Topical Products: Creams, Ointments and Gels

Barrier function may be compromised; e.g. Neomycin in burn wound sepsis

How does skin composition/condition affect permeability?

Anesthetics ◼ Anti-acne ◼ Antibacterials, antifungals, antiparasitics ◼ Antiseptics ◼ Corticosteroids ◼ Cytotoxic agents, etc.,…...

Types of drugs that can be delivered through skin

Barrier augmentation by topical products; eg, Sunscreen for sunburn, diaper rash, insect repelliant etc

What is the goal for treatments strictly for the skin surface?

Emollients and hydroscopic substances (humectants)

What treatment options are meant to soften the stratum corneum?

Treats or prevents dry, rough and scaly skin by holding onto moisture that diffuses out of the SC. Replaces natural lipids that are lost

What are emollients?

Glycerin, propylene glycol, sorbitol urea etc. Increases the ability of SC by holding onto moisture by binding to the water from the dermis up tot he epidermis

What are Hygroscopic substances? (Humectants)

Treatment of calluses and corns; dandruff, psoriatic scale

What is keratolytics?

anti-perspirants (astringent effect), anti-acne

Treatments involving glands include

Inflammation of skin with scaliness, watery discharge and formation of crusts

What is eczema?

Hyperproliferaive disease characterized by the formation of red, scaly patches aprticualry on the elbows and knees

What is Psoriasis?

A viral disease characterized by a painful skin rash with blisters in a localized area

What is Shingles?

Topical corticosteroids and anesthetics (benzocaine and lidocaine)

How do you treat disease states that effect past stratum corneum?

science of the flow of fluids and their deformation under the effect of an applied force

What is rheology

Force per unit area (F’/A) required to bring about the flow/deformation

What is shear stresss

how much a body deforms relative its original dimensions

Shear strain

Rate of deformation; Difference in the velocity (dv) between 2 planes of liquid separated by the distance (dr)

Shear Rate (G):

independent

Is viscosity independent or dependent on shear rate?

Decreases

Increasing shear force ____ viscosity (pseudoplastic flow)

At rest, polymer chains are coiled up in a globular form. When stressed, polymer chains untangle and align in direction of flow

What happens to polymer chains when shear stress increases? when at rest?

Viscosity increases with increasing shear force

Dilatant flow

high consistency in container at rest: increased stability

decreased viscosity under shear: easy to spread or rub

What does shear thinning in cream/ointment indicate

delay in reversion to original viscosity which ensures product remains uniform long enough for dispensing the correct dose/applying before it thickens agfain

Thixotropy in formulation

Solid, relatively large quantities of solids (20-25%), thicker and stiffer than ointment, will not soften and flow after application, offer greater occlusion and emollient effect than ointments, more effective in absorbing serous discharge

Paste characteristics

viscous semisolid preparation

soften or melt at body temp

spreads easily, non-gritty

can be dissolved or suspended in ointment base

Ointment characteristics

Liquid phase constrained in a 3D polymeric matrix

Aqueous colloidal suspensions

Transparent non-greasy

Drug can be dissolved, or suspended

Gel characteristics

Viscous liquid or semisolid emulsions

W/O or O/W emulsions

easier to spread and remove than ointments

drug can be dissolved or suspended

Cream characteristics

None to very little; uses oleaginous bases

Epidermic skin penetration and examples bases

Into dermis; absorption base

Endodermic skin penetration

Into and through the ksin, uses emulsion

Diadermic skin penetration and examples bases

Oleaginous/hydrocarbon bases → Absorption bases → Water removable bases → water soluble bases

Ointments: base types in relation to water (oily to aqueous)

emoolient effect

Occlusive dressing

will not absorb water; protective to water labile drugs

difficult to wash-off/remove

Oleaginous base characteristics

insoluble in water, can absorb water

emollient

less occlusive than oleaginous bases

W/

Absorption bases characteristics

Water-washable

will absorb water

non/less greasy

can be diluted with water

non/less occlusive

better cosemetic appearance

Water-removable bases (O/W emulsion) characteristics

No oleaginous components

water soluble and washable

only small amount of liquid incorporated

6-25% of liquid is to be incorporated, 50g of the PEG 3350 may be replaced with stearyl alcohol

Properties of water-soluble bases

Glycerin, Propylene glycol, Peg 400

What are some levigating agents for an aqueous system?

Mineral oil, Castor Oil, Cottonseed oil, Tween 80

What are some levigating agents for oleaginous systems?

Highest melting point, then decreasing

In fusion, in what order are ingredients added based on melting points?

as it cools down; prevents the breakdown and evaporation of drug

When should heat labile or volatile ingredients be added to the congealing mixture?

• loss of viscosity,

• pH sshifts

• Drug degradation

• Discoloration

• Development of rancid odor

  • modification of drug release

What are some potential problems that can occur when creating an ointment

semisolid system consisting of suspensions made up of either small or large inorganic molecules in a liquid

Definition of a gel product

• appereance

  • smooth and elegant

• Easily compounded

• Topical or systemic product (transdermal and transmucosal)

• spreadability

• Absorbs water

• Water soluble and washable

  • non-greasy

Advantages of gel products

Large organic molecules or macromolecules uniformly distributed throughout a liquid with no apparent boundaries between dispersed macromolecules and the liquid

• continuous phase usually aqueous, sometimes alcoholic or oleaginous

What is a single phase gel

Large or small discrete particles disperesed throughout gel mass.

What is a two phase gel

Gel that has a particle size that is large (within a two phase system)

What is a magma

taking up a certain amount of liquid without a measurable increase in volumeWS

Imbibition definition

Taking up a liquid by a gel with an increase in volume

Swelling

Contration of gel;

interaction between particles of the disperesed phase becomes so great that on standing, the dispersing medium is squeezed out in droplets and the gel shrinks

Syneresis

semisolid on standing, but liquefy when shaken and regains original structure after some time

• two phase systems are thixotropy

Thixotropy

Local: pH, enzymes

External factors: Temperature, Light

What are some local and external factors that affect hydrogel

Changes in solubility

volume changes

ex:

• Polymethyl metyacrylate

• polyacrylamide

  • polyacrylic acid

pH changes in hydrogels induce what?