Critical Considerations

(Topical Agents)
Why non-systemic nature is desirable for topical agents?

Ans. The term “topical” is generally placed for use of compounds

on body surfaces, which are devoid of systemic absorption and
distribution in various organs and tissues. Penetration into deep
tissues in many instances gives benefit to wounds below skin but
in other hand systemic effects of many of these compounds may
elicit toxic or allergic manifestations depending upon amount
absorbed. Eg. Topically applied mercury containing compounds
will react with polar groups on many amino acids nonspecifically
that are not desired and toxic thereby.
 What are the general uses of topical agents? Classify them with
examples.
Ans. The term “topical” is generally placed for use of compounds on body
surfaces, which are devoid of systemic absorption and distribution in various
organs and tissues. It should be stated further that topical application of
drugs may be accomplished within body cavities that open to the outside (eg.
Oral, vaginal and colonic cavities). This type of application is done with the
expectation that the compound will exert local or surface activity. But it
should be kept in mind that systemic absorption from these areas is more
extensive than the skin surface.
Topical agents are broadly classified in mainly categories

a. Protectives (Talc, insoluble Zinc compounds, TiO2, AlCl3.

6H2O, Silicon polymers) Topical protectives and adsorbents are
usually applied to areas of skin with constant irritation or areas
which have already irritated or inflamed due to friction, allergy
and the like.
b. Antimicrobials (H2O2 solution, KMno4 solution, Iodine
solution, Silver Nitrate) and astringents (alum, soluble Zinc
compounds, white lotion etc)
 What are the problems associated with Talc/ Talcum powder?
Ans. Talc, when used in broken skin (wounds and surgical incision)
can produce sterile abscesses or granuloma (a nodule of inflamed
tissue, in which granulation is occurring). It precludes use of talc on
surgical gloves, absorbable dusting powders are now recommended
for this purpose. No problems are associated with use of talc on the
intact skin.
Baby powder is used to keep babies dry and comfortable. It is
important to use baby powder properly. The powder easily floats into
the air. It can get into babies eyes. Breathing problems are the most
common problem. It may cause cough, eye and throat irritation.
Diarrhea, vomiting, skin rash, shedding (sloughing), twitching of
arms, hands; legs, feet and facial muscle is not uncommon. We
should not use baby powder when a child has broken skin resulting
from a diaper rash. Doing so can cause the rash to become inflamed
and infected.
 How we can use of talc as a filtering or distributing agent?
Ans. The insoluble and inert nature of talc, including its non-
absorbable properties renders the material useful as a filtering aid.
The best particle size for this purpose is 80/100 mesh i.e. the powder
that will pass through a no. 80 sieve but not a no. 100 sieve. Powder
finer than this will not be retained by usual filter papers and filtered
preparations will appear cloudy. Pharmaceutical preparations where
this phenomenon is common are aromatic waters, Mg-citrate
solutions, aromatic elixir, orange syrup etc.
 How official Calamine is obtained? Mention its areas of use
in detail.
Ans. The term calamine also describes impure naturally obtained
Zinc carbonate. The official calamine is obtained by calcinations
(powdered by heating) of the natural ore. The calcined product is
then passed through a 100-mesh sieve to obtain the finely powdered
material necessary for good cohesive and adhesive properties.
Use of official Calamaine USP
Official Calamine USP is a topical protective and anti-pruritic (itch guard) used
for minor skin irritation (itching, pain and discomfort) including poison ivy,
poison oak and poison sumac (Contact dermatitis, is an inflammation of the
skin caused by direct contact with an irritating substance). Calamine is used in
dusting powders, ointments and lotions (Calamine Lotion USP). It is applied
over skin surface for its soothing, adsorbent and protective properties. It has the
advantage over ZnO is that it has better cosmetic acceptability. Calamine
Lotion USP contains equal quantities of Calamine and ZnO suspended with
the aid of Bentonite magma (a smectite, a type of clay phyllosilicate mineral
that tends to swell when exposed to water) in a solution of Ca(OH)2. It has
good drying effect and mild astringent action. Phenolated Calamine Lotion USP
provides a local anesthetic effect and anti-pruritic action.
 Deduce solubility profile of Zinc stearate? What competitive
advantages it has over talc and other topical protectives?
Ans. Zinc stearate [Zn{C18H35O2}2] is a zinc soap that repels water. It is
insoluble in polar solvents such as alcohol and ether but soluble in aromatic
hydrocarbons (e.g., benzene and chlorinated hydrocarbons) when heated. It
contains 12.5% to 14% ZnO. It can be hydrolyzed by heating in dilute
mineral acids to form soluble mineral salt and insoluble stearic or palmitic
oily layer. It is neutral to moistened litmus paper.
Competitive Advantage
It has mild astringent and antimicrobial properties. It is employed in
dusting powders and ointments as protective. It has particular
advantage over talc in that it is not wetted by moisture and also repels
water. It makes Zn-stearate more desirable in healing dermatological
problems where large amounts of fluids are exuded because it will not
form crusty patches over the areas being treated. Since Zn-stearate
dust inhalation may cause pulmonary inhalation, its routine use in
infants and children is strongly discouraged.
 How TiO2 provides UV protection to be used as a sun screen?
Ans. Titanium dioxide (TiO2) has good ultraviolet (UV)-blocking power and
is very attractive in practical applications because of such advantages as non-
toxicity, chemical stability at high temperature, and permanent stability
under UV exposure, for example. Regular titanium dioxide is highly stable
under most conditions. The USP classifies it as a topical protective. The
protection is primarily for its opacity due to high refractive index (2.7).
Whereas the chemical sun screen agents like PABA acts chemically to absorb
UV radiations. As a solar ray protective it is used in a conc. 5% to 25% in
ointments and lotions. Like zinc oxide, it is an anti-irritant or skin protector.
However, since it is not absorbed into the skin, this effect may not be an issue
in topical use on unbroken skin. It is also used as a white pigment in
cosmetics and paints.
Caution
Titanium dioxide nano-particles appear to have much greater
photocatalytic activity than regular titanium dioxide powder and
might trigger formation of harmful free radicals when exposed to
sunlight. Most manufacturers of titanium dioxide nanoparticles coat
them to reduce or eliminate such effects.
 Why official Aluminum paste is used around intestinal fistulae and
colostomy opening after surgery of intestinal cancer?
Ans. Aluminum is present in 10% in aluminum paste USP. It is used as a
protective to prevent irritation around intestinal fistula (an abnormal opening
of the intestinal tract through the skin). The skin surrounding the fistula
opening is exposed to intestinal contents, leading to excoriation and
breakdown. Skin protection is an important part of fistula output control.
Skin protectants (eg, zinc oxide cream, aluminum paste, karaya gum powder,
tincture of benzoin) are used to liberally coat skin that is exposed to intestinal
contents. Similar protection is provided while applied around the colostomy
opening after surgery for intestinal cancer. The aluminum protects the skin
from digestive action of intestinal tract.
 Give general mechanism played by the Astringents.
Ans. The application of a very dilute solution of a metal cation to tissue
primarily provides a local or surface protein precipitation action. They are
protein precipitants with limited penetrating power. Being a surface
phenomenon, it does not usually result in the destruction of host tissue. The
effect can be generally described as shrinkage or firming of the tissue. For
example, astringents will cause the constriction of the capillaries and small
blood vessels; hence they are used as styptics to stop bleeding from small cuts.
Astringents are also used to reduce the volume of exudates from wounds and
skin eruptions. When applied topically to the wound, astringents may actually
stimulate the growth of new tissue. Higher conc. will create irritation and
further increase in conc. may impart corrosive effects. This corrosive effect can
be used to advantage in the removal of undesirable tissue (eg. Warts).
 What are the 4 general pathological conditions where astringents are
used?
Ans. Astringents in therapeutic use, beside anti-microbial actions, are also
capable of being used safely for their effects on human proteins.
Stypic: to stop bleeding from small cuts by promoting coagulation of blood and
constricting small capillaries.
Antiperspirant: to decrease secretion of perspiration by constricting pores at the
surface of the skin.
Anti-inflammatory: restriction of blood supply to the surface of the mucus
membranes as a means of reducing inflammation.
Unwanted tissue removal: direct action on skin to remove unwanted tissue (eg.
warts). It requires higher conc. or a stronger protein precipitant, sometimes
termed as corrosive.
 Give examples to control action of astringents through

a. Concentration change b. Altering solubility profile c. Complexation with ligands

Ans.
a. Concentration change: in case of water soluble compound, activities can be
controlled by concentration change for the desired use. These concentrations will vary
depending upon area of use (eg. Higher concentrations for skin rather than eye). The
various dosage forms and concentrations are formulated according to their use as
astringent or antiseptic and the area of application (eg. Skin, mouth, ear, eye).
b. Altering solubility profile: Insoluble ZnO acts as a protective but soluble ZnSO4 is an
astringent. Soluble compounds may also be controlled by placing them in a vehicle (eg.
H2O2 in solution containing glycerin or PEG) which would slower their release to the
site of action. Ointments are best example for controlled release of antimicrobial agents.
c. Complexation with a ligand: PV-I complex provides controlled release than other
Iodine preparations used as antimicrobial, minimizing toxicity and activities in host cell.
 What factors lead to instability of H2O2? What are the physicochemical
measures we can take to make it stable?
Ans. Hydrogen peroxide USP contains 2.5g to 3.5 g H2O2 in 100ml where
preservatives can be added up to 0.05%. The solution usually deteriorated upon
standing or protracted agitation, rapidly decomposed whenever comes in
contact with many oxidizing and reducing agents. It is unstable on prolonged
exposure to light and may decompose suddenly when rapidly heated. Although
unstable but it decomposes very slowly in pure form. When heated to 1000C,
pure explosively to form water and O2. Small amount of contaminants like di-
or polyvalent Cr, Fe, Cu, Hg will catalyze decomposition. Since aluminum does
not act as a catalyst, it can be stored in Alu-containers.
Complexing or chelating agents are frequently used to stabilize H2O2 solutions
(acetanilide, quinidine sulfate and 8-hydroxyquinoline) in conc. ranging from
0.02% to 0.05%. These compounds will chelate trace amounts of polyvalent
metals thereby making them unavailable to catalyze decomposition.
Many adsorbents (alumina/silica) will remove impurities from H2O2 solution.
Like complexing agents they made polyvalent metals unavailable that
destabilize the solution.
 Justify use of H2O2 in following areas
Antiseptic ii. Cleansing iii. Bleach iv. Mouthwash
v. Vaginal douche vi. Oral infections
Ans. Therapeutic uses of H2O2 are dependent upon its decomposition by
enzyme catalase and it will react to either oxidizing or reducing agents
depending upon the chemical environment.
Antiseptic: The primary use of Hydrogen peroxide is as a mild oxidizing
antiseptic. This action is produced when the solution comes in contact with
open or abraded tissue, exposing to the enzyme catalase, which breaks H2O2 to
water and O2. The O2 acts as an oxidizing agent on bacteria, providing
antiseptic actions on organisms (E. coli, Staphylococcus aureus, typhoid bacilli)
obliged to survive through anaerobic metabolism.
Cleansing: Mechanical cleansing action by the foaming release of oxygen. The
antiseptic action does not penetrate below the surface to which it is applied, the
surface action is fleeting (transitory). The effervescent action aids in the
removal of dirt, bacteria and the debris from the surface of the wound or
difficult to reach areas like ear canal.
Oral infections: Urea peroxide (H2N-CO-NH2. H2O2) is a comparatively
stable crystalline compound containing 34% H2O2. When placed solutions in
anhydrous 4-10% glycerin, stabilized with 0.1% 8-hydroxyquinoline, provides
more pronounced and more prolonged antiseptic properties than traditional
aqueous solutions of H2O2. Products of this type are preferable in the treatments
of infections in oral and ear cavity.
Bleach: 1ml of H2O2 solution will liberate 10ml of O2 at standard temperature
and pressure (official solution 3% H2O2 is a 10 volume solution). Extending this
further, a 6% H2O2 (20 volume) solutions used as hair and fabric bleach. Bleach
is a chemical that can remove or lighten color, usually via oxidation. Oxidizing
bleach works by breaking the chemical bonds of a chromophore (part of a
molecule that has color). This changes the molecule so that it either has no
color or else reflects color outside the visible spectrum. Low concentrations of
hydrogen peroxide will chemically bleach many types of clothing to a pinkish
hue. Caution should be exercised when using common products that may
contain hydrogen peroxide, such as facial cleaner or contact lens solution,
which easily splatter (a splash of liquid) upon other surfaces.
Mouthwash, face-wash and athlete’s foot: The FDA has only approved the
use of 3% food grade hydrogen peroxide as a mouthwash. Listerine is a brand
of antiseptic mouthwash. Its original formula has a notoriously strong flavor,
although variations have been released that are marketed as tasting milder,
advantages over generic H2O2 is better taste because of its volatile oil content.
The product is marketed under the slogan "Kills germs that cause bad breath".
4.5% Hydrogen peroxide can be used in a foot bath for athlete's foot, bunions,
corns, plantar warts and general foot health. Diabetics have found relief from
circulation problems by soaking their feet in this solution.
Vaginal douche: The word "douche" means to wash or soak in French. Douching
is washing or cleaning out the vagina (birth canal) with water or other mixtures of
fluids. Most douches are prepackaged mixes of water and vinegar, baking soda, aq
solutions of H2O2 or iodine. Women douche because they mistakenly believe it
gives many benefits. Women who douche say they do it to: Clean the vagina,
Rinse away blood after monthly, Get rid of odor, Avoid sexually transmitted
infections (STIs), Prevent pregnancy. Douching can change the delicate balance of
vaginal flora (organisms that live in the vagina) and acidity in a healthy vagina.
One way to look at it is in a healthy vagina there are both good and bad bacteria.
The balance of the good and bad bacteria helps maintain an acidic environment.
Any changes can cause an over growth of bad bacteria which can lead to a yeast
infection or bacterial vaginosis. Plus, if an individual has a vaginal infection,
douching can push the bacteria causing the infection up into the uterus, fallopian
tubes, and ovaries.
 Describe cautionary measures we should take during handling
KMnO4?
Ans. Chemically KMnO4 is a strong oxidizing agent both in dry state and in
solution. The USP gives a cautionary statement therefore “observe great care in
handling KMnO4, as dangerous explosions may occur if it is brought in contact
with organic or other readily oxidizable substances, either in solutions or in dry
state”. The compound in the dry state forms explosive mixtures with charcoal
and will produce fire when mixed with glycerin. It will also oxidize alcohol.
 What are the major shortcomings that limit use of KMnO4 as topical
astringent or antimicrobial?
Ans. The antibacterial action of KMnO4 is its dependent upon its oxidation of
protein or other bioorganic substances. The oxygen released is the effective
agent. The MnO2 formed as the permanganate is reduced leaves a brown stain
on skin.
Moreover it oxidizes all organic matters (non-selective). Its activity on MOs is
decidedly diminished in presence of extraneous organic substances.
Also A.M.A Drug Evaluations indicate that wet dressings inactivation of the
permanganate by the dressing materials.
KMnO4 can be used as antibacterial and antifungal but short duration of action
and low penetration power, unsightly staining of skin limit its use in these
areas.
 What are the instances where Tincture iodine, Iodine solutions or PV-I
individually gives specific advantages over others if used topically?
Ans. Iodine solution NF and Tincture Iodine USP both contain 1.8g to 2.2g Iodine and
2.1g to 2.6g of NaI in 100ml volume. They differ only in the solvent profile, Iodine
solution is aqueous and Iodine tincture has 50% alcohol as final solvent. PV-I NF is a
complex of Iodine in povidone, contains 9-12% available Iodine.
Iodine solution NF and Tincture Iodine USP both are probably the most effective topical
antiseptic agents available, they have been used as antiseptics on skin prior to surgery.
But Tincture Iodine is more suitable in this purpose due to wetting or spreading effect,
providing some better antibacterial effect. Also it is used to disinfect drinking water,
treatment of suspected supplied water with 3 drops per quart to kill amoebae and
bacteria within 15 minutes. At higher conc. Iodine tincture can disinfect household with
evaporation nature of alcohol.
A.M.A Drug evaluations recommends against use of Iodine Tincture on tissues.
Iodine solution is preferred for application on wounds as alcohol is irritating to
open tissues. Solutions are recommended for surgical scrubs and for
preoperative antisepsis of the skin.
PV-I complex has been used in mouthwashes and gargles for the treatments of
infections in oral cavity (Vincent’s angina). The major advantage of PV-I over
elemental solutions includes its non-irritating nature, comparatively less oral
toxicity, water solubility and low Iodine vapor pressure making it stable to
possible Iodine loss. PV-I complex is also non-staining and can be washed clear
from skin and clothing. Products available under trade names Betadine® and
Isodine®.
 Define Iodophores with their general mode of action.
Ans. Iodophores are mixture of Iodine with surface active agents (eg. PVP) that
act as a carrier and solubilizers of Iodine. Iodine is released slowly from the
complex. Iodophores posses the germicidal characteristics of Iodine and have
additional advantage of non-staining and low irritating properties. Iodine also
posses sporicidal activity; rate of which spores are killed is markedly
influenced by conditions under they are exposed (amount of organic material
and extent of dehydration).
 Mention in detail about the phenomenon “Oligodynamic action” for
Silver Nitrate USP with practical examples.
Ans. The oligodynamic action simply reveals its action in low concentration.
Water distilled through a silver condenser, will remain sterile for longer period
of time. This level of activity can be found in solutions containing 1: 0.2 billion
concentration of silver ion. Solutions of Silver Nitrate are bacteriostatic at
1:30000 and bactericidal at 1:4000 in presence of organic matter. Skin
irritation becomes a factor at concentration above 1:1000. Colloidal silver
preparations bacteriostatic at concentrations of 1:20000 but require 10%
concentration to be bactericidal. It has been used in concentration 1:10000 in
irrigation of urethra and bladder, largely replaced by colloidal silver
suspensions.
 What precondition we need to fulfill for using Silver Nitrate or Zinc
Sulphate as ophthalmic preparations? Mention use of Silver Nitrate in
ophthalmia neonatrum and Wet dressing in burn cases.
Ans. Buffering is most important precondition for using Silver Nitrate or Zinc
Sulphate as ophthalmic preparations. The USP suggests buffering of
ophthalmic Silver Nitrate solution with Na-acetate buffer and states that the pH
should be between 4.5 to 6.0. The solution may be rinsed from the eyes with
normal saline if desired. Similarly Ophthalmic ZnSO4 USP should have a pH
between 5.8 to 6.2 by appropriate borate buffer.
Ophthalmia neonatrum (Neonatal conjunctivitis) that is caused by an infection
with bacteria or viruses can be very serious. Bacteria that normally live in a
woman's vagina also cause neonatal conjunctivitis. .The most common bacterial
infections that can cause serious eye damage are gonorrhea (Neisseria
gonorrhea) and chlamydia (Chlamydia trachomatis), which can be passed from
mother to child during birth. 2 drops of 1% Silver Nitrate USP Ophthalmic
solution placed in each eye of as a prophylactic measure against this neonatal
conjunctivitis. Colloidal silver protein preparations also have major
effectiveness against gonococcal conjunctivitis. This procedure is required by
law in most states of developed countries and may be more effective than
penicillins, which have replaced it in some areas.
 What precautions we need to take before using Selenium? Mention its
role in Selsun®.
Ans. Selenium is toxic in large doses, although appeared to be an important
nutrient at trace amount. It has been employed in 2.5% w/v suspensions in the
treatment of seborrhea dermatitis (dandruff). Selenium sulfide appears to have a
cytostatic effect of the epidermis and follicular epithelium. Since it is not well
absorbed through skin, it is used topically in very limited areas. It should be
kept away from conjunctiva and prolonged contact with skin will produce
contact dermatitis (skin reactions from allergen). Topical application over scalp
is allowed for 5 minutes and then thoroughly washed off. Hands should be
thoroughly washed and fingernails should be meticulously cleaned after using
selenium sulfide.
 Mention use of Boric acid in eye wash and diaper rash.
Ans. Boric acid has been used in solutions, ointments and dusting powders as
antiseptic. It is a weak bacteriostatic agent, non-irritating when applied to skin
and mucus membranes. It is therefore used in ophthalmic preparations as a
buffer and in a saturated solution (about 4.5%) as a bacteriostatic eye wash. The
more concentrated solution should be diluted with equal volume of water
before use. The higher concentration is near saturation and tends to
crystallize with a slight drop of temperature. 5% ointments (Borax®) used as
emollient antiseptic in diaper rash instead of talc powder. The powdered form
of Boric acid is not recommended in infants.
 Why Arsenic compounds are called “Protoplasmic Poisons”.
Ans. Arsenic compounds interact with the sulfhydryl group of groups of
cysteine and other compounds containing the same group (glutathione and
thioglycolic acid) and cause disruption in cellular energy metabolism. That’s
why arsenic compounds are called protoplasmic poisons and distinguishes from
protein precipitants which will interact with many other polar groups on protein
molecules to cause generalized precipitation of albumin and other non-
sulfhydryl containing proteins
 What are the limitations of AlCl2. 6H2O to be used as an anti-
perspirant?
Ans. Deodorants do not prevent sweating, but are helpful in reducing body
odor. Products containing 10% to 20% aluminum chloride hexahydrate are the
first line of treatment for underarm sweating. Some patients may be prescribed
a product containing a higher dose of aluminum chloride, which is applied
nightly onto the affected areas. Aluminum chloride is a local external astringent
and mild antiseptic. It is used in aqueous solution in concentration ranging from
10 to 15%. The solution may be too irritating for sensitive tissues. The
compound may be initially employed as an antiperspirant, but was found to be
too irritating and also damage clothing due in part to the formation of HCl by
hydrolysis.
 What unparallel astringent action lies in ZnCl2? What are its other
uses?
Ans. Zinc Chloride is powerful astringent, beside ability to precipitate protein;
metal portion can interact with many other bacterial enzymes to inhibit their
functions. The strong astringent property makes it useful as an escharotic
(causes sloughing of tissue, aiding in the formation of scar tissue to improve
healing) which is more caustic than astringent action. Zinc Chloride USP
applied as solution containing 0.5 to 2% ZnCl2. The lower concentration may
be applied to mucous membranes and used as a nasal spray in office procedure
to aid drainage from infected sinus. The USP also recognizes it as a
desensitizer of dentin. For this reason 10% solution is applied topically to the
teeth.
 Define the terms acne vulgaris /cystic acne and seborrhea dermatitis.
Mention role of Zinc ion of white lotion NF in these conditions.
Ans: Acne is a skin condition that causes whiteheads, blackheads, and inflamed
red growths (papules, pustules, and cysts) to form. These growths are
commonly called pimples or "zits." The top of the plug may be white
(whitehead) or dark (blackhead).
Seborrheic dermatitis is a common, inflammatory skin condition that
causes flaky, white to yellowish scales to form on oily areas such as the scalp or
inside the ear. It can occur with or without reddened skin.
White lotion NF is a sulfurated potash solution (40g in 450ml of water) slowly
added to a solution of ZnSO4 (40g in 450ml of water) and then adding water to
a volume of 1000ml.
 What is ZPTO? Mention its role and precautions in anti-dandruff
shampoos.
Ans. ZINC PYRITHIONE, also known as Zinc Pyridine-2-Thiol-N-Oxide, has
been established as an effective ANTISEBORRHEIC AGENT. Because of its
limited aqueous solubility it is currently being marketed as a suspension in hair-
cleansing and hair-grooming preparation. A new study proposes that the mode
of action of zinc pyrithione arises from iron starvation of the substrate. Its
antifungal effect is proposed to derive from its ability to disrupt membrane
transport by blocking the proton pump that energizes the transport mechanism.
Have a nice day