Unit 8: Pharmaceutical Aids and Necessities (PDF)

Unit 8: Pharmaceutical Aids and Necessities Lyra Jane P. Mamuri Instructor 1 [email protected] COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Objectives: By the end of the unit, the student must have: 1.Recalled the fundamental concept...

Unit 8: Pharmaceutical Aids and Necessities Lyra Jane P. Mamuri Instructor 1 [email protected] COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Objectives: By the end of the unit, the student must have: 1.Recalled the fundamental concepts of acids, bases, buffers, different types of pharmaceutical waters, and antioxidants, and their roles in pharmaceutical formulations. 2.Calculated pH, pKa, and buffer capacity. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Topic Outline: A. Acids and Bases B. Buffers C. Waters D. Antioxidants COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Introduction  Pharmaceutical aids and necessities are essential substances used in the preparation, preservation, and storage of pharmaceutical products.  They are typically categorized into official inorganic acids and bases, buffers, antioxidants, various types of water, and glass materials. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  ACID-BASE THEORIES COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  ARRHENIUS CONCEPT  Limited because only acid and bases with H+ and OH- are considered and only applies to aqueous systems COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Arrhenius acid Name Arrhenius base Name formula HClO3 Chloric acid NaOH Sodium hydroxide HNO3 Nitric acid NH4OH Ammonium hydroxide HClO4 Perchloric acid KOH Potassium hydroxide H3PO4 Phosphoric acid Mg(OH)2 Magnesium hydroxide H2SO4 Sulphuric acid Ca(OH)2 Calcium hydroxide H2SO3 Sulfurous acid Al(OH)3 Aluminum hydroxide HCl Hydrochloric acid CH3COOH Acetic acid HBr Hydrobromic acid COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Examples COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  BRONSTED-LOWRY CONCEPT  Aka: Protonic Concept of Acid-Base Character  Acid = any substance capable of donating a proton (H+) in a chemical reaction (proton donor)  Base = any substance capable of accepting a proton in a chemical reaction (proton acceptor) Bronsted-Lowry acid-Hydrogen ion (Proton) donor. Bronsted-Lowry base-Hydrogen ion (Proton) acceptor. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Conjugate acid-base pairs  Conjugate acid: It forms when a base accepts proton.  Conjugate base: It forms when an acid donates proton.  Note: If an acid is strong, the conjugate base will be weaker and if the base is strong, the conjugate acid will be weak. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  EXAMPLES 1. HCl + H2O ⇌ H3O(+) + Cl- 2. H2O + NH3 ⇌ NH4(+)+ OH- 3. H3PO4 + OH- ⇌ H2O + H2PO4- 4. H3O(+)+ OH- ⇌ H2O + H2O COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  LEWIS ACID-BASE CONCEPT  Acid = any substance which can accept a share in a pair of electrons in a reaction (electron acceptor)  Base = any substance which can donate a pair of electrons to share with an acid in a reaction (electron donor) COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  DISSOCIATION CONSTANTS  Dissociation Constants for Acids and pH:  Bronsted acid strength is reflected by the degree of dissociation of the proton from the conjugate base when acid is dissolved in water HA + H2O ⇌ H3O+ + A-  Degree of dissociation or ionization is expressed in the equilibrium constant as Keq = [H3O+] [A-] / [HA] [H2O]  Ka (acid ionization constant) = Keq [H2O] = [H3O+] [A-] / [HA]  Ka varies directly with the strength of the acid: strong acids (HCl, H2SO4, HNO3) have large ionization constants (Ka > 1) COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Strength of an acid can also be expressed by the “hydrogen ion concentration”  In most polar solvents, the hydrogen ion will react with solvent to form a stable complex, and the concentration of this complex becomes equated with hydrogen ion concentration  In aqueous solution, the concentration of proton is usually equal to the hydronium (H3O+) ion concentration  Pure water ionizes to a small degree: 2H2O ⇌ H3O+ + OH-  Kw, ion product constant of water at 25℃ = [H3O+] [OH-] = 1 x10-14  In pure water, then, the concentrations of both ions are equal, each having a value of 1 x 10-7  [H3O+] = [OH-] = 1 x 10-7  Hydronium ion concentration is expressed in units moles/liter (M) or gram-equivalents/liter (N)  Sorensen introduced a more practical concept of expressing acidity as a negative logarithm to the base of 10 of the hydrogen (or hydronium) ion concentration: the pH or (-log [H+])  pH = -log [H+] = -log [H3O+] = log 1/[H3O+]  ↑ concentration of hydrogen ion = ↑ acidity = ↓ pH COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Example 1. What is the pH of a 3.43 x 10-5 M solution of hydrochloric acid? pH = -log[H3O+] pH = -log(3.43 x 10-5) pH = 4.46 2. What is the hydrogen ion concentration of a solution of HCl with a pH of 4.52? pH = log[H3O+] [H3O+] = antilog-pH [H3O+] = antilog-4.52 [H3O+] = 3.02 x 10-5 M COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Ka and pH are related in that it can give rise to the Henderson- Hasselbalch equation (for buffer solutions): -log Ka = pKa pKa = pH – log [A-]/[HA] pKa = pH + log [HA]/[A-] COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Dissociation Constants for bases and pOH: B + H2O ⇌ BH+ + OH- Keq = [BH+] [OH-] / [B] [H2O] Kb = Keq [H2O] = [BH+] [OH-] / [B] pH = 14 – pOH COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Relationships between Ka, Kb, pH, pOH, and pKw Ka x Kb = Kw = 1 x 10-14 pKa + pKb = pKw = 14 pKw = pH + pOH = 14 COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Let’s Practice: 1. You want to prepare a buffer solution with a pH of 4.50 using 0.20 M acetic acid (pKa = 4.76) and sodium acetate. How many moles of sodium acetate should be added to 1 L of the acetic acid solution to achieve the desired pH? 2. What is the pH of a 0.25 M ammonia (NH₃) solution if the dissociation constant (Kb) for ammonia is 1.8×10−5? 3. What is the pH of a 0.05 M hydrochloric acid (HCl) solution? 4. You mix 0.10 M formic acid (pKa=3.75) and 0.20 M sodium formate. What is the pH of the solution? 5. A solution has a pOH of 3.8. Calculate the pH. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Answers: 1. 0.110 moles 2. 11.33 3. 1.30 4. 4.05 5. 10.2 COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  PERCENT IONIZATION  Acids and bases can exist in various degree of ionization depending upon the strength of the acid and the pH of the solution  This is true for weak acids and weak bases which are not 100% ionized in aqueous solution  This is important to pharmacists when considering the biopharmaceutical parameters of absorption, distribution, and excretion of a drug molecule  Most drugs are weak acids or weak bases (weak electrolytes)  Ionized molecules do not easily cross biological membranes than nonionized molecules COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Ionized = polar  Nonionized = nonpolar  Example: a barbiturate, an acidic drug, is excreted more rapidly in cases of toxicity if the pH of the urine is made alkaline through the administration of sodium bicarbonate  For weak acids: % ionized = (ionized / ionized + unionized) x 100 % ionized = [10(pH – pKa) / 10(ph – pKa) + 1] x 100  For weak bases: % ionized = [1 / 1 + 10(pH-pKa)] x 100 COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Let’s Practice: 1. Calculate the percent ionization of acetic acid in a solution with a concentration of 0.1 M at a pH of 4.75. The pKa of acetic acid is 4.76. 2. Calculate the percent ionization of ammonia in a solution with a concentration of 0.2 M at a pH of 11.00. The pKa of ammonia is 9.25. 3. Calculate the percent ionization of formic acid in a solution with a concentration of 0.5 M at a pH of 3.75. The pKa of formic acid is 3.75. 4. Calculate the percent ionization of pyridine in a solution with a concentration of 0.1 M at a pH of 8.50. The pKa of pyridine is 5.25. 5. Calculate the percent ionization of benzoic acid in a solution with a concentration of 0.25 M at a pH of 4.20. The pKa of benzoic acid is 4.20. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Answers: 1. 49.4% 2. 1.75% 3. 50% 4. 0.056% 4. 50% COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Salts of Acids and Bases: Generally: Weak acids will have strong conjugate base Weak bases will have strong conjugate acid Strong acids will have weak conjugate base Strong bases will have weak conjugate acid COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  ACIDS AND BASE PRODUCTS INORGANIC ACIDS INORGANIC BASES Boric Acid (H3BO3) Strong Ammonia Solution Hydrochloric Acid (HCl) Calcium Hydroxide (Ca(OH)2) Nitric Acid (HNO3) Potassium Hydroxide (KOH) Phosporic Acid (H3PO4) Sodium Carbonate (Na2CO3) Sulfuric Acid (H2SO4) Sodium Hydroxide (NaOH) COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Boric acid (H3BO3)  Syn: boracic acid; orthoboric acid,hydrogen borate  Available in 3 forms: i.Colorless, odorless, pearly scales ii.Six-sided triclinic crystals iii.White, odorless powder which is unctuous to the touch (soapy feeling)  Soluble in water and alcohol; freely soluble in glycerin, boiling water, and boiling alcohol  Weak acid with pKa = 9.19  Official assay = titration with 1N sodium hydroxide in a solution of equal parts of glycerin and water  Commercial manufacture: 1) decomposition of certain naturally occurring borates; 2) from volcanic steam jets  Must contain nlt 99.5% but nmt 100.5% H3BO3 calculated as anhydrous form COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Uses:  buffer (official)  aqueous solutions are employed as eyewash, mouth wash and for irrigation of the bladder;  2.2% solution is isotonic with lacrimal fluid;  dusting powder;  used to prevent discoloration of physostigmine solutions  Boric acid + glycerin = boroglycerin glycerite (suppository base) COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Hydrochloric acid (HCl)  Syn: chlorhydric acid; muriatic acid; spirit of sea salt, marine acid, espiritu de sal marina  Contains 36.5% to 38% by weight of HCl  Muriatic acid – technical grade with impurities making it color yellow  Description: colorless, fuming liquid; pungent odor; fumes and odor disappear when it is diluted with 2 volumes of water; strongly acid to litmus even when highly diluted; spec. grav. = 1.18  Achlorhydria – absence of HCl in the gastric secretion  Gastric HCl functions by killing bacteria in ingested foods and drink, softening foods, and promoting formation of the proteolytic enzyme, pepsin (formed by pepsinogen when the pH of the gastric contents drops below 6) agedenic ulcers COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Test for Identity: i.Titration with standard 1 N sodium hydroxide using methyl red as indicator ii.Hydrogen evolution (displacement) by other metals in the electromotive series iii.Evolution of chlorine when HCl is added to KMnO4 iv.Hydrochloric acid or its soluble salts precipitate a white, curdy silver chloride from solutions of silver nitrate (insoluble chloride) Preparation: i.A by-product in the manufacture of sodium carbonate from NaCl by the Leblanc process in which NaCl is decomposed with H2SO4 ii.A by-product in the electrolytic production of NaOH from NaCl Uses: i.Acidifying agent ii.Used in preparing Dilute Hydrochloric acid Diluted Hydrochloric Acid – a solution of HCl prepared by mixing 234 mL of HCl with a sufficient amount of distilled water to make 1000mL; it is administered to patients with achlorhydria COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Nitric acid (HNO3)  Syn: Hydrogen nitrate, aqua fortis, azortic acid, acidum nitricum, nitrous fumes, nitryl hydroxide, spirit of nitre, aqua fuerte  Description: highly corrosive fuming liquid; characteristic, highly irritating odor; stains animal tissues yellow (xanthoproteic test); boils about 120℃; spec. grav. = 1.41  Preparation: i.By treating sodium nitrate with sulfuric acid ii.By catalytic oxidation of ammonia  Uses: acidifying agent; oxidizing agent; nitrating agent in the manufacture of Pyroxilin, USP; used in the manufacture of sulfuric acid, coal tar dyes, and explosives; source of nitrate ion in the preparation of Milk of Bismuth; externally used to destroy chancres and warts and phagedenic ulcers COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Phosphoric acid (H3PO4)  Syn: orthophosphoric acid; syrupy phosphoric acid; concentrated phosphoric acid, sonac, acidium phosphoricum, evits  Contains 85%-88% by weight H3PO4  Description: colorless, odorless liquid of a syrupy consistency; spec. grav. = 1.71  Preparation: Phosphorous is converted to phosphorous pentoxide (P2O5) by exposing it to a current of warm air, then the P2O5 is treated with water to form phosphoric acid COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Tests for Identity:  Responds to all tests or acids  When phosphoric acid is neutralized with KOH and a solution of silver nitrate, a characteristic yellow precipitate of silver phosphate results (ppt. is soluble in ammonium hydroxide and in nitric acid)  Orthophosphoric acid produces a canary yellow colored precipitate when digested as 40℃ with ammonium molybdate solution producing a precipitate of ammonium phosphomolybdate which is insoluble in acids but readily soluble in ammonia water  If 3 ml of the phosphoric acid dilution is rendered alkaline with ammonia water and magnesium sulfate is added, a white crystalline precipitate of magnesium ammonium phosphate is produced. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Uses: to make the diluted acid and as a weak acid in various pharmaceutical preparations; industrially, it is used in dental cements and in beverages as an acidulant; solvent in the preparation of Anileridine Injection, NF 13  Diluted Phosphoric Acid i.Prepared by mixing 69 ml of phosphoric acid with sufficient distilled water to make 1000 ml ii.Clear, colorless, odorless liquid; spec. grav. = 1.057 iii.Uses: pharmaceutical necessity; employed in lead poisoning and in other conditions in which it is desired to administer large amounts of phosphate and at the same time produce a mild acidosis; given in dose of 60 ml a day (5ml/hr) under carefully controlled conditions COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Sulfuric acid (H2SO4)  Syn: acidum sulfuricum; oil of vitriol; dihydrogen sulfate, mattling acid, vitriol brown oil  Description: colorless, odorless liquid of oily consistency containing not less than 94% but not more than 98% H2SO4; when strongly heated, the acid is vaporized giving off dense, white fumes of SO2; it dissolves in both water and alcohol with the evolution of much heat; high affinity with water COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Test for Identity: i.If barium chloride TS is added to a dilute solution of sulfuric acid, a white precipitate of barium sulfate is formed. ii.If dilute sulfuric acid is treated with lead acetate TS, a white precipitate forms which is soluble in ammonium acetate TS. iii.HCl produces no precipitates with sulfates. This distinguishes them from thiosulfates which do give precipitates. iv.Sulfuric acid chars many organic substances (ex: wood, sucrose, and fibers) due to abstraction of water elements from the substances leaving a carbon residue. NOTE: when sulfuric acid is mixed with other liquids, it should always be added to the diluent, and great caution should be observed COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Preparation (by principle, both processes involve sulfur conversion to SO2: i.Lead Chamber Process ii.Contact or catalytic process  Uses  dehydrating agent esp. in the preparation of Pyroxilin, USP; oxidizing agent; sulfonating/sulfating agent; used to form salts of basic organic drug molecules; used in the preparation of dilute sulfuric acid COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Dilute Sulfuric Acid (~10% Fuming Sulfuric Acid i.Aka: oleum H2SO4) ii.Fuming sulfuric acid consists of H2SO4 i.Prepared by adding 104 g of sulfuric acid to with free sulfur trioxide (SO3). It is 896 g of purified water with constant stirring prepared by adding sulfur trioxide to and cooling. Dilute sulfuric acid contains sulfuric acid. Available in grades containing between 9.5% and 10.5% w/w of H2SO4. up to about 80% free SO3. ii.Used medicinally in the treatment of iii.Fuming sulfuric acid is a colorless or achlorhydria slightly colored, viscous liquid that emits choking fumes of sulfur trioxide. iv.It is extremely corrosive and should be handled with great care and stored in tightly closed glass-stoppered bottles. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Inorganic Bases Strong Ammonia Solution  Syn: Stronger ammonium water; stronger ammonium hydroxide solution; spirit of hartshorn; concentrated ammonia solution  Contains nlt 27% but nmt 30% w/w of NH3  Caution—Use care in handling it because of the caustic nature of the Solution and the irritating properties of its vapor. Cool the container well before opening, and cover the closure with a cloth or similar mate- rial while opening. Do not taste it, and avoid inhalation of its vapor. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Description: Colorless, transparent liquid; exceedingly pungent, characteristic odor; even when well diluted it is strongly alkaline to litmus; specific gravity about 0.90.  Preparation: Ammonia is obtained commercially chiefly by synthesis from its constituent elements, nitrogen and hydrogen, combined un- der high pressure and at high temperature in the presence of a catalyst.  Uses: Bronsted base used in preparation of ammonium salts of acids; used in the manufacture of nitric acid and sodium bicarbonate; used in the preparation of Aromatic Ammonia Spirit NF where it serves as a source of ammonia to stabilize the ammonium carbonate against hydrolysis; used in the preparation of ammoniacal silver nitrate solution COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Dilute Ammonia Solution:  Syn: Ammonia water; diluted ammonium hydroxide solution; household ammonia  Contains 9%-10% NH3  Used as a reflex stimulant in ‘smelling salts’, as a rubefacient, and as a counter-irritant to neutralize insect bites or stings. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Calcium hydroxide [Ca(OH)2]  Syn: Slaked lime; calcium hydrate; hydrated lime  Description: White powder; alkaline, slightly bitter taste; absorbs carbon dioxide from the air, forming calcium carbonate; solutions exhibit a strong alkaline reaction.  Preparation: By reacting freshly prepared calcium oxide with water (slaking).  Tests for Identity: 1) When mixed with water to form “Milk of Lime’’ and allowed to stand, it settles to give a clear supernatant liquid; 2) When calcium hydroxide is dissolved with acetic acid the resulting solution gives all the tests for Calcium COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Uses  internally used as an antacid  solution is added to baby’s formula to prevent curdling of milk promoting the digestibility of milk  used in pharmaceutical preparations as a saponifying agent for oils  mildly astringent  carbon dioxide absorbent  combined with sodium hydroxide to form soda lime as CO2 absorber from expired air in metabolic function  used in preparation of lime water (calcium hydroxide solution)  common cosmetic ingredient in hair-straightening and hair removal products  used as filling agent and in dental pastes to encourage deposition of secondary dentine  formerly used as escharotic in Vienna paste COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Calcium hydroxide solution  Syn: lime water  Contains nlt 0.14g per 100ml of water at 25℃ (varies with temperature)  Prepared by adding 3g calcium hydroxide to 1000mL of purified water COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Potassium hydroxide (KOH)  Syn: caustic potash; lye; potash lye; kalium hydroxydatum  Caution—Exercise great care in handling, as it rapidly destroys tissues. Do not handle it with bare hands.  Description: White, or nearly white, fused masses, small pellets, flakes, sticks, and other forms; hard and brittle and shows a crystalline fracture; exposed to air it rapidly absorbs carbon dioxide and moisture and deliquesces; melts at about 360 to 380°; when dissolved in water or alcohol or when its solution is treated with an acid, much heat is generated; solutions, even when highly diluted, are strongly alkaline. COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Preparation: 1) by causticizing potassium with milk of lime; 2) by the electrolysis of a solution of potassium chloride  Test for Identity: 1) all solutions of KOH, even when greatly diluted, to litmus paper and phenolphthalein test solution; 2) it responds to all reactions of potassium ions  Uses: 1. cauterizing agent; 2. escharotic; 3. used in chemical and pharmaceutical processes where potassium ion is desired; 4. a pH adjuster; 5. alkaline reagent in analytical chemistry; can be used in place of NaOH in soda lime COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Sodium carbonate (Na2CO3)  Syn: monohydrated sodium carbonate; bisodium carbonate; calcined soda; cenzias de soda; crystal carbonate; soda ash  Decahydrate = “sal soda”; “washing soda”  Description: Colorless crystals or a white, crystalline powder; stable in air under ordinary conditions; when exposed to dry air above 50°C it effloresces, and at 100°C it becomes anhydrous; decomposed by weak acids, forming the salt of the acid and liberating carbon dioxide; aqueous solution alkaline to indicators (pH about 11.5). COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Preparation: i.LeBlanc Process ii.Cryolite-soda process iii.Solvay process iv.Recovery from natural brine  Tests for Identity: 1. A 1 in 10 solution is strongly alkaline to litmus paper and phenolphthalein TS 2. The salt responds to test for sodium and carbonates COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Uses:  for dermatitides topically as a lotion;  used as a mouthwash and vaginal douche;  as a pharmaceutical aid as an alkalizing agent (2-5% in compressed tablets; in the preparation of Nitromersol Solution, NF and with sodium hydroxide to form water soluble sodium salt of nitromersol) and 10% w/w as an effervescent agent;  oral antacid COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Sodium hydroxide (NaOH)  Syn: caustic soda; soda lye  Caution—Exercise great care in handling it, as it rapidly destroys tissues  Description: White, or nearly white, fused masses, small pellets, flakes, sticks, and other forms; hard and brittle and shows a crystalline fracture; exposed to the air, it rapidly absorbs carbon dioxide and moisture; melts at about 318°C; specific gravity 2.13; when dissolved in water or alcohol or when its solution is treated with an acid, much heat is generated; aqueous solutions, even when highly diluted, are strongly alkaline.  Test for Identity: a solution of NaOH (1 in 25) responds to tests for sodium COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Preparation: 1) by chemical method through causticizing milk of lime; 2) by electrolysis of brine using inert electrodes Uses:  pH adjuster;  used to react with acids to form salts;  alkalizing agent;  preferred over KOH because it is less deliquescent and less expensive;  pharmaceutical necessity in the preparation of Glycerin suppositories Soda Lime i.A mixture of Ca(OH)2 and sodium or potassium hydroxide or both ii.Intended for use in metabolism test, anesthesia, and oxygen therapy COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  BUFFER  Buffer systems are pairs 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  It is composed of a weak acid and its salt (conjugate base) or a weak base and its salt (conjugate acid) (NOTE: the latter is not widely employed because of stability problems encountered with most available weak bases)  Each component of the buffer pair will react with either acid or base to form the other component, repressing large changes in hydrogen ion concentration  Buffer solutions can be formulated to produce specific pH’s within particular ranges  The pH of a buffer solution is related to the pKa of the buffer acid and the log of the ratio of buffering species (described by the Henderson-Hasselbalch equation)  pKa any buffer acids should be close to the center of the pH range desired COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  PHARMACEUTICAL BUFFER SELECTION 1.The buffer should not react with other chemicals in the preparation. 2.The buffer system must exhibit reasonable chemical stability. 3.Buffers should be choses so that they have a pKa near the middle of the desired pH range. 4.The buffer should neither contribute nor detract from the pharmacological properties of the active ingredients. 5.The buffer should not support microbial growth (if possible, addition of preservative may be used). COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  PHARMACEUTICAL BUFFER SYSTEMS There are 5 various primary solutions which cover the pH range from 1.2 to 10.0 Hydrochloric acid buffer (pH 1.2-2.2) Acid phthalate buffer (pH 2.2-4.0) Neutralized phthalate buffer (pH 4.2-5.8) Phosphate buffer (pH 5.8-8.0) Alkaline borate buffer (pH 8.0-10.0) Only phosphate and borate buffer systems are of importance to pharmaceutical preparations COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Phosphate Buffer System Contains dihydrogen and monohydrogen phosphate anions The pKa of the dihydrogen phosphate anion is 7.2 Disadvantage: insolubility of phosphate salts of metals such as silver, zinc, and aluminum; supports microbial growth (can be avoided by addition of 0.002% benzalkonium chloride [Zephiran®] or benzethonium chloride [Phemerol®]) Modified Phosphate Buffer System (Sorensen Phosphate Buffer) 1.Inclusion of NaCl to make it isotonic with physiological fluid 2.Covers a range of pH 5.9 – 8.0 Acid buffer, M/15 NaH2PO4 Alkaline buffer, M/15 NaH2PO4 1.Sodium biphosphate, NF = 9.2 g 1.Disodium phosphate = 17.86g 2.Purified water, q.s. = 1000 mL 2.Purified water, q.s. = 1000 mL COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Borate Buffer System Used in many pharmaceutical preparations containing metals that would otherwise precipitate in the presence of phosphates Disadvantage: borates are toxic and internal administration is contraindicated pKa of boric acid is 9.2 making borate buffers quite inefficient at physiological pH, but can be used in alkaline pH ranges borates are weak bacteriostatic, but the solutions will support mold growth when stored for 1-2 months at room temperature COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  3 Borate Buffer Systems: 1.Feldman’s 2.Atkins and Pantin 3.Gifford’s COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Feldman’s Gifford’s  Boric acid, sodium borate, NaCl  pH 6.0 to 7.8  similar to Atkins and Pantin but  pH 7.0 to 8.2 modified to contain KCl instead of  prepared by mixing the indicated volumes of NaCl and volume adjustment to the acid solution containing boric acid and 30 mL the alkaline solution containing sodium  the quantity of KCl makes the borate (sodium tetraborate or sodium pyroborate) to make 100 mL of the buffer final solution hypertonic solution at the required pH COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Atkins and Pantin Boric acid, sodium carbonate, NaCl pH 7.6 to 11.0 Recognized the Feldman buffer system containing sodium borate as unstable Uses sodium carbonate in place of sodium borate Useful at alkaline pH but too alkaline for many drug purposes Can be used in ophthalmic solutions, contact lens solutions, and as a solvent for soluble fluorescein COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  OFFICIAL ANTIOXIDANTS Hypophosphorous acid (H3PO2) Contains 30% to 32% by weight H3PO2 Description: Colorless or slightly yellow, odorless liquid; solution is acid to litmus even when highly diluted; specific gravity about 1.13. Preparation: By reacting barium or calcium hypophosphite with sulfuric acid or by treating sodium hypophosphite with an ion-exchange resin. Test for Identity: 1.Acid to litmus even in diluted form. 2.It responds to all tests for hypophosphite ion. Uses: powerful antioxidant to prevent oxidation of hydroiodic acid in hydroiodic acid syrup and ferrous iodide in ferrous iodide syrup COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Sulfur dioxide (SO2) Sodium Bisulfite (NaHSO3) Syn: sulfurous anhydride; sulfurous oxide Syn: sodium hydrogen sulfite; sodium acid sulfite; leucogen Description: occurs as a colorless gas at room temperature and pressure, with a strong, Description: White or yellowish white suffocating, pungent odor. It is crystals or granular powder with the odor noncombustible and is a strong reducing of sulfur dioxide; unstable in air. agent. Uses: antioxidant and stabilizing agent Preparation: can be made by burning sulfur, (esp. in epinephrine HCl solution); useful or by roasting sulfide ores such as pyrites, for removing permanganate stains and for sphalerite, and cinnabar. solubilizing certain dyes and other chemicals; used topically to treat Uses: antioxidant in injectable preparations; dermatological problems caused by used in bleaching wood pulp, fumigating certain parasites; used to prepare water grains, fumigating houses, and arresting soluble derivatives of normally insoluble fermentation drugs such as Menadione sodium bisulfite NF COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Sodium metabisulfite (Na2S2O5) Sodium thiosulfate (Na2S2O3) Syn: disodium pyrosulfite Syn: disodium thiosulfate; sodium hyposulfite; sodium subsulfite; Amextox®; Sodothiol®; Description: White crystals or white to yellowish crystalline pow- der with an odor Description: occurs as odorless and colorless of sulfur dioxide; on exposure to air and crystals, a crystalline powder or granules. It is moisture, it is slowly oxidized to sulfate. efflorescent in dry air and deliquescent in moist air. Preparation: Formed when sodium bisulfite undergoes thermal dehydration. It Preparation: On an industrial scale, sodium also may be prepared by passing sulfur thiosulfate is produced chiefly from liquid waste dioxide over sodium carbonate. products of sodium sulfide or sulfur dye manufacture. Small-scale synthesis is done by Uses: reducing agent (in solution of drugs boiling an aqueous solution of sodium sulfite with containing phenol or cathecol nucleus esp. sulfur. in epinephrine HCl and phenylephrine HCl injections) Uses: antidote for cyanide poisoning; antioxidant limited to solutions containing iodides; antifungal; reagent in analytical chemistry COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Sodium nitrite (NaNO2) Description: White to slightly yellow, granular powder or white or nearly white, opaque, fused masses or sticks; deliquescent in air; solutions are alkaline to litmus. Preparation: By various methods, as by reduction of sodium nitrate with lead, a sulfite, or sulfur dioxide, or by absorption of NO obtained from catalytic oxidation of ammonia in sodium carbonate solution. Official Test for Identity: A solution of sodium nitrite responds to tests for sodium and nitrite. Uses: antidote for cyanide poisoning (to be followed by sodium thiosulfate); nitrite ion relaxes smooth muscle, so sodium nitrite causes hypotension; solutions are unstable and should be prepared directly before use COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Nitrogen (N2) Syn: nitrogenium; azote Description: occurs naturally as approximately 78% v/v of the atmosphere. It is a nonreactive, noncombustible, colorless, tasteless, and odorless gas. It is usually handled as a compressed gas, stored in metal cylinders. Preparation: by the fractional distillation of liquefied air Uses: used as an inert atmosphere to retard oxidation in oxidation-sensitive products (ex: cod liver oil, olive oil, multiple vitamin preparations); used to replace air in containers for parenterals and solutions for topical applications; used to retard oxidation in the qualitative test for carbon monoxide; aerosol propellant COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  WATERS 1. Mineral waters 2.Carbonated waters Natural spring or well waters containing Those which have been charged with carbon sufficient quantities of mineral or dioxide under pressure while in the earth gaseous matter (ex: dirt, silt, rust, They usually effervesce upon coming to the bacteria, dissolved electrolytes such as surface Na+, K+, Ca+2, Mg+2, Fe+3, Sr+2, It contains calcium and magnesium bicarbonates Ba+2, HCO3-, CO32-, Cl-, SO4-2, NO3-) to render them unfit for Artificial carbonated waters may be made domestic use charging waters under pressure with carbon dioxide COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy 3. Alkaline waters 4.Chalybeate waters 5.Lithia waters Usually contain Contain iron in solution or As a rule, it does not in suspension and are contain appreciable appreciable quantities of quantitites of lithium ions sodium and magnesium characterized by a ferruginous taste If lithium is present, it sulfates, together with occurs in the form of the Upon exposure to the carbonate or chloride some sodium bicarbonate atmosphere, the iron is usually precipitated as hydroxide or oxide Spring and well waters containing iron are very common COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy 6.Saline waters 7.Sulfur waters 8.Siliceous waters Syn: purgative waters Contains hydrogen sulfide Contain very small quantities Contains relatively large These waters deposit sulfur of soluble alkali silicates amounts of magnesium and upon exposure to the sodium sulfates with sodium atmosphere chloride COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  OFFICIAL WATERS 1.Water, USP 2.Purified Waters, USP Clear, colorless, odorless liquid Obtained by distillation or by ion exchange treatment which has specifications for pH, Occurs as clear, colorless, odorless liquid and is not zinc, and other heavy metals, intended for parenteral administration foreign volatile matter, total solid content, and bacteriological purity It is used for most preparation for most USP test Official as a solvent and is used to reagents make several official solutions, Specifications included are for pH, chloride, sulfate, tinctures, and extracts ammonia, calcium, carbon dioxide, heavy metals, oxidizable substances, total solids, and bacteriological purity Water of choice for extemporaneous compounding COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  4.Sterile Water for Injection, USP 3.Water for Injection, USP A water for injection sterilized and suitably Water purified by distillation and occurs as packaged a clear, colorless, and odorless liquid and no added substances It is a clear, colorless, odorless liquid which contains no antimicrobial agent It meets all the specifications called for in Most difficult to prepare the Purified Water monograph with the exception of bacteriological purity but must May be stored in single-dose containers, preferably Type I or Type II glass, of not pass a pyrogen test larger than 1000-mL size Intended for use as a solvent for the Label must indicate that no antimicrobial preparation of parenteral solutions or other substances has been added USP requires that WFI be stored at 4℃ or Not to be used intravenously without above 37℃ making it isotonic first COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy 5.Bacteriostatic Water for Injection, USP It is a sterile water for injection containing 1 or more suitable antimicrobial agents It was developed in response to a need for easily stored sterile water that could be use to compound small volumes of extemporaneous parenterals for intramuscular injection Occurs as a clear, colorless liquid, odorless or having the odor of the antimicrobial substance USP WARNING: use BWFI with due regard for the common compatibility of the antimicrobial agent/s it contains with the particular medicinal substance that is to be dissolved or diluted Benzyl alcohol – common bacteriostatic agent It is stored in single-dose or in multiple-dose containers, preferably Type I or Type II glass, of not larger than 30-mL size Not suitable for IV administration because of the bacteriostatic agent Label must indicate antimicrobial agent used COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  PHARMACEUTICALLY ACCEPTED GLASS Glass – a generic term referring to vitreous material (a material which softens gradually over a temperature range rather than melting sharply) Most commercial glasses are vitreous silicates with some type of additive which confers special properties oBoron – decreases the coefficient of expansion of glass oPotassium – gives a brown light-resistant glass oRare earths – absorbs light of certain wavelengths COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  Characteristics carbonate With MnO2 Mask blue- green color of iron usually present in glass With Boron (as borate) Decrease coefficient of expansion of glass With Potassium Render glass brown with light- resisitant property (amber) With Lead Increase refractive index of glass Rare Earths Selectively absorb light of certain wavelengths Group I VA Carbon Family COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy  SUMMARY INORGANIC ACIDS INORGANIC BASES 1. Strong Ammonia Solution 1. Boric acid-________ 2. Calcium Hydroxide - _____ 2. HCl-______________ 3. KOH- _________ 3. Nitric acid- _________ 4. Sodium Carbonate - _____ 4. Phosphoric acid-_____ 5. NaOH - ____________ 5. H2SO4 - ___________ ANTIOXIDANTS 1. H3PO2 -____________ 5. Sodium thiosulfate- ____ 2. SO2 - _____ 6. Sodium nitrite - ______ 3. Sodium Bisulfite- _________ 7. Nitrogen- _______ 4. Sodium Metabisulfite - ______ COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy TYPES OF WATERS OFFICIAL WATERS 1. Mineral waters 1. Water, USP 2. Alkaline waters 2. Purified Waters, USP 3. Carbonated waters 3. Water for Injection, USP 4. Chalybeate waters 4. Bacteriostatic Water for Injection, USP 5. Lithia waters 5. Sterile Water for Injection, USP 6. Saline waters 7. Sulfur waters 8. Siliceous waters COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy COLLEGE OF HEALTH AND SCIENCES Department of Pharmacy Get in Touch With Us Send us a message or visit us City of Batac, Ilocos Norte, Philippines (63) 77-600-0459 [email protected] Follow us for updates facebook.com/MMSUofficial www.mmsu.edu.ph