Week 1 - Intro To Semi-solid Formulations

Question 1

Describe the Structure of the Skin

Answer 1

3 Layers:
1. Epidermis
- has NO blood flow BUT has live cells undergoing mitosis = these cells get O2, H2O, nutrients etc,
- protects skin = also a barrier to drug delivery
- drug needs to be carried through epidermis into dermis (to enter body)
- has layer of dead cells (flattened cells)

2. Dermis
3. Hypodermis
   - subcutaneous injections are injected into this layer

Other:
- Hair folicles affect drug delivery
- Sweat glands secrete sweat onto skin which maintains low pH
- Have sensory cells in skin e.g. merkel cells

Question 2

List potential ways of drug delivery through skin

Answer 2

• Oral
• Topical
• Nasal
• Occular (eye)
• Rectal
• Aural (ear)

ALL routes EXCEPT RESPIRATORY (NO inhaled semi-solds)

Question 3

What is Transdermal Drug Delivery

Answer 3

Transdermal = delivery through the skin

• Sometimes we DONT want drugs to enter circulation, want to use the drug locally (NOT systemically)
• But some drugs can pass through skin
• Transdermal routes have a lag time (time depends on the route drug has to take)
  - skin saturates with drug = will see movement of drug into body even if drug has been removed / wiped off
  - lag time is realted to membrane thickenss + diffusion co-efficient

TYPES of Delivery Routes
1. Intracellular route - drug travels through matrix between dead vells
2. Follicular Route = drug goes through hair
3. Ecrine route - along sweat glands

Question 4

How does the resistance model explain transdermal drug delivery and formulation

Answer 4

4 Types of Resistance
R1 = vehicle resistance (drug diffusing out of the vehicle)
R2 and R3 = 2 diff. pathways / routes drug can go down
- R2 has small fractional area = high ressistance
- R3 = stratum corneum resistance
- stratum corneum is defining capacity
R4 = Drug diffusing to where we want it to be

If route has large fractional area = resistance is low

Question 5

List the possible Adminstration routes for semi-solids

Answer 5

• Oral
• Nasal
• Topical
• Rectal
• Occular
• Aural

ALL ROUTES except respiratory = NO INHALED SEMI-SOLIDS

semi solids can be used locally or transdermally

Question 6

List the 4 topical semi-solid preparations

Answer 6

1. Ointments
2. Creams
3. Gels
4. Pastes

Also includes: foams, lotions, plasters, suppositories

Question 7

What characteristics, application and excipients apply to OINTMENTS formulation

Answer 7

• Are single phase preparations, consisting of matrix former + liquid component
• can be transparent or coloured
• drug can be dissolved in base OR disperesed throughout base

4 Types of bases:
1. Hydrocarbon
- C30 and C50 hydrocarbon mixture
- shorter hydrocarbons (C16 to C30) are usually liquid
- are hydrophobic bases = occlusive

2. Other Hydrophobic / lipophilic
   - barrier to moisture = keeps moisture out = good emollient (keeps everything within skin)
   - greasy + difficult to remove
   - used on dry lesions but NOT wounds etc.
   - may have lower bioavaiability due to solubility of drug in highly lipophilic ointment
   - e.g. silicone
3. Hydrophillic
   - Miscible with water (base contains water as part of liquid component)
   - e.g. macrogols (polyethene glycol)
   - can be applied to wounds
   - bioavailability barely affected due to low vechile resistance
4. Water-emulsifying
   - have emulsifying excipients e.g.wool fat, wool alcohol, fatty alcohols, monoglyceridies, polysorbates
   - may have water incorporated into base (dispersed)
   - can be used on wounds as liquid / what is excreted from wounds will be emulsified

Question 8

What characteristics, application and excipients apply to PASTE formulation

Answer 8

• stiffer than ointments
• less greasy than ointment
• have high loading of insoluble solid
  - solid includes talc, starch, zinc oxide, sulfur
• generate protective barrier
• dry opaque

Question 9

What characteristics, application and excipients apply to CREAM formulation

Answer 9

• Are multiphase preparations (2 phases) ~ lipophilic and aqueous (hydrophillic)
• less greasy + easy to wash off (compared to ointment)

Liphophilic cream = w/o emulsion
Hydrophillic cream = o/w emulsion

Aqueous = dissolved in water

Question 10

What characteristics, application and excipients apply to GEL formulation

Answer 10

• Has 2 inter-penetrating networks ~ solid and liquid network
  
  • liquid phase is held by surface tension, immobilised by platelets or capillary forces
• Has sheer thinning = will breakdown into liquid at specific strength but may reform back into gel

Have many application routes:
- patches
- gel in tube

Question 11

What factors affect percutaneous absorption

Answer 11

Percutaneous Absorption - amount of substance that passes theough stratum corneum compared with the amount applied

Skin Factors:
- skin hydration (thiock water layer = easier to get drug through)
- skin age
- ethnicity
- skin temp. (hydration benefits)
- skin health
- occlusion

Drug Factors:
- drug conc.
- partition coefficient
- degree of ionisation (ionised drug wont go through skin)
- solubility (insoluble drug wont pass through)
- chemical structure