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Routes of Administration

1. Topical

applied directly to the skin

for systemic absorption and consequence

systemic effect

Transdermal Patch

o Outer: covering; waterproof

o Inner: for slow release of drug to

circulation

o Middle: medicine reservoir

Semisolid Preparation:

o Ointment, cream, gel, etc.

2. Intralesional

direct contact with underlying pathologic

process

no first pass metabolism

a drug depot that slowly releases the

active ingredient of the drug

3. Systemic

Oral:

♦ capsules, tablets

♦ syrup, oral suspension

Parenteral:

♦ IV, IM, SC

DRUG DELIVERY IN DERMATOLOGIC DISEASES:

1. through intact stratum corneum

2. through sweat ducts

3. through sebaceous follicle

Characteristics of Topical drugs:

1. Low molecular mass (600da)

2. Adequate solution in oil and water

3. High partition coefficient

Major Steps in Percutaneous Absorption :

1. Establishment of a concentration gradient,

which provides the driving force for drug

movement across the skin

2. Release of drug from the vehicle (partition

coefficient)

3. Drug diffusion across the layers of the skin

(diffusion coefficient)

Factors that Affect Percutaneous Absorption:

1. Dosage

♦amount of drug should be sufficient to cover

affected body surface

♦approximately 30 g is required to cover the whole

body surface

♦Sufficient contact time

Subject: Pharmacology Topic: Dermatologic Pharmacology 1 Lecturer: Dra. Dela Cruz Date of Lecture: 19/7/11 Transcriptionist: ior and yhtak Editor: ted failon Pages: 7

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2. Regional Anatomic Variation

♦permeability is generally inversely proportional to

the thickness of stratum corneum

♦drug penetration is higher on the face, in

intertriginous areas or skin sites with opposing

surfaces e.g. axilla, groin and inframammary areas

(This areas have thin stratum corneum)

♦vulnerable to drug related toxicity

3. Integrity of the skin

♦intact skin provides a formidable barrier for

passage of drugs

♦disrupted epidermal layer allows drug to readily

pass (compromised barrier function)

e.g. inflammation

Abnormal stratum corneum (i.e.

psoriasis)

4. Hydration

♦increase in the water content of the stratum

corneum due to inhibition of transepidermal loss of

water

♦increases drug penetration

♦hydration causes swelling of the stratum corneum

making it more permeable to drug molecules

Methods of Hydration:

4.1. Occlusion with an Impermeable film

4.2. Application of Lipophilic Occlusive vehicles e.g.

Ointments

(AN EXAMPLE OF OCLUSIVE DRESSING)

5. Vehicle

♦solvent through which most drugs for topical

administration is incorporated

♦markedly influence ability of drug to penetrate the

outer layers of the skin

6. Age

♦drug penetration is generally greater in infants and

in elderly because they have thinner stratum

corneum

♦children have a greater ratio of surface area to

mass than adults, so greater systemic absorption of

topical drugs

7. Lipid Solubility of Drug

♦lipid soluble compounds diffuse through lipids

within the stratum corneum

Dermatologic Vehicles

1. Dimethyl sulfoxide (DMSO)

♦penetrate deeply into the skin without damaging it

and carry other compounds deeper into the biologic

system

♦predominantly used vehicle for topical analgesics,

anti-inflammatory and anti-oxidant

2. Propylene glycol

♦vehicle for organic compounds

♦also an effective Humectant and increases the

water content of the stratum corneum

♦Keratolytic at 40-70% concentration

3. Urea

♦also possess hygroscopic property

♦makes cream and lotion less greasy

4. Liposomes

♦are concentric spherical shells of phospholipids in

an aqueous medium that may enhance

percutaneous absorption

♦penetrate compromised epidermal barriers more

efficiently

♦variations in size, charge and lipid content can

influence liposome function

5. Microgels

♦are polymers that may enhance solubilization of

certain drugs to enhance penetration and decrease

irritant effects

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Characteristics of an Ideal Dermatologic Vehicle:

1.Easy to apply and remove

2.Non-irritating, inexpensive

3.Odorless, non greasy

4.Cosmetically pleasing

5.Active drug must be stable in the vehicle

6.Active drug must be readily released once in

contact with the skin

Types of Dermatologic Preparation

1. Powder – Talc, Starch

♦consist of very fine particle size, which covers a

large surface area of the body

●absorb moisture and reduce friction

●soothing and cooling effect

●adhere poorly to the skin

2. Ointment

♦semisolid preparation intended for external

application to the skin or mucous membranes

♦creates and oily residue increase hydration of

stratum corneum

♦occlusive effects prolong and enhance drug

penetration

♦not suitable for weeping lesions

♦useful in chronic, dry lesions

♦anhydrous nature does not require preservatives

♦Typical ointment bases:

1.Petrolatum

2.Polyethylene glycol

3.Lanolin

♦good skin penetration and adherence to surfaces

♦NOT for wet lesions

3. Creams

♦classified as water-in-oil or oil-in-water

formulations

♦less messy and less occlusive than ointments

♦dry quickly

♦contain water so prone to bacterial or fungal

contamination

♦drying effect

♦preferred form for exudative dermatoses and for

use under wet dressings

♦for wet lesions

4. Emollient

♦substances in liquid form that soften and soothe

the skin

♦component of lipstick, lotion and other cosmetic

products

♦essential component is lipid

♦ Three different types of emollient

1. Oil in water emulsion – cream

2. Water in oil emulsion – ointment

3. Water free preparation – fatty ointment

♦provides a layer of oil on the surface of the skin to

slow water loss and thus increase the moisture

content of the stratum corneum

♦also known as:

●Moisturizer

●Lubricant

●Vanishing cream

♦employed as protective and as skin softening

agent

♦also serve as vehicles for more active drugs

(AN EXAMPLE OF AN EMOLIENT)

5. Lotion

♦usually applied to external body surfaces e.g. skin

with bare hands

♦used to soften and smoothen skin or used to

deliver medications to the skin

♦less viscous than cream or ointment

♦medicated lotions may contain:

●Antibiotics

●Antifungals

●Corticosteroids

●Antiseptics

●Skin Whitening

●Antipruritics

♦applied thinly on external body surface such as the

skin, scalp

♦cover a larger body surface area

♦applied to the skin more frequently without

rubbing

6. Gels

♦sticky, jelly-like semisolids or solids prepared from

high molecular weight polymers in an aqueous or

alcoholic base

♦liquefies upon contact with the skin

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Two Kinds of Gels:

1. Alcoholic gels

♦hand sanitizers

♦best suited for acute exudative, pruritic

eruptions

2. Non-alcoholic gels

♦ hair gels, sunscreens

♦more-lubricating best suited for dry scaly

lesions in the scalp

7. Liniment

♦viscous liquids containing substances possessing

analgesic, soothing or stimulating properties

♦should be rubbed when applied to the skin to

release active drug

♦should not be applied to broken skin

♦similar viscosity as lotion

8. Astringent

♦forms a protein precipitate which serve as a

protective coat allowing new tissues to generate

underneath

♦check oozing discharge or bleeding in skin and

mucous membrane by coagulating protein

♦commonly used to reduce extent of weeping

dermatitis

e.g.

•Zinc oxide

•Burrow’s solution

9. Humectants

♦substances that diffuse into the stratum corneum

and attract water

♦substances that promote water retention due to

their hygroscopicity

e.g. glycerine, urea, pyrrolidone carboxylic acid

(PCA), sorbitol

10. Collodion

♦liquid preparations consisting of a solution of

proxylin in a mixture of ether and alcohol

♦painted on the skin and allowed to dry to leave a

flexible film over the site of application

♦used to seal minor cuts and wounds or as a means

to hold a dissolved drug in contact with the skin for

prolonged periods

(TREAT WITH A COLLODION)

11. Paste

♦stiff preparations containing a high proportion of

finely powdered solids such as Zinc oxide, calcium

carbonate or starch

♦forms an unbroken, relatively water impermeable

film on the skin surface

♦less occlusive and messy than ointments

♦suitable for subacute or chronic dermatoses

♦useful for local application of irritating drugs

Corticosteroids

Mode of administration:

1. Local

♦Topical

♦ Intralesional

2. Systemic

♦Oral

♦Intramuscular

♦Intravenous

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Corticosteroid

Mechanism of action:

** Remember that steroids and lipid soluble drugs

utilizes a transcription factor type of hormone

receptor to enter the nucleus. (type 4 receptor)

Corticosteroids:

♦Anti-inflammatory

●inhibition of Phospholipase A2

♦Immunosuppression

♦classification of Topical Corticosteroids in order of

decreasing potency

♦more potent steroid is used initially followed by a

less potent agent

♦twice daily application is sufficient

♦more frequent application does not improve

response

Classification of Topical Corticosteroids:

(GIVE IMPORTANCE TO DRUGS WITH ASTERISK AS

THEY ARE THE PROTOTYPE DRUGS)

Class 1 - Highest Potency

♦Clobetasol propionate 0.05%

♦Betamethasone dipropionate in optimized vehicle

0.05%

Class 2 - High Potency

♦Fluocinonide 0.05%

♦Betamethasone dipropionate 0.05%

Class 1

♦Betamethasone dipropionate cream, ointment

0.05% (in optimized vehicle)*

♦Clobetasol propionate cream, ointment

♦Diflorasone diacetate ointment 0.05%

♦Halobetasol propionate ointment 0.05%

Class 2

♦Amcinonide ointment 0.1%

♦Betamethasone dipropionate ointment 0.05%*

♦Desoximetasone cream, ointment 0.25%, gel

0.05%

♦Diflorasone diacetate ointment 0.05%

♦Fluocinonide cream, ointment, gel 0.05%

♦Halcinonide cream, ointment 0.1%

Class 3

♦Betamethasone dipropionate cream 0.05%*

♦Betamethasone valerate ointment 0.1% \

♦Diflorasone diacetate cream 0.05%

♦Fluticasone proprionate 0.005%

♦Mometasone furoate 0.1%

♦Triamcinolone acetonide ointment 0.1%, cream

0.5%

Class 4

♦Amcinonide cream 0.1%

♦Desoximetasone cream 0.05%

♦Fluocinolone acetonide cream 0.2%*

♦Fluocinolone acetonide ointment 0.025%*

♦Flurandrenolide ointment 0.05%, tape 4 mg/cm2

♦Hydrocortisone valerate ointment 0.2%

♦Triamcinolone acetonide ointment 0.1%

♦Mometasone furoate cream, ointment 0.1%

Class 5

♦Betamethasone dipropionate lotion 0.05%*

♦Betamethasone valerate cream, lotion 0.1%

♦Fluocinolone acetonide cream 0.025%

♦Flurandrenolide cream 0.05%

♦Hydrocortisone butyrate cream 0.1%

♦Hydrocortisone valerate cream 0.2%

♦Triamcinolone acetonide cream, lotion 0.1%*

♦Triamcinolone acetonide cream 0.025%

Class 6

♦Aclometasone dipropionate cream, ointment

0.05%

♦Desonide cream 0.05%

♦Fluocinolone acetonide cream, solution 0.01%*

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Class 7

♦Dexamethasone sodium phosphate cream 0.1%

♦Hydrocortisone cream, ointment, lotion 0.5%,

1.0%, 2.5%*

♦Methylprednisolone aceponate cream, ointment 1

mg/g

♦Prednisolone cream 5 mg/g

Topical Corticosteroids

Selection Criteria:

1.Type of skin lesions

2.Location of the skin lesions

3.Severity of skin lesions

4.Age of the patient

5.Duration of treatment

Comparative Indications of Topical Corticosteroids

Low-Med

Potency

High Potency

Type of

lesion

Thin, acute Chronic,

hyperkeratotic,

lichenified,

endurated

Site areas with

thin

stratum

corneum

recalcitrant

lesion in face

and

intertrigneous

areas

Palms and soles

Extent or

size of

lesion

Large

areas

Smaller areas

Age of

patient

Young and

elderly

Adults

Duration of

treatment

longer not > 3 weeks;

longer for

recalcitrant

lesions

Topical Corticosteroids

(Preparation)

Ointment

♦is the most effective preparation for treating thick,

fissured, lichenified skin lesions

●choice for dry dermatoses

●the occlusive nature enhances corticosteroid

penetration

Creams

♦preferred for acute and subacute dermatoses

●used in moist skin and in intertriginous areas

●preferred for weeping or wet lesions

Lotions

♦preferred for lesions:

●in hairy areas

●involving large body surface areas

Topical Corticosteroids

(Site of the Skin Lesions)

♦face and intertriginous areas (axilla, groin,

perineum, and inframammary area) has thin

stratum corneum

●susceptible to local and systemic adverse effects

♦recalcitrant lesions of the face or intertriginous

areas may require more potent corticosteroids or a

longer duration of treatment

Topical Corticosteroids

(Special Considerations)

♦use the lowest potency corticosteroid that is

effective, especially in infants and children

♦use of topical corticosteroids under plastic wrap,

tight-fitting clothing, or under diapers may increase

absorption several fold

♦apply very thinly

Systemic Corticosteroids

♦ used for severe dermatologic conditions such as:

● allergic contact dermatitis to plants

e.g. poison ivy

● life-threatening vesicolobullous dermatoses e.g.

-pemphigus vulgaris

-bullous pemphigoid

♦ usually given in the morning to coincide with

circadian rhythm of endogenous steroid secretion

♦chronic administration predispose to greater side

effects

♦with chronic therapy, need to taper dose gradually

before stopping treatment

** It is best to give corticosteroids in the morning to

coincide with the endogenous cortisol that our body

produces.

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Local Adverse Effect:

-impaired wound healing

-brusing

-skin thinning

-striae (also known as stretch marks)

END OF TRANSCRIPTION

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