7. Topical Products

Question 1

Dermatologists aim at 5 main target regions:

Answer 1

1. Skin surface
2. Horny layer viable epidermis
3. Upper epidermis
4. Skin glands
5. Systemic circulation

Question 2

Rationales for topicals

Answer 2

• Build up of the skin’s barrier function with emollients, sunscreens etc
• Targeted delivery for skin’s outer layers - formulated to avoid systemic delivery
• Systemic drug delivery via transdermal patches (avoids 1st pass metabolism)
• Avoids GI tract

Question 3

Topical formulations - semisolids

Answer 3

• Ointments
• Creams (o/w & w/o)
• Gels (hydrogels, bioadhesive gels)
• Pastes

Question 4

Selection of excipients

Answer 4

• Should be safe & FDA approved
• Make up 90%+ of a topical product
• Improve drug/formulation solubility, permeability & stability
• Control drug release & permeation
• Prevention of microbial growth

Question 5

Commonly used excipients

Answer 5

• Solvents/co-solvents
• Humectants - glycerol
• Emollients - lipids
• Permeation enhancers
• Antioxidants
• Buffers
• Emulsifers - Surfactanrs
• Antimicrobials - alcohols

Question 6

Ointments

Answer 6

• Greasy preparations
• Biphasic vehicles - anhydrous with the active dissolved/dispersed in the base
• Occlusive - barrier to water loss
• Acts as emollient - softens skin

Question 7

Classification of ointment bases (5)

Answer 7

1. Hydrocarbon/Oleaginous bases:
   - Consists of soft paraffin or mix of hard paraffin
   - Water & aqueous ingredients can be incorporated into such bases in small amounts with difficulty
   - Melting point between 38 & 60 degrees - increases with chain length
2. Fats & fixed oils:
   - Non-volatile oils (vegetable origin)
   - Decompose upon exposure to air, light & high temp
   - Requires antioxidants
3. Absorption bases:
   - Contain emulsifying ointment (surfactant)
   - Bases soak up water while retaining their semi-solid consistency resulting in w/o emulsion
4. Emulsifying bases:
   - Oleaginous bases + high HLB surfactant (o/w)
   - Also known as water removable base
   - Anionic - emulsifying ointment
   - Cationic - cetrimide emulsifying ointment
   - Non-ionic - cetomacrogol emulsifying ointment
5. Water soluble bases:
   - Do not contain hydrocarbons/oleaginous components
   - Mix of high & low molecular weight PEG
   - Non-occlusive & easily washed from skin surface

Question 8

Selection of an appropriate base depends on:

Answer 8

• Desired release rate of drug
• Desirability for transdermal/topical drug effect
• Stability of drug in ointment base
• Effect of drug on consistency & other physical features of the base
• Occlusive or washable nature

Question 9

Preparation of ointment - incorporation method

Answer 9

Components of the ointment are mixed together until a uniform preparation has been obtained using:

• Mortar & pestle
• Spatula & ointment slab
• Reduces particle size of solid - not gritty texture
• Active may be added directly or by using compatible levigating agent

Question 10

Preparation of ointment - Fusion method

Answer 10

• Ingredients combined & melted together as they cannot be physically mixed

Question 11

Challenges of Fusion method

Answer 11

• Overheating can cause products to oxidise, discolour & degrade
• Mix phases at same temp
• High melting ingredients can solidify
• Phase separation - reheat & stir
• Low viscosity - add more high viscosity ingredients
• Poor dispersion - reheat & add more surfactant

When reheating use minimal heat

Question 12

Creams: O/W aqueous creams

Answer 12

• When applied on skin it evaporates & generates cooling sensation
• Non-occlusive but deposits moisturisers on the SC
• Vanishing creams

Question 13

Creams: W/O oily creams

Answer 13

• Preferred over ointment due to easy of spreading & removing & less greasy
• Occlusive layer forms on skin, reducing water evaporation - emollient effect
• Emollient/cleansing creams

Question 14

Creams: Overview

Answer 14

• Viscous semisolid for external application
• Mainly suitable for wet & weepy skin conditions
• Preferred by patients

Question 15

Gels

Answer 15

• (Semi)solid system with 2 consitutients - cross linked polymeric structure interpenetrated by a liquid
• Has low conc of gelato molecules (<15%)
• Liquify upon contact with skin & then dry as a non occlusive film

Question 16

Classification of Gels (2)

Answer 16

1. Organogels - prepared with organic or water-insoluble oleaginous materials
2. Hydrogels - Prepared with water or water-soluble materials

Question 17

Advantages & Disadvantages of Gels

Answer 17

Advantage: Easy to apply to hair bearing areas, non greasy

Disadvantage: Easily removed by perspiration, lack emollient & skin protective properties

Question 18

Hydrogels (3D)

Answer 18

• Semisolid formulation having an external polar solvent phase immobilised within a 3D network structure - cross linked
• Ability to absorb large amount of water & swell, while maintaining 3D structure

Question 19

Pastes

Answer 19

• Ointment containing as much as 50% powder dispersed in a fatty base
• High viscosity with good absorbing properties
• Less greasy than ointment alone

Question 20

Ointment vs cream

Answer 20

• Ointment used for very dry skin conditions

- Creams used for weeping skin conditions

Question 21

Barrier creams vs emollients

Answer 21

• Barrier creams contain dimethicone (silicone) to protect against water soluble irritants
• Silicone has water repellent properties
• Emollients soften & smooth skin
• Occlusive properties prevent water loss - correct drying
• Contains oils & humectants

Question 22

Keratolytics (KT)

Answer 22

• Helps with removal of outer layer of skin
• Found in many topical products for acne, psoriasis
• Enhances penetration of other topicals e.f. corticosteroids
• E.g. Salicylic acid, urea, benzoyl peroxide

Question 23

Nail lacquers- Actives

Answer 23

• Active ingredient is Ciclopirox (anti fungal)

Question 24

UV radiation (3)

Answer 24

UVA:

• Longest wavelength 315-400 nm
• Penetrates deep into skin surface
• Release free radicals -> DNA mutation -> carcinogenic

UVB:

• Longer wavelengths 289-315 nm
• Reaches skin surface
• Causes tanning, burning & skin ageing

UVC:

• Short wavelength
• 100-280 nm
• Do not penetrate earth

Question 25

Types of sunscreens (2)

Answer 25

Chemical sunscreens:

• Organic components that absorb UV
• Susceptible to photo-degeneration & generate free radicals
• Causes photo-irritant/sensitising reactions in susceptible individuals
• E.g. Avobenzone, Oxybenzone

Physical sunscreens:

• Inorganic components which reflect UV
• Broad spectrum UVs
• Benefit to those with skin sensitivity/irritiation
• Poor dispersion
• E.g. Oxides

Question 26

Sun Protection Factor (SPF)

Answer 26

• Measure of sunscreen effectiveness
• SPF = MED (protected skin) / MED (unprotected skin)
• MED: Minimum amount of UV that produces redness 24 hours after exposure
• SPF factors is not linear
• Used to determine level of protection

Question 27

Sun exposure - personal & environmental factors

Answer 27

• Individual response
• UV index
• Time of day
• Index of exposure of that region of the body