CHAPTER II

CHAPTER IIPHARMACEUTICAL AIDS AND NECESSITIESOfficial Inorganic AcidsBoric AcidHydrochloric AcidBoric Acid NF 26NF = National Formulary Formulary =specify particular medications that are approved to be prescribed under a particular insurance policy.

Boric AcidChem. Name: H3BO3 Mol. Weight: 61.83Synonyms: Boracic Acid, Hydrogen Borate, Orthoboric AcidOccurrence: Free Boric Acid sea waters, certain plants, nearly all fruits, some volcanic steam jetsBoric AcidNative Boric Acid (Sassolite)Largest material source is in combined forms e.g.Na2 B4O7.4H2O (Rasorite or Kernite)Na2 B4O7.10H2O (Borax)CaB4O7.4H2O (Borocalcite)Ca3B6O10.5H2O (Colemanite)H3BO3.NaB4O7.2CaB4O7.18H2O (Tincal)

Boric AcidProperties: solid available in 3 forms:(1) colorless, odorless, pearly scales(2) six-scaled triclinic crystals(3) white, odorless powder w/c is unctuous to touch (having a soapy feeling)Boric AcidThe scale & crystalline forms of comp. are more suitable for aqueous solns since powder floats on top of water.It is stable in air w/ a density: 1.46Soluble(10 to 30 parts): water, alcohol, Freely Soluble (1 to 10 parts): glycerin, boiling water, and boiling alcohol

Boric AcidClear solns are obtained when 1g is dissolved in 25mL of waterThe addition of HCl decreases its solubility in water.Due to weak acid nature, only salts produced by replacement of 1 proton per molec. (primary salts) can be obtained in aqueous soln

Boric AcidThose salts formed w/ alkali metals are the only ones soluble in water and these produce very alkaline solutionsSalts formed w/ other metals are hydrolyzed in water to produce insoluble hydroxidesNot absorbed through the intact skin but is highly toxic ingested orallyAbsorbed when applied over large areas of broken skin

Boric AcidUses: NF XV specifies that Boric Acid must contain n.l.t. 99.5% & n.m.t. 100.5% of boric acid calculated as an anhydrous (dried) formFor years, it has been used as solns, ointments, & dusting powder as an antiseptic. Boric AcidAt best, the comp. can be described as a weak bacteriostatic (stops bacteria) agentsIt will still be found in the form of soln in conc. From 2.5% to 4.5% for use as an eyewash.The more concentrated soln should be diluted w/ an = vol. of water before useBoric AcidHigher conc. is near saturation and boric acid tends to crystallize out w/ a slight drop of temp.This represents a danger & solns should be warmed or diluted before use in order to dissolve the crystals

Boric AcidUsed as a buffer in opthalmic solns & prep. Like Aluminum Acetate Soln USP XVIII & Aluminum Subacetate Soln USP XVIII USP - United States PharmacopeiaBoric AcidSince it is a weak acid, it constitutes a portion of what would be required for a buffer soln but used alone, it doesnt have such buffer capacityThe rxn of boric acid w/ equimolar quantities of glycerin at 140C- 150C produces a comp. known as Boroglycerin Glycerite NF XI (C3H5BO3)Boric AcidW/c has found some use as a suppository base.The toxicity of boric acid precludes its use in products that are to be taken internally.

Boric AcidCommercial Products:Insecticides

Boric AcidCommercial Products:Fungicides

Boric AcidCommercial Products:Herbicides

Boric AcidCommercial Products:Antiseptic for minor burns or cuts

Boric AcidCommercial Products:Opthalmic Soln

Hydrochloric Acid NF 26Synonyms: Muriatic Acid, Spirit of Sea Salt, Marine Acid, Espiritu de Sal MarinaOfficial Definition: An aqueous soln of hydrogen chloride gas containing n.l.t. 35% & n.m.t. 38% by weight of HClProperties: Colorless fuming liquid w/ a pungent odor Hydrochloric Acid NF 26Specific Gravity: 1.18A non-fuming soln can be prepared by diluting it w/ 2 volumes of waterMore highly ionized than most other strong acids & attacks many metals w/ evolution of hydrogenHydrochloric Acid NF 26Muriatic Acid (Latin: Muria brine) is a technical grade of hydrochloric acid containing 35% to 38% HCl & a no. of impurities including chlorine, arsenous, & sulfurous acids and ironImpurities give yellow colorHydrochloric Acid NF 26Uses: Categorized by the NF XV as a pharmaceutical aid or specifically as an acidifying agentBy virtue of strong acid character, it reacts w/ organic molecules w/c are weakly basic to form usually water soluble hydrochloride salts.Hydrochloric Acid NF 26This type of rxn is utilized to convert normally water insoluble organic bases into a water soluble form for extraction or other separation purposesSince salts of most organic amines are solids, treatment of liquid organic bases with hydrochloric acid can render the comp. suitable for the incorp. into a solid dosage formHydrochloric Acid NF 26One disadvantage of using HCl for this purpose is that some hydrochlorides are hygroscopic (readily taking up and retaing moisture). Nevertheless, most drugs are available as hydrochloride salts are related to their ease of preparation and to the very low toxicity of the chloride ion.Hydrochloric Acid NF 26Diluted Hydrochloric Acid NF XV a soln of hydrogen containing n.l.t. 9.5g & n.m.t. 10.5g of HCl in each 100 mL of solnDiluted Hydrochloric Acid exists in the normal gastric juice (about 0.2%) aiding in the conversion of pepsinogen into pepsin & proteids into peptones & as gastric antisepticHydrochloric Acid NF 26It maybe valuable in some forms of indigestion, especially in those conditions of gastric achlorhydria (absence of hydrochloric acid) & hypochlohydria (deficiency of hydrochloric acid)Usually given in doses from 1-10cc, highly diluted w/ water and to be supplied through a glass tube/ straw avoiding solvent action w/ on the enamel of the teeth.Hydrochloric Acid NF 26To avoid: prep. such as Glutamic Acid Hydrochloride & Betaine Hydrochloride have been advocated. They are crystalline and maybe administered in capsule form. They liberate HCl in the stomach, the glutamic acid or betaine residue being metabolized at the same timeHydrochloric Acid NF 26Commercial Products:Muriatic Acid

Hydrochloric Acid NF 26Other Uses:Hydrochloric acid is a common laboratory reagent.

NITRIC ACID NF 26

NITRIC ACID NF 26HNO3

Synonyms: Spirit of Nitre, Aqua Fortis, Agua Ferte

Properties: aqueous solution; 68% < HNO3 < 71% by weighthighly corrosive fuming liquid, irritating odorboiling point 120oCspecific gravity 1.41on animal tissues xanthoproteic test

NITRIC ACID NF 26strong monoprotic acidoxidizing and nitrating agentphotochemical decomposition of nitric acid oxidized all common metals to produce nitrate saltNitrating properties of nitric acid

NITRIC ACID NF 26Uses: Acidic properties similar to HClAcidifying agent in basesOxidizing and nitrating properties Manufacture of sulphuric acid, coal tar dyes and explosivesNitrating agent in pyroxylin External use: destroy chancres and warts

NITRIC ACID NF 26

Nylon, explosive, fertilizer, detergentPHOSPHORIC ACID NF 26

PHOSPHORIC ACID NF 26H3PO4

Synonyms: Orthophosphoric Acid, Acido Orthofosforico

Properties:Contains n.l.t. 85% and n.m.t. 88% by weight of H3PO4Colorless, odorless, syrupy liquidSpecific gravity: 1.71Non-volatile and no oxidizing properties

PHOSPHORIC ACID NF 26Uses:Can be used as an acidifying agentCan be treated with NaOH to produce mixtures pf HPO4-2 and H2PO4-Solvent in the preparation of Anileridine Injection NF XVDILUTED PHOSPHORIC ACID NF 26Properties:Contains n.l.t. 9.5 g and n.m.t. 10.5 g of H3PO4 in 100 mL of solution

Uses:Used as a tonic and stimulant to the gastric mucous membranesActs as synergistic to pepsinAids in the formulation of peptonesUsed in making some pharmaceutical preparations

PHOSPHORIC ACID NF 26

Fertilizer, cleaning products, food additiveSULFURIC ACID NF 26

SULFURIC ACID NF 26H2SO4

Synonyms: Oil of Vitriol, Vitriolic Acid, Aceite de Vitriolo

Properties:Colorless, odorless liquid of oily consistencyContains n.l.t. 94% and n.m.t. 98% of H2SO4Specific gravity: n.l.t. 1.84

oleum- commercial variety which contains about 10% of dissolved SO3

SULFURIC ACID NF 26Preparation:2 industrial processes of preparing sulfuric acid: Contact or Catalytic Process and Lead Chamber Process

Contact ProcessProduces most of the commercial sulfuric acid today

Lead Chamber ProcessMainly used in the manufacture of the fertilizer

SULFURIC ACID NF 26Uses:Strong diprotic acid which can form salts of basic organic drug moleculesUtilized as dehydrating agent in the preparation of Pyroxylin USP 26SULFURIC ACID NF 26

Fertilizer, lead-acid battery, drain cleanerOFFICIAL INORGANIC BASESSTRONG AMMONIA SOLUTION NF 26

STRONG AMMONIA SOLUTION NF 26Synonyms: Ammonium Hydroxide, Stronger Ammonia Water

Properties:Contains n.l.t. 27% and ammonia rapidlyClear, colorless liquid, exceeding pungent, characteristic odorSpecific gravity: 0.90

Caution:Be careful in handling because of the caustic nature of the solution and the irritating properties of its vaporsSTRONG AMMONIA SOLUTION NF 26Can serve as a liquid in forming soluble complex ions with many metal cations

Uses:Used as Bronsted base to form ammonium salt of acidsUsed in the manufacture of HNO3 and NaHCO3Used in the preparation of Aromatic Ammonia Spirit NF XVSTRONG AMMONIA SOLUTION NF 26

Fertilizer, cleanersDiluted Ammonia Solution

Also known as ammonia water or household ammoniait contains no less than 9 gram and not more than 10 grams of NH3, with an appropriate amount of purified water.it is used in cleaning floors, walls, and some appliances. Remove cloth and carpet stains. Repels insects in drawers and closets.Not to be used in contact with the skin and eyes. Avoid breathing ammonia vapors, use products in a well-ventilated area.

Calcium Hydroxide USP 31

Ca (OH)2; Mol. wt. 74.09Also known as slaked lime or calcium hydrate- it is manufactured from lime or calcium oxide through the addition of water in limited amounts (slaking).

(Ca OH)2; Mol. wt. 74.09- It is a solution containing not less than 140 mg of Calcium Hydroxide in each 100ml.- Slaked lime or Calcium Hydrate is a compound used to make mortars, plasters, and cement. In dentistry, Calcium Hydroxide is used as a root canal filling.

Potassium Hydroxide NF 26

KOH; Mol. wt. 56.11Also known as Caustic Potash or Potassa-has characteristics of white fused masses, small pellets, flakes, sticks that have a crystalline fracture.- it is a strong base that can cause corrosive effects on the skin.

KOH; Mol. wt. 56.11- it is used in bleaches and soaps, also used as treatment for fungal infection on the skin hair or nails.- it is also used in veterinary as a form of chemical cremation in order to hasten the decomposition of the tissues of dead animals, so that what is only left behind are the bones and hard tissues.Sodium Hydroxide NF 26

NaOH; Mol. wt. 40Also known as Caustic Soda or Soda LyeCharacterized as dry, hard, brittle, white sticks fused in an opaque, white stone-like masses in small pellets.- it is a strong base, therefore it is capable of damaging the skin.Like Potassium Hydroxide, it is used construction sites and the like.Sodium Carbonate NF 26

Na2CO3H2O; Mol. wt. 124Also known as monohydrated sodium carbonate.Classified as a colorless crystalline powder.Exists in three characterized hydrates:Monohydrate-Na2CO3H2OHeptahydrate- -Na2CO37H2ODedahydrate- -Na2CO310H2OSodium Carbonate is also commonly known as washing soda or soda ash. It is widely used as a cleaning agent at home, but it has side effects that may cause breathing problems, vomiting, diarrhea, drooling and low blood pressure if ingested.Soda Lime NF 26A mixture of calcium hydroxide and sodium or potassium hydroxide or both.Intended for use in metabolism tests, anesthesia and oxygen therapy.Soda Lime NF 26Its function is to absorb carbon dioxide in a closed system.Will react with the carbon dioxide in the form Na2CO3, to form calcium carbonate, thereby regenerating the sodium hydroxide. BuffersThe Control of pH in solutions is very important aspect of pharmaceutical chemistry and practice. Pair of related chemical compounds capable of resisting large changes in the pH of a solution caused by the addition of small amounts of acid or base. BuffersComposed of weak acid or and its salt or weak base and its salt. Buffer should not react with:1.Participate in oxidation-reduction reaction2.Alter the solubility of other components3.Form complexes with active ingredientsThree Primary Borate Buffer System1.Feldmans buffer system (pH 7-8.2) 2.Atkins and pantin buffer system (pH 7.6-11) 3.Gifford buffer system (pH 6-7.8)Na3BO3 NF 26 (Na2B4O7 . 10H2O ; Mol. Wt. 381.37)Synonyms: Borax, Sodium Pyroborate, Sodium Tetraborate, TinkalProperties: > colorless, transparent crystals or white crystalline powder> odorless and effloresces in warm, dry air> soluble in water & glycerin ; insoluble in alcohol> aqueous solutions are alkaline to phenolphthalein > same toxicity as boric acid; hydrolyzed to boric acid in aqueous solution

Na3BO3 NF 26 (Na2B4O7 . 10H2O ; Mol. Wt. 381.37)Uses:> best eyewash (acids mucosa)> 1-2% solution collyria> mouth washes, oral prep, powder (mouth ulcers)> weak bacteriostatic agent> borax soap - emulsifying agent preparation of ointments (Cold Cream USP , Rose Water Ointment NF) >Washing soda

AntioxidantsFunction: reducing agentUsed in pharmaceutical preparations containing oxidizable substances to maintain these substances in their reduced formMechanism of antioxidant action may be seen in two ways:Either the antioxidant is oxidizedIf active constituent is oxidized, the antioxidant reduces it back to its normal oxidation stateAntioxidantsFactors in selecting a suitable antioxidant:Physiologically inertAssessment of possible toxicity of reducing agent & oxidized productPossible solubility problems between reducing agent and the drugFormation of explosive mixture when the very strong reducing agents are combined with strong oxidizing agentsAntioxidantsExamples:Vitamin EVitamin CFruitsVegetables

Hypophosphorous Acid (HPH2O2 or H3PO2)Properties:Colorless or slightly yellow, odourless liquidContains not less than 30% and not more than 32% HPH2O2Pure acid: syrupy colorless liquid; solid at 17 C, melts at 26Coxidation state is 1+powerful reducing agentreduce compounds to form phosphorus acid (H3PO3) having oxidation state of 3+ and phosphoric acid (H3PO4) having oxidation state of 5+net transfer of 4 electrons

Hypophosphorous Acid (HPH2O2 or H3PO2)Uses:no important pharmacological actionantioxidantprevents the formulation of free iodine in Diluted Hydroiodic Acid and Syruppresent in Diluted Ferrous Iodide Syrup NF XI prevents the formulation of ferric ions and molecular iodineSalts: antioxidant propertiesSodium Hypophosphate preservative in certain foods

Hypophosphorous Acid (HPH2O2 or H3PO2)Uses:Ammonium Hypophosphate found in many preparations as preservativeHypophosphite never be triturated with oxidizing agents (nitrates, chlorates, or permanganates)Concentration ranges: never over 1%

Sulfur Dioxide (SO2)Synonym: Sulfurous AnhydrideProperties:Colorless, non-flammable gasStrong suffocating odor characteristic of burning sulfurSoluble in water (36:1) forming sulfurous acid (moderately strong acid)Oxidation state is 4+Strong reducing agent

Sulfur Dioxide (SO2)Uses:Antioxidant and pharmaceutical aidProtects many susceptible compounds from oxidationReducing the oxidized firm back againReacting with oxygen before the susceptible compounds doUsed in injectable preparations because of its gaseous natureEnclosed in single dose ampoules or in multiple does vialsExtensive use in industry: bleaching wood pulp, fumigating grains, arresting fermentationFumigate houses burning of sulfur dioxide

SODIUM BISULFITE ( NaHSO3 )Synonym: Sodium Hydrogen Sulfite, Sodium Acid Sulfite, LeucogenProperties:Mixture of sodium bisulfite (NaHSO3) and sodium metabisufite (Na2S2O5) Compound is white or yellowish white crystals or a granular powderOdor of sulfur dioxide Solid is unstable in air, giving off sulfur dioxide Should yield not less than 58.5 % and not more than 67.4 % sulfur dioxideSODIUM METABISULFITE NF 26 ( Na2S2O5 ) Properties:Compound is white crystal or white to yellowish crystalline powderOdor of sulfur dioxideShould contain Na2S2O5 equivalent to n.l.t. 66% and n.m.t. 67% sulfur dioxideSODIUM METABISULFITE NF 26 ( Na2S2O5 ) BisulfitesNaHSO3 is acidic enough to neutralize the stronger bases (sodium bicarbonate) to form sulfiteAddition of sulfites to acidic solutions will result to a shift in alkaline pH by the formation of bisulfite, w/c reduces concentrations of hydrogen ions One primary source of incompatibilities with bisulfites and sulfites is solubility:Salts of alkali metals solubleSalts of alkaline earth metal bisulfites less solubleSulfites of metals - insolubleUSES OF NaHSO3 and Na2S2O5Used almost exclusively as an antioxidantUsually found in acidic solutions of drugs that contain phenol or catechol nucleus to prevent oxidation of compounds to quininesMay also be found in ascorbic acid as a reducing agentMay be used to prepare water soluble derivatives of normally insoluble drugs

NITROGEN (N2)Molecular Weight = 28.01

Properties:Colorless & odorless inert gasNon-flammable and doesnt support combustionOne volume dissolves in about 65 volumes of H2O and in about 9 volumes of alcohol at 20C and at the pressures of 760 mmHgSold in black cylinders

Uses:Inert atmosphere to retard oxidation in oxidation sensitive products(Cod Liver Oil, Olive Oil, Multi Vitamins Preparations)To replace containers for parenterals and topical solutionsTo retard oxidation for carbon monoxide

88Water (H2O)Molecular Weight = 18.01528

Properties:Tasteless, odorless and clear liquid which is colorless in small quantities but greenish blue in deep layers.Density is 1, ice= -1 ~ makes ice float in waterAbility to form hydrogen bonds

Properties making water the solvent of choice:Constituent of the bodyHaving high dielectric constantBeing a small moleculeWhy is dielectric constant important to water? It is important to its capacity as a solvent as a stabilizer of structure. It is also responsible to the non linear bent shape of water.Hardness of water:-this property of water is due to the presence of varying amounts of Ca, Fe and Mg salts which convert ordinary soap (water soluble Na and/or K salts of high molecular weight fatty acids) into water insoluble Ca, Fe and Mg salts of fatty acids(water insoluble curd)

*Soap with hard water = Curdy Precipitate

Temporary hardness-caused by the presence of Ca(HCO3)2 or Mg(HCO3)2 -can be removed (softened) by boiling or addition of a source of OH-Permanent hardness-caused by the presence of SO4-2, Cl- or OH- of Ca and or Mg

-can not be removed by boiling or addition of a source of OH-Ways of purifying water:Addition of soluble Carbonates which precipitate Ca and Mg as insoluble CarbonatesEx. Washing Soda ( Na2CO310H2O)Ways of purifying water:Chelation by zeolite (permutit) ProcessZeolite=Na2OAl2O3 2SiO2 3H2OPassing the hard water through a zeolite column an exchange of water hardening cations is made for non-hardening sodium cations. When calcium zeolite reaches a high enough concentration the column can no longer exchange calcium ion for sodium ion efficiently. To restore its activity, a strong solution of NaCl is allowed to flow through the inactivated zeolite reconverting it to the Na form.

Ways of purifying water:Deionizer/DemineralizerMakes use of certain synthetic resins which are endowed with removing both cations and anions from water. Since the water produced from this apparatus compasses very favorably with distilled water at lower cost USP XX modified the name and monograph of distilled water to permit the use of deionized water under the title of purified water.Ways of purifying water:Polyphosphate ChalationThe detergent industry has been using basic phosphate and sodium meta-phosphate to chalate the divalent calcium making it unavailable for further reaction.Ca & Mg made unreactive by chelate bond(claw)Official WatersPurified Water USP 31obtained by distillation and ion exchange treatment clear odorless liquid with specifications for extemporaneous compounding used in preparation of most USP test reagents.

Water for Injection USP 31purified by distillationmust pass two tests: Pyrogen test and Endotoxin testpreparing extemporaneous parenterals would more likely use Bacteriostatic/Sterile water for injection

Sterile Water for Injection USP 31sterilized water for injectionmost difficult to prepareused for compounding of parenteralseither IV or IM injectionno antimicrobial substance

Sterile Water for Inhalation USP 31prepared from sterilized water for injection no antimicrobial agentsfor inhalation therapypackaging: glass or plastic container

Sterile Water for Irrigation USP 31from sterilized water for injectionpackaging: single-dose glass/ plastic containersno antimicrobial agents

Bacteriostatic Water for Injectionsterile water for injectionwith antimicrobial agentsused for parenterals for intramuscular injectionnot for use in newborns

Glassgeneric term referring to vitreous materialmay be considered as sodium silicateMost commercial ones are vitreous silicates and some type of additiveBoron-decreases the coefficient of expansion of Pyrex glassPotassium-gives brown light-resistant glassFour Types of GlassType 1 highly resistant, borosilicate glassType 2 treated with soda lime glassType 3 soda lime glassType NP general soda lime glassTypes of ContainersColorless Opaque- superior light protectiveColored Clear:1. patient likes to see what he is buying 2. amount left in the bottle is seen 3. ease of pouring

Four Types of Clear ContainersColorless Green Blue Amber screens out UV radiation