ANTIOXIDANTS

• Compunds capable of functioning as REDUCING AGENTS

• Pharmaceutical necessity- addition prevents oxidative decomposition in the products.

• Either the antioxidant oxidizes in place of the active constituent or inversely, the antioxidant reduces the already oxidized active constituent back to its normal oxidation state.

• In selecting a suitable antioxidant, the following factors should be considered:

a) An antioxidant in a pharmaceutical preparation should be PHYSIOLOGICALLY INERT

MECHANISM OF ACTION OF ANTIOXIDANTS

b) The possible TOXICITY of both the reducing agent and its oxidized product must be assessed c) One should consider possible SOLUBILITY problems between the reducing agent and the drug d) VERY STRONG reducing agent will form explosive mixtures when combined in dry form or in concentrated solution with strong oxidizing agents

HYPOPHOSPHOROUS ACID (HPH2O2)

• The formation of free iodine is prevented in diluted hydriodic acid and syrup.

• Its presence in ferrous iodide syrup ensures the non-formation of both ferric ions and molecular iodine.

• Salts of hypophosphorus acid are antioxidants.• Sodium hypophosphite is a preservative in

certain foods.• Ammonium hypophosphite is likewise a

preservative in many preparations.

USES:

SYNONYM : Sulfurous anhydride

SULFUR DIOXIDE (SO2)

• It will protect many susceptible compounds from oxidation by reducing oxidized forms back to their original compounds or by reacting with oxygen before the susceptible compounds do.

• It is usually in injectable preparations in ampules or vials.

• It is used in industry to bleach wood pulp, to fumigate grains and to arrest fermentation.

USES:

SYNONYMS: SODIUM HYDROGEN SULFITE, SODIUM ACID SULFITE AND LEUCOGEN

SODIUM BISULFITE (NaHSO3) or SODIUM METABISULFITE(Na2S2O5)

• It prevents oxidation of the compounds of phenol or catechol nucleus to quinones.

• Bisulfite may also be found in ascorbic acid injections as a reducing agent.

• It prepares water-soluble derivatives of normally insoluble drugs.

• Metabisulfite is an ascorbic acid injections as reducing agent.

USES:

NITROGEN(N2)

• As an inert atmosphere, it retards oxidation in oxidation-sensitive products, and replaces air in containers for parenterals and solutions for topical applications.

USES:

SODIUM THIOSULFATE

• Contains sulfur in two different oxidation states.

• The oxidized sulphur atom is in a +6 state resisting further oxidation, whereas the remaining sulphur atom is in a zero oxidation state. This oxidation polarity allows the compound to act as a reducing agent. Also, sodium thiosulfate acts as an antidote for cyanide poisoning.

USES:

SODIUM NITRITE

• Nitrites can act as both a reducing and oxidizing agent. Reduction of compounds with sodium nitrite results in formation of nitrates.

• It is an antidote for cyanide poisoning.• Nitrites in brine solutions are curing ingredients

of meats and fish for they are excellent color developer, enhance flavor production, and prevent microbial growth. However, nitrite ions remain in cured meats and react with organic amines to form potentially carcinogenic N-nitrosamines.

USES:

GLASS

• Glass is the container material of choice for most small volume infusions. It is composed chiefly of silicon dioxide, with varying amounts of other oxides like sodium, potassium, calcium, magnesium, aluminum, boron and iron.

• The following are added to imaprt color to the glass:

Substance added Color impartedCopper(I) oxide Opaque red, green, blueTin (IV) oxide Opaque

Calcium Fluoride Milky whiteManganese (IV) oxide Violet

Cobalt (II) oxide BlueFinely divided gold Red, Purple, Blue

Uranium compounds Yellow, GreenIron (II) compounds Green

Iron (III) compounds) YellowChromium Green

Cadmium sulfide YellowSelenium Red or Pink

• Glass is formed by the silicon oxide tetrahedron. Though boric oxide will enter into this structure, most of the other oxides do not.

• Glass types are determined from the result of two USP tests: the powdered glass test and water attack test. The latter is used for type II glass.

• Selecting the appropriate glass composition is critical facet of determining the overall specifications for each parenteral formulation.

• Glass can be a source or cause of leachables/extractables, adsorption formulation components, especially proteins, and cracks or scratches.

• Leachability- is a property in which ions from the glass container will leach out and interact with the product, thereby reducing the stability of the product.

• Delamination or glass particulate formation- is caused by the chemical attack on the glass matrix by the formulation solution, resulting in the weakening of the glass and eventual dislodgement of flakes from the glas surface.

GLASS TYPES

• Composed principally of silicon dioxide and boric oxide, with low levels of the non-network-forming oxides, it is a chemically resistant glass (low leachability) with low thermal coefficient of expansion.

• This type of container is suitable for all products although sulfur dioxide treatment sometimes is added to further increase its resistance.

1. TYPE I – BOROSILICATE GLASS

• The relatively high proportions of sodium oxide and calcium oxide makes this glass type chemically less resistant.

• Type II melts at lower temperature, rendering it easier to mold into various shapes; and has a higher thermal coefficient of expansion than Type I.

• It has a lower concentration of the migratory oxides than Type III.

2. TYPE II – SODA-LIME TREATED GLASS

• This type is treated under controlled temperature and humidity conditions with sulfur dioxide or other dealkalizers to neutralize the interior surface of the container.

• Type II glasses may be suitable for a solution that is buffered, has a pH below 7, or is not reactive with glass.

• These glasses are composed of relatively high proportions of sodium oxide and calcium oxide, a combination that renders the glass chemically less resistant.

• They melt at lower temperature, are easier to mold into various shapes, and have a higher thermal coefficient of expansion than Type I.

• Type III glasses are suitable principally for anhydrous liquids or dry substances.

• 4. NP – Soda- lime glass not suitable for containers for parenterals

3. TYPE III – SODA-LIME GLASS

Special addition/Composition

Desired Property

Large amounts of PbO with SiO2 and Na2CO3

Brilliance, Clarity, Suitability for optical structures; crystals or flint glass

SiO2, B2O3, and small amounts of Al2O3

Small coefficient if thermal expansion; borosillicate glass

One part SiO2 and four parts PbO

Ability to stop (absorb) large amounts of X-rays and gamma rays: lead glass

Large concentrations of As2O3

Transparency to infrared radiation

REAGENTS ADDED TO MODIFY THE CHARACTERISTICS/APPEARANCE OF

GLASS