Creams, ointments and topical preparations

What does topical mean?

Applied to any external body surface for a localised effect

E.g. eye, nasal mucosa, skin, scalp

What label goes on all topical formulations?

“For external use only”

Why do we give treatment locally to the skin?

• To enhance barrier function of the skin

• Targeted delivery to specific layers of the skin

  e.g. fungal infections are in the outermost part of the skin

  e.g. for eczema need to deliver drugs deeper into the skin

• Fewer side effects with topical preparation compared with oral delivery

How do topical formulations improve skin’s barrier function?

• Sunscreens protect against UV radiation

• Antibiotics for abrasions protect against infection

• Emollients (preparations that add moisture) improve dry skin conditions

• Moisturisers protect against drying atmospheric conditions

• Barrier creams prevent exposure of the skin to harsh chemicals

Describe the 3 main layers of the skin

• Epidermis

• Dermis

• Subcutaneous layer (hypodermis)

Describe where different components of the skin are located in each of the layers

• Stratum corneum is the outer layer of the epidermis

• Skin cells begin life in the stratum basale layer of the epidermis

• Blood vessels are present in the dermis but not the epidermis

• Sweat glands, hair follicles and sebaceous glands originate in the dermis

• Subcutaneous layer is fatty tissue and acts as a cushion for the skin

What topical dosage form should you select for application to the skin, depending on which layer of the skin needs treating?

• Skin surface = on the skin

• Stratum corneum = in the skin

• Viable epidermis = deeper in the skin

• Dermis = underneath the epidermis

• Skin appendages = hair, sweat glands, sebaceous glands, nails

Example of when we would need to treat the stratum corneum

Fungal infections present

What do we have to make sure about the formulation if treating the epidermis or dermis?

• The formulation must allow the drug to cross the stratum corneum

• AKA there must be percutaneous absorption of the drug

Types of topical dosage forms

• Semisolids e.g. ointments, pastes, creams, lotions, gels

• Topical solutions

• Soaps / shampoos

• Tinctures (alcoholic solutions)

• Powders

• Aerosols / foams

• Topical patches

What is an occlusive topical formulation?

• Occlusive means the formulation prevents water movement out of the body

• So an occlusive preparation increases skin hydration and moisture by ‘locking in’ the water present in the body

• Enhances skin barrier as forms a shield on skin

• Good for dry skin

• However, bad for infected skin

What are ointments?

What are the 2 types of ointments for the skin?

• Semisolid preparations intended for external application to the skin or mucous membranes

2 types:

1. Hydrocarbon ointments which are water soluble

2. Water soluble

Hydrocarbon ointments

What are the most common oils used?

• Soft paraffin is the most common ingredient

• Liquid paraffin or hard paraffin is used to thin or thicken the formulation as needed

Hydrocarbon ointments

Soft paraffin hydrocarbon ointments

What 2 types of soft paraffin can be used?

1. Yellow petrolatum Vaseline (petroleum jelly)

2. White petrolatum (white petroleum jelly) » has been bleached to remove yellow colour

Hydrocarbon ointments

What other oils can be used in hydrocarbon ointments?

• Vegetable oils from plant sources e.g. castor, olive, coconut

• Synthetic oils e.g. silicone oils » used as water repellants

• Isopropyl myristate » semisynthetic, similar properties to vegetable oil

Hydrocarbon ointments

What can cetostearyl alcohol be used for?

Thickening vegetable oils used in hydrocarbon ointments

Hydrocarbon ointments

Properties of hydrocarbon ointments

• Occlusive » forms a physical barrier on the surface of the skin, reducing water loss by preventing evaporation

• Emollient » hydrate skin due to moisture accumulation

• Skin hydration keeps skin supple

• Difficult to remove » cannot be removed with just water

• Greasy

• Good if drug not stable in water

Hydrocarbon ointments

Example of products

• Simple ointment » hard paraffin, soft paraffin, wool fat, cetostearyl alcohol

• Plantibase » liquid paraffin gelled with polyethylene

• Emulsifying ointment » soft paraffin, liquid paraffin, emulsifying wax

Water soluble ointments

What can water soluble ointments be made from?

Why is this useful?

• Polymers e.g. macrogol ointment AKA polyethylene glycol ointment

• We can control the length of the polymer to produce whatever type preparation we want

  e.g. longer chain polymer = higher melting point of ointment

• Can mix short and long chain polymers to produce different ointments with different melting points

Water soluble ointments

Properties of water-soluble ointments

• Water soluble

• Washable

• Non-greasy

• Not as occlusive as hydrocarbon ointments so they do not lock water in as well

Water soluble ointments

Examples of products with water soluble ointment bases

• Bactroban ointment

  » contains mupirocin composed of macrogol 400 and macrogol 3350

  » treats skin infections

• Iodosorb ointment

  » consists of iodine in a macrogol ointment base

  » used for wound management

Pastes

What are pastes?

• Ointments which have 20-50% solid material

• So they are stiffer than ointments

Pastes

What do pastes do?

• Provide a good protective barrier as water impermeable

• Prevent dehydration

• Prevent nappy rash (absorb ammonia from break down of urine)

Pastes

What is nappy rash paste made of?

What are its properties?

• Zinc oxide, starch, white petrolatum

• Has drying and protective properties

Creams

What are creams

• Creams have 2 phases, oil and water

• Can either be o/w or w/o

• Not as stiff as ointments

Creams

What must creams contain?

• Emulsifiers » to keep the droplets suspended

• Preservatives » to stop contamination as water is present in creams

Creams

What is the most common formulation of creams containing drugs?

o/w creams

Creams

Advantages of using creams for topical application

• Good patient acceptability

• Spreads easily

• Not as occlusive as ointments » lightweight and lets the skin breathe

• For o/w creams, water evaporates to leave a thin film on the skin

Creams

Examples of w/o emulsifiers

• Wool fat AKA lanolin » pale, yellow sticky material composed of fatty acid esters of cholesterol and other sterols

• Wool alcohols AKA lanolin alcohols » has more cholesterol and less impurities than wool fat

• Hydrous wool fat AKA hydrous lanolin » 7 parts wool fat and 3 parts water, softer than wool fat and wool alcohols

• Beeswax » contains fatty acid esters and long chain alcohols

• Calcium soaps » produced by mixing fatty acid with lime water

• Synthetic surface active agents » low HLB

Creams

Examples of o/w emulsifiers

1. Emulsifying waxes

• Emulsifying wax BP » contains sodium laurel sulphate and CSA (1:9)

• Cetrimide emulsifying wax BPC » contains cetrimide and CSA (1:9)

• Cetromacrogol emulsifying wax BPC » contains cetomacrogol 1000 and CSA (8:2)

• Each wax contains cetostearyl alcohol (CSA) and a surface active agent

2. Synthetic surface active agents » high HLB

Lotions

What are lotions?

• Liquids that contain insoluble solids which need to be suspended

Lotions

Why are lotions good topical formulations?

• Low viscosity so spread easily and are easy to apply

• Dry on skin quickly after application

Lotions

What are the components of calamine lotion?

Where does the pink colour of calamine lotion come from?

• Calamine, zinc oxide (solids)

• Glycerol » helps to keep the skin moisturised

• Phenol » antibacterial agent

• Bentonite » a clay which helps to keep the solids suspended in the lotion

• Water

• Pink colour comes from the iron oxide in calamine

What are liniments?

• A lotion with oils

• Similar viscosity to lotions but rubbed in with pressure

• May contain methyl salicylate or other materials which act to relieve pain and stiffness

What are powders?

Give an example

• Applied to the skin for a surface effect

  E.g. drying

  E.g. lubricating

  E.g. for antibacterial or antifungal action

• Made of fine particle size powders

E.g. Daktarin powder

What are tinctures / paints?

Give an example

• Alcohol based solutions

• Used for pre-operative disinfection

E.g. iodine tincture

Gels

What are gels?

• Gels are a dispersion of liquid within a solid where the solid is the continuous phase and the liquid is the disperse phase

• Usually transparent or translucent

• Require a gelling agent

Gels

Examples of natural gelling agents

• Tragacanth

• Pectin

• Alginate

Gels

Examples of synthetic gelling agents

• Synthetic polymers e.g. carbomer, cellulose

Gels

What do gelling agents do?

• Forms a cross-linked network in the liquid

• Allowing the dispersion of the liquid within the solid

Gels

What are hydrogels?

• Based on water

• Formed by a hydrophilic polymer selling in water

Gels

What are carbomer gels?

• Known for their stability, meaning they maintain their consistency and properties over time with minimal degradation

• Made up of carboxy vinyl polymers » in water, they form a low viscosity dispersion with an acidic pH

• When the dispersion is neutralised by adding an alkali, a gel is formed

• Types of neutralising agents:

  • Triethanolamine » used when formulation is water-based

  • Diisopropranolamine » used when formulation contains alcohol

Gels

Examples of topical gels

• Ibugel

• Isotrexin gel

What are topical patches?

Example?

• Hydrogel with a backing layer

E.g. Lidocaine to treat postherpetic neuralgia

What are collodions?

Example?

• Sticky liquid which dries to a film

• Used as a skin protectant

  » applied to skin to close small wounds, abrasions, cuts

  » keeps medications in contact with skin

E.g. Salactol to treat warts

What is the best topical formulation for sunscreens and why?

• Sunscreens must stay largely on skin surface

• So ointments too occlusive

• Gels, sprays, creams and lotions preferred

What is the best topical formulation for anti-fungal drugs and why?

• Fungal infections reside in the stratum corneum

• So anti-fungal drugs must be localised on the outer layers of the skin not in deeper layers

• So ointment not appropriate

• Gels, sprays, creams and lotions preferred

What is the best topical formulation to treat inflamed skin and why?

• Inflamed skin associated with problems in skin barrier

• Ointments preferred

What is the difference between transdermal delivery and topical delivery?

• Transdermal delivery aims to get the drug into the bloodstream whilst topical delivery does not

• Transdermal delivery avoids problems associated with oral delivery e.g. break down in stomach and gut

What is a transdermal patch?

Examples of drugs administered by patch and the corresponding transdermal patch name

• Adhesive patch placed on the skin to deliver medicine all the way through the skin and into the bloodstream

Drugs administered via patch:

• Fentanyl » Transiderm-nitro

• Nicotine » Nicotinell

• Nitroglycerine » Durogesic

• Estradiol » Estraderm

• Testosterone

Examples of transdermal gels

• Testogel

• Oestrogel

Limitations of transdermal patches or transdermal gels

• The skin is a good barrier and large amounts of drug cannot permeate

• Maximum attainable flux across the skin important to make sure not to exceed maximum daily dose