[Lecture Notes in Pharmaceutical Chemistry 1 CHAPTER 1 PHARMACEUTICAL AIDS AND NECESSITIES Pharmaceutical aids and. necessities includes topics important to the preparation, Preservation » and storage of pharmaceutical products. Major subjects areas are: and frequently employed in fhepersion Of drugs to chemical forma convenient ro their product formulation. 2) Buffers - maintain the pH of various formulations within prescribed limits. 3) Antioxidants - prevent oxidative decomposition of pharmaceutically active components. 4) Water ~ primary solvent or liquid phase in most liquid Pharmaceutical Preparations. 5) Glass - used for storage and as dispensing container for most drug products. Official Inorganic Acids BORIC ACID NF 26 (HaBO3 : Mol. Wt. 61.83) Synonyms: Boracid.Acid, Hydrogen Borate, Orthoboric acid, tap Boricada Occurrence: Free boric acid is found in sea waters, certain plants, in nearly all fruits and in some volcanic steam jets. © acid is cal + Its largest Raterial source is in the combined forms as, for example - CaBi0r. 4H20 HsBO3-NazB4072CaByOrs 18H For the exclusive use of Pharmacy students In the UST Faculty of PharmacyLecture Notes in Pharmaceutical Chemistry 1 Properties: Boric Acid is a solid available in three forms: (1) colorless, odorles earl 7 (2) six-scaled triclinic crystals and (3) white, odorless powder which ts unctuous to touch (having a soapy feéling)> The scale and crystalline forms of compounds are more suitable for Preparing aqueous solutions since the powder tend to float on top of the water. It is stable in air and has a density of 1.46. Boric acid is soluble in water and alcohol and freely cluble_in glycerin, “boiling water ahd boiling aleohor. Clear solutions of boric acid are obtained when 1 gram is dissolved in 25 mL of water. The addition of HCl decreases its solubility in water. Due to the weak acid nature of boric acid, only salts produced by the replacement of one Proton per molecule (primary salts) can be obtained in aqueous solution. Those salts formed with alkali metals are he only ones soluble in water and these produce very alkaline solutions. Salts formed with other metals are hydrolyzed in water to produce insoluble hydroxides. Boric acid is not absorbed through the intact skin but is hi + It is absorbed when applied over large areas of broken skins. Uses: The NF XV specifies that boric acid must contain n.l.t. 99.58 and n.m.t. 100.5% of boric acid calculated as an anhydrous (dried) form. For many years, boric acid has been used in solutions, ointments and dusting powder as an antiseptic. At best, the compound can be described as a weak bacteriostatic agent. 5 z use as an eyewash. The Pope eoncentrated Solution should be diluted with an equal Wolume of water before use. Also higher concentration ts peer Saturation and boric acid tends to crystallize out with a slight drop of temperature. is represents a Ganger and solutions should be warmed or diluted before used in order to dissolve the crystals. It is used as a buffer in ophthalmic soli itions and preparations like Aluminum Acetate Solution USP XVIII and Aluminum Subacetate Solution USP XVIII, Since it is weak acid, it constitutes a portion of what would be required for a buffer solution but used alone it does not have such buffer capacity. For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 24Lecture Notes in Pharmaceutical Chemistry 1 reaction of boric found some use as a 4 the toxicity of boric acid precludes its use in Products that are to be taken internally. (HCL ; Mol. wt. 36.46) Muriatiomaecid, spirivmof=seamSakt, Marine Acid, Official Definition: Hydrochloric Acid is an aqueous solution of hydrogen chloride gas containing n.1.t. 35% and n.m.t. 38% by weight of HCl. Properties: Hydrochloric Acid is @ colorless fuming liquid having a pungent odor and a specific gravity of about 1.18. A non-fuming solution can be Prepared by diluting hydrochloric acid with two volumes of water. It is more high: donized than mo: strong acids and attacks many metals with evolution of hydrogen. Muriatic acid (from the briiey is ¢ arsenot furoi and iron. impurities give it a characteristic yelbow=eoldr. Uses: The primary chemical uses of hydrochloric acid are Sebsgorizedssby< theltiNPe, XVexasigas:pharmaceltics® aid or specifically as an acidifying agent. By virtue of its strong acid character, it is capable of reacting w: rganic molecules which are weakly basic ‘o form usually water soluble hydrochloride salts, moe Sotuble hydrochloride salts Since salts of fost organic amines are solids, treatment of liquid organic bases with hydrochloric acid ca, suitable for incorporation into a Solid dosage form. sUitable for incorporation into lid d For the exclusive use of Pharmacy students inthe UST Faculty of Pharmacy Page 25{Lecture Notes in Pharmaceutical Chemistry 1 However, one disadvantage of using HCl for this Newest as that some hydrochlorides cre hygroscopic, avi Nevertheless, most drugs are failable as hi idrochloride very low toxicity of the chloride ion. "ety Tow toxicity of the chloride ton. NF XV is a solution of hydrogen chloride containing n.1.t. GwSeeGe and n.m.t. L0nSmg of HCl in each &00emi, of the solution. Piluted hydrochloric acid exists in the normal gastric juice (about 0.2%) aiding in the Conversion of pepsinogen into pepsin and proteids into Peptones and as gastric antiseptic. stcimaybe ivaluablie< im certain. forms. of indigestion, especially in those conditions of gastric (absence of hy i d) and hypochlohydria (deficiency of hydrochloric acid). It is usually given in doses of from 1-10 cc, highly diluted with water and to be supplied through a lass tube or stray, to avoid the solvent’ action—on the enamel of the teeth. To Sveig thts “dirriculty, theli preparations such as c Acid=sliyarOCHYOFPe and have been advocated. These compotnds are crystalline and maybe administered in Sabswhemtern. they Lib Stomach, the glutamic acid 1 ne Si ng ized at the Same Achi 'ydia- absence of HCl Aéidem ids sm digesting Muypoctiorydia~ ctebien od Peceryden seh NITRICACID'NF'S6 (HNO: + Mol. wt. 63.01) Synonyms: Spirit of Nitre, AdlaeFOrtis, Aguanfuerte . strong sater Properties: Nitric Acid is an aqueous solution containing n.l.t. 68% and n.m.t 71% by weight of HNO3. “It is described as ahi liquid having a characteristic, hi irritati - It has a boiling Point of about 120°C and a specific gravity of about 1.41, Nitric acid will produce a i we_to_mitration of the aromatic amine acids, phenylaming, e {utasine and teyptophan found inch of the skin. This is known as the Xanthoproteic Test, NitnicisACiGM dae onustrotige mong rotic acid, an oxidizing and nitrating agent~ The oxidizing power is enhanced by the presence of smaii amounts of nitrous aci For the exclusive use of Pharmacy students in te Us Faculty of Pharmacy Page 26Lecture Notes in Pharmaceutical Chemistry 1 HNO,, produced by photochemical decomposition of nitric acid. It oxidizes all common metals old and platinum to ‘Produce the Gikrate salt of the metal, the nitrating properties of nitric acid are used extensively in organic chemistry. The reaction involves the substitution of _the nitro group, -NOz, for some other group usually hydrogen on the organic molecule. For example, this reaction is used tO TidibtabGeestoluene to produce trinitrotoluene.(TNT). ao Uses: Although the acidic properties of nitric acid are similar to those of hydrochloric acid, making it useful as an acidifying agent with bases, its oxidizing and nitrating Properties as a unique dimension to its use as compared fh most other acids. It is used in the manufacture of sulfuric acid, coal tar dyes and explosives. It is used as a nitrating agent in Pyroxylin USP XVIII as a source of nitrate ion in the preparation of Milk of Bismuth. It has been externally used to destroy PHOSPHORIC'ACID NF 26 (H3PO, ; Mol. wt. 98) Synonyms: OrthophosphorécwAcid, Acido-Orthofosforico Properties: Phosphoric Acid is an aqueous solution containing n.1.t. 858 and n.m.t 88% by weight of H3P0,. It is a colorl £ i ific Gravity of about 1.71. It is non-volatile and has no oxidizing properties thus enabling its use whenever a non oxidizing acid is required. Uses: Phosphoric Acid can be used as an ing agent its limitation will i perarsmssrse of the various phosphate salts produced. It can be treated with sodium hydroxide at particular concentrations to produce mixtures of HPO," and HPO!” which serve as the basic and acidic species, respectively, of the The NF 21 categorizes phosphoric acid as a solvent in the preparation of Anileridine Injection NF XV. For the exclusive use of Pharmacy students in the UST Faculty of PharmacyLecture Notes in Pharmaceutical Chemistry 1 DILUTED PHOSPHORIC ACID NF 26 contains n.1.t. 9.5 g and nem.t. 10.5 g of H3PO, in 100 mL of solution. It is used as a to o the gastric Wusous-menbranes, acts as synergistic to pepsin and ciarns the formulation ‘of peptonss. Tt is ise aved ey see some pharmaceutical preparations. Pharmaceutical preparations SULFURIC ACID NF'26 (HeSOq + Mol. wt. 98) Synonyms: Of) of -Vitriol, Vitriolic Acid, Aceite de Vitriolo Properties: Sulfuric Acid is a colorless odorless liquid of oily consistency containing nvl.t. 948 ‘and n.m.t. 98% of SQ. It has a-spetific gravity of n.l.t. 1.84, When strongly heated, sulfuric acid is vaporized and Gives off dense, white fumes of sulfur trioxide, S03, it oes _not volatilize at lower levels oF heat. It is a strong diprotic acid. Tt is also useful asc deh drating agent, oxidizing agent and sulfonating or sulfating agent. A commercial variety of sulfuric acid which contains about #0# of dissolved $0; is called “eleum”, fuming Sulfuric acid, pyrosulfuric acid, _aisulfuric “acid or Nordhausen Acid, represented by the formule #2820). It is formed according to the following reaction: Sqniee HaSOGH DiSO; PLease 64H 80), Ereparation: There are 2 industrial processes of preparing sulfuric aci the and the S; Both processes employed essentially the same principle, i.e. the oxidation of sulfur dioxide to Sulfur trioxide and adding enough water to form sulfuric Sod ews ar ag ee water "EO ormesut toes The Contact Process produces most of the commercial sulfuric acid today with the advantage to obtaining a roduct of. ixed strength. Vanadium or platinized silica gels are used as catalysts. ES sed as catalysts. For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 28Se eee er he ee ae i In the Lead Chamber Process, the __concentrated product H2S04, hence it is mainly used in the mai re of the fertilizer, primary calcium phosphate, known in commerce as Superphosphate. Uses: Sulfuric acid finds chemical use as a strong diprotic acid which can be utilized to form salts of basic organic. ‘rug molecules~ It is also utilized as a dehydrating agent in the preparation of Pyroxylin USP 26. Official Inorganic Bases Jo. — Horehold ammonia STRONG AMMONIA SOLUTION NF 26 a sere or Synonyms: i + Stronger Ammonia Water Synonyms: Eroperties: Strong Ammonia Solution contains n.l.t. 27% and | crea oe ey Weight of NHs- Upon exposure to air, it loses ammonia rapidly. The solution isc). lear, colorless liquid, having an exceeding pun cteristic od Specific gravity of about 0.9 The NF XV issues the following caution concer ing Strong Ammonia Solution. Caution use care in handding Strong Ammonia Solution because of the i eof | the solution and the irrit; erties of its vapor, | Gool the container well before opening and cover the closure with ac similar material while opening. Do nia Solution and avoid inhalation of its vapors. ie? an ot + Fore ob Uatend & - Vgont (RQ NH} Since the ammonia molecule possesses an unshared pair of electrons, it can serve as a liquid in forming soluble complex ions with many metal cations namely Cu, Ag, | Au, Zn, Cd, Cr, Ni, Co, Mn and Pt. The hydroxides or dnsoluble salts of these metals become sol ble in Ammonia i Solution. grttee acceptor = Uses: Ammonia Solution is used as a Brofisted base in many | plications ds. It is also used in the manufacture of nitric acid and sodium bicarbonate, Nis + 4 ~ N&q For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 29 iSe nemistry 1 Se Strong Ammonia Solution is used in the Preparation of Aromatic Ammonia Spirit NF XV, where it serve: the ammonium carbonate against hydrolysis and St reparation of Ammoniacal Silver Nitrate Solution NF 21. —momeaca’ Silver Nitrate Solution N contains n.l.t. 9 g and n.m.t. 10 g of NHy in each 100 mL. Diluted Ammonia Solution can be Prepared by diluted Strong Ammonia Solution with the appropriate quantity of purified water. This product is also known as “ai er” or is. Occasionally, it is employed as circulatory “stimulant by inhalation of the Vapors. Externally, t is used as counter=irvitants ee eer ears CALCIUMHYDROXIDE°USPY31 (Ca(OH), ; Mol. wt. 74.09) Stan Synonyms: Siakedeldime, Catteiumstiydrate Properties: Calcium Hydroxide is official as white powder having an alkaline and biti taste. It is slightly soluble in water (I g in 630 mL) and very soluble in boiling water (1 g in 1300 mL). It is soluble in glycerin and in syrup, but is insoluble in alcohol. A special type of neutralizing action maybe illustrated by the ability of calcium hydroxide absorb carbon dioxide from the air, which the formation of calcium “carbonate giving the cloudy appearance of calcium hydroxide— solution Preparation: Calcium Hydroxide is manufactured from lime or calcium oxide, through the addition of water in Limite Qmounts. The process iS known as slakin 2, slaked lime) and is characterized by the avid absorption of water by the oxide, accompanied by i mi heat, swelling of Cao isi fine powder ot Sa0-lumps_and_a_final_disintegration_inta The official solution is Calcium _Hydroxid Solution-USP-26 (Lime Water) and is described ag a solut. Soueaining in each 100 mi, n-1.t. 140 mq of Ca(Ols. Tt te clear, Solesless Maia Waving on alkMing toate’ ands. alkaline to litmus. itis prepared by adding 3 g of For the exclusive use of Pharmacy students in the UST | Faculty of Pharmacy Page 30Lecture Notes in Pharmaceutical Chemistry 1 calci urified water. The mixture is agitated repeatedly over a peri and the excess calcium hydroxide is allowed to settle. The clear supernatant liquid is used, the undissolved portion is not suitable for preparing additional quantities of the solution. . 2 Use: Calcium Hydroxide is used medically as a fli electrolyte and as topical astringent. Calcium Hydrox: is used in pharmaceutical preparations for its potentially high hydroxide ion concentration. This alkalinity allows it to react with the free fatty acids in various oils e oleic acid, to form calcium soaps which have emulsifying Properties. The carbon dioxide absorbing properties of geicium_hydroxide are useful in certain (ypes of gas Step It is combined with NaOH in a mix Town as Soda Lime whichis—used—for_its ability to absorb CO. from expired air in metabolic function tests; POTASSIUM HYDROXIDE NF 26 (KOH ; Mol. wt. 56.11) Synonyms: CaustiesPetash, Rotassa Properties: Potassium Hydroxide is official as white or nearly white fused masses, small pellets, flakes or sticks that have a crystalline fracture. It is very delinquent and rapidly absorbs both moisture and carbon dioxide from the air. Potassium Hydroxide is a yexyestrongubase having a caustic or corrosive effect on tissues. The NF XV states: Caution: Exercise great care in handling potassium hydroxide as it rapidly.destroys.tissues. Uses: Potassium Hydroxide is used as a caustic pri Gn veterinary practice. It is Used in official preparations as a saponifying agent to hydrolyze esters of fatty acids into their constituent. ohols andthe potassium salt. Aqueous and alcoholic volumetric solutions for titrating acids are widely used. It_enjoys its widest use” as a base or alkaline reagent. te ances For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 31Lecture Notes in Pharmaceutical Chemistry 1 SODIUM HYDROXIDE NF 26 (NaOH ; Mol. wt. 40) Synonyms: GamsticsSeda, Sodasllye Properties: Sgdium Hydroxide occurs in dry, hard, brittle, white sticks, in large fused, opaque, white stone-like masses having a dense crystalline fracture, in small Pellets, in flakes and in other forms. It is very i t_and rapidly absorbs moisture and CO, from the ai ———_— One gram of NaOH dissolves in_0.9 mL of water at 25°C with the evolution of heat. It is very soluble in alcohol, ether and glycerin. Like potassium hydroxide, sodium hydroxide is highl ized _in solution making it one of the strongest Base available. Since it attacks soft glass, bottles which are use as containers should be made of hard glass using rubber stoppers. d_bottles can be used dittlespetrolieun or pamattimeis spread around _the stopper. Sodium Hydroxide reacts with the salts of al] Retals in solution precipitating alnest—all_of them except those the alkali metals and ammonium as the insoluble Seah hydeonipes: esters and the! It will catalyze the hydrolysis of ‘Ore employed as a saponifying agent. Sodium Hydroxide is a very strong base capable of -damaging—tissues. In fact, the NF XV cautions: Exercise great care in handling sodium hydroxide 4s it rapidly destroys tissues. Uses: Sodium Hydroxide is employed for the same purpose as KOH. It has the advantage over the latter of being less del inque: robably milder and cheaper. Because of this, sodium hydroxide is extensively used in industrial purposes. SODIUM:CARBONATESNF 26 (Na2C03.H20 ; Mol. wt. 124) Synonyms: Monchydrated=Sodium:Carzbonate Properties: monohydrate is a colorless or or white c: powder. It is odorless and has a strong alkaline taste. C saecngitniciniiige-aumenemrernenemnererscrssanescereemee For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 32Lecture Notes in Pharmaceutical Chemistry 1 qt will absorb small amounts of moisture from the air but in warm, dry air at 50°C or above, it s®RTOrese@®, becoming Rc. One gram of sodium carbonate dissolves i are ohmater and_in fm of boiling water and in 7 mL of glycerin, . It is Sodium Carbonate exists in three well gharacterized hydrates in addition to the anhydrous form (Soda Ash). These are: (1) Monohydrate - Na,C03.H20 (2) Heptahydrate - NaC03.7H,0 (3) Decahydrate - NazC0s.10H20 (Sal Soda, Washing Soda) Catcinaka Ereparation: Almost all of the commercial supply of sodium carbonate is made by the i i turating a thoroughly cooled conc. solution of sodium ghloride first with ammonia and then with carbon diswiae~ The NaHCO, formed being less soluble at low temperature (6.9:100 at 0°C) separates out. On calculation of the a la) is Gieaqued whichis an article of commerce. It has the disadvantage of bein Oo air, it gradually al one mole of water, forming then the more stable monohydrated sodium carbonate. Uses: Sodium Carbonate should not be given internall Pecause of its npkedalkaLinitysand Seiearingepronseeied, It is used for its basicity in pharmaceutical preparations where it will form sodium ¢ drugs. An where together with sodium hydroxide it is used to Nero ater eotubte—sodium—calt_of the water insoluble Aipaerosed ey eee SOc sae ore * NS wok hyphal SODA LIME NF 26 Sedamisime is a mixture of Galciumshydroxice and Or potassiumehyaroxi@e or both, intended for use in metabolism tests, anesthesia and oxygen therapy. The NE states that it may contain as indicator which will not react with the common anesthetic gases and which will change color i i e soda lime for carbon dioxide is exhausted. s0ee ime for carbon dioxide is exhausted. For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy. Page 33{Lecture Notes in Pharmaceutical Chemistry 1 The function of the soda lime in a closed system is to absorb the carbon dioxide which would otherwise cur r The sodium hydroxide is capable of picking up carbon. é i ining power is soon exhausted. the ‘calcium hydroxide present in the mixtecs will react with the accumulated carbon dioxide 9° form_calcium carbonate, thereby “zegenerating” the ‘sodium hydroxide. This process can caontinue until the calcium hydroxide and sodium hydroxide are exnaustet If an indicator is Present in the mixture, the golor will indicate when the soda 1ij le is_exhausted. When Tape cater is_present. a record of the leneth of time Space must be kept to determine when the soda lime _must_be changed. een ae Buffer The control of pH in solutions is very important gepsct Of Pharmaceutical chemistry and practice The are tees or controlling. pH within. certain specifies limits @res for? .(1): icq ty, (2) solubihitymofothe aug and (3) patienttsncomtert—— Some factors which can Produce alterations in pH include: alkali in the glass and gases and such as sopben, dickies “ant—amionta, which “can —duesciey “UC a8 solution accompanied by acidic and basic reactions. The effect that these factors have on the established pH of a medium can be controlled through the use of chemical systems known as buffers, Buffer systems are Pair of related chemical compounds capable of Zesisting large changes in the pH of solution caused by the addition of small amou f acid or se. More specifica. Y, a buffer system is composed of a weeR"ZETR and LES™S8It (conjugate base) or qeaklbase and ifs s@allé “(conjugate acid). The Istres is notenwided y BOSE OF The cause OE the_stabtadewsprobrehs encounterer ny, Rost of the auailable weak bases. For the exclusive use ‘of Pharmacy students in the ‘UST Faculty ‘of Pharmacy Page 34Lecture Notes in Pharmaceutical Chemistry 1 The operating theory behind these mixtures of compounds is that the two components of the—system,—the buffer pair, will complement each other. when smail amounts of hydrogen ion are introduced into the medium they will react with the conjugate base or basic members of the buffer to form the weak acid which, by definition will only slightly be ionized. Similarly, when a@ small amount of hydroxide ion (base) are introduced into the medium, they will react—witn—tne weak acid or acidic member of the buffer pair to form water and the conjugate base. Hence, ach Component of the buffer pair will react with sold or pase to form tne otner component, thessby ri g arge changes in hydrogen ton concentration. The selection of a buffer system for pharmaceutical purposes is based on both chemical and pharmacological factors. The buffer should not react with other chemicals in the preparation That is, the buffer pair should (1) ici ion reaction (2) siserethe-solubiiity of other components (3) th active ingredients The buffer system itself must also exhibit xeasonable chemical stability. Volatile species, e.g. ammonia and carbon dioxide must be avoided since their loss alter the pH and the buffer capacity of the system. The pharmacological factors of the buffer selection are concerned with how the particular product is going to be used. The buffer should neither contribute to nor detract from the pharmacological properties of thi tive ingredients. Among the inorganic buffers of importance which have particular advantages in pharmaceutical preparations are: (1) phOspHaPe"Hiffer"systeh and (2) DOFate™bufferssysten. The phosphate buffer system enjoys the advantage of containing the dahydnogen and_nonehydzogsm=phsSphaus=ins, one of the physiological buffer pairs normally found in the body. The disadvantages include the ipsolubility of the such as Ag, Zn, and Al and h. Example of this buffer system is the ra ee For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 35,Lecture Notes in Pharmaceutical Chemistry 1 ee Borate buffer system have been used in preparations containing metals t) otherwise precipitate in the presence of phosphate. Since borates are ic, these buffer system are__suitable in external preparations, ophthalmic and nasal solutions but are contraindicated in Parenteral solutions. There are 3 primary borate buffer systems presently recognized: 1) Beldman’s Buffer System (pi W=@92) - consists of acid solution containing boric—acid, sodiumechioride (to make it isotonic) and the afkaieme solution containing sodium=porate. 2) Sm ). - consists of alkadime solution of and @e@id buffer solution of boricuacid. 3) Gifford Buffer system (pH Gnu) - similar to Feldman’s Buff System however in place. of NaCl, PB sium is used to make it hypotoniev (NazBi07.10H20 ; Mol. wt. 381.37) Sodium Pyroborate, Sodium Tetraborate, Properties: Sodium Borate occurs as colorless, transparent er - + The compound is odorless and effloresces in warm, dry air often leaving the crystals coated with a white powder. It is soluble in water and glycerin and insoluble in alcohol. Its aqueous solutions are alkaline to phenolphthalein. Sodium Borate is used or formed in situ as the alkaline member of the borate buffer system, which is the ‘Dasls for Teej mecogmtiodiiny The He ot coe de eee connection is the fact that metals borates with the exception of the alkali metals (Na, K, etc.) borates, are insoluble in water. A possible incompatibility is found when mixing solutions containing sodium borate with those containing soluble zinc salts. The zinc maybe precipitated t i ic_hydroxide due to_ the alkalinity of th lium bors olution. This Problem is avoided by the use of boric acid because the acidic zine borate is water soluble. Beidic zinc borate is water soluble. For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 36Lecture Notes in Pharmaceutical Chemistry 1 Sodium Borate has the same toxicity as boric acid; in fact it is hydrolyzed t& boric acid in aqueous GoTution. Uses: Sodium Borate is one of the best eyewash when acids happen to enter the mucosa. A %=@% solution is used in eoliyria. It is one of the components of many mouthwashes and oral preparations and is frequently applied in the form of powder to ulcers in the mouth. It is weak bacteriostatic agent. It forms whi ve Particularly c and . Antioxidants Antioxidants are compounds which have the capability of functioning chemically as ueducingmagents, they are used in pharmaceutical preparations containing S, (@.g. iodide or ferrous) in order to maintain these substances in their reduced forms. The mechanism of antioxidant action maybe seen in two ways, both achieving the same net results: a. Either the antioxidant is oxidized in lace of the he active consti: Ay dized, the antioxidant redueesit_back to its normal oxidation state. For practical purposes, these two _— events indistinguishable. In selecting a suitable antioxidant, the following factors should be considered: 1. An antioxidant in a pharmaceutical preparation should be E 2. The of both the reducing agent and its oxidi 3. One should consider possible etween reducing agent and the dru 4 i agents will £ i or in concentrated solution with strong oxidizing agents. For the exclusive use of Pharmacy students in the UST Faculty of PharmacyOO NN—_—an—E —— A.W HYPOPHOSPHOROUS ACID NF: 26 (HPH202 ; Mol. wt. 66) Eroperties: Hypophosphorous Acid is a colorless or slightly yellow, odorless liquid containing n.l.t. 30% and n.m.t. 32% HPH202. The solution has a specific gravity of 1.13 at 25°. The pure acid is a syrupy colorless liquid which becomes a solid at 17°C and melts at 26°C. The oxidation state of the central phosphorus atom is ig, making the compound a very powerful reducing agent. It can reduce many compounds to form phosphorus acid (HPO. having an oxidation state of _3+ and finally phosphoric acid (H3P04) having an oxidation state of 5+, for a net transfer of Four electrons. Its reducing properties are readily illustrated by its reaction with molecular iodine to—form iodide ions and its ability to decolorize acidi utions, of _potassii i ‘um permanganate immediately. evita Uses: Hypophosphorous Acid and its salts (hypophosphites) have 1 action. Its use principally as an antioxidant. It serves the gerves to prevent th form ee _iodi Sd Hydriodic Acid and Syrup. It is also present in Ferrous Iodide Syrup NF XI where it prevent the formulation of both ferric ions and molecular iodine. Salts of hypophosphorous acid are also used for their antioxidant properties; sodium hypophosphate is present as Breservative in certain foods and ammonium hypophosphate may also be found in many preparations as preservative. Hypophosphites should never be triturated with oxidizing agents such as nitrates, chlorates or permanganates. The concentration ranges for hypophosphorous acid and its salts when used as antioxidants are never over 18. SULEUR-DIOXIDE NF 26 (S02 7 Mol wt. 64.06) Synonym: SuivfurousmAnhydride Properties: Sulfur Dioxide is a colorless, non-flammable gas possessing a strong suffocating odor characteristic of burning sulfur. This is the same odor noticed from the burning of high sulfur-containing fuel. It contains n.l.t. 97% by volume of $0. Under pressure, sulfur dioxide condenses to a colorless liquid which boils at -10°C and has For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 38Lecture Notes in Pharmaceutical Chemistry 1 a density of 1.5. It is soluble in water (36:1) forming a moderately strong acid -~ sulfurous acid. Sulfur Dioxide contains sulfur the 4+ oxidation state and functions as strong reducing agent. When sulfur dioxide is passed through an aqueous solution containing iodine, hydroiodic acid is formed. With potassium permanganate, it is oxidized to sulfate. Uses: Sulfur Dioxide is classified as an aabianider* It will protect susceptible compounds from oxidation by reducing the oxidized firm back again _or probably even_more important, by reacting with oxygen_before the susceptible compounds do. Because of its gaseous nature, sulfur dioxide is usually used in injectable preparations enclosed in single dose ampoules or multiple does vials. ( poaapebtbiieaes oy, Sulfur Dioxide also finds extensive use _in industry for such processes as bleaching wood pulp, fumigating grains and_arresting fermentation, It is also used _to—fumigate _houses—where_it is given off in the q ‘soprumaisutaie ‘| (NaHSO3 ; Mol. wt. 104.06) Synonyms: SodiumsHydrogenw=Suifite, Sodium Acid sulfite, Leucogen Properties: The NF XV describes sodium bisulfite as a mixture of sodium bisulfite (NaHS0:) and sodium metabisulfite (NazS20;) in varying proportions. The compound is white or yellowish white crystals or a granular powder having the odor of sulfur dioxide and should yield n.l.t, 58.5% and n.m.t. 67.4% S02. The solid is unstable in air, giving off S0,. soll SODIUM METABISULFITE NF 26 (Na2S20s ; Mol. wt. 190.10) Properties: The compound is also a white crystal or a white to yellowish crystalline powder having the odor of sulfur dioxide. It should contain an amount of NaS,0s equivalent to n.l.t, 66% and n.m.t. 67% of S02. For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy.Lecture Notes in Pharmaceutical Chemistry 1 is actually the Most commercial «sodium=bisulfite metabisulfite. This salt can be used when bisulfite is” specified because when dissolved in water, it is immediately converted to bisulfite. Treatment to bisulfites of the normal salts (sulfite) with aqueous acid yields sulfurous acid, which is essentially a solution of SO; in water. ium_bisulfite is acidic enough to neutralize the stronger Dadese ep Sea cere te neutrals ulfite- On the other hand, the—addition of sulfites to acidic solutions will result in a shift towards alkaline pH by the formation of bisulfite, which reduces the concentration of hydrogen ions. Qne_primary sources of incompatébthities with bisulfites and sulfites is si ble salts are those of the alkali s. The alkaline earth metal bisulfites are less soluble and the sulfites of the metals are insoluble. Use: Sodium Bisulfite or Sodium Metabisulfite is used almost_exclusively—as_an mt. It is usually found in acidic solutions of drugs that contain the henol or catechol nucleus to-prevent oxidation of the compounds to quinones. Bisulfites may also be found in ascorbic acid injections as a reducing agent. SBaseeine sa injections as a reducing agent. Sodium Bisulfite may also be used to prepare water soluble derivatives of normally insolublé drugs. Example is Menadione Sodium Bisulfite in which water insoluble menadione is converted to a water soluble form for preparing “parenteral products. The activity of menadione is maintained until regenerated in the tissues. Se ree Cmmene ra Ledeen: Lae wwiEsues Sage eet NSH NITROGEN NF 26 (Nz 7 Mol. wt. 28.01) Properties: Nitrogen occurs as a colorless, odorless inert gas. It is non-flammable and does not support combustion. One_volume dissolves in about e volumes of water and in a ohol at 20°C and at a pressure of 760 Hg. Nitrogen aE is usually sold in rr ee For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 40Lecture Notes in Pharmaceutical Chemistry Uses: Nitrogen is used as an _inertwatmosphere=towretard Ceagenne eionfex clon sensitive products - Cod Liver Oil, Olive Oil, Multiple Vitamin Preparations, ett.—It—ts—aiso sed to replace air in containers for parenterais~ and solutions for topical applications. Such usage must declared on the product label. Nitrogen is also used to retard oxidation in the qualitative fest— for carbon rionoxide.. Water Properties: Pure water is tasteless, odorless, clear liquid which is colorless in small quantities but greenish blue in deep layers. Water has the ability to form hydrogen bonds with other water molecules or other electronegative or positive ions or molecules. The density of ice is less than the density of liquid—water—between_0°c_and—40°c —due—to_a mn 4 4 The significance of this property is that ice remains on the surface rather than sinking. Water has a high dielectric constant, which is extremely important to its capacity as a solvent and stabilizer of structure. The dielectric constant is related to the separation 6f charge within the water molecule a f its non-linear “bent” shape. The combination of water being the predominant: constituent of the body, having a high dielectric constant, being a small molecule and readil forming hydrogen bonds makes water the solvent of choice in most” lignid dosaas forms. Because it’ istituent of the body, problems of toxicity, metabolism and excretion of the solvent do not normally have to be considered when water is used as a solvent. Having a high dielectric constant allows water to solvate ions readily and to stabilize macromolecules (proteins, etc.). The small molecular size allows water to penetrate into the free space within a crystal and to break the ionic bond. For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 41Lecture Notes in Pharmaceutical Chemistry 1 Hardness of Water: This property of water is d¥e=to=the=presence of Xarying amounts of cakeium, déxon and/or=magnesdum™salts which convert ordinary soap (water solub: for potassi high mol i into water insoluble calcium, i ium salts of fatty acids (water insoluble curd). Hardness of water maybe or it. maybe temporary or permanent ‘Temporary hardness (bicarbonate hardness) is caused by the Presence in the water of calcium or magnesium bicarbonates and can removed (softened) by boihing or saddition of a Sourcesofshydroxide. Rermanent” hardness is caused bythe s presence in solution of sulfates, chloride or hydroxides of and/or jum which cannot be removed by boiling or addition of @of hydroxide. Since many manufacturing laboratories consume large amounts of water free from dissolved solids and the Process of distillation is costly, other means of purifying water were devise 1. Addition of solublesseabonates (e.g. Washing Soda) which will precipitate calcium and magnesium as insoluble carbonates. 2. Chelation by the z - Zeolite is sodium aluminum silicate (Na,0.A1,03.2Si0,.3H,0) with the symbol NagZeol. Passing the hard water through a zeolite column, “an exchange of “water hardening” cations is made for “non-hardening” sodium cations. When the 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 sodium chloride is allowed to flow through the inactivated zeolite, reconverting it to the sodium form. 3. Dewoniver or pemineraizers - makes use of certain -Synthetic_resins which are endowed with removing both gations _and—anions from water. Since the water Produced from this apparatus compasses very favorably with distilled water in purity and at lower cost, USP XX modified the name and monograph of Distilled water to, he use of deion Wi £u of Purified water. of Purified wate For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 42Lecture Notes in Pharmaceutical Chemistry 1 4, = i ry has een using basic phosphate and sodiui sph: Chelate the divalent calcium making it unavailable for Official Waters: (1) PuwifiedstiatersUSPeal furified=WaterstSPu31 Purified Water USP is water obtained by distillation Cars emnnnahendeebiaaimen:. Tt occurs as a clear, odorless liquid which has specifications for PH, chloride, sulfide, total solids, ammonia, calcium, carbon dioxide, heavy metals, oxidizable substances and bacteriological purity. It is the water of choice for extemporaneous Compounding 27d RrsparatdonsofsnostalSPatestuxeagents. (2) Watersforsinjection=USB=3i Water for Injection USP is water purified by jtovtbbemnom It meets all the specifications called for in the Purified Water monograph. It__must meet _the reir using vabbita ag test enim for the Preparation of The finished Preparations should be sterilized. Water for Injection would be used by large scale pharmaceutical manufacturers, A Pharmacy preparing extemporaneous parenterals would be more likely use Bacteriostatic Water ‘tor Injection or sterile Water for Injection. (4) StortbestaternforsInjectionaUSP.32 Sterile Water for Injection is water for ingection sterilized and suitably packaged. This_water is the most Ci ééicultetomprepate, Sterile Water for Injection maybe stored in single=doses containers of not=larger than 1000-1 - The label must indicate that i 2 + It is used for extemporaneous fecammcing gf Parenterals for either temamanana oFLecture Notes in Pharmaceutical Chemistry 1 (5) StertlesWater=forsinhalation_USP.31 Sterile Water for Inhalation is prepared from Water for Injection that_is sterilized and suitably packaged. It ~contains fossantimicrobial=wagents, except when used in stumidifYer$ or other similar devices and where liable to contamination over a period of time. It is intended for inhavation™™ therapy and that it is not intended for parenteral administration. Packaged Suitably in glass (type T or Type II) or plastic containers. (6) Sterile Water for Irrigation USP.32 Sterile i is prepared from Water for_thjection thatis sterilized and suitably packaged—ia phagbomdowensiaas (Type I or Type II) or plastic containers with a volume of more than 1 liter and Maybe designed to empty rapidly. It contains momantiméerobial agents or other added substances. (5) Bacteriostatic Water for Injection USP_31 Bacteriostatic Water for Injection USP is sterile water for injection containing one or more suitable antimicrobial agents Benzylemakcohok is a common It is stored in single-dose or in s (er_than dr qotlarger than s0ambesiee. Tt ‘is intended for compourding small volumes of extemporaneous Parenterals for iwtramuscula@r injection. The bacteriostatic agent prevents “the use S water for intravenous administration. Label should include statement “Notmfonuuse “in boldface, capital letters “printed in contrasting color preferable in red. Glass The word “gkasg” is a generic term referring to Y8bweousematerial (material which softens gradually over a temperature range rather than melting sharply). Most of the commercial glasses are vitreous silicates with some type of additive which confers special Properties: Boxommcecreases the coéfficient=ofwexpansiion <8 _ SS: For the exclusive use of Pharmacy students in the UST Faculty of Pharmacy Page 44