Lecture 23 - formulation of preparations

Question 1

what are topical products used to achieve local effects ?

Answer 1

surface of the skin eg tiO2, UVA/ UVB sun cream
stratum corneum - used in the treatment of psoriasis, ichthyosis
epidermis - eczema, psoriasis, lichen plants and keratosis
dermis and epidermis - dermis interface eg warts, urticaria

Question 2

what are topical products that are used to achieve systemic effects?

Answer 2

HRT - menopause, andropause
nicotine - NRT
GTN - angina, anal fissures
hyoscine - Travel sickness, vertigo
fentanyl/ buprenorphine - analgesia

Question 3

what are the 3 tissues the human skin is comprised of?

Answer 3

epidermis, dermis and subcutaneous

Question 4

what are the functions of these tissues?

Answer 4

containment of body fluids and tissues
protective barrier eg microbial, chemical and radiation
reception of external stimuli eg pain, tactile, thermal
identification and/or attraction (apocrine secretion)
body temperature regulation - blood loss, sweats
synthesis and metabolism - vitamin D3

Question 5

describe the properties of stratum corneum as the barrier of the skin

Answer 5

stratum corneum is the largest Barrier of drug diffusion thorough the skin. moisture levels is 15-20% of dry weight. highly hydrated when the skin is occluded or covered

two main types of drug passage through the skin
transcellular and intercellular (enhanced when skin is occluded)

Question 6

describe the properties of the dermis as a barrier in the skin

Answer 6

there dermis is 1-4mm in thickness and comprises of a matrix cosnsitign of blood vessels, lymph vessels and nerves.

the cutaneous blood supply has an essential function in regulating the body temperature. it also provides nutrients and oxygen to the skin and removes wastes and toxins.

dermis provides a concentration gradient for transdermal drug permeation

Question 7

what is the concentration of drug n the first layer of membrane -Cs- dependant upon?

Answer 7

it is dependant upon the drug concentration dissolved in the delivery vehicle and the drug partition coefficient K between delivery vehicle and skin

Question 8

how are dermal penetration enhancement mediated?

Answer 8

direct enhancement of the skin permeability (some may cause permanent disruption to the stratum corneum): solvents eg ethanol., DMSO, DMF, amphiphilles eg anionic/ cationic/ non-ionic, pants derives eg terpenes and ureas

increasing the thermodynamics (solubility), the kinetic activity of the API and the resultant concentration gradient of the diffusing species

Question 9

describe creams as topical preparations

Answer 9

creams are a semi-solid, emulsions made for external use. emulsion are mixtures made of two or more immiscible liquids - unstable systems are stabilised by the addition of an emulsifier (surfactant). oil in water and water in oil phases available. hydrophobic drugs such as corticosteroids can dissolve in the oil phase of the emulsion.

Question 10

describe the stabilisation of a cream

Answer 10

The oil in water interface is stabilised by the addition of emulsifying agents - reduces interfacial tension. the o/w systems excess emulsifying agents such as ionic/ non-ionic surfactants or fatty alcohols interact with the bulk phase of water and traps a proportion of the gel network. increased viscosity prevents the dispersed oil phase droplets from coalescing.

Question 11

why do some creams contain preservatives?

Answer 11

some creams may also have preservatives as they are non-sterile multi-dose units products that can promote microbial growth as they have water present

Question 12

describe ointments

Answer 12

ointments are semi-solids that have less than 20% water and volatiles and more than 50% hydrocarbons, waxes and polyenes as the vehicle. ointment bases that are used as vehicles are divided into 4 classes:

hydrocarbon bases eg paraffin and microcrystalline - occlusive, use an emollients

absorptive bases that can incorporate additional water into them, use as an emollient

water - removable bases (o/w cream)

water -soluble bases contain PEG

Question 13

when are ointments useful in patients clinically?

Answer 13

ointments are preservative free as they do not contain preservatives as they down have water to support microbial growth so beneficial in patients with preservative allergies

Question 14

why is 17-ester more potent than 21-ester in betamethasone?

Answer 14

17-ester is more potent than 21-ester in betamethasone as it is esterase resistant - accumulates and remains in the epidermis for an extended period of time.

Question 15

what is the dose of FTU?

Answer 15

2 FTUs is equal to 1g topical, dosage likely to be per day, so if 1g per day than 30g tube lasts 30 days

Question 16

what is patient counselling required for the use of topical preparations ?

Answer 16

patient should clean the affected skin well with warm water and soap and apt it dry with a soft cloth before applying any product

ointments, goes and creams may be applied with clean fingers to form a thin layer over the affected area according to FTUs

touching eyes, mouth and any other area of the body should be avoided when applying a topical product

after each application, it is important to wash the hands thoroughly with soap and warm water
- minimises systemic absorption of the drug from the fingers
- prevents contamination of other region of the body with drug region