* See, AQUEOUS SYSTEMS +The most frequently employed vehicle for sterile products is water since itis the vehicle for all-natural body fluids. |. WATER FOR INJECTION + Also known as WFI. Clear, colorless, odorless. Pyrogen free. Having ph 5- 7. Dissolved solids 10ppm: Determined by 100ml of water or by conductivity method. ‘+ Itrmust be used within 24 hours and must be stored at temperature either 5°C or 60-90°C if to be held for 24 hours. ‘+ Manufactured by reverse osmosis process and distillation 11, STERILIZED WATER FOR INJECTION ‘+ Single dose container not exceeding 100ml. No bacteriostatic agent. Hardness not more than 30ppm. Used for dispensing parenteral solution, for mixing and making of dry powders. ‘+ Itshould not be placed in container greater than one liter. Itis prepared by filling a volume of WF! in final container and then sterilized by moist heat. ml, BACTERIOSTATIC WATER ‘+ Bacteriostatic water for injection unlike water for injection must be sterile. Bacteriostatic agents are present i. benzyl alcohol or mixture of ‘methyl propyl hydroxyl benzoate + Asi contains bacteriostatic agents, therefore not more than Sml is used to avoid the toxicity of substance. It must not be placed in container larger than 30m! IV. RINGER'S INJECTION ‘+The Ringer's injection USP is a sterile solution of sodium chloride, potassium chloride and calcium chloride in water for injection. The three ‘agents in the ringer’s solutions are present in the concentration similar to that found in physiological fluids. NON-AQUEOUS AND MIXED SOLVENTS + Inthe formulation of sterile pharmaceutical products, itis sometimes necessary to eliminate water entirely or in part from the vehicle, primarily because of solubility factors or hydrolytic reactions. + Itmust not be irritating, toxic, or sensitizing, and it must not exert an adverse effect on the ingredients of the formulation. ‘+ Solvents that are miscible with water, and that are usually used in combination with water as the vehicle, include dioxolanes, dimethylacetamide, N-(8-hydroxyediyl), lactamide, butylene glycol, polyethylene glycol 400 and 600, propylene glycol, glycerin, and ethyl alcohol. + Water-immiscible solvents include fixed oils, ediyl oleate, isopropyl ‘myristate, and benzyl benzoate. The most frequently used non-aqueous solvents are polyediylene glycol, propylene glycol, and fixed oils. ouse These are used when the use of water is contraindicated, like: * When the medicament is insoluble or slightly soluble in water i.e. steroids and hormones are not soluble in water but soluble in peanut, corn oil * To increase the stability of preparation * To prolong the duration of action of drug ¢ Whenever non-aqueous vehicles are used in the injection preparation, they must be administered by IM route. AQUEOUS NON-AQUEOUS AND MIXED VEHICLES « Water-miscible solvents we widely used to enhance solubility and to serve as stabilizers. The most common solvents include glycerin, ethyl alcohol, propylene glycol and polyethylene glycol 300.Be MAE EC ERTIES + Clear, colorless, odorless. Pyrogen free. Having ph -7. Dissolved solids 10ppm. + Determined by 100m! of water or by conductivity method + It must be used within 24 hours and must be stored at temperature either 50°C or 60.90°C if to be held for 24 hours. + Itshould not contain more than 1mg/100ml of total solids and may not contain added substances. ‘A. PREPARATION ‘+ Water for injection (Wi) is usually prepared by; + Distillation ina still specifically designed to produce the high- quality water required. + Reverse osmosis, however, is the process that is now approved by usp. PREPARATION THROUGH DISTILLATION ‘+ WFlis prepared by distillation of deionized water. The source of WFlis the tap water which contains the microorganism, dissolved organic and Inorganic substances, gases and suspended materials. The water is retreated for chemical softening, filtered, deionized and pH is adjusted. Mineral ions and inorganic substances are removed by distilation. ‘+ Membrane and depth filters are used to remove organic materials. The resultant purified water from the pretreatment is a feed for distillation system to produce WFi, Distillation is accomplished instills made of stainless steel or chemically inert glass In addition to conventional stills, vapor compression stils and multiple effect stills are also frequently used. Both these utiles heated feed water and steam to conserve energy consumption. These are capable of producing high purity water at rates of 50-1000 or more gallons/hr. Atl is equipped with; + An evaporator + Acollecting system + Acondenser ‘+The feed water is heated at atmospheric pressure in a horizontal evaporator to produce stream. The condenser, attached vertically has bezain angled baffles at the base to faciltates the entry of steam and prevent entry of water droplets in condenser. The distillate is usually free of ‘microbial contamination. PREPARATION THROUGH REVERSE OSMOSIS + Areverse osmosis system functions by applying pressure (usually 200 to 400 psi to raw water sufficient to force the permeation of water through a semipermeable membrane in the opposite direction to natural osmosis. The membranes most commonly used are composed of cellulose esters or polyamides (nylon) and are effective in retaining all ‘macromolecules and 85% or more of small ions such as Na" and Cr. Since yrogens are macromolecules, they should be retained as well as such viable particles as microorganisms. B, STORAGE + Aclosed system is desirable with ar exchange through after. t must be used within 24 hours and must be stored at temperature either 5°C or 60-90°C if tobe held for 24 hours. C. DISTRIBUTION + From storage tank tothe point of use, may be direct withdrawal from the tank or through pipes in large plants.