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suitable for preparing
aqueous solutions
Chapter 2: Pharmaceutical Aids and Necessities
o other substances needed in the preparation, preservation and storage of pharmaceutical products

Acids and Bases
o for the conversion of drugs to chemical forms (salt form) convenient to their product formulation.
o sources are plants and aimals composed of organic molecules





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

efficacy of drug depends on absorption

Buffers
o maintains the pH of various formulations
o made of Na
2
ONa
2
SiO
3

basic

Antioxidants
o prevent oxidative decomposition of pharmaceutically active components
o used as preservative

Water
o primary solvent/liquid phase

Glass
o for storage and as dispensing container


Official Inorganic Acids

o Boric Acid [H
3
BO
3
]
- Boracid Acid; Hydrogen Borate; Orthoboric Acid
- agua boricada
- used to wash eyes
- occurs free in sea waters, fruits and volcanic steam jets
sassolite native/natural boric acid

Sources: (combined forms)
Rasorite/Kernite Na
2
B
4
O
7
4H
2
O
Borax Na
2
B
4
O
7
10H
2
O
Borocalcite CaB
4
O
7
4H
2
O
Colemanite Ca
3
B
6
O
10
5H
2
O
Tincal H
3
BO
3
Na
2
B
4
O
7
2CaB
4
O
7
18H
2
O

Forms:
1. colorless, odorless pearly scales
2. six-scaled triclinic crystals
3. white odorless powder (soapy feeling)**tends to float on top of water, will not be dissolved
basic
H
2
O insoluble salt
*addition HCl para madissolve
acidic
H
2
O soluble salt


soluble in H
2
O
- for absorption

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ANTISEPTIC

turbid solution water insoluble impurities are present
clear solution water insoluble impurities are absent

Density: 1.46, stable in air.

o soluble in water and alcohol; freely soluble in glycerin, boiling water and boiling alcohol
o addition of HCl decreases the solubility in water
1g____ *clear solution of boric acid
25mL H
2
O
o salts produced with alkali metals are the only ones soluble in H
2
O, producing very alkaline solution
o Boric acid is not absorbed through intact (unwounded) skin, but is highly toxic when ingested orally
*cumulative poison
- absorbed when applied over large areas of broken skin
- must contain 100.5% anhydrous(dried) boric acid

APPLIED TOPICALLY as:
o ointments
o solutions
o dusting powder

- weak bacteriostatic agent (prevents multiplication)
3% concentration in ophthalmic solutions (eyewash collyrium)
- solutions should be warmed and diluted before use to dissolve crystals

- used as buffer in ophthalmic solutions and preparations
H
3
BO
3
+ Na
2
B
4
O
7
10H
2
O (partner)
alone does not have buffer capacity

Boroglycerin Glycerite (C
3
H
5
BO
3
)
suppository base, boric acid + glycerin @ 140-150
o
C


o Hydrochloric Acid [HCl]
- Muriatic Acid, Spirit of Sea Salt, Marine Acid, Espiritu de sal Marina
- used as DISINFECTANTS on inanimate objects
- aqueous solutions, 36% HCl, colorless fuming liquid with a pungent odor
- sp. gr = 1.18
- highly ionized
o Muriatic Acid Latin muria --> brine
technical grade containing the ff. impurities
chlorine
arsenous
sulfurous acids
iron (FeCl
3
)
- used as pharmaceutical aid, acidifying agent/solubilizing agent
- strong acid, reacts with organic molecules which are basic forming water soluble salts
Use of Endogenous HCl
aids in digestion of foods
gastric antiseptic
o should be taken with straw & diluted (can melt the enamel of the teeth)
o normally present in GI tract
yellow color

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- drugs are available in hydrochloride salts due to its ease of preparation and very low toxicity of chloride ion
- exists as normal gastric juice (diluted) [0.2%]
- aids in the conversion of pepsinogen pepsin
proteids peptones
- as gastric antiseptic
achlorhydria absence of hydrochloric acid
hypochlorhydria deficiency of HCl
DISADVANTAGE
hydrochlorides are hygroscopic (absorbs water from air and forms its water)

Glutamic Acid Hydrochloride
Betaine Hydrochloride





o Phosphoric Acid [H
3
PO
4
]
o Orthophosphoricacid
o an aqueous solution, colorless, odorless, syrup-y liquid having a sp. gr. of 1.71
o NON-VOLATILE, NON-OXIDIZING
USES:
o as acidifying agent limited to the solubilities of the various phosphate salts produced
o treated with NaOH HPO
4
-2
(basic)
H
2
PO
4
-1
(acidic)
o a solvent in the preparation of Anileridine injection

Diluted Phosphoric Acid: 9.5g
100 mL

10% solution used as a tonic and stimulant to gastric mucous membranes
*tonic-energizing
-synergistic to pepsin
- aids in formulation of peptones


o Sulfuric Acid [H
2
SO
4
]
- Oil of Vitriol, Vitriolic Acid, Aceite de Vitriolo
- colorless, odorless liquid of OILY CONSITENCY (sp.gr. 1.84)
- when heated vaporizes and gives off dense white fumes of SO
3
(sulfur trioxide)
does not volatilize at lower levels of heat
- strong dipriotic acid
- USEFUL DEHYDRATING AGENT, Oxidizing agent, Sulfonating/Sulfating agent

OLEUM- commercial variety of sulfuric acid containing 10% dissolved SO
3

o fuming sulfuric acid, pyrosulfuric acid, disulfuric acid or Nordhausen acid (H
2
S
2
O
7
)
*fuming because of the presence of a gas, SO
3

H
2
SO
4
+ SO
3
---> H
2
S
2
O
7
H
2
SO
4

+
SO
3

H
2
S
2
O
7


buffer
crystalline, administered in tablet or capsule form
- liberate HCl in the stomach, boths residue are being
metabolized at the same time

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Preparation:
2 Industrial Processes
Contact/Catalytic Process
Lead Chamber Process


Contact Process vanadium/platinized silica gel (99%)
*
as catalysts
stronger but more expensive

Lead Chamber Process 76% w/w
- used in the manufacture of fertilizer, primary calcium phosphate (superphosphate)

o Nitric Acid [HNO
3
]
- Spirit of Nitre, Agua Fortis, Agua Fuerte
- strong oxidizing acid, enhanced HNO
2
(produced by phytochemical decomposition of HNO
3
)
- highly corrosive fuming liquid, with highly irritating odor
- 120
o
C boiling point, sp gr=1.41
- produces yellow stain on animal tissue due to nitration of amino acids, phenylamine, tyrosine,
tryptophan in the proteins of the skin
Xanthoproteic Reaction
- strong monoproteic acid, oxidizing and nitrating agent
oxidizes all common metals except gold and platinum
used to nitrate toluene ---> trinitrotoluene (TNT)
- used in the manufacture of sulfuric acid, coal tar dyes, explosives
- nitrating agents for Pyroxylinin the preparation of Milk of Bismuth
externally used to destroy chancres/warts
Official Inorganic Bases

o Strong Ammonia Solution
- Ammonium Hydroxide, Stronger Ammonia Water
- clear, colorless solution with exceeding pungent odor, sp. gr = 0.90
28% (strong ammonia solution)
- CAUSTIC nature (corrosive) and irritating property of its vapor
- possesses an unshared pair of electrons, thus forms soluble complex ions with metal cations, Cu, Ag, Au,
Zn, Cd, Cr, Ni, Co, Mn & Pt
insoluble salts/ hydroxides of these metals become soluble in Ammonia Solution
USES:
Bronsted Base forming ammonium salts of acids
in the manufacture of nitric acid and sodium bicarbonate
- as circulatory stimulant (16
o
BaumeHousehold NH
3
)
preparation of Aromatic Ammonia Salt Spirit
- stabilizes the ammonium carbonate against hydrolysis and
the preparation of Ammoniacal Silver Nitrate

Diluted Ammonia Solution 9g
100 mL
diluted with purified water
Ammonia water/household ammonia
o as circulatory stimulant by inhalation of vapors
o counter-irritant, externally
oxidation of SO
2
SO
3

+ H
2
O
H
2
SO
4

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

Preparation:
CaO + H
2
O ------> evolution of heat, sweeling of CaO lumps ---> disintegration into fine powder
(slaking)
Solution n.l.t. 140mg Ca(OH)
2
/100mL

to prepare: 3g of Ca(OH)
2
+ 1000 mL purified water

USES:
as fluid electrolyte and as topical astringent
o used in pharmaceutical preparations for its high concentration of OH
-
ion
useful in gas traps for its absorbing properties
o combined with NaOH as Soda Lime
reacts with free fatty acids in various oils to form calcium soaps with emulsifying properties

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


o Sodium Hydroxide [NaOH]
- Caustic Soda, Soda Lye, Sosa
- to remove bara sa lababo
- dry, white, stone-like crystal, pellets, flakes
- less deliquescent than KOH, and is cheaper
- very soluble in alcohol, ether, & glycerin
1g/0.9mL @25
o
C
- attacks soft glass, container should have rubber stoppers
if not, glass-stoppered can be used, only if theres petroleum or paraffin around the stopper
- saponifying agent
- CAPABLE of damaging tissues, rapidly

USED in industrial purposes.


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o Sodium Carbonate [Na
2
CO
3
H
2
O]
- Monohydrated Sodium Carbonate
- colorless crystal or white crystalline powder
- odorless, strong alkaline taste
- it effloresces, becoming anhydrous @ 100
o
C (Soda Ash)
- 1g dissolves in 3 mL water
1.8 mL boiling water
7 mL glycerin
- insoluble in alcohol
- hygroscopic
Hydrated foms:
Monohydrate Na
2
CO
3
H
2
O
Heptahydrate Na
2
CO
3
7H
2
O
Decahydrate Na
2
CO
3
10H
2
O *Sal soda/ Washing Soda
(textile dye)


Preparation
- made by Solvay Process, saturating a thoroughly cooled solution of NaCl with ammonia then with CO
2

*Calcined Soda anhydrous sodium carbonate

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

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














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Buffers
- chemical systems that control the pH in solutions for:
chemical stability
solubility of the drug
patients comfort
- composed of a weak acid and its salt (conjugate base)
weak base and its salt (conjugate acid)**
- should not react with other chemicals in the preparation

Inorganic Buffers
o Phosphate buffer system
- contains dihydrogen and monohydrogen ions (physiological pair found in the body)
- disadvantage is the insolubility of its salts of Ag, Zn, Al
supports microbial growth
Example: Sorensen phosphate buffer system

o Borate buffer system
- toxic, suitable in external preparations (ophthalmic and nasal)

Three Primary Borate Systems
Feldmans Buffer System (pH 7-8.2)
H
3
BO
3
+ NaCl*+basic solution with Na
2
B
4
O
7
isotonic
Atkins and Pantin Buffer System (pH 7.6 11)
alkaline Na
2
CO
3
solution + acid buffer soln H
3
BO
3
+ NaCl
Gifford Buffer System (pH 6 7.8)
similar to Feldmans, but NaCl is replaced with KCl making it hypotonic

o Sodium Borate [Na
2
B
4
O
7
]
- Borax, Tinkal, Sodium Pyroborate, Sodium Tetraborate
- colorless, transparent crystals or as white crystalline powder
- odorless, effloresces with warm air making the crystals coated with white powder
- soluble in water and glycerin, insoluble in alcohol
aqueous solutions are alkaline to phenolphthalein
- has the same toxicity as boric acid

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











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Antioxidants
- compound that function chemically as reducing agents
- to maintain these substances in their reduced forms
- should be physiologically inert in pharmaceutical preparations
-
o Hypophosphorous Acid [HPH
2
O
2
]
- colorless/slightly yellow odorless liquid. 30% concentration
- pure acid is a syrupy colorless liquid, becomes solid @ 17
o
C
- very powerful reducing agent
- Hypophosphorous acid and its salt is used as an antioxidant, preventing the formulation of free iodine in
Diluted Hydriodic Acid; also in Ferrous Iodide Syrup, preventing the formulation of both ferric ions and
molecular iodine
also used as preservatives
its salts when used as antioxidants must never exceed 1% concentration

o Sulfur Dioxide [SO
2
]
- Sulfurous anhydride
- colorless, non-flammable gas with suffocating odor characteristic of burning sulfur
- condenses to a colorless liquid which boils at -10
o
C
- soluble in water forming sulfurous acid
- contains sulfur +4, strong reducing agent

Uses:
protects susceptible compounds from oxidation
reacts with oxygen before any other compounds do
for injectable preparations in a single-dose ampoules or multiple dose vials

bleaching wood pulps
fumigating grains
arresting fermentation
fumigate houses (burning of sulfur candles)

o Sodium Bisulfite [NaHSO
3
]
- Sodium Hydrogen Sulfite, Leucogen
- mixture of NaHSO
3
+ Na
2
S
2
O
5
(sodium bisulfate&sodium metabisulfite)
- white/yellowish white crystals OR granular powder
with sulfur dioxide odor
- unstable in air, giving off SO
2


o Sodium Metabisulfite [Na
2
S
2
O
5
]
- white crystal/white to yellowish crystalline powder
- most commercial
- converted to bisulfate when dissolved in water
- acidic, neutralizes the stronger bases forming sulfite
USES
found in acidic drug solutions containing phenol or catechol to prevent oxidation to quinines
in ascorbic acid injections as strong reducing agent
to prepare water soluble derivatives of normally insoluble drugs
Menadione Sodium Bisulfite
for parenteral products


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o Nitrogen [N
2
]
- colorless, odorless inert gas
- non-flammable, does not support combustion
- sold in black cylinders

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

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

Properties making water the solvent of choice:
1. constituent of the body
2. having high dielectric constant
3. being a small molecule

Hardness of Water
- due to the prescence of Ca, Fe & Mg salts which converts to ordinary soap
*soap with hard water = curdy precipitate
temporary hardness (HCO
3
-
)
- Ca(HCO
3
)
2

- Mg(HCO
3
)
2

*can be removed by boiling
permanent hardness (Cl
-
& SO
4
-2
)
- CaCl
2
& MgCl
2

- Ca(SO
4
) & Mg(SO
4
)
Ways of Purifying Water
Adding washing soda (Na
2
CO
3
10H
2
O)
Chelation by Zeolite (Permutit) Process
*sodium silicate Na
2
Zeol
*parang filtration
Deionizer/ Demineralizer
- machine that uses synthetic resins, ion exchange treatment
- produces somewhat like distilled water
- Purified Water
o Distillation and Ion exchange treatment
Polyphosphate Chelation
- used in detergent industry
- Ca
+2
&
Mg
+2
made unreactive by chelate bond (claw)

P P
Mg
+2

P P





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

2. Water for Injection
- purified by distillation ONLY
- must meet the requirement for pyrogen test using rabbits as test animals using Linulus Amebocytes
Lysate (LAL) reagent
- pyrogen causes fever

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

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


5. Sterile Water for Irrigation
- from sterilized water for injection, single-dose
- panlinis ng abdominal cavities

6. Bacteriostatic Water for Injection
- contains one or more antimicrobial agents
- Benzyl Alcohol is a common bacteriostatic agent
- single dose/multiple dose n.l.t. 30 mL
- for extemporaneous compounding of parenterals for IM injection
- not for IV injection because of the bacteriostatic agent
- NOT FOR USE IN NEWBORNS

Glass
- refers to vitreous material, material which softens gradually
- sodium silicate, Na
4
SiO
4
(Na
2
ONa
2
SiO
3
)
- added substances:
Boron decreases the coefficient of expansion of Pyrex glass
Potassium gives a brown light-resistant glass
Rare earth absorbs light of wavelengths
4 Types of Glass
1. Type 1 highly resistant, borosilicate glass
- for parenterals and base sensitive drugs
2. Type 2 treated with soda lime glass
- parenteral
3. Type 3 soda lime glass
- for reagents
4. Type NP general soda lime glass
- non parenteral

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Types of Containers
Colorless
Opaque
Colored

Opaque superior light protective, except for ointments

Clear
1. pt likes to see what he is buying
2. amount left in the bottle is seen
3. ease of pouring

4 Types of Clear Containers:
1. Colorless
2. Green
3. Blue
4. Amber screens out UV radiation