Topical

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Topical Drug Delivery
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1.Anatomy of the skin
Hair follicle
Sebaceous gland
Stratum corneum
(0.8mm 0.006mm)
Epidermis
Dermis
(3 5mm)
Subcutaneous tissue
Hair matrix
Endocrine sweat gland
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2. Topical preparations

1. Retinoic acid (acne)

2. Tetracycline (sores)
3. Corticosteroids (psoriasis)
4. Bacitracin (ecthyma)
5. Coal tar extracts (contact dermatitis)
6. Cromatin (scabies)
7. Zinc oxide (general healing)
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3. Functions of skin
1. Containment function

• 2. Protective function
• Microbial barrier
• Chemical barrier
• Radiation barrier
• Electrical barrier
• Mechanical barrier
• Heat barrier

3. Temperature regulation
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4. Rational approach to topical treatment
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5. Target regions of topical treatment
Interfacial boundries Penetration routes Some
treatments
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Interfacial boundries Penetration routes Some
treatments
(5) Circulation Removal via 1.
Transdermal circulation system 2.
Nitroglycerin
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(1) Diffusion - random molecular motion. Must
have concentration gradient.
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6. 1 Ficks second law of diffusion
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6. 2 Complex diffusional barriers
Stratum corneum
Epidermis
Dermis
Where, Rt Total diffusing resistance Pt
Thickness weighted permeability coeff.
Series
Subcutaneous
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Parrallel
Sebaceous gland
Hair follicle
Sweat gland
FOR EACH
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7. Factors influencing the rate of
percutaneous diffusion
1. Diffusant solubility (C0)
2. Partition coefficient (K)
3. pH variation (K)
4. Co-solvents (K and C0)
5. Surface activity and micellization (C0)
6. Complexation (K)
7. Diffusivity (D)
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Answer 1.
Because the unionized is so low, it should
not partition well into the membrane.
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9.1 Biological factors
9.1.1. Skin age 9.1.2. Skin condition 9.1.3.
Regional skin sites 9.1.4. Skin
metabolism 9.1.5. Circulatory effects
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9.2 Physicochemical factors
9.2.1. Skin hydration 9.2.2. Drug/skin
binding 9.2.3. Temperature 9.2.4. Penetration
enhancers 9.2.5. Drug/vehicle interaction
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10.1 Surfactants
Enhance transport of polar drugs via (1)
Solubilization and removal of intercellular
lipids. (2) Interaction and binding to
keratin filaments of intracellular matrix
resulting in disruption of cell order.
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10.2 Penetration enhancers
Enhance transport of polar drugs via (1)
Extraction of stratum corneum lipids,
lipoproteins, and nucleoproteins. (2) Loosening
of the polymeric structure of the
keratinocyte of the cytoplasmic
matrix. (3) Changing the solvent properties of
the stratum corneum.
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10.3 Non passive transport?
Compounds like disopropanolamine and
isopropyl myristate may help transport drugs via
active Mechanisms, i.e. carrier mediated
transport.
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1- dodecylazocycloheptane 2- one
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11. Methods for studying percutaneous absorption
11.1 In vitro methods
11.1.1 Without a rate limiting membrane
stirrer
Ointment
Alcohol in water
Chloroform sink
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11.1.2 With a rate limiting membrane
Donor compartment With formulation
Membrane (cellulose acetate, Silicone, Isopropyl
myristate)
Sampling port
Receptor compartment (mainly chloroform)
Bar magnetic stirrer
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11.2 In vivo methods
11.2.1 Direct methods

• Measurement of Pharmacological response
• Antihypertensives by means of measuring blood
  pressure
• Antihistamines by means of measuring the
  reduction in swelling

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12. Dermatological formulations
12.1 Liquid preparations
Liniments Sloans Embrocation Methyl salicylate
Lotions Histamed Mepyramine maleate
Paints Pyralvex Extract rhei, salicylic acid
Ear drops Waxol NF Docusate Na
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12.2 Gels
Indocid Indomethacin
Voltaren emulgel Diclophenac Na
12.3 Powders
Cicatren Neomycin sulphate
Mycota powder Zn undecanoate, undecanoic acid
12.4 Ointments
Betnovate ointment Betamethazone
Betadine ointment Povidone - iodine
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12.5 Gels
Acnidazil cream Miconazole nitrate
Lotocreme Hexachlorophene
12.6 Aerosols
Solarcaine spray Benzocaine
Mycota spray Zn undecanoate, undecanoic acid
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13. Transdermal Therapeutic Systems
Nitroglycerin lactose in silicone
Impermeable plastic laminate
Rate controlling EVAc membrane
Adhesive
Releases 0.5mg/cm2 per day
Transderm-Nitro
The rate of permeability of the drug through the
rate controlling Membrane must be less than that
of the tissues.
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13.1 Advantages of TTSs
1. Eliminates oral absorption variables.
2. Eliminates first-pass metabolism
3. Provides controlled constant drug.
4. Can accommodate potent drugs
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13.2 Examples of TTSs
Nitoderm TTS - 25mg and 50mg nitroglycerin
Nicotinell TTS - 17.5 mg, 35mg, and 52.5mg
nicotine
Etraderm TTS - 2mg, 4mg, and 8mg estradiol
Scopoderm TTS - 1.5mg scopolamine
Nitradisc TTS - 16mg and 32mg nitroglycerine
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14. Iontophoresis
Constant current generator
Buffer
Drug formulation
D
A2-
Anode
Cl-
A1-
Cathode
Na
H
Skin (indifferent site)
Skin (application site)
Blood
CAN VARY VIA CURRENT MANIPULATION
Release is controlled by (1) ionization of
drug (2) rate of migration to opposite electrode
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