Zarah Pauline P.

Jimenez 1D Ph Chapter 2: Pharmaceutical Aids and Necessities o o o other substances needed in the preparation, preservation and storage of pharmaceutical products Acids and Bases for the conversion of drugs to chemical forms (salt form) convenient to their product formulation. sources are plants and aimals composed of organic molecules basic H2O insoluble salt
*addition HCl para madissolve

acidic H2O soluble salt

*organic molecule(basic) + acid salt organic molecule(acidic) + base salt

soluble in H2O - for absorption

efficacy of drug depends on absorption o o Buffers maintains the pH of various formulations made of Na2ONa2SiO3 basic Antioxidants prevent oxidative decomposition of pharmaceutically active components used as preservative Water primary solvent/liquid phase Glass for storage and as dispensing container

o o o o

Official Inorganic Acids

o Boric Acid [H3BO3]

- Boracid Acid; Hydrogen Borate; Orthoboric Acid - agua boricada - used to wash eyes - occurs free in sea waters, fruits and volcanic steam jets sassolite native/natural boric acid Sources: (combined forms) Rasorite/Kernite Na2B4O74H2O Borax Na2B4O710H2O Borocalcite CaB4O74H2O Colemanite Ca3B6O105H2O Tincal H3BO3 Na2B4O72CaB4O718H2O 1 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

Forms: suitable for preparing 1. colorless, odorless pearly scales 2. six-scaled triclinic crystals aqueous solutions 3. white odorless powder (soapy feeling)* *tends to float on top of water, will not be dissolved turbid solution water insoluble impurities are present clear solution water insoluble impurities are absent Density: 1.46, stable in air. o o soluble in water and alcohol; freely soluble in glycerin, boiling water and boiling alcohol addition of HCl decreases the solubility in water 1g____ *clear solution of boric acid 25mL H2O salts produced with alkali metals are the only ones soluble in H2O, producing very alkaline solution Boric acid is not absorbed through intact (unwounded) skin, but is highly toxic when ingested orally
*cumulative poison

o o -

absorbed when applied over large areas of broken skin must contain 100.5% anhydrous(dried) boric acid APPLIED TOPICALLY as: ointments ANTISEPTIC solutions dusting powder weak bacteriostatic agent (prevents multiplication) 3% concentration in ophthalmic solutions (eyewash collyrium) solutions should be warmed and diluted before use to dissolve crystals

o o o

used as buffer in ophthalmic solutions and preparations H3BO3 + Na2B4O710H2O (partner) alone does not have buffer capacity Boroglycerin Glycerite (C3H5BO3) suppository base, boric acid + glycerin @ 140-150oC

o Hydrochloric Acid [HCl] - Muriatic Acid, Spirit of Sea Salt, Marine Acid, Espiritu de sal Marina - used as DISINFECTANTS on inanimate objects - aqueous solutions, 36% HCl, colorless fuming liquid with a pungent odor - sp. gr = 1.18 - highly ionized o Muriatic Acid Latin muria --> brine technical grade containing the ff. impurities
2 chlorine arsenous sulfurous acids iron (FeCl3) yellow color

Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

used as pharmaceutical aid, acidifying agent/solubilizing agent strong acid, reacts with organic molecules which are basic forming water soluble salts

Use of Endogenous HCl aids in digestion of foods gastric antiseptic o should be taken with straw & diluted (can melt the enamel of the teeth) o normally present in GI tract drugs are available in hydrochloride salts due to its ease of preparation and very low toxicity of chloride ion exists as normal gastric juice (diluted) [0.2%] aids in the conversion of pepsinogen pepsin proteids peptones - as gastric antiseptic achlorhydria absence of hydrochloric acid hypochlorhydria deficiency of HCl DISADVANTAGE hydrochlorides are hygroscopic (absorbs water from air and forms its water) Glutamic Acid Hydrochloride Betaine Hydrochloride crystalline, administered in tablet or capsule form - liberate HCl in the stomach, boths residue are being metabolized at the same time -

o Phosphoric Acid [H3PO4]

o Orthophosphoricacid o an aqueous solution, colorless, odorless, syrup-y liquid having a sp. gr. of 1.71 o NON-VOLATILE, NON-OXIDIZING USES: as acidifying agent limited to the solubilities of the various phosphate salts produced treated with NaOH HPO4-2(basic) buffer H2PO4-1(acidic) a solvent in the preparation of Anileridine injection

o o o

Diluted Phosphoric Acid: 9.5g 100 mL 10% solution used as a tonic and stimulant to gastric mucous membranes
*tonic-energizing

-synergistic to pepsin - aids in formulation of peptones

o Sulfuric Acid [H2SO4]

Oil of Vitriol, Vitriolic Acid, Aceite de Vitriolo colorless, odorless liquid of OILY CONSITENCY (sp.gr. 1.84) when heated vaporizes and gives off dense white fumes of SO3 (sulfur trioxide) does not volatilize at lower levels of heat strong dipriotic acid USEFUL DEHYDRATING AGENT, Oxidizing agent, Sulfonating/Sulfating agent

OLEUM- commercial variety of sulfuric acid containing 10% dissolved SO3 3 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

fuming sulfuric acid, pyrosulfuric acid, disulfuric acid or Nordhausen acid (H2S2O7) *fuming because of the presence of a gas, SO3 H2SO4 + SO3 ---> H2S2O7 H2SO4 + SO3 H2S2O7 Preparation: 2 Industrial Processes Contact/Catalytic Process oxidation of SO SO 2 3 Lead Chamber Process + H2 O
H2SO4

Contact Process vanadium/platinized silica gel (99%) * as catalysts stronger but more expensive Lead Chamber Process 76% w/w - used in the manufacture of fertilizer, primary calcium phosphate (superphosphate)

o Nitric Acid [HNO3]

Spirit of Nitre, Agua Fortis, Agua Fuerte strong oxidizing acid, enhanced HNO2 (produced by phytochemical decomposition of HNO3) highly corrosive fuming liquid, with highly irritating odor 120oC boiling point, sp gr=1.41 produces yellow stain on animal tissue due to nitration of amino acids, phenylamine, tyrosine, tryptophan in the proteins of the skin Xanthoproteic Reaction - strong monoproteic acid, oxidizing and nitrating agent oxidizes all common metals except gold and platinum used to nitrate toluene ---> trinitrotoluene (TNT) - used in the manufacture of sulfuric acid, coal tar dyes, explosives - nitrating agents for Pyroxylinin the preparation of Milk of Bismuth externally used to destroy chancres/warts Official Inorganic Bases -

o Strong Ammonia Solution

Ammonium Hydroxide, Stronger Ammonia Water clear, colorless solution with exceeding pungent odor, sp. gr = 0.90 28% (strong ammonia solution) CAUSTIC nature (corrosive) and irritating property of its vapor possesses an unshared pair of electrons, thus forms soluble complex ions with metal cations, Cu, Ag, Au, Zn, Cd, Cr, Ni, Co, Mn & Pt insoluble salts/ hydroxides of these metals become soluble in Ammonia Solution

USES: Bronsted Base forming ammonium salts of acids in the manufacture of nitric acid and sodium bicarbonate - as circulatory stimulant (16o BaumeHousehold NH3) preparation of Aromatic Ammonia Salt Spirit - stabilizes the ammonium carbonate against hydrolysis and the preparation of Ammoniacal Silver Nitrate 4 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

Diluted Ammonia Solution

9g 100 mL diluted with purified water Ammonia water/household ammonia o as circulatory stimulant by inhalation of vapors o counter-irritant, externally

o Calcium Hydroxide [Ca(OH)2]

Slaked Lime, Calcium Hydrate calcium oxide, CaO + H2O*for slaking---> Ca(OH)2 solid white powder having an alkaline and bitter taste alkaline to litmus slightly soluble in water (1g/630mL) very soluble in boiling water (1g/1300mL) soluble in glycerin INSOLUBLE IN ALCOHOL neutralizing action, absorbs CaO from air forming a cloudy Ca(OH)2 solution

Preparation: CaO + H2O ------> evolution of heat, sweeling of CaO lumps ---> disintegration into fine powder (slaking) Solution n.l.t. 140mg Ca(OH)2/100mL to prepare: 3g of Ca(OH)2 + 1000 mL purified water USES: as fluid electrolyte and as topical astringent o used in pharmaceutical preparations for its high concentration of OH- ion useful in gas traps for its absorbing properties o combined with NaOH as Soda Lime reacts with free fatty acids in various oils to form calcium soaps with emulsifying properties

o Potassium Hydroxide [KOH]

Caustic Potash, Potassa white small pellets, flakes or sticks like crystalline deliquescent, absorbs water from air to dissolve/melt strong base, alkaline reagent RAPIDLY CAUSTIC or CORROSIVE EFFECT ON TISSUES saponifying agent, hydrolyzes esters of fatty acids into constituent alcohols for titrating acids COVER WITH PARAFFIN, do not use Geissler burret with bases (*Mohr for acids)

o Sodium Hydroxide [NaOH]

Caustic Soda, Soda Lye, Sosa to remove bara sa lababo dry, white, stone-like crystal, pellets, flakes 5 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

less deliquescent than KOH, and is cheaper very soluble in alcohol, ether, & glycerin 1g/0.9mL @25oC attacks soft glass, container should have rubber stoppers if not, glass-stoppered can be used, only if theres petroleum or paraffin around the stopper saponifying agent CAPABLE of damaging tissues, rapidly

USED in industrial purposes.

o Sodium Carbonate [Na2CO3H2O]

Monohydrated Sodium Carbonate colorless crystal or white crystalline powder odorless, strong alkaline taste it effloresces, becoming anhydrous @ 100oC (Soda Ash) 1g dissolves in 3 mL water 1.8 mL boiling water 7 mL glycerin - insoluble in alcohol - hygroscopic Hydrated foms: Monohydrate Na2CO3H2O Heptahydrate Na2CO37H2O Decahydrate Na2CO310H2O *Sal soda/ Washing Soda (textile dye) -

Preparation
made by Solvay Process, saturating a thoroughly cooled solution of NaCl with ammonia then with CO2 *Calcined Soda anhydrous sodium carbonate

Uses: o

should not be given internally, (alkaline and irritating) forms sodium salts of acidic drugs Nitromerosal Solution + NaOH ----> water soluble salt of Nitromerosal solubilizing action

Soda Lime
used as gas trap (pampautot) calcium hydroxide + sodium/potassium hydroxide - for use in metabolism test, anesthesia and oxygen therapy - may contain an indicator, H2O *its color will indicate when the soda lime is exhausted - regenerates sodium hydroxide until Ca(OH)2 and NaOH is exhausted -

Buffers chemical systems that control the pH in solutions for: chemical stability solubility of the drug patients comfort 6 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

composed of a weak acid and its salt (conjugate base) weak base and its salt (conjugate acid)** should not react with other chemicals in the preparation

Inorganic Buffers o Phosphate buffer system - contains dihydrogen and monohydrogen ions (physiological pair found in the body) - disadvantage is the insolubility of its salts of Ag, Zn, Al supports microbial growth Example: Sorensen phosphate buffer system o Borate buffer system toxic, suitable in external preparations (ophthalmic and nasal) Three Primary Borate Systems Feldmans Buffer System (pH 7-8.2) H3BO3 + NaCl*+basic solution with Na2B4O7
isotonic

Atkins and Pantin Buffer System (pH 7.6 11) alkaline Na2CO3 solution + acid buffer soln H3BO3 + NaCl Gifford Buffer System (pH 6 7.8) similar to Feldmans, but NaCl is replaced with KCl making it hypotonic

Sodium Borate [Na2B4O7]

Borax, Tinkal, Sodium Pyroborate, Sodium Tetraborate colorless, transparent crystals or as white crystalline powder odorless, effloresces with warm air making the crystals coated with white powder soluble in water and glycerin, insoluble in alcohol aqueous solutions are alkaline to phenolphthalein has the same toxicity as boric acid

USES: one of the best eyewash when acids enter the mucosa 1-2% solution used in collyria component of mouthwashes and oral preparations weak bacteriostatic agent forms borax soap, as emulsifying agent in the preparation of ointments e.g Cold Cream

Antioxidants - compound that function chemically as reducing agents - to maintain these substances in their reduced forms - should be physiologically inert in pharmaceutical preparations o Hypophosphorous Acid [HPH2O2] - colorless/slightly yellow odorless liquid. 30% concentration - pure acid is a syrupy colorless liquid, becomes solid @ 17oC - very powerful reducing agent - Hypophosphorous acid and its salt is used as an antioxidant, preventing the formulation of free iodine in Diluted Hydriodic Acid; also in Ferrous Iodide Syrup, preventing the formulation of both ferric ions and molecular iodine 7 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

also used as preservatives its salts when used as antioxidants must never exceed 1% concentration

Sulfur Dioxide [SO2]

Uses: Sulfurous anhydride colorless, non-flammable gas with suffocating odor characteristic of burning sulfur condenses to a colorless liquid which boils at -10oC soluble in water forming sulfurous acid contains sulfur +4, strong reducing agent

protects susceptible compounds from oxidation reacts with oxygen before any other compounds do for injectable preparations in a single-dose ampoules or multiple dose vials bleaching wood pulps fumigating grains arresting fermentation fumigate houses (burning of sulfur candles)

Sodium Bisulfite [NaHSO3]

Sodium Hydrogen Sulfite, Leucogen mixture of NaHSO3 + Na2S2O5 (sodium bisulfate&sodium metabisulfite) white/yellowish white crystals OR granular powder with sulfur dioxide odor unstable in air, giving off SO2

Sodium Metabisulfite [Na2S2O5]

white crystal/white to yellowish crystalline powder most commercial converted to bisulfate when dissolved in water acidic, neutralizes the stronger bases forming sulfite USES found in acidic drug solutions containing phenol or catechol to prevent oxidation to quinines in ascorbic acid injections as strong reducing agent to prepare water soluble derivatives of normally insoluble drugs Menadione Sodium Bisulfite for parenteral products

Nitrogen [N2]
colorless, odorless inert gas non-flammable, does not support combustion sold in black cylinders USES

inert atmosphere to retard oxidation in oxidation sensitive products (Cod Liver Oil, Olive Oil, Multivitamins Preparations) to replace containers for parenterals and topical solution to retard oxidation for carbon monoxide

Water 8 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

tasteless, odorless, clear colorless liquid in small quantities greenish blue in deep layers density is 1, ice= -1 (makes ice float in water) ability to form hydrogen bonds

Properties making water the solvent of choice: 1. constituent of the body 2. having high dielectric constant 3. being a small molecule Hardness of Water - due to the prescence of Ca, Fe & Mg salts which converts to ordinary soap *soap with hard water = curdy precipitate temporary hardness (HCO3-) - Ca(HCO3)2 - Mg(HCO3)2 *can be removed by boiling permanent hardness (Cl- & SO4-2) - CaCl2 & MgCl2 - Ca(SO4) & Mg(SO4) Ways of Purifying Water Adding washing soda (Na2CO310H2O) Chelation by Zeolite (Permutit) Process *sodium silicate Na2Zeol *parang filtration Deionizer/ Demineralizer - machine that uses synthetic resins, ion exchange treatment - produces somewhat like distilled water - Purified Water o Distillation and Ion exchange treatment Polyphosphate Chelation - used in detergent industry - Ca+2 & Mg+2 made unreactive by chelate bond (claw) P Mg+2 P Official Waters P P

1. Purified Water
obtained by distillation and ion exchange treatment clear colorless liquid for extemporaneous compounding incorporated with the preparation of drugs

2. Water for Injection

purified by distillation ONLY must meet the requirement for pyrogen test using rabbits as test animals using Linulus Amebocytes Lysate (LAL) reagent pyrogen causes fever 9 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

3. Sterile Water for Injection

most difficult to prepare because of its aseptic condition maybe stored in single dose container n.l.t. 1000mL No Antimicrobial substance has been added used for extemporaneous compounding of parenterals for either IV or IM injections

4. Sterile Water for Inhalation

prepared from sterilized water for injection for use in inhalation therapy, NOT intended for parenteral administration *for people with difficulty in breathing, goes directly to the lungs

5. Sterile Water for Irrigation

from sterilized water for injection, single-dose panlinis ng abdominal cavities

6. Bacteriostatic Water for Injection

Glass refers to vitreous material, material which softens gradually sodium silicate, Na4SiO4 (Na2ONa2SiO3) added substances: Boron decreases the coefficient of expansion of Pyrex glass Potassium gives a brown light-resistant glass Rare earth absorbs light of wavelengths contains one or more antimicrobial agents Benzyl Alcohol is a common bacteriostatic agent single dose/multiple dose n.l.t. 30 mL for extemporaneous compounding of parenterals for IM injection not for IV injection because of the bacteriostatic agent NOT FOR USE IN NEWBORNS

4 Types of Glass 1. Type 1 highly resistant, borosilicate glass - for parenterals and base sensitive drugs 2. Type 2 treated with soda lime glass - parenteral 3. Type 3 soda lime glass - for reagents 4. Type NP general soda lime glass - non parenteral Types of Containers Colorless Opaque Colored Opaque superior light protective, except for ointments Clear 1. pt likes to see what he is buying 10 Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos

2. amount left in the bottle is seen 3. ease of pouring 4 Types of Clear Containers: 1. Colorless 2. Green 3. Blue 4. Amber screens out UV radiation

11

Chapter 2: Pharmaceutical Aids and Necessities | Suzette Pamela G. Santos