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Topical agents
“Topical”- Use of pharmaceuticals on body surfaces
(unlike systemic administration in which the compounds are
absorbed in to the systemic circulation and distributed to various
body organs).
The action is supposed to be limited to the site / surface of
application.
Deeper penetration of topical agents are also seen in many
cases which are beneficial. (Penetration of antiseptics into the
tissue below the skin prevents the possibility of deeper
infections)- Advantage
Systemic absorption of many of these compounds in good
amounts after topical application is very common. (Allergic
reactions of mercury salts when applied topically)-
Disadvantage
Topical applications for systemic activity is very common through
body cavities which are open outside like oral, vaginal,
colonic/rectal.
Systemic absorption from these body cavities may be more
extensive than the skin; in fact drugs are often applied to these
areas as a route of systemic administration. (Buccal &
suppositories)
These pharmaceuticals are absorbed into the circulatory system
and get distributed in various organs and tissues.
They by-pass burden of metabolism.
Commonly applied as powders, ointments, creams, pastes,
lotions, spray and trans-dermal patches.
Rate of absorption depends on thickness of outer skin and its
blood circulation.
Protective: are those which are applied to skin to protect from
ulcers and open wound from irritation.
Ideal characters:
Insolubility in water-to limit the absorption through skin and to
avoid wash with water.
Chemically inert-to prevent local irritation and allergy.
Biologically inert-so that no biological activity.
Availability as fine particles-for more surface area and better
action.
TALC IP: 3MgO.4SiO2.H2O, Purified Talc; Talcum
Talc is a powdered, selected natural hydrated magnesium
silicate. It may contain varying amounts of aluminium and iron in
forms insoluble in 1M sulphuric acid.
Preparation: The mineral (native silicate having same general
formula) obtained naturally is treated with dilute HCl. The
supernatant liquid is washed and removed till it becomes free
from acid. The precipitate is dried and powdered.
Category: Pharmaceutical aid (dusting powder).
Solubility: Practically insoluble in water and in dilute solutions of
acids and alkali hydroxides.
Storage: in well-closed containers.
Standards: Identification, Acidity or alkalinity, Iron, Acid-soluble
substances, Water-soluble substances and Carbonates,
chlorides, Organic compounds and Loss on drying.
Zinc oxide IP: ZnO, Mol. Wt. 81.38
Category: Mild astringent; topical protectant.
Description: Soft, white or faintly yellowish white amorphous
powder, free from grittiness. It gradually absorbs carbon dioxide
from air.
Solubility: Practically insoluble in water and in ethanol (95%). It
dissolves in dilute mineral acids.
Preparation: In large scale it is obtained by heating metallic zinc
to bright redness in a current of air. The vapors of the metal
burns to form oxide which is collected as fine power.
Zn O2 ZnO+
A solution of Zinc sulphate is added to a boiling solution of
sodium carbonate. The precipitated basic carbonate of zinc is
collected, washed until is free from sulphate, dried, and ignited
to lose CO2 and water, giving ZnO.
Standards:
Zinc Oxide contains not less than 99.0 per cent and not more
than 100.5 per cent of ZnO, calculated with reference to the
ignited substance.
Identification, Alkalinity, Carbonate and substances insoluble in
acids, Arsenic, Iron, Lead, Loss on ignition.
Assay: Complexometry: Dissolve 0.15 g in 10 ml of 2M acetic
acid and dilute to 50 ml with water. To the resulting solution add
about 50 mg of xylenol orange triturate and sufficient hexamine
to produce violet-pink colour. Add a further 2 g of hexamine and
titrate with 0.1 M EDTA until the solution becomes yellow. Each
ml of 0.1M disodium edetate is equivalent to 0.008138 g of ZnO.
Zinc Oxide Cream IP, Zinc Cream
Zinc Oxide Cream contains 32% w/v of Zinc
Oxide in a suitable water-in-oil emulsified base.
Standards:
Zinc Oxide Cream contains not less than 30.0 per cent and not
more than 34.0 per cent w/w of zinc oxide, ZnO.
Calamine: ZnO. X Fe2O3, Prepared Calamine
Calamine is Zinc Oxide with a small
proportion of ferric oxide.
Category: Topical protectant.
Description: Fine, amorphous, impalpable,
pink or reddish-brown powder.
Solubility: Insoluble in water. Practically completely soluble in
mineral acids.
It is zinc oxide colored with ferric oxide which is used in lotions,
ointments etc as soothing agent in irritating skin condition
including urticaria, eczema and sunburn. The coloring is for
cosmetic reason.
Preparation: The naturally occurring Zinc carbonate is
subjected to calcinations (powdered by heating). The fine
powder thus obtained is mixed with small portion of ferric oxide
(1%) which imparts pink color to the solution.
Standards:
Calamine contains not less than 98.0 % and
not more than 100.5 % of ZnO, calculated
with reference to the ignited substance.
Identification: Acid-insoluble substances: Alkaline substances:
Water-soluble dyes: Ethanol-soluble dyes, Arsenic: Lead:
Calcium: Soluble barium salts: Chloride, Sulphate: Loss on
ignition:
Calamine color
Assay: Weigh accurately about 1.5 g and digest with 50.0 ml of
0.5 M sulphuric acid, applying gentle heat until no further
solution occurs. Filter and wash the residue with hot water until
the last washing is neutral to litmus paper.
To the combined filtrate and washings, add 2.5 g of ammonium
chloride, cool and titrate with 1M sodium hydroxide using methyl
orange solution as indicator. Each ml of 0.5M sulphuric acid is
equivalent to 0.04068 g of ZnO.
Calamine Lotion IP:
Calamine, Zinc Oxide, Bentonite, Sodium Citrate, Liquefied
Phenol Glycerin, Purified Water ( freshly boiled and cooled) as
solvent.
Preparation: Triturate the Calamine, the Zinc Oxide and the
Bentonite with a solution of the Sodium Citrate in about 700 ml
of Purified Water and add the Liquefied Phenol, the Glycerin
and sufficient Purified Water to produce 1000 ml.
Storage: Store in well-closed containers in a cool place. Do not
freeze.
Labelling: The label states
Concentrations of Calamine and Zinc Oxide in the preparation
The preparation is intended for external use only
The contents should be shaken before use
The conditions under which the preparation should be stored.
Zinc Stearate IP: (C17H35COO)2Zn, Mol. Wt. 632.34
Zinc stearate consists mainly of zinc stearate but many contain
variable proportions of zinc palmitate, (C15H31COO)2Zn, and zinc
oleate, (C17H33COO)2Zn.
Category: Pharmaceutical aid; dusting powder.
Description: Fine, white, bulky, amorphous powder, free from
grittiness; odour, faint and characteristic.
Solubility: Practically insoluble in water, in ethanol (95%) and in
ether.
Preparation: Stearic acid is added gradually, with constant
stirring, to a hot solution of sodium hydroxide. The solution of
sodium stearate so produced is left to cool and a solution of zinc
acetate or any soluble zinc salt is added.
The precipitated zinc stearate is then filtered, collected, washed
and dried.
C17H35 COOH
+
NaOH
C17H35COONa
Zinc acetate/soluble Zinc salt
(C17H35COO)2Zn
Standards: Zinc Stearate contains not less than 10.0 per cent
and not more than 12.0 per cent of Zn.
Identification: Acidity or alkalinity: Colour of solution, Alkalis and
alkaline earths, Arsenic: Heavy metals, Chloride: Sulphate:
Assay: Weigh accurately about 1 g and boil with 50 ml of 2M
acetic acid until the fatty acid layer which separates is clear,
adding more water if necessary to maintain the original volume.
Cool, filter and wash the filter and the flask thoroughly with water
until the last washing is not acidic to blue litmus paper. To the
combined filtrate and washings add about 50 mg of xylenol
orange triturate and sufficient hexamine to produce violet-pink
color. Add a further 2 g of hexamine and titrate with 0.1 M
disodium edetate until the color changes to yellow. Each ml of
0.1M disodium edetate is equivalent to 0.00654 g of Zn.
TITANIUM DIOXIDE IP: TiO2, Mol. Wt. 79.88
Category: Pharmaceutical aid and topical protectant.
Description: White or almost white, infusible powder; odourless.
Solubility: Practically insoluble in water and in dilute mineral
acids, slowly soluble in hot sulphuric acid.
Storage: Store in well-closed containers. Avoid contact with
aluminium.
Preparation: The naturally occurring ilmenite (FeTiO3) is treated
with hydrochloric acid and chlorine. The precipitate is filtered off,
washed calcined to give anhydrous TiO2.
STANDARDS: Titanium Dioxide contains not less than 98.0 per
cent and not more than 100.5 per cent of TiO2.
Identification: Clarity and color of solution: Acidity or alkalinity:
Water-soluble substances: Arsenic: Barium: Heavy metals: Iron
Assay: Weigh accurately about 0.5 g, transfer to a 300-ml
Kjeldahl flask, add 5 g of anhydrous sodium sulphate and 10 ml
of water, mix and add 10 ml of sulphuric acid. Boil gently until
clear, cool, add slowly 40 ml of cooled sulphuric acid (25%), cool
again and dilute with water to 100.0 ml (solution B). To 300 g of
zinc, in granules, add 300 ml of a 2% w/v solution of mercuric
nitrate and 2 ml of nitric acid, shake for 10 minutes and wash
with water. Pack the zinc amalgam into a glass tube (400 mm x
20 mm) fitted with a tap and a filter plate.
Pass through the column, at a rate of about 3 ml per minute, 100
ml of 1M sulhuric acid followed by 100 ml of water, ensuring that
the amalgam is covered with liquid throughout. Pass slowly
through the column, at a rate of about 3 ml per minute, 200 ml of
0.5 M sulphuric acid followed by 100 ml of water.
Collect the combined eluates in a 500-ml conical flask containing
50 ml of a 15% w/v solution of ferric ammonium sulphate in
sulphuric acid (25%) and titrate immediately with 0.1 M ceric
ammonium nitrate using ferroin solution as indicator until a
greenish colour is obtained (n1 ml).
Pass slowly through the column 100 ml of 0.5M sulphuric
acid followed by 20.0 ml of solution B, wash with 100 ml of
0.5M sulphuric acid followed by 100 ml of water.
Collect the combined eluates in a 500-ml conical flask containing
50 ml of a 15% w/v solution of ferric ammonium sulphate in
sulphuric acid (25%), rinse the lower end of the
column with water and titrate immediately
with 0.1M ceric ammonium nitrate using ferroin
solution as indicator until a greenish colour is obtained (n2 ml).
Calculate the percentage content of TiO2 from the expression :
3.99(n2 - n1)/w, where w is the weight, in g, of the substance
being examined used in the preparation of solution A.
Kaolinite is a clay with the chemical composition
Al2Si2O5(OH)4.
Rocks that are rich in kaolinite are known as china clay or kaolin.
Used in ceramics, medicine, coated paper, as a food additive, in
tooth paste and in cosmetics.
It is generally the main component in porcelain. It is also used in
paint to extend titanium dioxide (TiO2) and modify gloss levels.
In rubber for semi-reinforcing properties & In adhesives to
modify rheology.
Kaolin mine in Bulgaria
HEAVY KAOLIN IP: Al2O3.2SiO2.2H2O
Heavy Kaolin is a purified, natural, hydrated
aluminium silicate of variable composition.
Category: Pharmaceutical aid.
Description: Fine, white or grayish white, soft powder; odorless.
Solubility: Practically insoluble in water and in organic solvents.
It does not dissolve in mineral acids and in solutions of alkali
hydroxides.
Storage: Store in well-closed containers.
STANDARDS
Identification: Acidity or alkalinity: Arsenic: Heavy metals:
Chloride: Sulphate: Substances soluble in mineral acids:
Organic impurities:
Adsorption power: In a ground-glass-stoppered
test-tube shake 1.0 g with 10 ml of a 0.37% w/v solution of
methylene blue for 2 minutes and allow to settle. Centrifuge and
dilute 1 volume of the solution to 100 volumes with water. The
solution should not be more intensely colored than a 0.003% w/v
solution of methylene blue to pass the test.
Swelling power: Triturate 2 g with 2 ml of water; the mixture
does not flow.
Loss on ignition:
LIGHT KAOLIN IP (Kaolinite)
Light Kaolin is a native hydrated aluminium silicate, freed from
most of its impurities by elutriation and dried. It may contain a
suitable dispersing agent.
Category: Antidiarrhoeal.; Dose: 15 to 75 g.
Description: Light, white powder free from gritty particles;
odorless; almost tasteless; unctuous to the touch.
Solubility: Practically insoluble in water and in mineral acids.
Kaolinite
STANDARDS
Identification: Coarse particles: Fine particles: Arsenic: Heavy
metals: Chloride: Soluble matter: Loss on drying: Loss on ignition:
Preparation: Kaolin is purified form of natural having an approx
composition Al2O3.2SiO2.2H2O. Natural clay which is
contaminated with Calcium, Magnesium and ferric oxide is easily
removed by treatment with HCl followed by filtration.
Light and heavy variety differs in the degree of purity and in
particle size. Light var. is prepared from heavy var. by elutriation,
reducing gritty and coarse particles.
Silicone polymers:
They are inert protective materials of liquid forms and called as
silicone oils. They are primarily Di-methyl silicone ethers having
following general formula.
One such is dimethicone or semethicone
Silicone forms covalent compounds similar to carbon, giving rise
to polymers. Silicone compounds can also be substituted by
organic carbon containing radicals like methyl, ethyl etc. These
may be called organo-silicon compounds.
Si
CH3
CH3
O Si
CH3
CH3
CH3OSi
CH3
CH3
H3C
n
Silicone dioxide is anhydride of silicic acid.
Two molecules of silicic acid lose a molecules of water to give
disilicic acid. Several such silicic acid condenses togethre to
form Polysilicic acid which has got high affinity for water (silica
gel).
Polymers prepared from silicic acid, substituted by organic alky
or aryl radicals are silicone organo-polymers.
Si Si OHHO
OH
OHO
O
Si OO
OH
OH
Si O
OH
OH
Siliconedioxide
Orthosilicic acid Part of polysilicic acid chain
Si OHHO
CH3
CH3
Si OO
CH3
CH3
Si O
CH3
CH3Dimethyl silane diol Part of polydimethyl silane diol
DimethiconePolydimethyl siloxane; silicone linear polymer
Si OHHO
R
R
Si OHHO
OH
R
Organo silane diolR=alkyl, aryl
Organosilane triol
Si OO
R
R
Si O
R
R n
SiliconePolyorgano siloxane; linear polymer
Si O Si OO Si O
R O R
R R' R
Si OOSi SiO O
R
R R'
R
R
Silicone: Poly-organo-siloxaneCross linked polymer
Preparation:
SiCL4R. Mg X
R2SiCl2H2O
R2Si(OH)2
Silicone tetrachloride
Grignard'sDichlorosilane Dialkyl-silane diol
R2Si(OH)2
PolymerisationSilicone linear polymer
R2SiH(OH)2 RSi (OH)3+Polymerisation
Silicone cross linked polymer
DIMETHICONE, ACTIVATED DIMETHICONE IP
Simethicone, Polydimethylsiloxane,
Activated Dimethicone Simethicone;
Activated Polydimethylsiloxane
Dimethicone Activated Dimethicone is a
mixture of fully methylated linear siloxane
polymers containing repeating -(CH3)2SiO- units stabilised with
trimethylsiloxy, (CH3)3SiO-, end-blocking units and finely divided
silicon dioxide.
Category: Defoaming agent. Often included along with antacid
preparations which facilitates the belching of stomach due to
excess of gastric acid.
H3C Si
CH3
CH3
O Si CH3
CH3
CH3
+ SiO2
n
(CH3)3Si[OSi(CH3)2]CH3 + SiO2
Activated dimethicone, a mixture of polydimethylsiloxanes and
silicone dioxide (sometimes called Simethicone), is used in OTC
as an anti-foaming agent and carminative.
As a food additive, it has the E number E900 and is used as an
anti foaming agents and an anti caking agent.
Dose: 40 to 100 mg, four times daily.
Description: Clear to translucent, colorless, viscous liquid,
almost odorless Translucent, grey viscous liquid, almost
odorless.
STANDARDS: Identification: Acidity: Heavy metals: De-foaming
activity
Solubility: Miscible with carbon tetrachloride, with chloroform,
with ether, with ethyl acetate, with methyl ethyl ketone and with
toluene; very slightly soluble in ethanol, but silicon dioxide
remains as a residue in the solvents; practically insoluble in
water and in methanol.
Storage: Store in tightly-closed containers.
Assay: ??!!
Astringents: substance is a chemical that tends to
shrink or constrict body tissues,
usually locally after topical medicinal
application.
They have limited penetrative power.
They conjugate the protein primarily on the surface
of the cells, an action which does not result in the
death of the cell.
The general construction of tissues like small blood vessels
occur under the influence of astringents.
Therapeutic uses of astringent compounds includes;
1. styptic, to stop bleeding from small cuts by promoting
coagulation of blood and constricting small capillaries.
2. Antiperspirant, to decrease secretion of perspiration by
constricting pores at the surface of the skin
3. Restriction of the blood supply to the surface of mucus
membrane there by reducing inflammation
4. By direct action on skin, to remove unwanted tissues (requires
a higher concentration or stronger precipitant)
Most of the topical astringents are aluminium, Zinc salts and to
some extent Zirconium salts.
Alums
Alum of pharmacopoeia (not official in IP)
Is either potash alum (KAl(SO4)2. 12 H2O
(MW=474.4) or Ammonium alum
NH4Al(SO4)2. 12 H2O
They are sulphates of univalent metals (potassium or
ammonium) with a trivalent metal having general formula
XY(SO4)2. 12 H2O.
Thus alum may not contain ammonium always, in fact contain
aluminium.
Preparation: Alums are prepared by adding a hot concentrated
solution of either potassium or ammonium sulphate to a hot
solution of an equimolar aluminium sulphate. The alum
crystalises out on cooling.
It is also prepared from Alunite ore by purification.
Potash alum: colorless, odorless, transparent powder. Soluble in
water, giving acidic solution.
It is a Powerful astringent, used in the form of solid
or solutions in preparing mouth washes, gargles.
Also used in the preparation of vaccine to precipitate bacterial
toxins or toxoids.
K2SO4 + Al2(SO4)3 2 KAl(SO4)2
Aluminium sulphate IP: Al2(SO4)3,xH2O, Mol. Wt. 342.14
(anhydrous)
Category: Pharmaceutical aid (mineral
carrier for adsorbed vaccines).
Powerful astringent, and used as antiperspirant and in
purification of water by flocculation method like alum.
This in included as a carrier for certain vaccine in IP. The
Aluminium sulphate should be 51-59% which corresponds to 16-
18 moles of water per molecule of Al. sulphate.
Preparation: It is prepared by treating freshly prepared
Al.hydroxide with sulphuric acid. The solution is concentrated
and the salt crystallized.
Description: Colourless, lustrous crystals or white, crystalline
powder or masses; odourless.
Solubility: Soluble in water; freely soluble in hot
water; practically insoluble in ethanol (95%).
STANDARDS:
Identification: pH: Clarity and colour of solution: Alkalis and
alkaline-earth metals: Ammonium salts: Arsenic: Heavy metals:
Iron:
Al(OH)3 + H2SO4 Al2(SO4)3 + H2(g)
Assay: Weigh accurately about 0.6 g and dissolve in 2 ml of 1M
HCl and 50 ml of water. Add 50.0 ml of 0.05 M disodium edta and
neutralise to methyl red solution with 0.1M NaOH. Heat the
solution to boiling, leave on a water-bath for 10 minutes, cool
rapidly and add about 50 mg of xylenol orange mixture and 5 g of
hexamine. Titrate with 0.05M lead nitrate. Perform a blank
determination and make any necessary correction.
Zinc sulphate IP, ZnSO4. 7 H2O, MW=287.54
It is prepared by treating Zinc metal or Zinc oxide with Dil.
Sulphuric acid. The solution is filtered, concentrated and allowed
to crystallize.
Category: Astringent.
Zn++ S
O
O
OO
Zn + H2SO4 ZnSO4 + H2 (g)
ZnO + H2SO4 ZnSO4 + H2O
Description: Colourless, transparent crystals or white, crystalline
powder; odourless; efflorescent.
Solubility: Very soluble in water; practically
insoluble in ethanol (95%)
Storage: Store in tightly-closed, non-metallic containers.
STANDARDS
Zinc Sulphate contains not less than 99.0 per cent and not more
than 104.0 per cent of ZnSO4,7H2O.
Identification, pH,Clarity and colour of solution, Arsenic,Chloride
Assay: Weigh accurately about 0.5 g and dissolve in 5 ml of 2M
acetic acid and dilute to 50 ml with water. To the resulting
solution add about 50 mg of xylenol orange triturate and
sufficient hexamine to produce violet-pink colour. Add a further 2
g of hexamine and titrate with 0.1M disodium edetate until the
colour changes to yellow. Each ml of 0.1M disodium edetate is
equivalent to 0.02875 g of ZnSO4,7H2O.
ZINC SULPHATE EYE DROPS IP
Zinc Sulphate Eye Drops are a sterile solution containing 0.25%
w/v of Zinc Sulphate in Purified Water.
Storage: Store in well-closed containers of glass or any other
suitable material and sealed so as to exclude micro-organisms.
STANDARDS
Zinc Sulphate Eye Drops contain not less than 0.22 per cent and
not more than 0.28 per cent w/v of zinc sulphate, ZnSO4,7H2O.
Description: Clear, colourless solution.
ZINC CHLORIDE IP: ZnCl2, Mol. Wt. 136.29
Category: Pharmaceutical aid (for insulin preparations).
Preparation: It can be prepared from Zinc oxide or Zinc metal
by reacting with dilute HCl, concentrating, purifying and
crystallizing.
Description: White or practically white, crystalline powder;
odourless; very deliquescent.
Solubility: Very soluble in water; freely soluble
in ethanol (95%) and in glycerin.
Zn + 2 HCl ZnCl2 + H2 (g)
ZnO + 2 HCl ZnCl2 + H2O
Storage: Store in tightly-closed, non-metallic containers.
STANDARDS
Zinc Chloride contains not less than 95.0 per cent and not more
than 100.5 per cent of ZnCl2.
Identification, Ph, Aluminium, calcium, heavy metals, iron and
magnesium, Ammonium salts, Oxychloride, Sulphate.
Assay: Weigh accurately about 3 g, dissolve in 125 ml of water,
add 3 g of ammonium chloride and add sufficient water to
produce 250.0 ml. To 25.0 ml of the resulting solution add 100 ml
of water and 10 ml of strong ammonia-ammonium chloride
solution. Titrate with 0.1M disodium edetate using eriochrome
black T solution as indicator until a deep blue colour is obtained.
Each ml of 0.1M disodium edetate is equivalent to 0.01363 g of
ZnCl2.
Antimicrobials:
There are several terms used in describing antimicrobial
activity based on their specific aspect of their activity.
Antiseptics- Agents which either kill or inhibits the growth of
microbes (Bacteria, fungi, protozoa).
However the term is used only for those agents used against
microbes growing on human being specifically or living
tissues in general.
Germi “cide”: Agents which kills microbes. Ex: Bactericide,
fungicide etc. Those agents which do not
kill microbes but function by inhibiting
their growth is “stats”, Bacteriostat,
fungistat etc.
Disinfectants: have similar action as that of germicides. The
usage differ in that it is applied to those
agents which are used on inanimate objects.
Ex: instruments, rooms, equipments etc.
Sterilization: Use of a disinfectant or other procedure to
render an object completely free from microorganisms.
Mechanism of action:
Inorganic antimicrobials act by 3 ways;
1. Oxidation
2. Halogenation and
3. Protein precipitation
based on the primary chemical interaction occur between
the agent and the microbial protein. This results in the death
of the microbe or inhibition of its growth.
Oxidation:
Non metals and certain molecules like H2O2, metal
peroxides, permanganates and halogens reduces the groups
present in the most proteins like sulfhydril group of
Cysteine.
SHHS S
S
PROTIEN PROTIEN
The specific function of the protein or enzymes is altered
because of the alteration in the confirmation of the structure
which is due to the disulphide bridge and there by alter its
function.
This leads to the destruction of microbes.
Halogenation: Antiseptics like hypochlorites bring about
chlorination of primary and secondary amines.
R C
O
NH2
It is expected that similar reaction take place even on the
peptide linkage of protein molecules. The reaction is
ultimately destructive to the function of specific protein.
C
O
NPROTIEN
H
PROTIEN
C
O
NPROTIEN
Cl
PROTIEN
OCl-
Protein precipitation:
Interaction of protein with metallic ions having high
electrostatic fields.
Transition Metal cations like Ag, Cu, Zn and Al (Gp IB, IIB,
IIIA) are the examples.
Most metal cat ions with the exception of alkali and alkaline
earth metals have the property of protein precipitation.
Various polar groups of the proteins act as a ligand and are
complexed with the metals ions which results in the radical
change in the properties of the protein or precipitation of
protein.
PROTEIN
SN
M+H
HH
HYDROGEN PEROXIDE SOLUTION (20 VOL) IP
Hydrogen Peroxide Solution (6%); Dilute
Hydrogen Peroxide Solution
Hydrogen Peroxide Solution (20 Vol) is an aqueous solution
of hydrogen peroxide. It may contain a suitable stabilizing
agent.
Category: Antiseptic; deodorant.
Preparation: On small scale it is prepared by the action of
dilute acids on metal peroxides like barium peroxides or
sodium peroxide.
In first two cases, the insoluble barium salts were taken out
by filtration. In the last case hydrated sod. Sulphate
crystallizes and can be easily separated.
BaO2 8H2O + H2SO4 BaSO4 (s) + 8 H2O + H2O2
BaO2 8H2O + CO2BaCO3 (s) + 7 H2O + H2O2
Na2O2 + H2SO4 + 10 H2O Na2SO4. 10 H2O + H2O2
On large scale, electrolysis of 50% sulphuric acid or
ammonium hydrogen sulphate gives persulphuric acid
which can be decomposed easily by heat, liberatinf
hydrogen peroxide which is recovered by distillation under
reduced pressure.
2H2SO4 H2S2O8 + H2 (g)
H2S2O8 + 2H2O 2H2SO4 + H2O2
Description: Clear, colourless liquid; odourless.
It decomposes in contact with oxidisable organic matter and
with certain metals and also if allowed to become alkaline.
Storage: Store in light-resistant containers resistant to
hydrogen peroxide in a cool place. If the solution does not
contain a stabilising agent, it should be stored at a
temperature below 15o. It should not be stored for long
periods.
Labelling: The label states whether or not the solution
contains a stabilising agent.
STANDARDS
Hydrogen Peroxide Solution (20 Vol) contains not less than
5.0 per cent w/v and not more than 7.0 per cent w/v of H2O2,
corresponding to about 20 times its volume of available
oxygen.
Identification; Acidity:
Assay: To 1.0 ml add 20 ml of 1M sulphuric acid and titrate
with 0.02M potassium permanganate. Each ml of 0.02M
potassium permanganate is equivalent to 0.001701 g of
H2O2 or 0.56 ml of oxygen.
HYDROGEN PEROXIDE SOLUTION (100 VOL) IP
Hydrogen Peroxide Solution (27%); Strong Hydrogen
Peroxide Solution
Hydrogen Peroxide Solution (100 Vol) is an aqueous
solution of hydrogen peroxide. It may contain a suitable
stabilising agent.
Description: Clear, colourless liquid; odourless.
It decomposes vigorously in contact with oxidisable organic
matter and with certain metals and also if allowed to become
alkaline.
Storage:
Store in light-resistant containers resistant to hydrogen
peroxide in a cool place. If the solution does not contain a
stabilising agent, it should be stored at a temperature below
15 degree C
Labelling: The label states whether or not the solution
contains a stabilising agent.
Sodium perborate:
NaBO3. 4H2O or NaBO2. H2O2 . 3H2O, MW=153.86
Sodium perborate is a white, odorless, water-soluble.
Sodium perborate is manufactured by reaction of sodium
tetraborate (borax), hydrogen peroxide and sodium
hydroxide.
Perborate is not just an addition compoundof peroxide, but
contains true peroxygen bonds. This makes the material
more stable, safer for handling and storage.
The monohydrate form dissolves better than the
tetrahydrate and has higher heat stability; it is prepared by
heating the tetrahydrate.
OB
O
O
Na
Sodium perborate undergoes hydrolysis in contact with
water, producing hydrogen peroxide and borate.
It serves as a source of active oxygen in cleaning products.
Present in some tooth bleaching formulas.
It has antiseptic properties and can act as a
disinfectant.
Preservative in some brands of eye drops.
Sodium perborate releases oxygen rapidly at temperatures
over 60 °C. To make it active at lower temperatures (40-60
°C), it has to be mixed with a suitable activator, typically
tetra acetyl ethylenediamine.
KMnO4 Mol. Wt. 158.03
Category: Antiseptic.
Preparation: It is prepared by heating together potassium
hydroxide and manganese dioxide, in presence of oxygen
to give potassium manganate.
The oxygen may be obtained by air or by potassium
chlorate
4 KOH + 2 MnO2 + O2 2K2MnO4 + 2H2O
The green colored potassium manganate obtained thus is
converted to permanganate by any one of the following
Method.
By passing CO2 through the solution
By passing chlorine gas (better yields)
2 KMnO4 + MnO2 (s) + 2K2CO3
3K2MnO4 + 2 CO2 (g)
2K2MnO4 + Cl2 2KMnO4 + 2 KCl
By electrolytic oxidation of manganate:
The solution obtained by above methods is filtered and
concentrated and crystallized.
2 K2MnO4 + H2O 2 KMnO4 + 2KOH + H2 (g)
Mn
O
O
O
OK
Description: Dark purple or brownish black, granular
powder or dark purple or almost black slender, prismatic
crystals, having a metallic lustre; odourless.
Decomposes on contact with certain organic substances.
Solubility: Soluble in cold water; freely soluble in boiling
water.
CAUTION — Great care should be taken in handling
potassium permanganate as dangerous explosions are
liable to occur if it is brought into contact with organic or
other readily oxidisable substances, either in solution or in
the dry condition.
STANDARDS
99.0-100.5%
Identification: Colour of solution: Chloride: Sulphate: Water-
insoluble matter:
Assay: Weigh accurately about 0.3 g, dissolve in sufficient
water to produce 100.0 ml. To 20.0 ml add 20 ml of water, 1 g
of potassium iodide and 10 ml of 2M HCl and titrate the
liberated iodine with 0.1M sodium thiosulphate using starch
as indicator.
Sodium hypochlorite:
(Dakin’s solution)-Chlorinated soda.
NaOCl, MW=74.44.
Very unstable and available only in solutions.
It is prepared by mixing chlorinated lime and sodium
carbonate solution and kept aside.
After occasional shaking and filtration a clear solution of
chlorinated soda is obtained.
2 CaCl(OCl) + Na2CO3 2 NaOCl + CO2 2 CaCl2
The solution is alkaline and unstable.
Addition of boric acid neutrlises the alkali with a buffering
action (surgical solution of chlorinated soda-Dakin’s soln).
The chlorine content is 0.5-0.55%.
Used for skin disinfection and as an antiseptic.
Iodine IP; I2, Mol. Wt. 253.81
Category: Antiseptic; used in the treatment of thyroid
deficiency.
Description: Grayish violet brittle plates or small crystals
with a metallic sheen; odor, irritant. It volatilizes slowly at
room temperature.
Preparation:
widely distributed in nature but in small quantities.
Sea water contains minute traces of combined iodine and
are absorbed by marine plants.
Nitrate minerals from Chile saltpeter (NaNO3) contain good
amounts of Iodates from which iodine can be obtained
(0.2%).
Most sea weeds contain iodine (highest in dried stems of
Laminaria digitata (up to 0.5%).
Dried sea weeds are burned and the ash or kelp is extracted
with water.
Sulphates and chlorides of potassium and sodium are
separated from this extraction by concentration and
crystallization.
By the addition of sulphuric acid, small quantities of
sulphides and thiosulphates present are decomposed to
give sulphur.
This acidic solution containing the freely soluble iodides
and small portions of bromides and chlorides is treated with
correct proportion of chlorine.
The precipitated iodine is collected and purified by
sublimation with a small amount of KI. (makes free from ICl,
IBr and traces of ICN).
The solution left behind after the recovery of nitrates from
Chile saltpeter, contains sodium iodate.
Addition of sodium bisulphite causes liberation of free
iodine which is then precipitated and purified by
sublimation.
The advantage here is the iodine has very less impurity.
Solubility: Soluble in chloroform and in ethanol (95%);
slightly soluble in glycerin; very slightly soluble in water.
Very soluble in concentrated solutions of iodides.
Storage: Store in ground-glass-stopper containers or in
earthenware containers with waxed bungs.
2 NaIO3 + 5 NaHSO3 2 Na2SO4 + 3 NaHSO4 + I2 (s) +H2O
STANDARDS
99.5- 100.5 of Iodine
Identification: Bromides and chlorides: Non-volatile matter:
Assay: Weigh accurately about 0.2 g, transfer to a flask
containing 1 g of potassium iodide and 2 ml of water, add 1
ml of 2M acetic acid, dissolve completely and add 50 ml of
water. Titrate with 0.1M sodium thiosulphate using starch
solution as indicator. Each ml of 0.1M sodium thiosulphate
is equivalent to 0.01269 g of I.
IP 96- no official solutions.
Strong solution of Iodine (strong tincture of iodine)
10%w/v of iodine and 6%w/v KI in alcohol.
Weak solution of Iodine (weak tincture of iodine)-
2.5%w/v each of iodine and KI in alcohol.
Aqueous solution of iodine (Lugol’s solution)- 5% w/v of
iodine and 10% w/v of KI in water.
Mandl’s paint- 1.25% w/v of iodine in glycerine.
POVIDONE-IODINE IP
A complex produced by interaction between
iodine and poly(2-oxopyrrolidin-1-ylethylene).
Category: Topical anti-infective; antiseptic.
Description: Yellowish brown amorphous powder; odour,
slight and characteristic of iodine.
Solubility: Soluble in water and in ethanol (95%); practically
insoluble in chloroform, in acetone and in ether.
N
HC CH2
OxI
Storage: Store in tightly-closed, light-resistant containers.
STANDARDS: 9.0-12.0 % of available iodine, calculated with
reference to the dried substance.
POVIDONE-IODINE SOLUTION IP
A solution of Povidone-Iodine in Purified Water.
It may contain a small amount of ethanol.
Usual strengths: 5% w/v; 7.5% w/v; 10% w/v.
Description: Deep brown liquid; odour, characteristic of
iodine.
Storage: Store in tightly-closed, light-resistant containers.
Labelling: The label states the quantities of iodine and
ethanol (if present) as percentages w/v.
STANDARDS: Povidone-Iodine Solution contains not less
than 85.0 per cent and not more than 120.0 per cent of the
stated amount of iodine, I.
BORIC ACID IP, H3BO3 , Mol. Wt. 61.83
Category: Local anti-infective.
Description: White, crystalline powder or colourless shiny
plates unctuous to the touch or white crystals; odourless.
Preparation: It is obtained naturally in volcanic jets of steam
which condenses naturally or artificially to get the liquid.
This is concentrated and cooled to crystallize boric acid.
It is also prepared by decomposing native borates with
sulphuric acid.
In lab it involves the process of addition of concentrated
sulpuric acid and water to a hot solution of borax in water.
Solubility: Soluble in water and in ethanol (95%); freely
soluble in boiling water, in boiling ethanol (95%) and in
glycerin.
Storage: Store in well-closed containers.
Labelling: The label states that it is not meant for internal
use.
Na2B4O7 + H2SO4 + 5 H2O Na2SO4 + 4 H3BO3
STANDARDS
99.5- 100.5 % of H3BO3.
Identification: pH: Clarity and colour of solution: Solubility
in ethanol: Arsenic: Heavy metals: Sulphate: Loss on drying:
Assay: Weigh accurately about 2 g, dissolve in a mixture of
50 ml of water and 100 ml of glycerin, previously neutralized
to phenolphthalein solution. Titrate with 1M sodium
hydroxide using phenolphthalein solution as indicator. Each
ml of 1M sodium hydroxide is equivalent to 0.06183 g of
H3BO3.
Borax, Sodium borate, Na2B4O7
The Crude borax or sodium pyroborate occur
in deposits from inland lakes in Tibet and India.
Good amount of borax is obtained by calcium borate
(Colemanite) in North America by a process called double
decomposition with sodium carbonate.
It is also obtained from Kernite by re crystallization from
water.
A 2.6% soln is isotonic with body fluid. Also used as
bacteriostatic.
SILVER NITRATE IP
AgNO3, Mol. Wt. 169.87
Category: Local anti-infective and antibacterial at a
concentration of 0.5-1% (the action is mainly due to silver
ions).
Description: Colorless crystals or white, crystalline powder;
odorless.
Preparation: It is prepared by the action of fairly
concentrated, hot nitric acid with metallic silver.
The solution is evaporated to dryness and the residue is
heated to expel all nitric acid. The product is then
recrystallised from water.
Solubility: Very soluble in water; soluble in ethanol (95%).
Storage: Store in tightly-closed, light-resistant, non-metallic
containers.
Ag + 2 HNO3 AgNO3 + NO2 + H2O
STANDARDS
99.0- 100.5% AgNO3.
Identification: Acidity or alkalinity: Clarity and colour of
solution: Aluminium, bismuth, copper and lead: Foreign
salts:
Assay: Weigh accurately about 0.3 g, dissolve in 50 ml of
water, add 2 ml of 2M nitric acid and 2 ml of ferric
ammonium sulphate solution and titrate with 0.1M
ammonium thiocyanate until a reddish yellow color is
produced. Each ml of 0.1M ammonium thiocyanate is
equivalent to 0.01699 g of AgNO3.
Toughened silver nitrate:
This is prepared by melting silver nitrate with small portion
of potassium nitrate or with about 4% of HCl and pouring the
fused mass into cylindrical or conical silver or platinum
moulds.
The rods or cones so formed have the caustic property
associated with silver nitrate, but are less brittle than the
pure substance.
Mild silver protein
The silver is rendered colloidal by protein in which NLT 19%
and NMT 23% Ag is present.
Black shining scales, odorless, hygroscopic, light sensitive.
Freely soluble in water, insoluble in ethanol. When dissolved
in water forms a colloidal solution.
They devoid of irritation or stringent action as shown by
silver salts. This allows them to be applied to sensitive areas
and mucus membranes.
Solutions of 5-20%w/v is antibacterials.
Sulphur: S MW=32.02:
Widely distributed in nature both free and as sulphides and
sulphates of many metals.
Free sulphur occurs deep underground.
For pharmaceutical purposes sulphur can be purified by
sublimation of sulphur.
Sublimed sulphur (flowers of sulphur) is practically
insoluble in water and alcohol and sparingly soluble in olive
oil.
Precipitated sulphur-
On a small scale it may be obtained in a very pure form by
precipitation from its salts by reduction or by acidifying
thiosulphates.
Both variety can be easily distinguished by solubility in CS2
where sublimed sulphur is soluble up to 80% and
precipitated is completely soluble.
Both the forms are used as scabicides (lotions or
ointments).
It is also used in the treatment of seborrhea (abnormal
secretion of sebum from sebaceous gland giving an oily or
scaly appearance to the skin), acne and psoriasis.
Along with glycyrrhia globra it is mild laxative.
Selenium sulphide/selenium disulphide: SeS2 143.09,
contain NLT 52% and NMT 55.5% of selenium.
Bright orange powder, practically insoluble in water and
organic solvents.
It is prepared by adding selenious acid solution to a solution
of aluminium chloride saturated with H2S, meanwhile
continuing the passage of the gas.
Aluminium chloride acts as a coagulant. The precipitate of
SeS2 is filtered off , washed and dried.
H2SeO3 + 2H2S SeS2 + 3H2O
ZINC UNDECENOATE, Zn++ (CH2=CHCH2(CH2)7COO -)2
C22H38O4Zn, MW.- 431.92, Zinc undecylenate
Zinc Undecenoate is zinc di(undec-10-enoate).
Category: Antifungal (topical).
Description: White or almost white, fine powder.
Solubility: Practically insoluble in water, in ethanol (95%)
and in ether.
Preparation: It is prepared by reacting ZnO with undecenoic
acid.
STANDARDS
98.0-102.0% C22H38O4Zn.
Identification: Alkalinity: Alkalis and alkaline earths:
Sulphate: Degree of unsaturation: Loss on drying.
CH2=CH(CH2)8COOH [CH2=CH(CH2)8COO]2 Zn
ZnO
Assay: Weigh accurately about 0.35 g, add 25 ml of 2M
acetic acid, heat to boiling, cool and dilute to 50 ml with
water. Add about 50 mg of xylenol orange triturate and
sufficient hexamine to produce a violet-pink colour. Add a
further 2 g of hexamine and titrate with 0.1M disodium EDTA
until the colour changes to yellow. Each ml of 0.1M
disodium edetate is equivalent to 0.04319 g of C22H38O4Zn.
ZINC UNDECENOATE OINTMENT,
Zinc Undecylenate Ointment
20% w/v of Zinc Undecenoate in a suitable ointment basis.
STANDARDS
18.0-22.0% of C22H38O4Zn, 4.5-5.5 per cent of free
undecenoic acid, C11H20O2.
Other requirements: Complies with the requirements of tests
stated under Ointments.
Assay: ?????!!!!!
For zinc undecenoate — Weigh accurately about 2 g, add 20 ml
of dil. HCl and boil under a reflux condenser for at least 20
minutes or until the fatty layer is clear.
Filter while hot and wash the residue with hot water. Cool the
combined filtrate and washings, neutralise to litmus paper with dil.
Ammonia, add 3 ml of dil. HCl and 5 g of hexamine and titrate
with 0.05M disodium edta using xylenol orange solution as
indicator, until the colour changes to yellow. Each ml of 0.05M
disodium edetate is equivalent to 0.02160 g of C22H38O4Zn.
For free undecenoic acid —
Weigh accurately about 5 g, add 100 ml of dil. HCl and heat to
70degree C with constant stirring. Cool and transfer to a
separator with the aid of four quantities, each of 25 ml, of ether
and add the rinsings to the mixture in the separator. Dilute the
aqueous phase to 300 ml, saturate it with sodium chloride and
shake the mixture. Transfer the aqueous layer to a second
separator and extract with another 100 ml of ether. Wash the
combined ether extracts with successive quantities, each of 10
ml, of water until the washings are free from chloride.
Transfer the ether solution to a beaker and evaporate on a water-
bath to about 5 ml. Add 20 ml of carbon tetrachloride, mix,
transfer the mixture to a small separator and drain the carbon
tetrachloride layer into a 100-ml volumetric flask. Rinse the
beaker with three quantities, each of 5 ml, of carbon tetrachloride
and transfer the rinsings to the volumetric flask, dilute to volume
with carbon tetrachloride and mix. Evaporate 50.0 ml of the
resulting solution to about 5 ml, add 100 ml of ethanol (95%),
previously neutralised, and 0.15 ml of phenolphthalein solution
and titrate the total undecenoic acid with 0.1M sodium hydroxide.
Each ml of 0.1M sodium hydroxide is equivalent to 0.01843 g
of C11H20O2.
Calculate the content of free undecenoic acid from the difference
between the total undecenoic acid and the undecenoic acid
equivalent to the determined zinc undecenoate (the content of
zinc undecenoate multiplied by 0.8533 gives the equivalent of
undecenoic acid).
