraocular hemorrhages of various etiology (267 patients but in cases with compensation of the main pathological process and in the absence of hemorrhages relapses were treated. Proteolytic drugs, when administered in therapeutic dosages (0.7 Fip in 0.2 ml of isotonic solution) by subconjunctival injection (made every other day, 5 injections per one course, treatment courses were repeated every 6 months), favored prevention of blood clots and accelerated blood resorption. 

We have worked out a new method of treating chalazion by injecting lekosim into a pathological formation The doses of 1-5 Fip of lekosim in 0.1-0.5 ml of saline/isotonic solution were dependent on a size of the pathological formation (smaller injection volumes in smaller lesions). Complete resorption of chalazion following 1-3 injections was recorded for 17 patients out of the total number of 28 persons who received this treatment, and in 9 patients complete resorption was recorded after 4-6 injections (8 months observation). 

Magnesium sulfate can be prepared by neutralizing sulfuric acid with magnesium carbonate, or from natural soimces as the mineral kieserite, for the monohydrate form, and epsomite, for the heptahydrate form. It is an effective and widely used saline laxative. The laxative action probably results from two factors. The first is that the magnesium sulfate is not absorbed from the intestinal tract and thus retains sufficient water within the liunen of the bowel to make an isotonic solution. The second is that the magnesimn ion stimulates the release of cholecystokinin-pancreozymin which causes an accumulation of fluid and electrolytes within the small intestine. Magnesium Sulfate Injection USP is also used as a parenteral anticonvulsant. 

Solutions of sodimn chloride more closely approximate the composition of the extracellular fluid of the body than solutions of any other single salt. A 0.9% solution has the same osmotic pressure as body fluids, and is thus isotonic with body fluids. An isotonic solution can be injected without affecting the osmotic pressure of the body fluids and without causing any appreciable distortion in chemical composition. An isotonic solution is the... 

Sodium Chloride Injection USP is a sterile isotonic solution of sodium chloride in Water for Injection USP. It contains 154 mEq of sodium and chloride ions per each liter, and may be used as a sterile vehicle in preparing solutions or suspensions of drugs for parenteral administration. 

Parietal secretion is evoked by histamine injection, and is essentially an isotonic solution of HCl, approximating in value to 0-1 N, or 0-365 per cent. Non-parietal secretion is evoked by pilocarpine injection, and is rich in nitrogenous solutes and neutral chloride, but poor in free HCl. As collected, gastric juice may have a concentration of HCl up to 0-1 N, in man and 0 17 N, in dogs. The pH range is 1-1-1-8. 

Aqueous solutions introduced into the bloodstream by injection must have the same osmotic pressure as blood that is, they must be isotonic with blood. At 25°C, the average osmotic pressure ofblood is 7.7 atm. What... 

Blood and lymph are approximately isotonic to a cell so that cells do not gain or lose liquid when bathed in these fluids. Pure water is hypotonic and may cause cells to swell and burst. During intravenous feeding, injections, and storage of cell tissue, a salt (saline) solution is used with a concentration of solutes that is essentially isotonic with blood (and hence, with the cell) to prevent cell damage. 

Some types of injections must be made iso-osmotic with blood serum. This applies particularly to large-volume intravenous infusions if at all possible hypotonic solutions cause lysis of red blood corpuscles and thus must not be used for this purpose. Conversely, hypertonic solutions can be employed these induce shrinkage, but not lysis, of red cells which recover their shape later. Intraspinal injections must also be isotonic, and to reduce pain at the site of injection so should intramuscular and subcutaneous injections. Adjustment to isotonicity can be determined by the following methods. 

In contrast, parenteral suspensions have relatively low solids contents, usually between 0.5 and 5%, with the exception of insoluble forms of penicillin in which concentrations of the antibiotic may exceed 30%. These sterile preparations are designed for intramuscular, intradermal, intralesional, intraarticular, or subcutaneous injection. Syringeability is an important factor to be taken into consideration with injectable dosage forms. The viscosity of a parenteral suspension should be sufficiently low to facilitate injection. Common suspending vehicles include preserved isotonic saline solution or a parenterally acceptable vegetable oil. Ophthalmic and optic suspensions that are instilled into the eye/ear must also be prepared in a sterile manner. The vehicles are essentially isotonic and aqueous in composition. The reader should refer to Chapter 12 for further discussion on parenteral products. 

Commonly administered LVPs include such products as Lactated Ringers Injection USP, Sodium Chloride Injection USP (0.9%), which replenish fluids and electrolytes, and Dextrose Injection USP (5%), which provides fluid plus nutrition (calories), or various combinations of dextrose and saline. In addition, numerous other nutrient and ionic solutions are available for clinical use, the most popular of which are solutions of essential amino acids or lipid emulsions. These solutions are modified to be hypertonic, isotonic, or hypotonic to aid in maintaining both fluid, nutritional, and electrolyte balance in a particular patient according to need. Indwelling needles or catheters are required in LVP administration. Care must be taken to avoid local or systemic infections or thrombophlebitis owing to faulty injection or administration technique. 

It is important that injectable solutions that are to be given intravenously are isotonic, or nearly so. Because of osmotic pressure changes and the resultant exchange of ionic species across red blood cell membranes, nonisotonic solutions, particularly if given in quantities larger than 100 mL, can cause hemolysis or cre-nation of red blood cells (owing to hypotonic or hypertonic solutions, respectively). Dextrose, sodium chloride, or potassium chloride is commonly used to achieve isotonicity in a parenteral formula. 

Parenterais The most important criterion for parenterals is that they have to be sterile for injection or infusion administration. Excipients are added to make parenterals isotonic with blood, improve solubility, and control pH of the solution. The solvent vehicles include water-for-injection, sterile sodium chloride, potassium chloride, or calcium chloride solution, and nonaqueous solvents such as alcohol, glycol, and glycerin. Preservatives, antioxidants, and stabilizers are normally added to enhance the properties of the drug product. 

In any setup, it is paramount that the electrodes get cleaned regularly. The minimum frequency, e.g., once a week, should be described in the instrument standard operation procedure (SOP), but for some methods or samples more frequent cleaning is necessary. An example is the determination of the enantiomeric purity of adrenaline in local anesthetic solutions. The samples are isotonic and contain high concentrations of local anesthetics (5—20mg/ml). The determination concerns very low concentrations of adrenaline (typically 5 pg/ml of 1-form and only a few percent of that of the d-form) and the samples are therefore injected undiluted. Furthermore, relatively high concentrations of cyclodextrin are present in the BGE. Eong sequences therefore require electrode cleaning for every sequence and this is thus described in the method procedure. ... 

Resuspend the pellet in 3 mL of sterile water for injection, and gently mix (by inversion) the cell suspension for 20 s. Then add 1 mL of 3.5% NaCl to make the solution isotonic. Centrifuge at 500g for 7 min to pellet the cells. 

Sodium chloride (normal saline)- 0.9% Sodium chloride (normal saline), which is isotonic, restores both water and sodium chloride losses. Other indications for parenteral 0.9% saline include Diluting or dissolving drugs for IV, IM, or subcutaneous injection flushing of IV catheters extracellular fluid replacement treatment of metabolic alkalosis in the presence of fluid loss and mild sodium depletion as a priming solution in hemodialysis procedures and to initiate and terminate blood transfusions without hemolyzing red blood cells. 

Tonicity agent/stabilizer Provides isotonicity to the formulation such that it is suitable for injection Examples include polyols, salts, and amino acids Help maintain the protein in a more compact state (polyols) Minimize electrostatic, solution protein-protein interactions (salts) Stabilizers include cryo and lyoprotectants Examples include polyols, sugars, and polymers Cryoprotectants protect proteins from freezing stresses Lyoprotectants stabilize proteins in the freeze-dried state... 

Solutions that are injected into the bloodstream (for blood transfusions and intravenous feeding) must be isotonic with the blood (that is, have the same... 

Figure 5. Effect of the H3 receptor agonists R(a)methylHA (RHA 10 mg/kg) or BP 2-94 (BP 25 mg/kg) administered ip at -24, -18,-6 and -2 hours on the AVP and OT responses to 24 hours of dehydration. The animals were decapitated at time 0. Isotonic saline served as control solution. p<0.01 vs. euhydrated rats. p<0.01 vs. saline injected dehydrated rats.

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