PHARMACEUTICAL INORGANIC CHEMISTRY OF MEDICINALS

1. Dr. Althea Rodriguez Arenajo PHARMACEUTICAL INORGANIC CHEMISTRY OF MEDICINALS Oxygen,Ozone,Hydrogen,Water Hydrogen Peroxide

2. OXYGEN • A particular gas present in the atmosphere was consumed during oxidation and respiration (Mayow) • The Chinese named the gas yne • Steven Hales was able to obtained the gas by heating minium (lead tetroxide) • Joseph Priestley obtained the gas by heating mercuric oxide and named it dephlogisticatedair

3. OXYGEN • In 1774, Priesley published the properties of the gas he discovered • Karl Wilhelm Scheele, a Sweedish apothecary, discovered oxygen using nitrates in 1773 and named it empyreal air • Antoinne Laurant Lavoisier, a French chemist, made correct interpretations of Priestley’s work and the role played by oxygen in combustion and respiration

4. OXYGEN • Lavoisier named the gas oxygen, from the Greek word meaning “sour” and “I produce” • Oxygen then is an “acid former” Official test A glowing splinter will burst into flame when placed near a container with the gas Pharmacologic action 1.Oxygenation of the blood 1.0 minute- normal oxygenation of the blood 10-15 seconds – when the body is exerted

5. OXYGEN The processes by which oxygen reaches the tissues 1.Diffusion from alveolar air to blood plasma 2. Surrender from blood plasma to red blood corpuscles to form oxyhemoglobin 3. Abstraction of oxygen from oxyhemoglobin by the tissues via complex physiochemical processes and by diffusion • 15gm/ml - hemoglobin in the blood • 1 gm of hemoglobin canhold 1.34 mL of oxygen • 100mL of blood can hold 20 mL of oxygen

6. OXYGEN Calassification of oxygen once in the by 1. Anorexic – supply of O2 to the tissue is inadequate, blood arrives at a lower tension 2. Anemic – O2 tension is normal, amount of hemoglobin is inadequate 3. Stagnant – general circulation is inadeqaute or when circulation is locally retarded 4. Histotoxic – the tissue cell oxidation may be interferred within several ways: a. Dehydration b. Cyanide poisoning

7. OXYGEN 2. Neutralization of toxic materials • 2.5 atm – counters the lethal dose of cyanide • It is a routine procedure, together with sodium nitrite and sodium thiosulfate, in the antidotal treatment of cyanide posoning • The efficient utilization of oxygen by the body in its normal process demands a smooth functioning of oxygen transport from inspired air to utilization in the tissue

8. OXYGEN Important preparations 1. Oxygen USP – has not less than 99% of Oxygen uses: • in medical practice and surgery. • in all pathological conditions, e.g. pneumonia,angina, bronchitis etc., that are accompanied by cyanosis and dyspnea • in chloroform poisoning and in threatened death from inhalation of coal gas or nitrous oxide

9. OXYGEN d. in the resuscitation drowned individuals e. in conditions where there is scarcity of oxygen like: airplanes in high altitudes, diving bells and submarines • 20% Oxygen with Helium for therapeutic purposes is stored in brown-green colored cylinders • Oxygen and Carbon dioxide mixture is stored in gray-green cylinders

10. OXYGEN 2. Liquid Oxygen uses: a. in treating growths such as warts b. in industry such as: steel industry, steel fabrication and industrial maintenance c. as ingredient in the fuel of rockets

11. OZONE • Van Marum, a Dutch chemist, has observed the peculiar irritating odor when electric spark is passed over oxygen or air • Schonbein named the gas ozone from the Greek word which means “to smell” • It is an allotrope of oxygen • O3is stable at very low tempt , at ordinary tempt it slowly decompose to oxygen • More O3 is formed, higher O2 is heated

12. OZONE • The transformation of O2 into O3 involves the changing of electrical energy into chemical energy • It needs 68,820 cal to change O2 into O3 • Ozone is a more active chemical agent than is oxygen, therefore, O3 is an ideal and a powerful oxidizing agent • Ozone has a bluish tinge and an irritating garli-like odor

13. OZONE Uses of Ozone: 1. Oxygen or air containing ozone is used as bleaching agent for oils, waxes, delicate silk or wool fabrics, flour, starch, ivory etc. 2. As disinfectant for drinking water 3. As deodorant of foul animal matter esp in large public halls and food warehouses 4. Inhibitor of molds and bacteria on meats and fruits in cold storage

14. OZONE 5. Manufacture of synthetic camphor, and many other organic compounds • Ozone is a highly lethal and toxic substance in acute exposure • Individuals in continued exposure to about 0.1 ppm, experienced headache and throat dryness • Studies show that less than 5.0 ppm is fatal to 50% of exposed rats

15. OZONE • Ozonides are subs of ozone dissolved in turpentine, cinnamon and olive oils some of which are antiseptics Ozonide preparations with olive oil : 1. Oilzo – liquid 2. Ozettes –vaginalppository • Ozonide air is the one containing 1-2% ozone

16. HYDROGEN • Paracelsus was the first to recognized hydrogen in the 16th century • Turquet de Mayenne payed attention to its combustible nature • Cavendish was the first to experiment on H2 by the action of dil HCl upon metals • He named the gas “inflammable air” • Lavoisier named the gas “hydrogen” from the Greek word which means “water” and “toproduce”

17. HYDROGEN • H2 occurs in volcanic gases in the free state • In combined form it is in the air, meteorites, stars and nebulae and also occurs in the sun • H2 is found in acids and in anaerobic fermentation • A colorless, tasteless, and odorless gas, soluble in water & occluded by many metals • H2 is a powerful reducing agent, burns with a pale blue, non-luminous flame

18. HYDROGEN Uses: 1. Nitrogen fixation and inflating balloons 2. Production of high temperatures when burned in oxygen 3. Hydrogenation of oils used for edible such as oleomargarine and hydrogenated fats 4. As a laboratory agent in the preparation of many chemical compounds • H2 is never used in pharmacy or medicine

19. WATER • Lavoisier decomposed water, he proved that it is composed of 1 part by weight of hydrogen and 8 parts by weight of oxygen • The ocean is the most abundant of all natural sources of water • Mineral waters are natural spring or well waters containing minerals or gaseous matter to render it unfit for domesic use

20. WATER Waters with medicinal constituents: 1. Alkaline waters – contains Na & Mg sulfates with calcium carbonate 2. Carbonated waters – while in the earth, they are charged with CO2, effervesce on coming to the surface 3. Chalybeate water – containing iron in soulution or suspension and are characterized by a ferruginous taste

21. WATER 4. Lithia waters – no appreciable amount of lithium, Li occurs in carbonates or chlorides 5. Saline waters – also known as “purgative waters”, contain large amount of Na & Mg sulfates with NaCl 6. Sulfur waters – contain H2S, deposit sulfur upon exposure to the atmosphere 7. Siliceous waters – contain very small quantities of soluble alkali silicates

22. WATERS • Green plants contain 75-80% water • Fresh fruits contain 80-98% water • The animal body contains 70% water • Water is a tasteless, odorless and limpid • Colorless in small quantities but greenish-blue in deep layers • Only slightly compressible and a poor conductor of heat and electricity

23. WATER • H2O exists as liquid between zero and 100 degrees at 760 atm • Its greatest density is at 4 degrees celcius • It is solid below zero degrees and vapor above 100 • Viscosity decreases rapidly with rise of temperature (8X greater at zero degrees as at 100 degrees)

24. WATER • This is an important property of filtering and washing precipitates • As water passes from one state to another, heat (energy) is consumed or liberated • 79.71 cal of heat are needed to effect the change of 1 gm of ice to 1 gm of water at zero degrees • 539.55 cal are consumed to change 1 gm of water to 1 gm of steam at 100 degrees

25. WATER • Melting-or freezing points – the temp at which solids to liquids or vice versa occurs • Boiling points – the temp at which liquid are transformed to vapor • Specific heat – quantity of heat, in calories required to raise 1 gm, 1 degree celcius • The specific heat of water at 14.5 degrees is 1 • Calorie (cal) – the unit quantity of heat • Kilocalorie – is a large calorie, 1000X larger

26. WATER Methods of removing particles in water: 1. Chlorination- 2. Coagulation- 3. Filtration- 4. Sidementation

27. WATER • A pharmacuetical can be altered in clarity, color, taste, and in therapeutic effect by the water used • Hardness is a property of water that determines its value for domestic and commercial purposes • Hard water is water containing varying amounts of calcium, iron and magnesium salts

28. WATER Kinds of hardness in water: I. Temporary – is caused by the presence of ion soluble calcium or magnesium carbonates Methods to soften temporary hardness: a. Boiling b. Clark’s lime process – addition of slaked lime (calcium hydroxide) c. Addition of Soluble Alkali Carbonates or hydroxides

29. WATER d. Addition of ammonia e. Zeolite process – softens both temporary and hard water. This makes use of sodium aluminum silicate by ion exchange f. De-ionized or Demineralized Water- the latest method for softening both types of water. This makes use of resinous ion-exchange (Hresin-for cation; amine formaldehyde resin-for anion)

30. WATER II. Permanent - caused by the presence in solution of the sulfates chlorides or hydroxides of calcium or magnesium Ways to soften permanently hard water 1. Addition of soluble carbonates- precipitation of calcium and magnesium occurs 2. Zeolite process 3. De-ionized or Demineralized Water

31. WATER 4. Sequestration and chelation sequestration- the act of removing or withdrawing or to take possession of by confiscating or appropriating • Sequestering agent decreases the concen- tration of a multivalent positve ion (Cu,Ca, Fe 2+,3+ ) in solution, by combining wit it to form a complex negative ion

32. WATER • Graham salt or Sodium metaphosphate, the most widely used sequestering agent is coverted to a polymer known as Calgon • Calgon is a very effective water- softener by acting to remove the calcium ions as a very slightly ionized complex • Trilon B (Versene) is the sodium salt of ethylene diamine tetraacetic acid (EDTA), this is more described as chelating agent

33. WATER Recognized water by USP 1 . Water USP- is Water USP; Purified water; Water for Injection; Sterile Water for Injection Requirements: a. Clear, colorless, odorless liquid b. pH range of not less than 6.3 and not more than 8.3 c. Freedom from bacteriological impurities

34. WATER 2. Purified Water USP/Distilled Water USP- water obtained by distillation or by ion-exchange treatment requirements: a. Clear, colorless, odorless liquid b. pH approaches neutrality • Not to be used for parenterals but as solvent • Carbon dioxide –free water is Purified water

35. WATER that has been boiled for 5 minutes or more and protected from reabsorption of CO2 3. Water for Injection USP- is purified by distillation and contains no added subs • Water for injection is intended for use as a solvent for parenteral solutions • For parenteral solutions prepared under aseptic conditions and not sterilized by appropriate filtration or not in the final

36. WATER container, first render the water for injection and therafter protect it from contamination • Water for Injection should be free of pyrogens (bacterial decomposition products causing fever) • It is to be preserved in tight containers, stored at a temperature below/above the range when microbes grow/occurs

37. WATER 4. Sterile Water for Injection/Water for Parenterals- is water for injection sterilized and packaged for pharmaceutical use Requirements: a. clear, colorless and odorless liquid b. contains no bacteriostatic agent c. absent of pyrogens d. chlorine content does not exceed 0.5ppm e. stored insingle dose containers

38. HYDROGEN PEROXIDE • Thenard discovered hydrogen peroxide and and called it”oxygenated acid” • Later it was called “oxygenated water” – as we now know as hydrogen peroxide • Its use in medicine as well as hair bleach began in 1873 in Berlin • It occurs naturally in small quantities in air, dew, rain and snow • It is an unstable colorless, astringent and

39. HYDROGEN PEROXIDE syrupy liquid at room temperature • Pure hydrogen peroxide will decompose very slowly with explosive violence to form water and hydrogen peroxide • It is miscible in all proportions with water but is more soluble in ether • Aluminum tanks are good storage containers because it does not catalyze decomposition of H2O2

40. HYDROGEN PEROXIDE • H2O2 is stable in solutions of high purity, contaminants will decompose it unless a stabilizer is present • For pharmaceuticals of hydrogen peroxide, an excellent stabilizer is 0.02 % quinine • Acetanilid 0.03% is present in H2O2,protects the peroxide from the effects of sunlight • Alkalis increase the decomposition of peroxide

41. HYDROGEN PEROXIDE • An evalescent blue color will appear on the equeous layer of H2O2 with dil sulfuric acid, ether and pot dichromate test solution • A blue color is produced when a solution of H2O2 is added to a mixture of tincture of guiac and malt infusion • A better test to identify H2O2in the blood is benzidine (p,p’ - diaminodiphenyl)

42. HYDROGEN PEROXIDE Physiological properties: a. H2O2 solutions and vapors are nontoxic b.The 30% sol’n is caustic c. Ingestion and injection into body cavities is dangerous, evolution of too much O2 that may cause irritation and bleeding d. Vapor is irritating to the nose and eyes e. It gives an stinging sensation with the skin and cause to whiten

43. HYDROGEN PEROXIDE Important Compounds: 1. Hydrogen Peroxide USP • a clear, colorless , having the odor of ozone • stored in tight, light resistant containers below 350 C • contains preservative(acetanilid) that not to exceed 50mg/100mL sol’n • as antiseptic, it liberates O2 when comes with tissues and referred as” auto-oxidation”

44. HYDROGEN PEROXIDE • its mechanical cleansing action is impt in removing surgical dressings and earwax • used in treating Vincent’s stomatitis and as mouth wash several times daily • may cause “hairy tongue”(hypertrophied filiform papillae), disappears if discontinue • use as hair (6%) and fabric bleaches • 0.1% retards bacterial flora in milk thus, souring is extended

45. HYDROGEN PEROXIDE Volume strenghts of H2O2 3% = 10 volumes 9% = 30 volumes 6% = 20 volumes 12% = 40 volumes 9% = 30 volumes 15% = 50 volumes • 30% ( 100 volumes) – a common commercial strenght (Superoxol and Perhydrol) 2. Urea Peroxide (Perhydrit or carbamide peroxide) showed greater bacteriostatic action against Cl. welchii and Cl.tetani