SL22107-Lec P12: Topical Drug Delivery 2

what are some considerations in formulation of pharmaceuticals

• Interactions of vehicle with skin (but be careful of risk of damage of stratum corneum)

• Interaction between drug and vehicle

Why can vehicles be irritating to the skin

May induce an immunological response if skin barrier is damaged

Drug physicochemical properties

• MW

• Lipophilicity

• H-bonding ability

• Solubility in solvents

all these properties are assessed via a decision tree

Describe 4 types of formulation

O/W: can cause occlusion

W/O

Anhydrous absorption

Hydrocarbon

What is preferred for chronic skin disease

hydrocarbon-based formulations preferred for their occlusive and protective properties

good emollients

limited release system due to poor solubility

anhydrous fomrulation and hydrocarbon

Anhydrous formulations are usually very sticky and greasy, providing a  high level of skin occlusion.

Water free formultions

Semi-solid system

PEG or triglycerides

used for psoriasis, eczema

used for small areas of application

Steroid ointment

Composed of

oil

surfactant: stabiliser allows movement of drug from oil into mortar (lipids) of the skin

Buffer system: baalnces. PH

preseratives

Polar gel

Single phase

water + alcohol based, low lipid content

not good for psorasis and excema as it is drying

preferred for anti-allergics, anti inflammatories

Gelling agents

thickens solutions and suspensions

ØHydrogels containing a dispersed lipid phase = emulsion gel (e.g., emulgel*).

ØSuspension gels = suspensions of water-insoluble drugs in hydrogels

Anti-virals

are slightly basic

may change pH balance

causes immunological response

Gel formulations

Hydrogels: holds water semi solid large molecules interpenetrated with water

Emugel: 2 phase system

usually transparent or small semi solids

readily absorbed

cool: evaporative cooling of skin due to latent heat of evaporation

However residual film formulation of polymers

Creams

Emulsion: 2 immiscible liquids

requires emulsifies to stabilise O/W

dispersion of O/W determines on strucute and arrangment of micelles

w/o creams

lotion: hydrophobic semi liquid water and lipid phase

cream: hydrophobic semi'-solid water and lipid phase

2 phase system

hydrating

treats psorasis

O/W

Lotion: hydrophilic, semi sold, 2 phase

Cream: hydrophilic, semi solid, 2 phase

Dry skin: coats the area

treats acne

low lipid replenishing effect

hydrating

non-occlusive

cooling

emulsions

o/w emulsions more cosmetically appealing (less sticky and greasy) as lipids therein are finely dispersed.

however, o/w emulsions can withdraw moisture from skin due to surfactant-like emulsifiers (SC lipid extraction/perturbation).

ointment vs cream

non-equivalence

have different pharmacological outcome in terms of efficiency, consistency also rate of delivery and concentration

Vehicles of delivery

Absorption base: composed of hydrocarbon base which is largely inabsorbed by skin

liposome: phospholipid outer layer and hydrophilic core

nanoemulsion: vesicles of phospholipid, surfactant, lipid + water

microemulsion: smallest, tiny emulsions of lipophilic and hydrophilic surfactants in water

emulsifier free system

2 phases

semi solid

hydrophilic and continuous aqueous phase and lipids

multiple emulsion

3 phases

semi solid

hydrophilic

hydrophobic

spray emulsion

e.g. sunscreen

needs to hit skin and coat the skin

difficult for permeation of drug

foam/mousse

gas dispersion in liquids

lipids + water

stablasised with surfactant

water free systems

2 non-miscible phases

partitions from one phase into the other

Lacquers

e.g. nail polish

polymeric firm builds

used for skin and nail

what is formulation metamorphis

when a formulation is applied to the skin it changes dynamically over time

due to absorption, reaction with skin, characteristics, concentrations, time to reach max saturation

as its rubbed into the skin

volatile excipients evapoate

increased viscosity of formulation

what can rubbing cause

increases elasticity leading to emulsifying effects

what can evaporation lead to

desired cooling effect

desirable for repellent/fragrance

Can increase or decrease drug solubility and skin penetration

changing to supersaturated system leading to increased flux rate

solvents/co-solvents

used to alter solubility of drug in stratum corneum

can enhance delivery

e.g. PEG can limit dehydration of skin

however if improperly prepared can lead to mass poisoning

nsaids

targets cox inhibits cox 2

reduces prostaglandins, leukotrines

decreased mucus

gi effects

considerations of delivery

• targeting pathways

• targeting pain site

• regional differences due to different properties in the populations skin

• side effects

• bioavailability

gels

used to treat muscle and joint pain for inflammation e.g. NSAID

through SC delivery

good for local inflammation reduces side effects of systemic exposure

good distribution with systemic side effects

diffusion and partition of NSAIDS

mostly water soluble

alcohols on skin

Hydrophilic

Very volatile substance it will evaporate on the skin which can be safe in some instances as it does’t absorbed into the skin less risk of systemic effects

non newtonian

its solid when force isn’t applied as gravity doesn’t affect it

no distribution no flocculation

which leads to consistent dosing

decision tree

water/oil soluble, does it partition?

do we choose cream, ointment, lotion

intended location skin surface, does it need to travel to a target site