Chapter 2: Pharmaceutical Aids and Necessities (Properties)

Pharmaceutical Aids and Necessities

substances important to the preparation, preservation, and storage of pharmaceutical products

Acids and Bases

_____________________ are frequently employed in the conversion of drugs to chemical forms convenient to their product formulation, serves the purpose of rendering the therapeutic agent into a drug form more soluble in water.

Buffers

_____________ are used to maintain the pH of various formulations within prescribed limits

Antioxidants

_________________ are used to prevent oxidative decomposition of pharmaceutically active components

Water

_______________ is the primary solvent or liquid phase in most liquid pharmaceutical preparations

Glass

__________ is the dispensing container and storage for most drug components.

1. colorless, odorless, and pearly scales

2. six-scaled triclinic crystals

3. white odorless powder that is unctuous to touch (having a soapy feeling)

forms of boric acid

because powder floats on top of the water

why is scale and crystalline forms more preferred forms in aqueous solutions?

aqueous solutions

Most pharmaceuticals are dispensed in the form of ______________________, which are absorbed in the body more easily.

Boric Acid

stable in the air and has a density of 1.46

Boric Acid

soluble in glycerin, boiling water, and boiling alcohol

1g : 25 mL H₂O

how is clear boric acid obtained

hydrochloric acid

The addition of ________________________ decreases the boric acid’s solubility in water.

one proton per molecule

Due to the weak acid nature of boric acid, only salts produced by the replacement of __________________________ (primary salts) can be obtained in aqueous solutions

alkali metals

In boric acid, those formed with _______________ are the only ones soluble in water, producing very alkaline solutions.

hydrolyzed in water

In boric acid, salts formed with other metals are ______________________ to produce insoluble hydroxides.

large areas of broken skin

Boric acid is not absorbed through the intact skin but is highly toxic ingested orally; its is aborbed when applied over _______________________________-.

Hydrochloric Acid

aqueous solution of hydrogen chloride gas containing n.l.t. 35% and n.m.t. 38%

Hydrochloric Acid

colorless fuming liquid that has a pungent odor and a specific gravity of 1.18

diluting hydrochloric acid with 2 volumes of water

how to prepare a nonfuming solution of hydrochloric acid

highly ionized

Hydrochloric acid is __________________ than most other strong acids and attacks many metals with the evolution of hydrogen.

muria

Muriatic Acid came from the Latin word _______________, meaning brine

Muriatic Acid

technical grade of hydrochloric acid containing 35-38% HCl and a number of impurities, including chlorine, arsenous, and sulfurous acid ion, giving it a yellow color

Nitric Acid

aqueous solution containing n.l.t. 68% and n.m.t. 71%

Nitric Acid

described as a highly corrosive fuming liquid that has a characteristically highly irritating odor, with a boiling point of about 120 degree Celsius and a specific gravity of 1.41

yellow; Xanthoproteic Test

Nitric Acid will produce a ________ stain on animal tissue due to the nitrariob of the aromatic amino acids, phenylamine, tyrosine, and tryptophan found in the peoteins of the skin. This is known as _______________.

Nitric Acid

strong monoprotic acid, an oxidizing and nitrating agent

nitrous acid (HNO2)

The oxidizing power of Nitric acid is enhanced by the presence of small amounts of ________________, produced by the photochemical decomposition of nitric acid.

gold and platinum

It oxidizess all common metals, except ____________________, to produce the nitrate salt of the metal.

nitro group, -NO2

The nitrating properties of nitric acid are used extensively in Organic Chemistry. The reaction involves the substitution of the ____________, for some other group which can usually be hydrogen on the organic molecule.

Trinitrotoluene (TNT)

The nitrating properties of nitric acid is used to produce _____________ from toluene.

Phosphoric Acid NF

aqueous solution containing n.l.t 85% and n.m.t. 88%

Phosphoric Acid NF

colorless, odorless, and syrupy liquid that has a specific gravity of 1.71

nonvolatile and no oxidizing properties

Phosphoric Acid is ___________________, thus enabling its use whenever a non-oxidizing acid is required.

Sulfuric Acid NF

colorless and odorless liquid of oily consistency containing n.l.t. 94% and n.m.t. 98% of H2SO4 with a specific gravity of not less than 1.84.

dense white fumes

When strongly heated, sulfuric acid vaporizes and gives off ____________________ of sulfur trioxide, SO3, but it does not volatilize at lower levels of heat.

Sulfuric Acid NF

strong diprotic acid, dehydrating agent, oxidizing agent, sulfonating or sulfating agent

Oleum, Fuming Sulfuric Acid, Pyrosulfuric Acid, Disulfuric Acid, Nordhausen Acid

commercial variety of sulfuric acid which contains about 10% of dissolved SO3

Strong Ammonia Solution NF

contains n.l.t. 27% and n.m.t. 30% by weight of NH3; loses ammonia when exposed to air; has an exceeding pungent, characteristic odor, and a specific gravity of 0.90

soluble

As ammonia molecule possesses an unshared pair of electrons, it can serve as a liquid in forming _________ complex ions with many metal cations.

Calcium Hydroxide

officially characterized as a white powder that has an alkaline and bitter test; slightly soluble in water (1 g in 630 mL) and very soluble in boiling water (1 g in 1,3000 mL)

carbon dioxide

A special type of neutralizing action may be illustrated by the ability of calcium hydroxide to absorb _________________ from the air, which the formation of calcium carbonate giving the cloudy appearance of calcium hydroxide s

lime

Calcium Hydroxide is manufactured from __________________ or calcium hydroxide through the addition of water in limited amounts. This is known as Slaking.

because it is prepared by slaking

Why is Slaked Lime another name for Calcium Hydroxide?

Slaking

avid absorption of water by oxide, accompanied by the evolution of much heat, swelling of CaO lumps and a final disintegration into a fine powder

Calcium Hydroxide Solution USP

a solution containing in each 100 mL, n.l.t. 140 mg of Ca(OH)2; clear and colorless liquid that has an alkaline taste and alkaline in litmus; prepared by adding 3 g of calcium hydroxide to 1000 mL of purified water. This mixture is agitated repeatedly over a period of 1 hour, and the excess calcium hydroxide is allowed to settle. The clear supernatant liquid is used while the undissolved portion is not suitable for preparing additional quantities of the solution.

Potassium Hydroxide NF

white or nearly white fused masses, small pellets, flakes, or sticks that have a crystalline fracture

deliquescent

Potassium hydroxide is very __________________________ and rapidly absorbs both moisture and carbon dioxide from the air.

tissues

Potassium hydroxide is a very strong base that has a caustic/corrosive effect on ___________.

Sodium Hydroxide

occurs in dry, hard, brittle, white stocks, in large, fused, opaque white stone-like masses that have a dense crystalline fracture, in small pellets, in flakes, and in other forms

deliquescent, CO2

Sodium Hydroxide is very _______________ and rapidly absorbs ______ from the air

one gram of NaOH : 0.9 mL of water

at a temp of 25 degrees Celsius, how much of NaOH will dissolve in water?

alcohol, ether, and glycerin

Sodium hydroxide is soluble in _______________________________________________.

highly ionized

Sodium Hydroxide is _______________________ in solution, making it one of the strongest base available

hard glass with a rubber stopper

Sodium Hydroxide attacks soft glass, bottles which are used as containers should be made of _____________________________

petroleum or paraffin

Glass-stoppers can be used if a little ________________ or _____________________ is spread around the stopper

alkali metals and ammonium

Sodium Hydroxide reacts with the salts of all metals in solution precipitating almost all of them except _________________________ as the insoluble metal hydroxides. It will catalyze the hydrolysis of esters and therefore employed as a saponifying agent.

tissues

sodium hydroxide is a very strong base capable of damaging _______________.

Sodium Carbonate NF

officially characterized as a monohydrate, colorless crystal or white crystalline powder, odorless and has a strong alkaline taste

anhydrous (Soda Ash or Calcined Soda)

Sodium Carbonate absorbs small amounts of moisture from the air but in warm, dry air at 50 degrees Celsius or above, it effloresces, becoming _________________ at 100 degrees Celsius.

water, boiling water, glycerin, alcohol

One gram of sodium carbonate dissolves in 3 mL of ______________________, 1.8 mL ____________________, and 7 mL ____________________. It is insoluble in __________.

Monohydrate

Hydrates in Sodium Carbonate: Na₂CO_{3 ^.} H₂O

Heptahydrate

Hydrates in Sodium Carbonate: Na₂CO_{3 ^.} 7H₂O

Decahydrate (Sal Soda, Washing Soda)

Hydrates in Sodium Carbonate: Na₂CO_{3 ^.} 10H₂O

Solvay Process

process in which almost all of the commercial supply of sodium carbonate

1. saturating a thoroughly cooled concentrated solution of Sodium Chloride with Ammonia and Carbon Dioxide.

2. The NaHCO₃ is less soluble at low temperatures so it separates out.

3. NaHCO3 calcinates, forming anhydrous sodium carbonate (Calcined Soda) which is hygroscopic.

4. When exposed to air, it gradually absorbs about 15% or 1 mol of water, forming a more stable monohydrated sodium carbonate.

Solvay Process

Soda-lime NF

mixture of calcium hydroxide and sodium or potassium hydroxide or both, intended for use in metabolism tests, anesthesia, and oxygen therapy

Soda-lime NF

may contain an indicator that will not react with the common anesthetic gases and which will change color when the absorption capacity of the compound for carbon dioxide is exhausted. When no indicator is present, record the length of time usage.

absorb carbon dioxide

The function of the soda lime in a closed system is to ________________________ which would otherwise accumulate in the system.

1. Sodium Hydroxide is capable of picking up carbon dioxide, but its combining power is soon exhausted.

2. Calcium Hydroxide activates and combines with the accumulated carbon dioxide in the form of Na2CO3 to form Calcium Carbonate which regenerates Sodium Hydroxide

3. Process continues until the calcium and sodium hydroxides are exhausted.

How do Soda-lime absorb carbon dioxide in a system?

1. chemical stability

2. solubility of the drug

3. patient’s comfort

Reasons why one should control the pH

because only adding acids and bases will not remain at that point indefinitely

Why should we have buffer systems when we can add acids and bases to control the pH level of solutions

Buffer Systems

pair of related chemical compounds capable of resisting large changes in the pH pf a solution caused by the addition of small amounts of acid or base

1. weak acid and conjugate base

2. weak base and conjugate acid

a buffer system can be:

Weak base and conjugate acid because of its stability issues

Which buffer system is not commonly used?

two components of the buffer system will complement each other

operating theory behind the buffer system

1. Reaction of the Buffer with other chemicals during preparation (involvement in the oxidation-reduction reaction, change in the solubility of other components, and formation of complexes with the active ingredients)

2. Achieve and maintain reasonable chemical stability (avoid using volatile components, such as ammonia and carbon dioxide)

3. Must not exhibit any contributions or detraction of the pharmacological properties of the active ingredients.

Chemical and Pharmacological Aspects to be Considered:

Phosphate Buffer System

commonly found in the body, can obtain the dihydrogen and monohydrogen phosphate ions; may obtain microbial growths and Ag, Zn, and Al is insoluble

Sorensen

phosphate buffer system

Borate Buffer System

used for ophthalmic and nasal solutions but not parenteral solutions

Feldman’s, Arkin’s and Pantin, Gifford

Buffer Systems

isotonic

Sodium Chloride in a buffer system makes the solution ______________

hypotonic

Potassium Chloride in a buffer system makes the solution ______________

Sodium Borate NF

colorless and transparent crystals or as a white crystalline powder; odorless and efflorescence in warm, dry air, often leaving water and glycerin are insoluble in alcohol; aqueous solutions are alkaline to phenolphthalein

Sodium borate

______________________ is used/formed in situ as the alkaline member of the borate buffer system.

alkali metals

Metal borates except ______________, are insoluble in water.

water-soluble

In Zinc, boric acid is used because the acidic zinc borate is __________________.

boric acid

Sodium borate has the same toxicity as ________________________

Antioxidants

compounds that chemically act as reducing agents and are mostly used to prepare pharmaceutical products that contain oxidizable ions, namely, iodide and ferros

Hypophosphoric Acid NF

colorless acid is colorless or slightly yellow odorless liquid containing n.l.t. 30% and n.m.t. 32% HPH2O2; with a specific gravity of 1.13 at 25 degrees Celsius; pure acid is a syrupy colorless liquid that becomes solid at 17 degrees Celsius and melts at 26 degrees Celsius

Sulfur Dioxide NF

colorless, non-flammable gas possessing a strong suffocating odor; contains n.l.t. 97%; under pressure, it condenses to a colorless liquid that boils at - 10 degrees Celsius and has a density of 1.5; soluble in water, forming a moderately strong acid

Sodium Bisulfite

describes as a mixture of sodium sulfite and sodium metabisulfite; has white or yellowish-white crystals or a granular powder that has a odor of sulfur dioxide and should yield n.l.t. 58.5% and n.m.t. 67.4% SO2; solid is unstable in air, giving off SO2.

Sodium Metabisulfite NF

compound is a white crystal or a white yellowish crystalline powder that has the odor of sulfur dioxide; contain an amount of Na2S2O5 equivalent to n.l.t. 66% and n.m.t. 67% of SO2

metabisulfite

Most commercial bisulfite is actually ________________________ because when it is dissolved in water, it is immediately converted to bisulfite.

neuralize

Sodium bisulfite is acidic enough to _________ the stronger bases to form sulfite

solubility

One primary source of incompatibilities with bisulfites and sulfites is ___________. The only soluble salts are those of the alkali metals, alkaline earth metals are less soluble, and the sulfites of the metals are insoluble.

Nitrogen

colorless and odorless inert gas; nonflammable and does not support combustion; usually sold in black cylinders

Water

tasteless, odorless, and clear liquid that is colorless in small quantities but greenish-blue in deep layers

hydrogen bonds

Water has the ability to form _____________________ with other water molecules or other electronegative or positive ions or molecules

dielectric constant

Water has a high _______________, which is extremely important to its capacity as a solvent and stabilizer of structure.