Pharmaceutical Aids and Necessities PDF

Pharmaceutical aids and necessities Overvie w  Pharmaceutical aids and necessities are agents important to:  Preparation  Preservation  Storage of pharmaceuticals. Classification  Acids and bases  Buffers  Antioxidants  Water...

Pharmaceutical aids and necessities Overvie w  Pharmaceutical aids and necessities are agents important to:  Preparation  Preservation  Storage of pharmaceuticals. Classification  Acids and bases  Buffers  Antioxidants  Water  Glass  NO therapeutic value  For making dosage forms  ACIDS, BASES, AND BUFFERS  Bronsted-Lowry theory is the acid base theory we use in the pharmacy because physiologic functions and pharmaceuticals are often times dispensed as an aqueous solution.  General chemical expression:  HA + B = Aˉ + HB˖  Acid + Base = conjugate base + conjugate acid Electrolyte s  Strong acids and bases are strong electrolytes  Weak acids and bases are weak electrolytes  Relation  The stronger the acid, the weaker its conjugate base, and vice versa.  The stronger the base, the weaker its conjugate acid, and vice versa. OFFICIAL INORGANIC ACIDS  Boric acid (H3BO3)  Synonym: boracic acid, hydrogen borate, orthoboric acid  Occurrences: found in seawaters, certain plants, in nearly all fruits and in some volcanic stem jets. The native boric acid is called sassolite.  Properties: available in three crystalline forms: a) colorless,odorless, pearly scales b) Six-sided triclinic crystals c) White, odorless powder with a soapy feel Uses: antiseptic because it is a weak bacteriostatic  agent; in 2% w/c concentration as eyewash and as buffer in ophthalmic solutions *the toxicity of boric acid makes it unfit to be taken orally.  Hydrochloric acid (HCl)  Synonym: chlorhydric acid, spirit of sea salt, muriatic acid  Use: a pharmaceutical aid as an acidifying agent  Diluted Hydrochloric acid  Diluted HCl exists in the normal gastric juice aiding in the conversion of pepsinogen into pepsin and of proteins into peptones and serving as a gastric antiseptic. It is also used in the management id gastric achlorhydria, the absence if HCl in the stomach; and hypochlorhydria, the deficiency of HCl production of the stomach.  Nitric acid (HNO3)  Synonym: spirit of nitre, aquafortis, aqua fuerte  Properties: nitric acid will produce a yellow stain on animal tissue due to the nitration of the aromatic amino acid, phenylamine, tyrosine and tryptophan found in the proteins of skin. This reaction is known as xanthoproteic test. It oxidizes common metals except gold and platinum to produce the nitrate salt of the metal.  Uses: the manufacture of sulfuric acid, coal tar dyes and explosives; a nitrating agent in pyroxylin USP XVIII; a source of nitrate ion in the preparation of milk of bismuth; externally, the elimination of chancres and warts.  Phosphoric acid(H3PO4)  Synonym: orthophosphoric acid, acido orthofosforico  Use: acidifying agent  Diluted phosphoric acid  Uses: a tonic and stimulant to the gastric mucous membranes; a synergistic substance to pepsin and acids to the formulation of peptones  Sulfuric acid (H2SO4)  Synonym: oil of vitriol, vitriolic acid, aceite de vitriole  Preparation: there are two ways to prepare sulfuric acid: contact pr catalytic process and the Lead chamber process. Both have the same principle, that is, the oxidation of the sulfur dioxide to sulfur trioxide by adding enough water to form sulfuric acid. In the catalytic process, vanadium and platinized silica gels are catalyst.  Use: dehydrating agent in the preparation of pyroxylin USP XX  Acetic acid (CH3COOH)  Synonym: glacial acetic acid  Use: irrigation solution with some bacteriostatic properties  Official Inorganic Bases 1. Strong Ammonia Solution 2. Diluted Ammonia Solution 3. Calcium Hydroxide 4. Potassium Hydroxide 5. Sodium Hydroxide 6. Sodium Carbonate 7. Soda Lime 8. Potassium Bicarbonate 9. Sodium Bicarbonate  Strong Ammonia Solution (NH4OH) USP38/NF33 Other Names:  Ammonium Hydroxide  Stronger Ammonia Water Precautions:  Use care in handling (caustic nature and irritating properties of its vapor)  Cool the container well before opening  Cover the closure with cloth while opening  Do not taste or inhale the vapors Bronsted base Manufacture of nitric acid and sodium bicarbonate Preparation of aromatic spirit Preparation of ammoniacal silver nitrate solution  Tollens' reagent is an alkaline solution of ammoniacal silver nitrate and is used to test for aldehydes  Diluted Ammonia Solution (NH4OH) USP38/NF33  Prepared from strong ammonia solution  Known as ammonia water or household ammonia  Employed as circulatory stimulant through inhalation of vapors USES  When used externally, it is counter-irritant  Calcium Hydroxide Ca(OH)2 USP38/NF33 Other Names:  Slaked lime Calcium hydrate Preparation:  Manufactured from lime or Calcium Oxide by slaking process. Medicinally used as fluid electrolyte and topical astringent Utilized for its high hydroxide ion concentration in pharmaceutical preparations. Its alkalinity reacts with free fatty acids in various oils to form calcium soaps which have emulsifying properties. Due to its ability to absorb CO2 from expired air, it is combined with NaOH or KOH in a mixture known as soda lime  Potassium Hydroxide (KOH) USP38/NF33 Other Names:  Caustic potash  Potassa Properties:  Deliquescent  Very strong base with caustic/ corrosive effect on tissues (handle carefully) Uses:  As a caustic in veterinary practice  As a saponifying agent to hydrolyze esters of fatty acids into their constituent alcohols and potassium salt  Sodium Hydroxide (NaOH) USP38/NF33 Other Names:  Caustic soda  Soda lye Properties:  It attacks soft glass (containers should be made of hard glass with rubber stoppers  Glass-stoppered bottles can be used if a liitle petroleum or paraffin is spread around the stopper  Not borosilicate, a soft glass has high coefficients of thermal expansion; thus it does not require a high temperature to make them soft. Uses: same as potassium hydroxide but has more advantage since it is less deliquescent, milder, and cheaper.  Sodium Carbonate (Na2CO3.H2O) USP38/NF33 Other Names: Monohydrated sodium carbonate Use:  In pharmaceutical preparations, its basicity forms sodium salts of acidic drugs  Soda Lime USP38/NF33 Uses:  A mixture of Ca(OH)2 and NaOH or KOH or both intended for metabolism tests, anesthesia, and O2 therapy.  Potassium Bicarbonate USP38/NF33 Other Names:  Potassium Hydrogen Carbonate  Potassium Acid Carbonate Use:  Buffering agent for pharmaceutical preparations  Sodium Bicarbonate USP38/NF33 Other Name: Sodium Hydrogen Carbonate Use:  Preferred in preparation of effervescent mixtures containing sodium bicarbonate and organic acids such as tartaric or citric. These additives react to liberate CO2 that acts as a disintegrator producing effervescence when in water. BUFFERS A buffer is a solution of a weak acid and its salt or the salt of its conjugate base or a weak base and its salt or the salt of its conjugate acid that resists drastic changes in pH when small amounts of acid or base are added to it. Buffers control the pH of pharmaceutical products within certain specified limits for these reasons: A. Chemical Stability B. Solubility of the drug C. Patient’s comfort Some factors which can produce alterations in pH include: D. Alkali in certain inexpensive containers E. Gases present in air such as CO2 and NH3  MECHANISM OF ACTION  When small amounts of hydrogen ion are introduced into the medium, they will react with the conjugate base and basic members of the buffer to form a weak acid.  Similarly,when small amounts of hydroxide ion are introduced into the medium, they will react with the weak acid or acidic member of the buffer pair and form water and the conjugate base.  Hence,each component of the buffer pair will react with either acid or base to form the other component If base (OH) is added, it will react with the acid to neutralize the base, forming acetate ion and water H2C3O2 + OH → C2H3O2 + H2O The selected buffer should not: A. Participate in oxidation-reduction reaction B. Alter the solubility of other components C. Form complexes with active ingredients EXAMPLE S: ACETIC ACID AND ITS CONJUGATE BASE, ACETATE ION: HC2H3O2 (acid) + H20 → H3O + C2H3O2 (conjugate base) If acid (H3O) is added, it will react with the conjugate base to neutralize the acid, forming acetic acid and water C2H3O2 + H3O → HC2H3O2 + H2O Consider the following when choosing a buffer: 1. Volatile species should not be used as buffers 2. It should not have any influence on the pharmacological activity of the API 3. The use of the pharmaceutical should be considered in choosing a buffer for a product. If it is to be ingested, buffers containing borates should not be used as they are toxic systemically.  TWO INORGANIC BUFFER SYSTEMS A. PHOSPHATE BUFFER SYSTEM ADVANTAGE: it contains dihydrogen and monohydrogen phosphate ions which are found normally in the body DISADVANTAGE: The insolubility of the phosphate salts of such metals such as Ag, Zn, and Al support microbial growth B. BORATE BUFFER SYSTEM It contains metals that would precipitate in the presence of phosphate. They are toxic and it is suitable in external preparations, ophthalmic, and nasal solutions but is contraindicated in parenteral solutions.  THREE PRIMARY BORATE BUFFER SYSTEMS: 1. FELDMAN’S BUFFER SYSTEM - pH of 7.6 – 8.2 - consists of : BORIC ACID, NaCl ( to make it isotonic), and Sodium Borate 2. ATKINS AND PANTIN BUFFER SYSTEM - pH of 7.6 – 11 - consists of: Sodium carbonate, Boric acid, and NaCl 3. GIFFORD BUFFER SYSTEM - pH of 6 – 7.6 - similar to Feldman’s Buffer System but NaCl is replaced by KCl to make it hypotonic  STANDARD BUFFER SOLUTIONS Buffer systems in pharmacy can be roughly categorized into: 1. Standard buffer systems – designed to provide a solution having a specific pH for analytical purposes. 2. Actual pharmaceutical buffers – designed to maintain pH limits in drug preparations Standard buffer solutions having pH ranges between 1.2 and 1. can be prepared by appropriate combinations of: - BORIC ACID AND POTASSIUM CHLORIDE, 0.2M - HYDROCHLORIC ACID, 0.2M - POTASSIUM CHLORIDE, 0.2M - POTASSIUM PHOSPHATE, MONOBASIC 0.2M - POTASSIUM BIPHTHALATE, 0.2M - SODIUM HYDROXIDE, 0.2M - ACETIC ACID, 2N All the crystalline reagents except boric acid should be dried at 110 – 120 degrees Celsius for an hour before use. The water should also be CO2-free. The solution should be stored in Type 1 glass bottles and the solutions used within 3 months. The solutions, prepared and standardized, will later be combined in specific quantities to make the following standard buffer solutions to achieve a certain pH.  BUFFER pH COMPOSITION HYDROCHLORIC ACID 1.2 -2 50ml KCl solution with a specified volume of 0.2 HCl and water F ACID PHTHALATE BUFFER 2.2-4.O 50 ml of potassium biphthalate solution with a specified volume of 0.2 HCl and water NEUTRALIZED PHTHALATE BUFFER 4.5-5.8 50 ml of potassium biphthalate with a specified volume of NaOH and water PHOSPHATE BUFFER 5.8-8.0 50 ml of monobasic potassium phosphate with NaOH and water ALKALINE BORATE BUFFER 8.0-10.0 50ml of boric acid and KCl with NaOH and water ACETATE BUFFER 4.1-5.5 Specified amount of acetate with acetic acid and sodium water Antioxidants  REDUCING AGENTS Pharmaceutical necessity  MECHANISM OF ACTION OF ANTIOXIDANTS 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  b) The possible TOXICITY ofboth 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) USES: 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.  Sulfur dioxide (So2) SYNONYM : Sulfurous anhydride USES: 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 Sodium bisulfite (NaHSO3) or SODIUM METABISULFITE(Na2S2O5) SYNONYMS: SODIUM HYDROGEN SULFITE, SODIUM ACID SULFITE AND LEUCOGEN USES: 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. Nitrogen( N2) Uses : As an inert atmosphere, it retards oxidation in oxidation-sensitive products, and replaces air in containers for parenterals and solutions for topical applications.  Sodium thiosulfate  Uses : 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. Sodium nitrite  Uses : 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. Glass Substance added Color imparted Copper(I) oxide Opaque red, green, blue Tin (IV) oxide Opaque Calcium Fluoride Milky white  Red or Pink Manganese (IV) oxide Violet Cobalt (II) oxide Blue Finely divided gold Red, Purple, Blue Uranium compounds Yellow, Green Iron (II) compounds Green Iron (III) compounds) Yello Chromium w Cadmium sulfide Green Selenium Yello  Glass is the container material of choice for most small volume infusions. It is composed chiefly of silicon dioxide, with varying amounts other like potassium, of calcium,oxides magnesium, sodium, aluminum, boron and iron. The following are added to imaprt color to the glass  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.  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  TYPE I – Borosilicate glass 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.  TYPE II – Soda-lime treated 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.  This type is treated under temperature controlled humidity conditions sulfur dioxide andor other with neutralize interior surface dealkalizers of to the container. may be suitable for the Type II is buffered, solution that a has a pH below 7, or glasses is not reactive with glass.  TYPE III – Soda-lime 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 Water Reagents added to modify the characteristics/appearance of glass Special Desired Property addition/Composition Large amounts of PbO with Brilliance, Clarity, Suitability SiO2 and Na2CO3 for optical structures; crystals or flint glass SiO2, B2O3, and small Small coefficient if thermal amounts of Al2O3 expansion; borosillicate glass One part SiO2 and Ability to stop (absorb) large four parts PbO amounts of X-rays and gamma rays: lead glass Large concentrations of Transparency to infrared As2O3 radiation  Water acts as a primary solvent for most substances due to its properties: small size, string permanent dipole,high dielectric constant and availability for protons for hydrogen bonding.  Pure water is a tasteless, odorless, clear liquid which is colorless in small quantities and greenish blue in deep layers.  Due to solvent powers and physiological inertness, water is an extremely important pharmaceutical agent.  Natural water  Alkaline water- usually contain appreciable quantities of sodium and magnesium sulfates  Carbonated waters- charged with carbon dioxide under pressure while in earth.  Chalybdate waters- have iron in solution or in suspension and are characterized by a ferrigenous taste.  Lithia waters- occur in the form of carbonate or chloride  Saline waters- also known as "purgative waters" , hold relatively large amount of magnesium and sodium sulfates with sodium chloride.  Sulfur waters- have hydrogen sulfide  S iliceous waters- include very small amounts of soluble alkali silicates.  Official USP waters  Most liquid injections are quite dilute; the component present in the highest proportion  1.) Purified water  2.) Water for injection Description: clear colorless odorless liquid purified by distillation or reverse osmosis and contains no added substances. Use: pharmaceutic aid as a vehicle or solvent  3.) Bacteriostatic water for injection Description : it is prepared from water for injection that is sterilized and packaged in prefilled syringes or in vials containing not more than 30 mL. It also has one or more suitable antimicrobial agents. Use: sterile vehicle for parenteral preparations NOTE: label should state: "NOT FOR USE IN NEONATES" as there were problems encountered with neonates and the toxicity of the bacteriostat, benzyl alcohol. 4.) Sterile water for injection Description: clear colorless odorless liquid for parenterals; sterilized; no antimicrobial agent or other added substances 5.)Sterile water for irrigation Description: clear, Colorless, odorless liquid; water for injection that has been sterilized; no antimicrobial agent or other substances Use: an irrigating solution NOTE: label must say "For irrigation only and not for injection"  6.) Sterile water for inhalation Description: it is prepared from water for injection, sterilized and packaged,with no added antimicrobial agents. Heavy water is isotopes of hydrogen (deuterium and tritium) END