3 AntioxidantsAntioxidants are agents which prevents atmospheric oxidation. They have the capability of functioning chemically as reducing agents.Antioxidants are used to prevent oxidative decomposition of pharmaceutically active components.They are used in pharmaceutical preparations containing easily oxidized substances (e.g., iodide or ferrous ions) in order to maintain these substances in their reduced form.
4 Mechanism of antioxidant action The mechanism of antioxidant action may be seen in two ways, both achieving the same net result:Either the antioxidant is oxidized in place of the active constituent orIf the active component is oxidized, the antioxidant reduces it back to its normal oxidation state.Half-reactions:Ox1 + e ↔ Red1Red2 ↔ Ox2 + eTotal redox reaction:Ox1 (Easily oxidized substance) + Red2 (Acting as antioxidant) ↔ Red1 + Ox2
5 The selection of Antioxidants The following criteria’s should be brought into consideration while selecting a suitable antioxidant for pharmaceutical purposes: It should be capable of ensuring desired redox reaction when used in pharmaceutical preparations. It should be chemically compatible i.e. it should not react with other chemicals in the preparations. It should not alter the solubility of other components. It should also exhibit reasonable chemical stability. It should be effective at a very low concentration. It should be physiologically inert. It should be safe and nontoxic.
7 Hypophosphorous acid (HPH2O2; Mol.Wt. 66.00) It is a colorless or slightly yellow, odorless liquid containing not less than 30.0% and not more than32.0% HPH2O2. The oxidation state of the central phosphorous atom is +1, making the compound a very powerful reducing agent. It can function in dilute solution as a very effective reducing agent or antioxidant.Uses: It serves to prevent the formation of free iodine in Diluted Hydriodic Acid and Hydriodic Acid Syrup. It is also present in Ferrous Iodide Syrup where it prevents the formation of both ferric ions and molecular iodine. Sodium hypophosphite is used as preservative in certain foods and ammonium hypophosphite is also found as preservatives in many preparations. The concentration ranges for hypophosphorous acid and its salts when used as antioxidants are never over 1%, and usually between 0.5 and 1%.
8 Sulfur Dioxide (SO2; Mol.Wt. 64.06) It is a colorless, nonflammable gas containing not less than 97.0% SO2. It contains sulfur in the +4 oxidation state and function as strong reducing agents. Sulfur, an antioxidant pharmaceutical aid protects many susceptible compounds from oxidation by reducing the oxidized form back again, or, preferably by reacting with oxygen before the susceptible compounds do. Uses: Sulfur dioxide due to its gaseous nature is usually used in injectable preparations enclosed in single-dose ampules or multi-dose vials. The concentrations employed vary with the compound to be protected and the type of dispensing container. The usual concentration is about 0.1% and seldom exceeds 1.0%.
9 Sodium Bisulfite (NaHSO3; Mol.Wt. 104.06) It is white or yellowish white crystals or agranular powder of sodium bisulfite (NaHSO3) and sodium matabisulfite (Na2S2O5) mixture equivalent to not less than 58.5% and not more than 67.4% SO2. It is a strong reducing agent and like sulfur dioxide contains sulfur in the +4 oxidation state. It is exclusively used as an antioxidant in solutions of drugs that contain the phenol or catechol nucleus (e.g., phenylephrine hydrochloride and epinephrine hydrochloride solutions) to prevent oxidation of these compounds to quinones or like substances. It is also used as a reducing agent in ascorbic acid injection.
10 Sodium Metabisulfite (Na2S2O5; Mol.Wt. 190.10) It is a white crystal or white to yellowish crystalline powder having the odor of sulfur dioxide. It should contain an amount of sodium matabisulfite (Na2S2O5) equivalent to not less than 66.0% and not more than 67.4% of SO2. It is a strong reducing agent and like sulfur dioxide contains sulfur in the +4 oxidation state. It is exclusively used as an antioxidant in solutions of drugs that contain the phenol or catechol nucleus (e.g., phenylephrine hydrochloride and epinephrine hydrochloride solutions) to prevent oxidation of these compounds to quinones or like substances. It is also used as a reducing agent in ascorbic acid injection.
11 Sodium Thiosulfate (Na2S2O3.5H2O; Mol.Wt. 248.18) Sodium thiosulfate contains sulfur in two different oxidation states.the oxidized sulfur atom is in a +6 state resisting further oxidation,while the remaining sulfur atom is in a zero oxidation state.This allows the compound to act as a reducing agent or as an antioxidant. Due to its reducing power it is used as the titrating reagent in iodine determinations. The use of this compound as an antioxidant is usually limited to solutions containing iodides. 0.05% solution is used as antioxidant in Potassium Iodide solution.
13 Pharmaceutically acceptable glass and glasswares VialsAmpoulesBottles
14 Pharmaceutically acceptable glass and glassware Glass is commonly used in pharmaceutical packaging because it possesses superior protective qualities, which are as follows- It is economical, and containers are readily available in a variety of sizes and shapes. It is essentially chemically inert, impermeable, strong, and has FDA clearance. It does not deteriorate with age and with a proper closure system, it provides an excellent barrier against particularly every element except light. It offers transparency, sparkle, easy cleaning, effective closuring and reclosuring where applicable. It ensures high-speed handling, good rigidity and stackability. Colored glass, especially amber, can give protection against light when it is required. The major disadvantages of glass as a packaging material are its fragility and weight.
15 Composition of Glass Sand is almost pure silica. The word glass is a generic term referring to vitreous material (material which softens gradually over a temperature range rather then melting sharply). Glass may be considered as sodium silicate (Na4SiO4). Glass is composed principally of sand, soda-ash, limestone and cullet. Sand is almost pure silica. Soda-ash is sodium carbonate (Na2CO3) Limestone is calcium carbonate. (CaCO3) Cullet is broken glass that is mixed with the batch and acts as a fusion agent for the entire mixture.
16 Elements of glass The composition of glass varies and is usually adjusted for specific purposes. Many useful properties of glass are affected by the kind of elements it contains. The most common cations found in pharmaceutical glass are Silicon (Si), Aluminum (Al), Boron (B), Sodium (Na), Potassium (K), Calcium (Ca), Magnesium (Mg), Zinc (Zn) and Barium (Ba). The only anion of consequence is Oxygen (O2).
17 Role of different elements in glass Sodium (Na): Reduction in the proportion of sodium ions makes glass chemically resistant; however without sodium and other alkalies, glass is difficult and expensive to melt. Aqueous solutions will slowly become alkaline upon standing for prolonged times in soft glass containers. 4Na+ + SiO H2O = H3 SiO Na OH - Potassium (K): Potassium gives a brown light resistant glass. Lead (Pb): Lead in small traces gives clarity and brilliance but produces a relatively soft grade of glass.
18 Role of different elements in glass Boron (B): Boron oxide is incorporated mainly to aid in the melting process through reduction of the temperature required. Boron decreases the coefficient of expansion in Pyrexglass. Aluminum (Al): Alumina (aluminum oxide) is often used to increase the hardness and durability and to increase resistance to chemical action. Iron (Fe): Iron oxide is added to confer amber color to the glass. But iron oxide could leach into the product. Therefore, if the product contains ingredients subject to iron-catalyzed chemical reactions, amber glass should not be used.
19 Colored glass Certain drugs must be protective from light. Therefore there are numerous types of containers, colorless, opaque and colored for packaging. The opaque container would be the superior light-protective container. Clear containers are preferred for dispensing (except ointments), if for no other reason than that the patient likes to see what he is buying, the amount left in the bottle and ease of pouring. There are four types of clear containers available: colorless, green, blue and amber. For the most part blue glass does not confer much protection. Green glass may or may not, depending upon the type and intensity of green. Only amber glass (or red glass) are effective in protecting the contents of a bottle from the effects of sun light by screening out harmful ultraviolet rays. Both the U.S.P and N.F. have identical standards for percent transmission of light in the 290 to 450 nm region.
20 U.S.P. Glass Types and Test Limits General DescriptionType of TestGeneral UseIHighly resistant borosilicate classPowdered GlassBuffered and unbuffered aqueous solutions, All other uses.IITreated soda-lime glassWater AttackBuffered aqueous solutions with pH below 7.0, Dry powders, oleaginous solutions.IIISoda-lime glassDry powders, oleaginous solutions.NPGeneral-purpose soda-lime glassNot for parenterals. For tablets, oral solutions, ointments and external liquids.
22 Solvents: Water Water is omnipresent. Water is the solvent of choice for most pharmaceutical preparationsOfficial WatersU.S.P has defined Five grades of water:WaterPurified WaterWater for InjectionBacteriostatic Water for InjectionSterile Water for Injection
23 Water Water U.S.P is a clear, colorless and odorless liquid. It has specifications for pH, zinc, other heavy metals, foreign volatile matter, total solid content and bacteriological purity. Its pH is 5-8. It contains 1000 ppm total solids. It is official as a solvent and is used to make several official solutions,tinctures and extracts.
24 Purified Water It occurs as a clear,colorless,odorless liquid. It has specifications for pH, chloride, sulfate, ammonia, calcium, carbon dioxide, heavy metals, oxidizable substances, total solids and bacteriological purity. It is not intended for parenteral administration. Its pH is 5-7. It contains 10 ppm total solids. It is called for in the preparation of most U.S.P test reagents. It is the water of choice for extemporaneous compounding.
25 Water for Injection Water for injection U.S.P is water purified by distillation. It occurs as a clear,colorless,odorless liquid. It contains no added substance. It meets all specifications of Purified water except bacteriological purity. Its pH is 5-7. It contains 10 ppm total solids. It must pass a pyrogen test. It must be stored at a temperature below 40C or above 370C. It is intended for use as a solvent for the preparation of parenteral preparations. It would be used by the large scale pharmaceutical manufacturers.
26 Bacteriostatic Water for Injection It is sterile water for injection containing one or more suitable antimicrobial agents. It is clear colorless liquid,odorless or having the odor of the antimicrobial agent. Its pH is and it contains 40 ppm total solids. It must pass a pyrogen test. It is stored in single-dose or in multiple-dose containers, preferably of Type I or Type II glass of not larger than 30ml size. It is used to compound small volumes of extemporaneous parenterals for intramuscular administration. The bacteriostatic agent prevents the use of this water for i.v administration
27 Sterile Water for Injection It is water for injection sterilized and suitably packaged. It is clear, colorless, odorless liquid which contains no antimicrobial agent. Its pH is 5-7 and it contains ppm total solids. It must pass a pyrogen test. It is stored in single-dose containers, preferably of Type I or Type II glass of not larger than 1000ml size. It is used for the extemporaneous compounding of parenterals for either intravenous or intramuscular injection.