Topical route_Dr. Mansij Biswas

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Topical Route of Drug Administration And Dosage Forms Dr. Mansij Biswas, FYR Department of Pharmacology & Therapeutics Seth G S Medical College & KEM Hospital 1

Transcript of Topical route_Dr. Mansij Biswas

Page 1: Topical route_Dr. Mansij Biswas

Topical Route of Drug

Administration And

Dosage Forms

Dr. Mansij Biswas, FYR

Department of Pharmacology & Therapeutics

Seth G S Medical College & KEM Hospital

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defined as the application of a drug containing

formulation to the skin or mucous membrane, to treat

specific cutaneous disorders (e.g. acne) or cutaneous

manifestations of a generalised disease (e.g.

psoriasis), with the intent of containing the

pharmacological effect of the drug only to the surface

or within the layers of skin or mucous membrane.

Ansel H.C., Allen L.V., “Pharmaceutical Dosage Forms and Drug Delivery System”, 7th edition, Lippincott

Willlams and Wilkens, Baltimore, 2000, 244-246,249-251, 253-255,264-265

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Includes two basic types:

A) External- that are spread or dispersed on the cutaneous surface

covering the affected area.

B) Internal- that are applied to the mucous membrane of eye

(conjunctiva), ear, oropharyngeal cavity, nasal cavity, vagina

or anorectal region for local activity.

Classification Based on physical state-

(A) Solid:

Powder, Aerosol, Plaster

(B) Liquid:

Lotion, Liniment, Solution, Emulsion, Suspension, Aerosol

(C) Semi-solid:

Ointment, Cream, Paste, Gel, Jelly, Suppository

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Advantages of Topical Drug

Delivery System:

Avoidance of first pass metabolism

Easy application

Avoidance of the risks and inconveniences of administration and the

varied conditions of absorption, like pH changes, presence of

enzymes, gastric emptying time etc in enteral or parenteral routes

Achievement of efficacy with lower total daily dosage of drug by

continuous drug input

Avoids fluctuation in drug levels, inter- and intra-patient variations

Easy termination of medications, when needed

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Advantages: contd…

Relatively large area of application

Drug can be delivered more selectively to a specific site

Avoidance of gastro-intestinal incompatibility

Provide utilization of drugs with short biological half-life &

narrow therapeutic window

Improved physiological and pharmacological response

Improved patient compliance

Suitable for self-medication

Surver, C. and Davis, F.A., Bioaviability and Bioequivalence, In Walter, K.A..(Ed. ) , Dermatological and Transdermal

Formulation, Marcal Dekker, INC. NewYork , 119,2002,pp. 403,323,326,327,403

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Disadvantages of Topical Drug

Delivery System:

Skin irritation/contact dermatitis due to drug and/or excipients

Poor permeability of some drugs through the skin

Possibility of allergic reactions

Can be used only for those drugs which require low plasma

concentration for action

Enzymes in epidermis may denature the drugs

Drugs with larger particle size are difficult to get absorbed

through the skin

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Cross Section of Human Skin:7

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Absorption through skin:

Two principal absorption route are identified:

A) Trans-epidermal absorption:

Principally responsible for diffusion across the skin. The resistance encountered along this pathway mostly arises in the stratum corneum. Maybe trans-cellular or inter-cellular.

B) Trans-follicular (shunt pathway) absorption:

The skin’s appendages, mainly sebaceous glands, sweat glands, hair follicles offer secondary avenues for permeation, which are considered as shunts bypassing the trans-epidermal route.

Basic principle of permeation-

initial transient stage- shunt pathway predominates, but when a steady state has been reached, diffusion through stratum corneum becomes the dominant pathway.

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Factors Affecting the Extent and Rate of

Topical and Percutaneous Drug Absorption

and Transportation:-

skin physiology & pathology:- hydration, blood flow, lipid content

physico-chemical properties of drugs and excipients:-

• Partition coefficient

• pH-condition

• Drug solubility

• Concentration

• Particle size

• Polymorphism

• Molecular weight

fabrication and design of the delivery systems:-

release characteristics, composition, nature of vehicle, presence of penetration enhancers

The rate of drug transport across the stratum corneum follows Fick’s Law of Diffusion

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Topical Dosage Forms:-

Ointment:-

Viscous semisolid preparation

Applied externally to skin or mucous membrane (eye, nose, vagina, rectum)

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Vehicle of an ointment is known as ointment base

1) Hydrocarbon (oleaginous) bases:

Emollient, occlusive, greasy, non water washable, prolonged contact period

E.g.- white/yellow petrolatum

2) Absorption (anhydrous) bases:

Permits the incorporation of additional quantities of aqueous solutions

E.g.- Lanolin

3) Water removable Bases:

Oil in water type, non occlusive, less greasy, creamy in appearance, water-washable.

4) Water soluble Bases:

Do not contain oleaginous components, completely water-washable, greaseless, mostly

used for the incorporation of solid substances.

E.g.- Polyethylene Glycol

5) Simple base:

Wool fat (5%) + hard paraffin (10%) + yellow soft paraffin (85%)

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Evaluation of ointments

Penetration

Rate of release of medicaments

Absorption of medicaments into

blood stream

Irritant effect

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Methods of preparation of ointments:

a) Trituration: finely subdivided insoluble medicaments are

evenly distributed by grinding with a small amount of the

base followed by dilution with gradually increasing amounts

of the base.

b) Fusion: the ingredients are melted together in descending

order of their melting points and then stirred to ensure

homogeneity.

Difficult to measure precise dose- by weighing the tube before

& after use or measuring the length of the ribbon squeezed.

Only the medicine that is touching the skin will work, so thin

layer is always preferred to thick layer.

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Cream:

Viscous semisolid emulsion- medicaments dissolved or suspended in

water removable bases.

Applied to skin or mucous membrane (vagina, rectum)

Most are O/W (small droplets of oil dispersed in a continuous

aqueous phase), only cold creams and emollients are W/O (small

droplets of water dispersed in a continuous oily phase).

O/W (vanishing) - water washable, non greasy, non occlusive, more

cosmetically acceptable.

W/O (oily) - for some hydrophobic drugs, more emollient.

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Advantages over ointment:-

1. Less greasy 2. Spreads easily3. Soothing sensation4. Easily washable

• Uses:-

1. Physical or chemical barrier to protect the skin e.g. sunscreens2. Cleansing agent3. Emollient 4. Retention of moisture (especially water-in-oil creams)5. Vehicle for drug substances such as local anaesthetics, anti-

inflammatory agents, hormones, steroids, antibiotics, antifungals or counter-irritants

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Evaluation of cream

Rheology

Sensitivity

Biological testing

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Paste:-

Pastes are basically ointments into which a high percentage of

insoluble solids have been added

Less greasy than ointments

Provide protective coating on skin due to it’s stiff consistency

Poorly occlusive, so suited for application around moist areas

Absorb secretion from the oozing lesions

Forms an unbroken, water impermeable, opaque film on the skin

Effective sun filter & prevent excessive wind dehydration (windburn)

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Evaluation of paste

Abrasiveness

Particle size

Cleansing property

Consistency

pH of the product

Foaming character

Limit test for arsenic and lead

Volatile matters and moisture

Effect of special ingredients

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Gels & Jellies:

Semisolid systems- dispersions of small or large molecules in an

aqueous liquid vehicle by addition of gelling agent

Gelling agents- either Synthetic macromolecules (Carbomer 934) or

Cellulose derivatives (Carboxymethylcellulose)

Non greasy, moisture rich

Compatible with many substances

May contain penetration enhancers for anti-inflammatory and some

other medications

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Types:-

·Single phase: macromolecules are uniformly distributed throughout a

liquid with no apparent boundaries between the dispersed macromolecules

and the liquid.

·Double phase: Gel mass consists of floccules of small distinct particles,

often referred to as a magmas.

Gel rich in liquid is called jelly

Prepared from either natural gums such as pectin, alginate etc. or from

synthetic derivatives of natural substance such as methylcellulose

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Applications:

sustained-release delivery system

dressings for healing of burn or other hard-to-heal wounds

reservoirs in topical drug delivery, particularly ionic drugs,

delivered by iontophoresis

e.g. Diclofenac gel, Lignocaine jelly

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Evaluation of gel

Drug content

Homogeneity of drug content

Measurement of pH

Viscosity

Spreadability

Extrudability

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Lotion:

Clear solution/suspension/emulsion containing 25-50% alcohol

Low to medium viscosity

May contain extract of witchhazel, menthol, glycerin, boric acid,

alum, chloroform etc but NOT camphor

Applied without friction

Can be applied on abraded/wounded skin or on mucous membrane

Antiseptic, anti inflammatory, astringent, emollient, cooling,

moisturizing or protective actions

e.g. Calamine lotion

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Evaluation of lotion

Antiseptic property

Determination of alcohol content

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Liniment (Balm):

Low- to medium-viscosity emulsions

Formulated from quickly evaporating solvents, contain aromatic chemical compounds

As a rule contain camphor

Always applied with friction

Applied only on unbroken skin, never on mucus membrane

Mechanism of action:

• Rubefacient

• Local irritant

• Counter irritant

Typically used to relieve pain and stiffness such as from sore muscle cramp or arthritis

e.g. Turpentine

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Poultices/Cataplasms:-

Now obsolete

Heated & spread on dressing & applied as hot as the patient can bear

Heat is retained, soothing in pain and inflammation

Ingredients may have counter-irritant/ absorptive properties

e.g. Kaolin poultice

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Solution:

Solutions are liquid preparations of soluble chemicals dissolved in

solvents such as water, alcohol or propylene glycol

E.g:

· Tincture of iodine

· Sterile Indian ink for surgical procedures

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Emulsion:

Two-phase preparations - the dispensed (internal) phase is finely

dispersed in the continuous (external) phase

Because there are two incompatible phases in close conjunction, a

physical stabilizing system is needed- surfactant (ionic or nonionic),

polymers, polyelectrolytes etc

Types-

· Water-in-oil emulsion

· Oil-in-water emulsion

· Water-in-oil-in-water emulsion

· Oil-in-water-in-oil emulsion

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Evaluation of emulsions

Phase separation

Globule size

Rheological properties

Effect of thermal stresses

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Suspension:

Heterogeneous system consisting of two phases:

1. The continuous or external phase is generally a liquid or semisolid

2. The disperse or internal phase is made up of particulate matter that is dispersed throughout the continuous phase

Almost all suspension systems get separated on standing, the rate of settling and ease of resuspendability is the concern

A satisfactory suspension must remain sufficiently homogenous for at least the time necessary to remove and administer the dose after shaking its container

Types:

· Flocculated

· Deflocculated

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Evaluation of suspension

Sedimentation volume

Rheologicmethods

Electrokinetictechniques

Particle size changes

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Medicated shampoos:-

e.g. Selenium sulphide, Cetrimide, Ketoconazole

Paints:-

Applied to broken skin/mucus membrane

Applied in throat with an applicator

e.g. Mandl’s paint

Nail lacquers:-

e.g. Amorolfine (a newer antifungal) for tinea unguium

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Collodion:-

• Protective, occlusive, water repellant film on the skin

surface following evaporation of the solvent

• Seals small cuts and scratches

• Occlusion prolongs contact with active medicaments

• Contains pyroxylone (a nitrocellulose) in an ether alcohol

mixture

• Applied using a brush or applicator

• e.g. Salicylic acid collodion

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Eye/Ear Drops:-

Solution/ suspension

Relatively brief contact time with absorbing surface

pH, tonicity, viscosity important for local comfort.

Sterile; require aseptic handling

Use droppers with attached or separate plastic nozzle, avoid touching

the application surface

Use: to prevent or treat infections

E.g. Ciprofloxacin eye/ear drop, Artificial tear

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Ophthalmic strips:-

Used for delivering diagnostic

dyes topically for eye, by simply

touching the conjunctival surface

e.g. Fluorescein sodium

Ocular insertion:-

Continuous release multilayered

polymeric insertion in

conjunctival fornix

Ocusert (pilocarpine- for

treatment of glaucoma), Lacrisert

(artificial tear substitute- for

treatment of dry eye)

Not available in India

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Medicated plaster, dressing, sticks:-

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Belladonna plaster, Keratolytic plaster, neocapsicum plaster

Framycetin dressing

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Suppository:

Solid dosage forms intended to deliver medicine into rectal,

vaginal or urethral orifice

Prepared by cold compression or fusion technique

An appropriate base is selected for its compatibility, stability,

melting point, and aesthetics. Commonly used bases are cocoa

butter, glycerin, hydrogenated vegetable oils, and polyethylene

glycol

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Advantages:

Bypasses first pass metabolism

Suitable when oral route cannot be used (e.g. patient unconscious, excessive nausea, vomiting, malabsorption disorder)

Suitable when drug is not suitable for oral use (unstable in GI tract, degraded by digestive enzymes )

Disadvantages:

Absorption slower & unpredictable (BA ~50%)

Inconvenient & embarrassing

The contained fat often melts at the high temperatures of the tropics

Used in kids only where controlled delivery possible

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Rectal Suppository:

Tapered at one or both ends (torpedo shape is most common), weight= 2g

They are meant for local (e.g. OTC preparation for hemorrhoids

containing a moisturizer or vasoconstrictor; Glycerin or Bisacodyl

as laxative ) and for systemic (e.g. Paracetamol, Aminophylline,

Promethazine) effects

Active ingredient(s) usually mixed with a suitable base which is

solid at room temperature to assist insertion, but melts at body

temperature to enable dispersion

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Vaginal suppositories/pessaries:

Globose or oviform, weight=5g

Mostly meant for local effects (clotrimazole, miconazole, metronidazole)

Urethral suppository/bougies:

Cylindrical, longer for males than for females, obsolete now a days

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Evaluation of suppository

Melting range test

Dissolution test

Liquefaction or softening time

test

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Douche:-

Douche is a device used to rinse any

body cavity but usually applies to

vaginal irrigation

Vaginal douches may consist of water,

water mixed with vinegar, or even

antiseptic chemicals

Disadvantage: Can lead to irritation,

pelvic inflammatory disease (PID),

fertility problems

Use - Treatment of bacterial vaginosis

with a vaginal douche containing a

strain of L. acidophilus

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Medicated Vaginal Rings:-

Doughnut-shaped polymeric drug delivery devices designed to provide controlled

release of drugs to the vagina over extended periods of time

Vaginal ring products are used for the treatment of vaginal atrophy, relief of hot

flashes and as a contraceptive

Vaginal ring technology is currently being developed for the controlled release of

microbicides and vaccines for the prevention of HIV/HPV infection

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Intra uterine Devices:-

An intrauterine device is a small

contraceptive device, often 'T'-

shaped, containing either copper

(Cu-T) or levonorgestrel (LNG-

IUS), inserted into the uterus

most effective types of reversible

birth control

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Aerosol:

A system that depends on the power of compressed or liquefied gas to expel the

contents from the container.

Topical pharmaceutical aerosols utilize hydrocarbon (propane, butane, and

isobutene) and compressed gases such as nitrogen, carbon dioxide, and nitrous

oxide.

Advantages:

• Rapid onset

• at site delivery

• Less amount of drug required

• Less systemic absorption – less side effects

• No first pass effect

• Dose titration possible

• Acceptable & convenient to patient

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Disadvantages:

• Difficult to maintain particle size ≈ 2-8 microns and moisture content ≈ 100-300

ppm

• Only 10-20% drug is deposited at site

• Aerosol droplets facilitate microbial invasion

• Propellants can cause ADR

• Proper technique is difficult to maintain

Devices:

MDI ± Spacer

Nebuliser

Rotahaler

Inhaled insulin device

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Evaluation of aerosol

Flame projection

Flash point

Vapor pressure

Density

Moisture

Aerosol valve discharge rate

Spray patterns

Dosage with metered valves

Net contents

Foam stability

Particle size determination

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Dusting Powder:-

Free flowing

Applied on skin, wounds, ulcers

Very fine particle size produces large surface area per unit weight

Mechanical protective action against irritation/itching due to friction

Dries the skin by absorbing water & adsorbs toxic material

Medicated powders are used for prickly heat or preventing

microbial growth on skin

e.g. Starch, Talc

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Evaluation of powder

Shade control and lighting

Pressure testing

Breakage test

Flow property

Particle size and abrasiveness

Dispersion of color

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Intranasal Drug Delivery:- This route involves administration of drugs directly into the nose

Agents include nasal decongestants such as xylometazoline & corticosteroid like mometasone furoate.

Desmopressin is administered intranasally in the treatment of diabetes insipidus

Calcitonin, a peptide hormone used in the treatment of osteoporosis, is also available as a nasal spray

Ketorolac nasal spray for pain management

The abused drug, cocaine, is generally taken by intranasal sniffing

Applied via drops/sprays/powder or aerosols

Advantages of nasal delivery

• Lower dose needed

• More rapid attainment of therapeutic blood levels

• Quicker onset of pharmacological activity

• Fewer side effects

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Transdermal Drug Delivery

System (TDDS):-

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Topically administered medicaments in the form of patches or other

techniques, that deliver drugs for systemic effects at a

predetermined and controlled rate.

Transderm Scop® Patch, Novartis,1979- first FDA approved-

opened the door to the current TDDS as a successful alternative to

systemic drug delivery.

TDDS use the percutaneous route for systemic drug delivery, but

the skin is not the primary target organ, active ingredient is moved

across the layers of skin for subsequent systemic distribution.

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Advantages of TDDS:-

Consistent serum drug levels as IV

The lack of peaks in plasma concentration

Drugs that require relatively consistent plasma levels are very good

candidates

Convenience and high adherence

• non invasive

• usually once weekly /once in 15/30 days application

• removal of the patch in case of toxicity

Avoids FPM and GI irritation

Great advantage in patients who are nauseated or unconscious

Useful for drugs that are degraded by the enzymes and acids in the

gastrointestinal system

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Disadvantages:- local irritation

• rotation to minimize

• if severe allergic reactions- discontinue

skin's low permeability limits the number of drugs that can be

delivered

after removal, most patches contain at least 95% of the total amount

of drug initially in the patch

- patients must exercise care when disposing of patches

Damage to a transdermal patch

• patients should be advised to discard a patch if the outer

packaging or the patch itself appears damaged or altered in any

way

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Design of TDDS:

Patch design is the first & commonest type

Factors influencing:-

1. Properties of the drug- Systemic absorption of transdermal is better

with

• low dose

• low molecular weight

• lipid soluble drugs

2. Desired delivery profile

3. Target patient group

-- determine which design is best for a given application

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Components of a TD patch:-

Liner - protects the patch during storage, removed prior to use

Drug reservoir- drug solution in direct contact with release liner

Adhesive - adhere the components of the patch together and to the skin

Membrane – controls release of the drug from reservoir and multi-layer patches

Backing - protects the patch from the outer environment

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Types of TD patch:-

Single layer drug in adhesive

Multi -layer drug in adhesive

- immediate drug release layer

Vapour patch

- for releasing of essential oils in decongestion

Reservoir system

- liquid drug solution containing reservoir is embedded between an impervious backing layer and a rate controlling semi permeable membrane

Matrix system

- similar to that of the reservoir, but the drug is instead provided as a semisolid formulation, and there is no membrane layer

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Evaluation of patch

21-day cumulative

irritancy patch test

Kligman“maximization”

test

Draize-shelanskirepeat-insult

patch test

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Advanced designs for TDDS:-Jet injectors:-

Jet injectors are hand-held devices that deliver a high-pressure liquid stream

through a small nozzle orifice

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Iontophoresis:-• Technique involving the transport of ionic or charged molecules into tissue

by the passage of direct or periodic electric current through an electrolyte

solution

• Limitations: Hair follicle damage is possible

• E.g. Pilocarpine Iontophoresis in sweat test for Cystic Fibrosis

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Ultrasound (Phonophoresis / Sonophoresis):-

Skin is made permeable under the influence of ultrasonic waves

• Sonophoresis: involves the usage of the low frequency ultrasound waves. The

ultrasonic energy disturbs the lipid packing in stratum corneum by cavitation

• Phonophoresis: movement of drugs through living intact skin and into soft

tissues under the ultrasound perturbation. The technique involves placing an

ultrasound-coupling agent on the skin over the area to be treated and massaging

the area with an ultrasound source

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Microfabricated Microneedles Technology:-

This technology employs micron-sized needles (10 to 200 μm in height and 10 to

50 μm in width) made of silicon. These microneedles after insertion into the skin

create conduits for transfer of drug through the stratum corneum. The drug after

crossing stratum corneum diffuses rapidly through deeper tissues and are taken up

by capillaries for systemic action

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Penetration or Permeation Enhancers:-

Chemical penetration enhancers:

• reversibly reduce the barrier resistance of the stratum corneum without

damaging the skin cells

• E.g. Dimethyl sulphoxides, long chain alkanes, pyrrolidone, urea, alcohol,

surfactants

Skin ablation:

• doubling of the TEWL (Trans Epidermal Water Loss) using surgical tapes

• Microsecond thermal ablation- a promising mechanism to increase

permeability of the skin's outer barrier layer of stratum corneum while

sparing deeper living tissues to aid skin permeation

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Novel Topical Drug Delivery System:

Aerosol Foams:-

• becoming increasingly popular topical formulation

• vehicle base is of liquid or semi-solid, sharing the same physicochemical characteristics of conventional vehicles

• maintains desirable properties such as moisturizing/ fast-drying effects,higher drug bioavailability

• aerosol is dispensed through a gas-pressurized can

• In acne, foams may be preferred for application on large hairy surfaces or on the face as they are easy to apply

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Liposomes:-

• frequently used as vehicle for controlled and optimized delivery to skin layers

• spherical phospholipid vesicles whose membrane consists of amphiphilic lipid

(hydrophilic on outer side and lipophilic on the inner side) that enclose an

aqueous core

• thus they may encapsulate hydrophilic substances in their aqueous core and

lipophilic substances in their lipid bilayer.

• unique dual release capability enables the delivery of two types of substances

simultaneously once they are applied on the skin, which may enhance the

desired therapeutic benefit

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Niosomes:-

Niosomes are microscopic lamellar structures composed of non-ionic surfactants

and cholesterol

Carrier + surfactant = Proniosomes

Proniosomes + water = Niosomes

Niosomes and liposomes have similar application in drug delivery but chemically

differ in structure units. Niosomes constitute of non-ionic surfactant whereas

liposomes comprise of phospholipids

Mixture of acorbyl palmitate, cholesterol and highly charged lipid diacetyl

phosphate leads to the construction of vesicles named aspasomes. Aspasomes

are first hydrated with water/aqueous solution and then sonicated to attain the

niosomes

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Nano-emulsions:-

• class of emulsions - water-in-oil or oil-in-water, dispersion of very

small- sized droplets (5-200 nm) when mixed

• require unique thermodynamic conditions, specialized manufacturing

processes, and specific surfactants that can stabilize the nano droplets

• suitable for the transport of lipophilic compounds into the skin- ideal

vehicle for use in acne to increase the penetration of the active

compounds inside the lipophilic environment

• in addition, they do not clog the pores & can produce additional

therapeutic effects, such as increased skin hydration and

viscoelasticity

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Polymers:-

• large molecules consisting of repeating structural units or monomers connected

by covalent chemical bonds

• in pharmaceutical industry, there are new acrylic-acid polymers that turn into a

gel in the presence of water by trapping water into microcells. Inside these

aqueous microcells, hydrophilic compounds can remain in a solution, whereas

hydrophobic compounds may be dispersed in suspension. The result is a stable

gel like formulation that is easy to use and releases the active compound(s) once

they are applied on the skin.

• moreover, these polymer-based gels can be mixed with other excipients, such as

moisturizers and emollients, to provide additional clinical benefits.

• recently introduced anti-acne formulations that combine clindamycin 1% with

benzoyl peroxide 5% utilize this novel polymer-based gel technology that

exhibits efficacy and excellent tolerability.

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Microsponges:-

• biologically inert particles

• made of synthetic polymers with the capacity to store a volume of an active

agent up to their own weight

• the particles serve to protect the entrapped active compound from physical and

environmental degradation

• more frequently manufactured as gels

• once applied on the skin, they slowly release the active agent(s)

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Emulsifier-free Formulations:-

• growing area of development for dermatologic and cosmetic products

• most skin care products are emulsions - mixture of 2 or more materials

that are not miscible with each other, thus requiring addition of

surfactants (emulsifiers) that stabilize the formulation to guarantee an

adequate shelf life

• once these surfactant agents are applied on the skin, they tend to

emulsify and remove the natural lipids of the epidermis

• consequently, the pharmaceutical industry has been developing

surfactant-free emulsions as alternatives by using stabilizers, in order to

yield sufficiently stable products with a cosmetically pleasant appearance

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Fullerenes:- molecules composed entirely of carbon that resemble a hollow sphere

Rouse, et al., showed that once fullerenes come into contact with the skin, they

migrate through the skin intercellularly, as opposed to moving through cells

therefore, a fullerene could be used to “trap” active compounds and then release

them into the epidermis once they are applied on the skin

moreover, fullerenes, themselves, are thought to be potentially potent

antioxidants

they are well tolerated & hold substantial promise in dermatologic and cosmetic

applications.

Rouse JG, Yang J, Ryman-Rasmussen JP, et al. Effects of mechanical flexion on the penetration of fullerene amino acid- derivatized

peptide nanoparticles through skin. Nano Lett 7(1):155-60 (2007 Jan)

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Conclusion:-

• Topical preparations are used for the localized effects at the site of their

application by virtue of drug penetration into the underlying layers of skin

or mucous membranes

• The main advantage of topical delivery system is to bypass first pass

metabolism

• Avoidance of the risks and inconveniences of parenteral therapy and of the

varied conditions of absorption, like pH changes, presence of enzymes,

gastric emptying time are other advantage of topical preparations

• Iontophoresis, Electroporation, Sonophoresis, Phonophoresis, Vesicular

concept and Microfabricated microneedles technology are some advanced

technique which are being used to increase delivery through skin

• Semi-solid formulation in all their diversity dominate the system for topical

delivery, but foams, spray, medicated powders, solution, and medicated

adhesive patches are also widely used

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