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TOPICAL DRUG DELIVERY SYSTEM

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 ISSN: 2277- 7695
CODEN Code: PIHNBQ
ZDB-Number: 2663038-2
IC Journal No: 7725

Vol. 1 No. 9 2012

Online Available at www.thepharmajournal.com

THE PHARMA INNOVATION

Recent Advances In Novel Topical Drug Delivery

System
Debjit Bhowmik1*, Harish Gopinath 1, B. Pragati Kumar1, S.Duraivel1, K.P.Sampath Kumar2

1.Nimra College of Pharmacy, Vijayawada, Andhra Pradesh, India.

2.Department of pharmaceutical sciences, Coimbatore medical college, Coimbatore

Drug delivery systems are methods which are used to ensure that drugs get into the body and reach the
area where they are needed. These systems must take a number of needs into account, ranging from ease
of delivery to effectiveness of the drugs. Several companies specialize in developing methods of drug
delivery, marketing these products to pharmaceutical companies, and other pharmaceutical companies
develop their own systems. Many of these methods are patented and proprietary. When a drug is
administered, the dosage must be carefully calculated so that the body can use the drug, which requires a
drug delivery system which allows for precise dosing. Drug delivery systems also need to consider the
way in which a drug is metabolized by the body. For example, some drugs are destroyed in the intestinal
tract, which means that they cannot be introduced to the body in this way. Others may be dangerous in
large amounts, which means that a time release method should be used to deliver the drug for patient
safety. Topical drug delivery systems involve the introduction of a drug to the surface of the body, in a
formulation which can be absorbed. Skin patches are an example of topical drug delivery systems. Other
systems involve sprays applied to the mucus membranes of the nose, inhalation aerosols, eye drops, or
creams which may be rubbed into the skin. These systems are often very easy for patients to use, which
makes them appealing.In all cases, the goal of a drug delivery system is to get the right dosage to the right
place. Patients tend to prefer methods which are painless and easy, which is why many pharmaceuticals
come in the form of topical and enteral methods which can be taken by mouth or applied directly to the
skin. In clinical environments, perenteral routes can be more common, especially for controlled
substances, because these methods allow for greater control over how and when the drugs are used.
Keyword: Topical Drug Delivery Systems, Skin Patches, Skin Penetration, Localized Drug Delivery System

INTRODUCTION: Topical drug administration Skin is one of the most readily accessible organs
is a localized drug delivery system anywhere in on human body for topical administration and is
the body through ophthalmic, rectal, vaginal and main route of topical drug delivery system. This
skin as topical routes. review is concern with all detail information
regarding rational approach to topical
Corresponding Author’s Contact information: formulations, principles of topical permeation and
Debjit Bhowmik * basic components of topical drug delivery
Nimra College of Pharmacy, Andhra Pradesh, India systems. Overall, the clinical evidence indicates
E-mail: [email protected] that topical gel is a safe and effective treatment

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TPI JOURNAL

option for use in the management of skin related localized target sites in the body. Topically
disease.Topical preparations are applied to the applied dermal and transdermal delivery systems
skin for surface, local or systemic effects. In could replace needles required to administer
some cases, the base may be used alone for its many of the new biologics-based drugs and
therapeutic properties, such as emollient, vaccines, in addition to other significant
soothing or protective action. Many topical advantages such as avoiding first-pass hepatic
preparations, however, contain therapeutically metabolism, gastric degradation and frequent
active ingredients which is dispersed or dissolved dosing. However, the limited dermal and
in the base. The combination of active transdermal delivery of many small and large
ingredients and base provides the opportunity for molecules is a significant challenge because of
a wide range of topical preparations, appropriate the unyielding barrier properties of the skin. This
for many types of drug delivery and therapy paper reviews the application of a novel topical
terms used to classify the bases of topical delivery system, biphasic vesicles built from
preparations in which therapeutically active nanoscale components, to the delivery of several
ingredients are incorporated, may be based on therapeutic agents and vaccine antigens and
their physical properties (suspension) or on their discusses progress toward clinical use
intended use (liniments) or on their composition
((hydrophilic creams).1Skin disease CHALLENGES OF DEVELOPING TOPICAL DRUG DELIVERY
SYSTEM
(dermatological conditions') affects at the
population and has been cited as one of the top 15 The challenge of developing a successful topical
medical conditions for which prevalence and product stems from the several requirements that
healthcare spending increased in the last decade. a formulation must meet:
The outcome of topical dermatological drug
treatment is significantly influenced by the choice 1. Container Selection and Product Stability
of vehicle or delivery system. Advancements in Depending on the properties of the combined
the life sciences coupled with a growing market ingredients, a dispensing container will be chosen
for dermatologicals have facilitated the (i.e., tube, jar, can, etc.) to provide a stable
emergence of improved topical formulations and physicochemical environment that protects the
drug delivery systems. The current and emerging active compound(s) from chemical degradation.
approaches of optimizing the topical delivery of The formulation can be a liquid or semi-solid,
dermatological agents (small and large monophasic or multiphasic (e.g., oil-in-water or
molecules) include the use of chemical water-in-oil); it is largely dependent on the
enhancers, bio-polymers (e.g. sodium characteristics of the active compound(s) and on
hyaluronate), liposomes, particulate carriers the condition of the skin to be treated.
(microspheres and lipid nanoparticles), topical
sprays and foams, occlusion (via dressings and 2. Skin Penetration
patches) topical peels, temperature (heat), Once the product is applied on the skin, a
iontophoresis, and ultrasound. These delivery complex interaction occurs between the
approaches (when used solely or in a synergistic formulation, the active compounds, and the skin
manner) are a significant improvement over itself. The penetration of the active compound(s)
conventional systems (creams, lotions, ointments into the skin follows Fick’s first law of diffusion,
and pastes) and have the potential to enhance which describes the transfer rate of solutes as a
efficacy and tolerability, improve patient function of the concentration of the various
compliance (including dermatology life quality), ingredients, the size of the treatment surface area,
and also fulfil other unmet needs of the topical and the permeability of the skin. However, the
dermatological market. Non-invasive drug skin’s permeability can be influenced by many
delivery systems provide alternative routes of factors, such as the drying, moisturizing, or
administration and improved delivery of drugs to occluding effects of the excipients in the

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TPI JOURNAL

formulation, which, in combination, can modulate Purpose of Topical Preparation

the release of the product at the treatment site. In In order to formulate an effective and efficient
acne, the site of action is inside the pilosebaceous topical preparation, consideration must be given
unit and, therefore, an efficacious anti-acne to the intended purpose. This is directly
formulation should facilitate the penetration of concerned with the site of action and the desired
the active compound(s) into this extremely effect of the preparation. Topical preparations
lipophilic environment. may be used for: i) Surface effects: cleansing
(removal of dirt and germs), cosmetic
3. Cosmetic Acceptability (enhancement of appearance), protective
In today’s self-image conscious world, patients (prevention of moisture loss, sunscreen),
are looking for topical products that are not only antimicrobial (reduction of infection).
safe and effective, but also cosmetically ii) Stratum corneum effects: protective (e.g.
acceptable and easy to apply. This is especially sunscreens that penetrate this layer), keratolytic
true in acne, where the esthetic aspect is one of (a sloughing of the skin, useful in the treatment of
the primary reasons why patients seek psoriasis), protective (moisturizing).
dermatologic consultation. Moreover, acne iii) Viable epidermal and dermal effects: several
patients are mainly comprised of teenagers or classes of drugs may penetrate to these layers
young adults, and therefore, products that offer (anti-inflammatory, anesthetic, antipruritic,
convenience and are minimally disruptive to daily antihistamine). Although it is difficult for drugs
routines increase the level of compliance, and to penetrate the stratum corneum, once they are in
ultimately, the efficacy of the topical therapy. For the dermis, they can diffuse into the general
example, vehicle considerations for prescribing circulation. It is difficult to formulate a drug with
should take into account the application of the only a local effect without subsequent uptake by
drug on large, hairy surfaces like the chest and the blood.
the back. This may require formulations that iv) Systemic effects: a few drugs, such as
spread easily, or in the case of facial acne, the scopolamine, nitroglycerin, clonidine, and
ideal formulation should leave minimal residue or estradiol, have been formulated in a manner to
oiliness. achieve systemic effects.
v) Appendage effects: some classes of drugs are
Topical Route of Drug Administration intended to exert their action in these portions of
Although the intact skin is much less permeable the skin (depilatory, exfolient, antimicrobial, and
than other tissues many substances do penetrate antiperspirant).1 Infection remains major cause of
the skin to some degree, at relatively slow rates morbidity and mortality following the shock
the penetration of the drugs and other .phase in the burn patient. Measures to reduce the
substances through skin depends on; the risk of wound infection and subsequent sepsis
physiochemical properties of the penetrant, the include early excision where possible, and the use
state of the skin and the nature of the vehicle. of topical antimicrobial creams such as silver
Drugs applied topically, mainly for local action, sulphadiazine.4 The patient suffering major burns
include anti-septic, anti-fungal, anti-inflammatory is at risk from both cutaneous and systemic
agents as well as skin emollients for protective infection.5
effects. Whilst this route can also be used for
systemic drug delivery.2Topically applied drug DERMATOLOGICAL BASES
may diffuse through the skin by hair follicles, Generally, topical preparations meant for
sweat glands or sebaceous glands but permeation systemic or local effect are classified as
through the multiple lipid bilayers of stratum
corneum is the dominant pathway through the Solids – Dusting powder
rate is very slow.3

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Semi-solids – Creams, Gel, Ointments, Paste and general classification of ointments: hydrocarbon
other bases, absorption bases (anhydrous form and
Liquids – Solution, Emulsion, Liniments, emulsion form) water removable bases and water
Suspension, Soaps, Shakes, soluble bases.9
Collidons, Lotion, Paints and other.8
1. Hydrocarbon bases
In these semi-solid formulations are more These bases are immiscible with water and are
promising over solid and liquids considering its not absorbed by the skin. There are almost inert
property to cling to surface of application for and absorb very little water from a formulation or
reasonable duration before they worn off. from skin exudates. However, they inhibit water
Pharmaceutical semi-solid preparations include loss from the skin by forming a waterproof film
ointments, pastes, cream emulsions, gel and rigid and by improving hydration, may encourage
forms.9 absorption of the medications through the skin.11
Petrolatum and white ointment which is
Ointments petrolatum with 5% beeswax are typical of this
Ointments, in general, are composed of fluid classes of lipophilic vehicles.9 They are the most
hydrocarbons meshed in a matrix of higher occlusive of the topical preparations and thus are
melting solid hydrocarbons.9They usually only recommended in chronic-type skin
contain a medicament or medicaments dissolved, disorders.12
suspended or emulsified in an ointment base
(vehicles). There are greasy in nature.10 2. Absorption bases
The absorption bases are formed by the addition
Ointment bases of substances that are miscible with
The ointment base is that substance or part of an hydrocarbons and possessing polar groupings
ointment, which serves as carrier or vehicle for such as the sulfate, sulfonate, carboxyl, hydroxyl
the medicament. While selecting a suitable or an ether linkage.9 Absorption bases may be of
ointment base, the factors such as the action two types:
desired, nature of the medicament to be
incorporated and the stability of an ointment are i) Those that permit the incorporation of aqueous
to be considered.10 solutions, resulting in the formation of water in
oil emulsions. (e.g. Hydrophilic petrolatum and
An ideal ointment base should possess the anhydrous lanolin)
following properties:
ii) Those that are already water in oil emulsions
1. It should be inert, odorless and smooth. (emulsion bases) that permit the incorporation of
2. It should be physically and chemically small, additional quantities of aqueous solutions.
stable. (E.g. Lanolin and cold cream) e.g. sodium
3. It should be compatible with the skin and sulfacetamide into oleaginous bases.13
with the incorporated medicaments.
4. It should be of such a consistency that it 3. Water-removable bases
spreads and softens when applied to the Water removable bases are oil-in-water
skin with stress. emulsions that are capable of being washed from
5. It should not retard healing of the wound. skin or clothing with water. For this reason, they
6. It should not produce irritation or are frequently referred to as “water washable”
sensitization of the skin. ointment bases. These bases, which resemble
creams in their appearance, may be diluted with
The United States Pharmacopoeia (USP) XX water or with aqueous solutions. From a
recognizes four classes of semisolids under the therapeutic viewpoint, they have the ability to

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TPI JOURNAL

absorb serious discharges in dermatological stratum corneum and so restore the tissue’s
conditions. Certain medical agents may be better hydration ability, i.e. the preparation has
14
absorbed by the skin when present in a base of emollient properties.
this type than in other types of bases.13
Pastes
4. Water-soluble bases Pastes, like ointments, are intended for external
Water soluble vehicles are prepared from application to the skin. They differ from
mixtures of high and low molecular weight ointments primarily in that they generally contain
polyethylene glycol. Suitable combinations of a larger percentage of solid material and as a
high and low molecular weight polyethylene consequence are thicker and stiffer than
glycol yield products having an ointment like ointments because of their large percentage of
consistency, which soften or melt when applied solids. Pastes are generally more absorptive and
to the skin. No water is required for their less greasy than ointments prepared with the
preparations. These are water soluble because of same components. Because of stiffness and
the presence of many polar groups and their absorptive qualities of paste, they remain in place
linkages. The “water soluble” bases are also after application with little tendency to soften
known as greaseless ointment bases. These bases and flow. Therefore these are effectively
are non-toxic and non-irritating to the skin and employed to absorb serous secretions from the
have the advantages of being non-occlusive, site of application. Pastes are therefore preferred
miscible with exudates, non-staining and easily over ointments for acute lesions that have a
removed by washing.9 tendency toward crusting, vesiculation or oozing.
However, because of their stiffness and
Creams impenetrability, pastes are not generally suited
Creams are semisolid emulsion systems with for application to hairy part of the body.
opaque appearances as contrasted with Example: zinc-oxide paste.13
translucent ointments. Their consistency and
rheologic character depend on whether the Gels
emulsion is water in oil or oil-in-water type Gels are relatively newer class of dosage forms
and/or the nature of the solids in the internal created by entrapment of large amounts of
phase.9 Oil-in-water emulsions are most useful as aqueous or hydro-alcoholic liquid in a network of
water-washable bases where as water-in-oil colloidal solid particles, which may consist of
emulsions are emollient and cleansing. Patients inorganic substances such as aluminum salts or
often prefer water in oil cream to an ointment organic polymers of natural or synthetic origin.
because the cream spreads more readily, less Depending upon the nature of colloidal
greasy and the evaporating water soothes the substances and the liquid in the formulation, the
inflamed tissue. Oil in water creams (vanishing gel will range in appearance from entirely clear
creams) rub into the skin; the continuous phase to opaque. Most topical gels are prepared with
evaporates and increases the concentration of a organic polymers such as carbomers which
water soluble drug in the adhering film. The impart an aesthetically pleasing, clear sparkling
concentration gradient for a drug across the appearance to the product and are easily washed
stratum corneum therefore increases, promoting off the skin with water.14 Gels are two-
percutaneous absorption. To minimize drug component semisolids systems rich in liquids. In
precipitation, a formulator may include a non- a typical polar gel, a natural or synthetic polymer
volatile, water miscible co-solvent such as builds a three dimensional matrix throughout a
propylene glycol. An o/w cream is non-occlusive hydrophilic liquid. Typical polymers used
because it does not deposit a continuous film of include the natural gums tragacanth,
water-impervious liquid. However such a cream carrageenan, pectin, agar and alginic acid; semi
can deposit lipids and other moisturizers on the synthetic materials such as methylcellulose,

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hydroxyethyl cellulose, hydroxypropylmethyl oxyquinoline sulfate & chloro form. Most of the
cellulose, and carboxymethylcellulose; and the lotions are used as after-shave preparation.
synthetic polymer, carbopol may be used. Certain Lotions are not rubbed when applied.
clays such as bentonite, veegum, and laponite
provided that the drug does not bind to the Types
polymer or clay. Such gels release medicaments · Hand lotion
well; the pores allow relatively free diffusion of · Face lotion
molecules, which are not too large.13Gels are · Body lotion
semisolid systems consisting of dispersions of · After shave lotion
small or large molecules in an aqueous liquid · Antiperspirants lotion
vehicle rendering jelly-like through the addition
of gelling agent. Liniment: 15
Liniments are same as lotion but they are rubbed
Among the gelling agents used are: when applied.
· Synthetic macromolecules: Carbomer 934
· Cellulosederivatives:Carboxymethylcellulose, Suppository:48
Hydroxypropylmethyl-cellulose Suppositories are solid dosage forms intended to
Gels are compatible with many substances and deliver medicine into the rectal, vaginal, or
may contain penetration enhancers for anti- urethral orifice. Suppositories may prepare by the
inflammatory and anti-nauseant medications. cold compression or fusion technique. An
appropriate base is selected for its compatibility,
Types stability, melting point, and esthetics. Commonly
used bases are cocoa butter, glycerin,
 Single phase gels: Gels in which the hydrogenated vegetable oils, and polyethylene
macromolecules are uniformly distributed glycol.
throughout a liquid with no apparent
boundaries between the dispersed Powder:15,48
macromolecules and the liquid. Powder differs from liquid skin care preparation
in their physical characteristics. Very fine particle
 Double phase gels: Gel mass consists of size produces large surface area per unit weight,
floccules of small distinct particles, often which covers a large surface area of the body &
referred to as a magmas. Milk of result in strong light dispersion. There are body
magnesia (or magnesia magmas) powders, which are also known as dusting
powder or talcum powder, face powder and
Jelly:48 compact. Medicated powders are used for prickly
Jellies are water-soluble bases prepared from heat or preventing microbial growth on skin.
natural gums such as tragacanth, pectin, alginate,
and boroglycerin. Or from synthetic derivatives Solution:3,49
of natural substance such as methylcellulose and Solutions are liquid preparations of soluble
carboxymethylcellulose. chemicals dissolved in solvents such as water,
alcohol, or propylene glycol.
Lotion:15 · Aromatic waters
Definition · Tinctures
The lotions are clear solution containing 25-50% · Tincture of iodine
alcohol. Additionally they may contain antiseptic, · Sterile Indian ink for surgical procedures
emollient, and haemostypic substance. Also they
may contain extract of witchhazel, menthol,
glycerin, boric acid, alum, potassium

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Emulsion:35,36,48,50 Aerosol:48
Emulsions are two-phase preparations in which A system that depends on the power of
one phase (the dispersed or internal phase) is compressed or liquefied gas to expel the contents
finely dispersed in the other (continuous or from the container. The propellants responsible
external phase). The dispersed phase can have for developing the proper pressure within the
either a hydrophobic-based (oil-in-water), or be container, and it expel the product when the valve
aqueous based (water-in-oil). Because there are is opened and aids in the atomization or foam
two incompatible phases in close conjunction, the production of the products. Topical
physical stabilizing system. In most pharmaceuticals aerosols utilize hydrocarbon
pharmaceutical emulsions, the stabilizing system (propane, butane, and isobutene) and compressed
comprises surfactant (ionic or nonionic), gases such as nitrogen, carbon dioxide, and
polymers (nonionic polymers, polyelectrolytes, or nitrous oxide.
biopolymers), or mixtures of these.
Other Additives Used in Semisolids
Types Antioxidants
· Water-in-oil emulsion Antioxidants are added to semisolid whenever
· Oil-in-water emulsion oxidative deterioration is anticipated. Example:
· Water-in-oil-in-water emulsion Butylated hydroxyanisole (BHA), Butylated
· Oil-in-water-in-oil emulsion hydroxytoluene (BHT) and EDTA.9

Suspension:31-34,48 Preservatives
Suspensions are heterogeneous system consisting Preservatives are added to semisolids to prevent
of two phases. The continuous or external phase contamination, deterioration, and spoilage by
is generally a liquid or semisolid and the disperse bacteria and fungi, since many of the components
or internal phase is made up of particulate matter in the topical preparations serve as substances for
that is essentially insoluble in, but dispersed there microorganisms. Example: Mehtyl Paraben
throughout, the continuous phase; the insoluble and Propyl Paraben.11
matter may be intended for physiologic
absorption or for internal or external coating Humectants
function. The dispersed phase may consist of Loss of water can quickly lead to skin formation
discrete particle, or it may be a network of in gel and humectants such as glycerol,
particles resulting from particle-particle propylene glycol or sorbitol solution may be
interactions. Almost all suspension system added to retain water.11
separated on standing. The formulator’s main
concern, there fore, is not necessarily to try to Chelating agents
eliminate separation, but rather to decrease the Bases and medicaments sensitive to heavy metals
rate of settling and to permit easy are sometimes protected by a chelating agent
resuspendability of any settled particulate matter. such as EDTA (Ethylenediamine tetra acetic
acid).11
A satisfactory suspension must remain
sufficiently homogenous for at least the period of Perfumes
time necessary to remove and administered the Most ointments these days have a pleasant smell
required dose after shaking its container. imparted by incorporation of selected perfume
blends. The selection of a perfume blend is very
Types tricky business and every manufacturer would
· Flocculated suspension like to use one in his product. The blend selected
· Deflocculated suspension

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must be compatible with other ingredients. congealed, the ointment may be further levigated
Example: lavender. 11 Penetration enhancer on an ointment slab or if a large volume is being
prepared, a commercial mill can be used.2
To reduce the resistance of the stratum corneum
and its biological variability, penetration
enhancers (accelerants or absorption promoters) Route of Penetration through the Skin
are incorporated into skin preparations. An idle At the skin, molecules contact cellular debris,
penetration enhancer can be define as a chemical microorganisms, sebum and other materials,
with the unique property in relation to skin that it which negligibly affect permeation. The penetrant
reversibly reduces the barrier resistance of the has three potential pathways to the viable tissue -
horny layer without damaging any viable cells. through hair follicles with associated sebaceous
Example: Dimethylsulfoxide (DMSO).15 glands, via sweat ducts, or across continuous
stratum corneum between these appendages. The
Compounding of Ointment and Gels route usually contributes negligibly to steady
Whether for large or small scale production the state drug flux. This pathway may be important
manufacturer of ointments generally involves for ions and large polar molecules that struggle to
either of two processes: incorporation or fusion. cross intact stratum corneum. Appendages may
The method for a particular preparation depends be providing shunts, important at short times
upon the nature of the ingredients. prior to steady state diffusion. Additionally,
polymers and colloidal particles can target the
Incorporation follicle. The intact stratum corneum thus
Incorporation involves the blending of an provides the main barrier; its ‘brick and mortar’
ingredient into the vehicle. This is most structure is analogous to a wall .The coenocytes
frequently done on a small extemporaneous scale of hydrated keratin comprise of ‘bricks’,
by using either a mortar and pestle or glass slab embedded in ‘mortar’, composed of multiple lipid
and pair of spatulas. Stainless steel spatulas bilayers of cermides, fatty acids, cholesterol and
should be used if interaction between the cholesterol esters. These bilayers form regions
substance and the spatula blade. In that case hard of semi crystalline, gel and liquid crystals
rubber spatulas should be used. domains. Most molecules penetrate through skin
via this intercellular micro route and therefore
Fusion many enhancing techniques aim to disrupt or
Fusion method is used to incorporate ingredients bypass elegant molecular architecture. Viable
into solids with hard properties such as waxes or layers may metabolize a drug, or activate a
spermaceti with soft oleaginous substances. prodrug. The dermal papillary layer is so rich in
Frequently, all the components are combined, capillaries that most penetrant clear within
melted together, and cooled with constant stirring minutes. Usually, deeper dermal regions do not
until congealing occurs and a homogenous significantly influence absorption, although they
mixture is formed. When heat-labile substances may bind e.g. testosterone, inhitibiting its
are incorporated, those substances with the systemic removal.16
highest melting point are usually heated first and
then as the liquid cools the other ingredients are
added a few degrees above their respective Methods for Studying Percutaneous
melting points. This method prevents Absorption
decomposition or volatilization of heat labile The important general techniques for evaluation
substances. On a small scale, the fusion process of percutaneous absorption can be divided into in
can be conducted in a porcelain dish or glass vivo and in vitro procedures. The former uses the
beaker; on a large scale it is commonly carried skin of living human or experimental animals in
out in a large steam jacketed kettle. Once

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situ whereas the latter employs isolated formulation. The donor compartment may be
membranes and includes simple release studies. close or open to ambient conditions or to
controlled temperature and humidity; the skin
In Vitro Methods may washed and material is added during an
These are valuable techniques for screening and experiment. The test formulation may be a solid
for measuring fluxes, partition coefficient and deposited from volatile solvent, a liquid, a
diffusion coefficient. semisolid, a film or a drug device. 14
Release method without Rate – limiting
membrane. In Vivo Methods

These procedures record drug release a simple Animal models

immiscible phase. They measure only Most animals differ significantly from man in
drug/vehicle interactions, which affect release features that affect percutaneous absorption; the
characteristics and they do not determine skin thickness and nature of stratum corneum, the
absorption. density of hair follicles and sweat glands, the
nature of pelt, the papillary blood supply and
Diffusion methods with a rate – controlling biochemical aspects. Few techniques produce
membrane animal disease similar to human afflictions. Thus
animal models are valuable for studying the
Stimulated skin membrane: Because human skin anatomy, physiology and biochemistry of skin,
is variable and difficult to obtain, workers use for screening topical agents, for detecting
other materials, E.g. cellulose acetate, silicon possible hazards, and for biopharmaceutical
rubber, isopropyl myristate, or egg shell investigations. However experiments with
membrane; however, these membranes are not as animals can not substitute for human studies.
complex as human skin. Techniques
Observation of a pharmacological response: If the
Natural skin membrane: Excised skin from rat, drug stimulates a reaction in the viable tissue, we
mice (normal and hairless), rabbits, guinea pigs, may use this to determine penetration kinetics.
hamsters, pigs, hairless dogs, monkeys etc. have Local allergic, toxic or physiological reactions
been mounted in diffusion cells. However, include sweat gland secretion, pigmentation and
mammalian skin varies widely in stratum sebaceous gland activity, vasodilatation,
corneum properties and the number density vasoconstriction, vascular permeability,
appendages. Thus it is best to obtain human skin epidermal proliferation and keratinization. The
from autopsies, amputation or cosmetic surgery. most productive biopharmaceutical technique has
Investigators use either stratum corneum or been the vasoconstrictor or blanching response to
whole skin clamped in a diffusion cell and topical steroids. Other response methods include
measure the amount of compound passing from changes in blood pressure (e.g. topical,
the stratum corneum side through to a fluid bath. application of nitroglycerine), and production of
Diffusion cells: Steady sate Flux - A well stirred convulsion, reduction in the pain threshold.
donor solution at constant concentration releases Tests on Physical properties of skin: Relevant
penetrant through a membrane into an agitated methods include measurement of transepidermal
‘sink’ receptor liquid, stimulating to blood water loss, thermal determinations, mechanical
supply. analysis, use of ultrasound classification of
function and dimension, spectral analysis and the
Diffusion Cells: Simulation of In vivo conditions use of photo acoustic and electrical properties.
- Cells for initiating topical therapy use an Analysis of body tissue or fluids: Analysis of
agitated receptor solution to correspond to the urine, blood, faecal matter can be used for the in
blood and unmixed donor phase to represent the vivo studies. Sometimes the drug has an affinity

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for an animal organ which can be removed and shows different temperatures and period of
analyzed e.g. for iodine, iodides and mercury. stability testing.17
Tissue biopsy may be analyzed and even
individual section measured. Table 1: Storage condition for stability study`

Conditions Temperature Duration

Surface loss: We should be able to determine the
Freezer Conditions -20 to –10 C -
flux of material into skin from the loss rate from Refrigerator 2 C to 8 C -
the vehicle. However, because of skin Till expiry
impermeability, the decrease in concentration Controlled room temperature 15 C to 30 C
date
would generally be small and analytical Accelerated temperature 40 C to 50 C 6 months
techniques would have to be sensitive and
accurate. Loss techniques have mainly been used
to monitor radioactive species. EVALUATION OF TOPICAL DOSAGE
FORM
Histology: Experiments may try to locate skin
penetration routes from microscopic sections; Evaluation of patch:27
however, the cutting, handling and development 21-day cumulative irritancy patch test:
of skin sections encourage leaching and In this test the test compound is applied daily to
translocation of materials away from their the same on the back or volar forearm. Test
original sites, a problem with histological materials are applied under occlusive tape, and
methods is general. Histochemical techniques scores are read daily. The test application and
have been used for those few compounds, which scoring are repeated daily for 21 days or until
produce colored end products after chemical irritation produces a predetermined maximum
reaction. A few compounds fluoresce, revealing score. Typical erythema scores range from 0 (no
their behavior by microscopy e.g. vitamin A, visible reaction) to 4 (intense erythema with
tetracycline and benzpyrene. Tritium- labeled edema and vesicular erosion). Usually, 24
isotopes are useful because of their weak subjects are used in this test
emissions; strong beta emitters darken areas up to
2 or 3 mm away, a great distance at cellular Draize-shelanski repeat-insult patch test
levels. This test is designed to measure the potential to
cause sensitization. The test also provides a
Stability study measure of irritancy potential. In the usual
Stability testing of substance, drug and drug procedure the test material or a suitable dilution is
product begins as a part of drug and synthesis or applied under occlusion a 7-day rest period, the
development-preformulation efforts and ends test material is applied again to a fresh site for 24
only with the demise of the compound or hours. The challenge sites are read on removal of
commercial product. FDA and ICH specifies the the patch and again 24 hours later. The 0-4
guidelines for stability testing of new drug erythema scale is used. A test panel of 100
products, as a technical requirement for the individuals is common.
registration of pharmaceuticals for human use.
The ICH Tripartite Guidelines have established Kligman “maximization” test
that long term stability testing should be done at This test is used to detect the contact sensitizing
25 C/60% RH; stress testing should be done at 40 potential of a product or material. The test
C/75% RH for 6 months. If significant change material is applied under occlusion to the same
occurs at these stress conditions, then the site for 48-hr periods. Prior to each exposure the
formulation should be tested at an intermediate site may be pretreated with a solution of sodium
condition i.e. 30 C/75%RH. The following table lauryl sulfate under occlusion. Following a 10-
day interval the test material again is applied to a

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different site for 48 hours under occlusion. The are used for judging the irritancy to the eyes.
challenge site may be treated briefly with a Presence of patches on the skin within 2 weeks
sodium lauryl sulfate solution. The indicate irritancy to skin.
“maximization” test is of shorter duration and
makes use of fewer test subjects than the Draize- Evaluation of cream:15
Shelanski test. Rheology
Rheology is very important as these creams are
Evaluation of ointments:3,48 marketed in tubes or containers. The rheology or
Penetration viscosity should remain constant. As these
For assessing the penetration some very simple products are normally non-newtonian in nature,
experiments have been suggested. Weighed the viscosity can be measured using viscometers
quantities of the ointments are rubbed over used for such liquids.
definite areas of the skin for a given length of
time. Thereafter the unabsorbed ointment is Sensitivity
collected from the skin and weighed. The As various types of ingredients are used with
difference between the two weights roughly occasional use of antiseptic, hormones. etc., there
represents the amount absorbed. is a possibility of sensitization or
Rate of release of medicaments photosensitization of the skin. This should be
To assess the rate of release of a medicament tested beforehand. This test is normally done by
small amount of the ointment can be placed on patch test on skin and can be either open or
the surface of nutrient agar contained in a petry occlusive. The test sample is applied along with a
dish or alternately in a small cup cut in the agar standard market product at different places and
surface. If the medicament is bactericidal the agar effect is compared after a period of time.
plate is previously seeded with a suitable Biological testing
organism like S. aureus. After a suitable period of
incubation the zero of inhibition is measured and This is particularly essential for products
correlated with the rate of release. Another containing antiseptics, hormones, vitamins, etc.
method for finding out release rate is to smear Evaluation of emulsions:35,36,48
internal surface of test tubes with thin layers of
ointment, fill the tubes with saline or serum and Phase separation
after a gap of time estimating the amount of drug The rate and degree of phase separation in an
present in the serum/saline. emulsion can be easily determined by keeping a
certain amount in a graduated cylinder and
Absorption of medicaments into blood stream measuring the volume of separated phase after
The diadermatic ointments should be evaluated definite time intervals. The phase separation may
for the rate of absorption of drug into the blood result from creaming or coalescence of globules.
stream. This test can be in vivo only. Definite The phase separation test can be accelerated by
amounts of ointments should be rubbed the skin centrifugation at low/moderate speeds. One can at
under standard conditions and medicaments best expect a mixture of creamed and coalesced
estimated in the blood plasma or urine. particles and in such a situation it may be difficult
to make correct interpretations.
Irritant effect
In general no ointment should possess irritant Globule size
effect on the skin or the skin or mucous Growth in the globule size after the preparation of
membranes. The tests for irritancy can be carried an emulsion is an indication of its physical
out on the skin and eyes of rabbits or the skin in instability. The globule size is measured by
rats. Reactions are noted at intervals of 24, 48, 72 microscopic methods or by electronic devices
and 96 hours. Lesions on cornea, iris, conjunctiva such as coulter counter. In either of these two

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techniques the original product has to be suitable

diluted before estimation. The dilution may Consistency
introduce errors because of incomplete It is important that the product, paste, should
deflocculation or new patterns of flocculation. maintain the consistency to enable the product
press out from the container. Study of viscosity is
Rheological properties essential for these powders from the container.
The rheological characteristics of an emulsion
system depend upon globule size, emulsifier and pH of the product
its concentration, phase volume ration etc. Use of pH of the dispersion of 10% of the product i9n
a heliapath attachment with Brookfield water is determined by pH meter.
viscometer helps in detection of creaming Foaming character
tendency and hence it is advisable to study This test is specially required for foam-forming
rheological properties over extended periods of tooth pastes or tooth pastes or tooth powers.
time, which can help in prediction of their long- Especially amount of product can be mixed with
term behaviour. Many emulsion show change in specific amount of and water to be shaken. The
consistency with time which follows linear foam thus formed is studies for its nature,
relationship when plotted on a log-log scale over stability, washability.
a number of ten fold time intervals.
Limit test for arsenic and lead
Effect of thermal stresses This is very important, as these are highly toxic
It is usual to evaluate thew stability of an metals. Specific tests are there to estimate these
emulsion by subjecting it too high and low two metals. However, if the raw materials are
temperatures in alternating cycles. The samples tested for the limit of these two metals,
are first exposed to 60 C for a few hours and then products may not have excess of such metals.
to o to 40 C. Such exposures are repeated a Volatile matters and moisture
number of times and emulsion stability assessed A specific amount of the product required to be
after each cycle. taken in a dish and drying is to be done till
constant weigh. Loss of weigh will indicate
Evaluation of paste:15,41,42 percentage of moisture and volatile matters.
Abrasiveness Effect of special ingredients
The teeth were mechanically brushed with pastes Special tests should be done for the special
or powders and then the effects were studied by ingredients if any like antiseptic, enzymes, etc.
observation, mechanical or other means. Abrasive For each one special and specific test are to be
character normally depended on the particle size done.
Particle size
This can be determined by microscopic study of Evaluation of powder:15
the particles or other means. Shade control and lighting
Cleansing property This is to control and determine the variation of
This is studied by measuring the change in the color shade from batch to batch and with the
reflectance character of a lacquer coating on a stander, Proper test is to be done to prevent in
polyester film caused by brushing with a tooth shades. One such method is comparison of the
cleanser (paste or power). Also an in vivo test has appearance of the body of the power with a
been suggested in which teeth were brushed for 2 standard when it is spread out and flattened on a
weeks and condition of teeth was assessed before white paper background. The other method of
and after use with the help of photographs. evaluation is comparison of the sample with the
standard by skin tone or undertone. Powers
should be applied by the same puff that is to be
used for finished pack. This is the final

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TPI JOURNAL

judgement for the shade test. Artificial lighting is basic evaluative procedures. The concept of
used for color evaluation. sedimentation volume is simple. In short, it
Dispersion of color considers the ratio of the ultimate height (Hu) of
Color should be homogeneously distributed in the the sediment to the initial height (Ho) of the total
power base. There should not be segregation or suspension as the suspension settles in a cylinder
bleeding of color. This can be tested by spreading under standard conditions. The larger this
the power on a white paper and checking if with a fraction, the better is the suspendability. First
magnifying glass. obtain the Hu /Ho ratios and plot them as
ordinates with time as the abscissa. Note that
Pressure testing although the height at any particular time. The
Pressure applied to compact powder should be plot just described will at time zero start at 1.0,
uniform to the hardness can be tested by with the curve then being either horizontal or
penetrometer. Reading on hardness is checked at gradually sloping downward to the right as time
various points of compact tablet to see the goes on. One can compare different formulation
uniformity of hardness. and choose the best by observing the lines, the
better formulations obviously producing lines that
Breakage test are more horizontal and/or less steep.
This is carried out by dropping the compact tablet
of powder on a wooden surface several times The evaluation of redispersibility is also
from a height of 8 to 10 inches and checking the important. To help quantitate this parameter to
breakage or clipping of the resistance against some extent, a mechanical shaking device may be
travel and normal handling. used. It simulates human arm motion during the
shaking process and can give reproducible results
Flow property when used under controlled conditions.
This is very important, particularly for body
powders, as they should come out easily from the Rheologic methods
container for easy application. This can be Rheologic methods can be used to help determine
studied by measuring angle of repose of powder the setting behavior and the arrangement of the
product by allowing to fall on a plate from a vehicle and particle structural features for
funnel and measuring the height and radius of purpose of comparison. A practical rheologic
heap formed. method involves the use of the Brookfield
viscometer mounted on a helipath stand. The T-
Particle size and abrasiveness bar spindle is made to descend slowly into the
Particle size can be determined by microscope, suspension, and the dial reading on the
sieve analysis or by using sophisticated viscometer is then a measure of the resistance the
instrument and techniques. Abrasiveness can be spindle meets at various levels in a sediment. In
studied by rubbing the powers on a smooth this technique, the T-bar is continually changing
surface and then studying the effect on the position and measures undisturbed samples as it
surface using microscope. advances down into the suspension. This
technique also indicates in which level of the
Moisture content and limits for color suspension the structure is greater, owing to
These can be estimated by using suitable particle agglomeration, because the T-bar
analytical methods. descends as it rotates, and the bar is continually
entering new and essentially undisturbed
Evaluation suspension:48 material.
Sedimentation volume
Measurement of the sedimentation volume and its
ease of redispersion from of the most common

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water bath, test gauges, and special equipment.

Electrokinetic techniques Methods are available for aerosols packaged in
Instrumentation permitted measurement of the both metal and glass containers.
migration velocity of the particles with respect to
the surface electric charge or the familiar zeta Density
potential; the latter has units of viscosity times The density of an aerosol system may be
electrophoretic mobility, or more familiarly, accurately determined through the use of a
volts. hydrometer or a pycnometer. These methods,
Particle size changes which have been modified to accommodate,
The freeze-thaw cycling technique is particularly liquefied gas preparations. A pressure tube is
application to stressing suspension suspension for fitted with metal flanges and a Hoke valve, which
stability testing purposes. This treatment allow for the introduction of liquids under
promotes particle growth and may indicate the pressure. The hydrometer is placed into the glass
probable future state of affairs after long storage pressure tube. Sufficient sample is introduced
at room temperature. Thus, it is of prime through the valve to cause the hydrometer to rise
importance to be alert for changes in absolute halfway up the length of the tube. The density can
particle size, particle size distribution, and crystal be read directly. Specific gravity can be
habit. Particle size distribution is sometimes determined through the use of a high-pressure
determined by microscopic means. This method cylinder of about 500-ml capacity.
of necessity requires dilute suspensions that are
counted with the aid of an ocular grid. In some Moisture
instances, photomicrographs may to take for Many methods have proven useful for this
permanent records. purpose. The Karl Fischer method has been
accepted to a great extent. Gas chromatography
Evaluation of aerosol:48 has also been used.
Flame projection
This test indicates the effect of an aerosol Aerosol valve discharge rate
formulation on the extension at an open flame. This is determined by taking an aerosol product
The project is sprayed for about 4 sec into a of known weight and discharging the contents for
flame. Depending on the nature of the a given period of time using standard apparatus.
formulation, the flame is extended, the exact By reweighing the container after the time limit
exact length being measured with a ruler. has expired, the discharge rate, which can then be
expressed as grams per second.
Flash point
This is determined by use of the standard Tag Spray patterns
Open Cup apparatus. The aerosol product is The method is based on the impingement of the
chilled to a temperature of about -250 F and spray on a piece of paper that has been treated
transferred to the test apparatus. The test liquid is with a dye-talc mixture. Depending on the nature
allowed to increase slowly in temperature, and of the aerosol, an oil-soluble or water-soluble dye
the temperature at which the vapors ignite is is used. The particles that strike the paper cause
taken as the flash point obtained is usually the the dye to go into solution and to be absorbed
flash point of the most flammable component, onto the paper. This gives a record of the spray,
which in the case of topical pharmaceuticals is which can then be used for comparison purposes.
the hydrocarbon propellant. To control the amount of material coming into
contact with the paper, the paper is attached to a
Vapor pressure rotating disk that has an adjustable slit.
The pressure can be measured simply with a
pressure gauge or elaborately through use of a

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Dosage with metered valves Evaluation of lotion:15

Method that can be used involves accurate Antiseptic property
weighing of filled container followed by As these preparations contain antiseptics, it is
dispensing of several doses. The container can necessary to evaluate antiseptic property by in-
then be reweighed, and the difference in weigh vitro test.
divided by the number of doses dispensed gives Determination of alcohol content
the average dose. This must then be repeated and This can be determining by any suitable method
the results compared. Determination of the does as these preparations contain alcohol it is
received by a patient is a rather difficult necessary to estimate the alcohol content.
procedure, since all of the respiratory system has Evaluation of gel:44-48
been developed and is satisfactory for this Drug content
purpose. 1gm of gel was accurately weighed in a 50ml of
volumetric flask to which 20ml purified water
Net contents was added with continuous shaking. Volume was
 The tared cans that have been placed onto adjusted with a mixture of 10% methanol in
the filling line are reweighed, and the difference water. Plain bases were also treated in similar
in weigh is equal to the vet contents. manner for blank determination. Absorbance of
 Method is a destructive method and the solution with the blank was measured at
consists of weighing a full container and then 360nm using UV-spectrophotometer.
weighed, with provision being made for the Homogeneity of drug content
amount retained in the container. For homogeneity of drug contents, six tubes
 Opening the container and removing as weretaken randomly and assayed for the drug
much of the produce as possible. These tests are content as stated above. Studies were performed
not indicated in determining the actual net weight in triplicate and mean values were used for the
of each container as related to the amount that analysis of data.
can actually be dispensed.
Measurement of pH
Foam stability The pH of carbopol gels ofTN were determined
The life of a foam can range from a few seconds by digital pH meter. One gram of gel was
(for some quick breaking foams) to one hour or dissolved in 100ml of distilled water and stored at
more depending on the formulation. Several 4°C for two hours. The measurement of pH of
methods have been used, which include a visual each formulation was in triplicate and the average
evaluation, time for a given rod that is inserted values are presented.
into the foam to fall, and the use of rotational
viscometers. Viscosity
Brookfield synchrolectric viscometer model RVT
Particle size determination attached with spindle D was used for
Cascade impactor and “light scatter decay”. The determination of viscosity. Gels were filled in jar
cascade impactor operates on the principle that in andspindle was lowered perpendicularly taking
a stream of particles projected through a series of care that spindle do not touch bottom of the jar.
nozzles and glass slides at high velocity, the The spindle was rotated in the gel at increasing
larger particles become impacted first on the shear rates 0.5, 1, 2.5 and 5rpm. At each speed,
lower velocity stages, and the smaller particles the corresponding dial reading was noted. The
pass on and are collected at higher velocity reverse reading were also noted and average was
stages. Light scatter decay method as the aerosol taken for these two readings.The viscosity of the
settles under turbulent conditions, the change in gel was obtained by the multiplication of the dial
light intensity of a Tyndall beam is measured.

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readings with the factors given in the Brookfield

viscometer catalogues. Dissolution test
Testing for the rate of in vitro release of drug
Spreadability substances from suppositories has always posed a
A modified apparatus consisting of two glass difficult problem, owing to melting, deformation.
slides containing gel in between with the lower and dispersion in the dissolution medium. Early
slide fixed to a wooden plate and the upper one testing was carried out by simple placement in a
attached to a balance by a hook was used to beaker containing a medium. In an effort to
determine spreadability. control the variation in mass/ medium interface,
Extrudability various means have been employed, including a
A simple method was adopted for determination wire mesh basket, or a membrane, to separate the
of extrudability in terms of weight in grams sample chamber from the reservoir. Samples
required to extrude a 0.5cm ribbon of gel in 10 sealed in dialysis tubing or natural membranes
seconds from the collapsible tube. have also been studied. Flow cell apparatus have
been used, holding the sample in place with
Evaluation of suppository:48-54 cotton, wire screening, and most recently with
Melting range test glass beads.
This test is also called the macro melting range
test and is a measure of the time it takes for the NOVEL TOPICAL DRUG DELIVERY
entire suppository to melt when immersed in a SYSTEM
constant-temperature (37C) water bath.
Aerosol Foams
Liquefaction or softening time test Aerosol foams have become an increasingly
It consists of a U-tube partially submersed in a popular type of topical formulation for a variety
constant temperature water bath. A constriction of skin conditions including acne vulgaris. The
on one side holds the suppository in place in tube. vehicle base of the foam can have a liquid or
A glass rod is placed on top of the suppository, semi-solid consistency that shares the same
and the time for the rod to pass through to the physicochemical characteristics of conventional
constriction is recorded as the “softening time”. vehicles like creams, lotions and gels, but it
maintains desirable properties such as
Breaking test moisturizing/ fast-drying effects, or higher drug
The apparatus used for the test consists of a bioavailability. The aerosol base is dispensed
double-wall chamber in which the test through a gas-pressurized can that discharges the
suppository is placed. Water at 37°C is pumped foam. The product characteristics (i.e., texture,
through the double walls of the chamber, and the bubble size and thickness, viscosity, density,
suppository, contained in the dry inner chamber, persistence, stability, and spreadability) are
supports a disc to which a rod is attached. The determined by the type of formulation and the
other end of the rod consists of another disc to dispensing container that are selected to suit the
which weights are applied. The test is conducted specific treatment needs. In acne, foams may be
by placing 600 g on the platform. At 1-min preferred for application on large hairy surfaces
intervals, 200-g weights are added, and the (e.g., chest and back) or on the face as cleansers,
weight at which the suppository collapses is the because they are easier to apply.
breaking point, or the force that determines the
fragility or brittleness characteristics of the Liposomes
suppository Liposomes are frequently used as vehicles in
pharmaceuticals and cosmetics for a controlled
and optimized delivery to particular skin layers.
Liposomes are spherical vesicles whose

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TPI JOURNAL

membrane consists of amphiphilic lipids (i.e., into microcells. Inside these aqueous microcells,
lipids that are hydrophilic on one side and hydrophilic compounds can remain in a solution,
lipophilic on the other side) that enclose an whereas non-hydrophilic compounds may be
aqueous core, similar to the bilayer membranes of dispersed in suspension. The result is a stable gel-
living cells. Because liposomes offer an like formulation that is easy to use and releases
amphiphilic environment, they may encapsulate the active compound(s) once they are applied on
hydrophilic substances in their aqueous core and the skin. Moreover, these polymer-based gels can
lipophilic substances in their lipid bilayer. This be mixed with other excipients, such as
unique dual release capability enables the moisturizers and emollients, to provide additional
delivery of 2 types of substances once they are clinical benefits. Recently introduced anti-acne
applied on the skin; each differs in its effects on formulations that combine clindamycin 1% with
skin permeability, which may enhance the desired benzoyl peroxide 5% (Duac®, Stiefel
therapeutic benefit.4,5 Laboratories; BenzaClin®, Dermik) utilize this
novel polymer-based gel technology that exhibits
Nanoemulsions efficacy and excellent tolerability.
Nanoemulsions are a class of emulsions (i.e.,
water-in-oil or oil-in-water formulations) that are Microsponges
characterized by the dispersion of very small- Microsponges are biologically inert particles that
sized droplets when mixed. Nanoemulsions are are made of synthetic polymers with the capacity
not formed spontaneously, as they require unique to store a volume of an active agent up to their
thermodynamic conditions, specialized own weight. Furthermore, the particles serve to
manufacturing processes, and specific surfactants protect the entrapped active compound from
that can stabilize the nano droplets. physical and environmental degradation. The
Nanoemulsions are suitable for the transport of microsponge technology can be utilized in a
lipophilic compounds into the skin and, therefore, variety of formulations, but is more frequently
they may be an ideal vehicle for use in acne to manufactured as gels. Once applied on the skin,
increase the penetration of the active compounds microsponges slowly release the active agent(s).
inside the lipophilic environment of the
pilosebaceous unit. In addition, nanoemulsion Emulsifier-free Formulations
particulates will not clog the pores and they can Emulsifier-free formulations are also a growing
produce additional therapeutic effects, such as area of development for dermatologic and
increased skin hydration and viscoelasticity. cosmetic products. Most skin care products are
emulsions, i.e., a mixture of 2 or more materials
Polymers that are not miscible with each other; as such,
Polymers are large molecules consisting of according to the second law of thermodynamics,
repeating structural units, or monomers that are they are inherently unstable. As a result, they
connected by covalent chemical bonds. These require the addition of surfactants (“emulsifiers”)
compounds serve as the building blocks of that stabilize the formulation to guarantee an
natural (e.g., paper and amber), biological (e.g., adequate shelf life. Furthermore, once these
proteins and nucleic acid), or synthetic (e.g., surfactant agents are applied on the skin, they
plastics and polyethylene) materials. Today, tend to emulsify and remove the natural lipids of
applications for synthetic polymers can be found the epidermis. Consequently, the pharmaceutical
in nearly every industry, and their versatility has industry has been developing surfactant-free
given rise to technological advancements within emulsions as alternatives to conventional
the pharmaceutical sector that address a variety of formulations by using stabilizers, such as
medical needs. For example, in dermatology, polymeric emulsifiers or solid particles, in order
there are new acrylic-acid polymers that turn into to yield sufficiently stable products with a
a gel in the presence of water by trapping water cosmetically pleasant appearance.

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7. Zerweck C, Grove G, Fraser JM.

Fullerenes Moisturization potential of two acne gels
Fullerenes are molecules composed entirely of containing 5% benzoyl peroxide and 1%
carbon that resemble a hollow sphere. Rouse, et clindamycin. Presented at: AAD Summer
al., showed that once fullerenes come into contact Academy Meeting, July 26-30, 2006, San
with the skin, they migrate through the skin Diego, CA; P100.
intercellularly, as opposed to moving through 8. Rouse JG, Yang J, Ryman-Rasmussen JP,
cells.8 Therefore, a fullerene could be used to et al. Effects of mechanical flexion on the
“trap” active compounds and then release them penetration of fullerene amino acid-
into the epidermis once they are applied on the derivatized peptide nanoparticles through
skin. Moreover, fullerenes, themselves, are skin. Nano Lett 7(1):155-60 (2007 Jan).
thought to be potentially potent antioxidants. 9. Huczko A, Lange H. Fullerenes:
Data are reported in the literature showing that experimental evidence for a null risk of
fullerenes are well tolerated and they hold skin irritation and allergy. Fullerene Sci
substantial promise in dermatologic and cosmetic Technol 7:935-9 (1999).
applications. 10. Fumelli C, Marconi A, Salvioli S, et al.
Carboxyfullerenes protect human
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