Semi-solid Formulations🧴

Question 1

5 skin functions

Answer 1

Protective barrier
Prevents water loss
Sensory function
Thermoregulation
Site of vitamin D synthesis

Question 2

According to Flicks law how can we improve drug delivery and what are the corresponding strategies? (2 ways)

Answer 2

1) Increase Diffusion coefficient
2) Increase concentration gradient

Question 3

Biological factors affecting percutaneous absorption

Question 4

Physiochemical factors affecting percutaneous absorption

Question 5

Define and describe the two types of cream composition

Answer 5

• Creams: Semi-solid emulsions, typically a mix of oil and water.

Two Types:
Oil-in-water (O/W): Water is the continuous phase, non-greasy, easy to wash off.
• Water-in-oil (W/O): Oil is the continuous phase, more occlusive, better for dry skin.

Question 6

Advantages of creams

Answer 6

Moisturizing effect: Hydrates the skin and softens the stratum corneum.

Enhanced Drug Absorption: Creams can facilitate the penetration of active ingredients.

Patient Compliance: Non-greasy texture, easy to apply, and pleasant feel.

Versatile: Suitable for various drugs (anti-inflammatory, antifungal, antibiotics).

Question 7

Mechanism of cream drug delivery

Answer 7

Drug Release: The drug diffuses from the cream matrix into the skin.

Barrier Penetration: Moisturizing properties help overcome the skin barrier (stratum corneum).

Occlusive (‘blocking’) Effect (W/O creams): Traps moisture, increasing skin hydration and permeability.

Question 8

Factors influencing cream drug delivery

Answer 8

Cream Composition: Emulsion type (O/W vs. W/O). lipid content.

Drug Properties: Solubility, molecular weight, lipophilicity.

Skin Condition: Intact vs. damaged skin, hydration levels.

Question 9

Cream excipients and role

Answer 9

Water: Solvent for hydrophilic ingredients; hydrates the skin and forms the base for oil-in-water emulsions.

Oils/fats: Provide emollient eftects, soften skin, and form the base for water-in-Oil emulsions; dissolve lipophilic drugs.

Emulsifying agents: Stabilize oil-water mixtures and prevent separation (e.g., cetyl alcohol, polysorbates).

Thickening agents: Increase viscosity for better texture and spreadability (e.g.. carbomers, cetyl alcohol)

Humectants: Retain moisture in the skin (e.g., glycerin, propylene glycol).

Preservatives: Prevent microbial growth, extending shelf life (e.g., parabens, phenoxyethanol).

Penetration enhancers: Increase drug absorption through the skin (e.g., ethanol, propylene glycol).

Question 10

Gel definition and describe two types

Answer 10

Semi-solid systems with three-dimensional matrix that traps a liquid or semi-liquid phase.

Types:
Hydrogels (water-based)

Organogels (organic solvent-based)

Question 11

Advantages of gels (4)

Answer 11

Enhanced drug release: Gels can provide controlled or sustained release of drugs.

High patient compliance: Easy to apply, non-greasy, and comfortable on the skin.

Targeted drug delivery: Suitable for topical (e.g., diclofenac gel), transdermal (e.g., testosterone gel), ophthalmic (e.g., pilocarpine gel for glaucoma), and other applications.

Good penetration: Better drug permeation through the skin due to increased hydration.

Question 12

Challenges of gels (3)

Answer 12

Stability issues: Gels may be sensitive to temperature changes

Compatibility: Drugs and excipients should be compatible with the gel matrix.

Limited use with hydrophobic drugs: aggregation (reduces solubility). Hydrogels may not be suitable for lipophilic drugs.

Question 13

Gel excipients and role

Answer 13

1. Gelling Agents
   Create and stabilize the gel structure (e.g., carbomers, xanthan gum).
2. Solvents
   Dissolve active ingredients (e.g., water, alcohol).
3. Humectants
   Retain moisture in the gel and skin (e.g.., glycerin, sorbitol).
4. Preservatives
   Prevent microbial growth (e.g., phenoxyethanol, parabens).
5. pH Adiusters
   Maintain optimal pH for stability and skin compatibility (e.g., citric acid).
6. Stabilizers
   Prevent degradation and separation (e.g., antioxidants like vitamin E).
7. Penetration Enhancers
   Improve drug absorption through the skin (e.g., ethanol, DMSO).
8. Thickening Agents
   Adjust viscosity and texture (e.g., cellulose derivatives).

Question 14

Ointments definition

Answer 14

Less water than creams - greasy feeling

Question 15

Ointment excipients and role

Answer 15

Vehicle/Base: Forms the main structure of the ointment: provides a medium for the
API. Types include oleaginous (e.g., petrolatum), absorption, water-removable, and water-soluble bases. More oil than water (opposite from the creams)

Stabilizers: Preserve API stability and prevent degradation. Examples include antioxidants (e.g., BHT:Butylated Hydroxytoluene) and preservatives (e.g., parabens).

Penetration Enhancers: Increase skin permeability to enhance API absorption.
Examples include ethanol and dimethyl sulfoxide (DMSO).

Emulsifiers: Facilitate mixing of oil and water phases in emulsions. Examples include sorbitan esters and polysorbates.

Thickeners: Adjust the viscosity and consistency for ease of application. Examples include hydroxyethyl cellulose and carbomers.

Humectants: Attract and retain moisture in the skin to enhance hydration. Examples include glycerin and hyaluronic acid.

Question 16

Advantages of ointments (3)

Answer 16

Enhanced Skin Contact: Prolonged retention and contact with the skin.

Moisturizing Effect: Useful for dry or rough skin conditions.

Versatility: Can be formulated for various therapeutic purposes.

Question 17

Challenges of ointments

Answer 17

Patient Acceptance: Ointments can be greasy and may stain clothing.

Stability: Formulation stability over time.

Penetration: Limited for drugs with low skin permeability

Question 18

Benefits of pastes

Answer 18

Protective barrier: Forms a barrier on the skin to
protect against irritants or infections.

Localised action: Delivers the API directly to the affected area, enhancing the therapeutic effect.

Enhanced stability: Thicker consistency reduces the risk of the API being washed away or diluted.

Question 19

Paste excipients and role

Answer 19

Active Pharmaceutical Ingredient (API)
Therapeutic Effect: Provides the intended therapeutic effect, such as anti-inflammatorv or antimicrobial action.

Base (vehicle)
Medium: The foundation of the paste, providing the bulk and consistency.
Often includes agents like petrolatum, lanolin, or waxes.

Thickening agents
Consistency: Enhance the paste’s viscosity to ensure it remains in place upon application. Examples include clays (bentonite), starches, or cellulose
derivatives.

Emollients
Skin Softening: Help to soften and smooth the skin, improving the application and feel of the paste. Examples include lanolin and various oils.

Preservatives
Stability: Prevent microbial growth and extend the shelf life of the paste.
Common preservatives include parabens or phenoxyethanol.

Stabilisers
Formulation Intearity: Maintain the physical and chemical stability of the paste over time. This can include agents that prevent phase separation or degradation.

Question 20

Creams excipients and role (specific)

Answer 20

Distilled water: Solvent for hydrophilic ingredients, hydrates skin and forms base for oil in water emulsions

Cetostearyl Alcohol (emulsifying and thickening agent): Stabilises oil-water mixtures and prevents separation and provides a moisturising effect.

Liquid Paraffin: Emollient. Moisturiser that softens and smooths the skin by forming a barrier to prevent moisture loss.

Chlorocresol: Preservative that prevents microbial growth

Macrogol cetostearyl ether: Surfactant that contributes to the hydration of the skin by forming a barrier that helps to reduce water loss

White soft paraffin: Base. Emollient. Provides occlusivity and helps with skin hydration. Emollient properties for moisture barrier.

Sodium Dihydrogen Phosphate Dihydrate: buffer system

Glycerine: humectant. Draws moisture into skin & prevents dryness.

Phosphoric Acid: PH adjuster

Sodium Hydroxide: Balance and maintain pH levels

Zinc oxide paste (the product): paste provides protective barrier and mild antiseptic to provide soothing and promote healing.

Question 21

Ointment specific components and role

Answer 21

Castor oil: preservative, prolongs shelf life, antimicrobial. Hydrogenated one traps moisture abs helps moisture skin to enhance absorption.

Question 22

Why are creams good?

Answer 22

Effective for inflamed skin conditions: combines nydraung. emollient, and anti-inflammatory properties. The ointment base allows for a prolonged retention time on the skin, enhancing the efficacy of the drug.

Question 23

Why are ointments good?

Answer 23

The high oil content provides a barrier, making it suitable for treating fungal infections on dry, cracked skin.

Question 24

Why are pastes good?

Answer 24

Provides a thick. protective barrier ideal for conditions needing moisture protection, such as diaper rash.

Question 25

Why are transdermal patches good?

Answer 25

Offers controlled nicotine release, enabling steady absorption through the skin into the bloodstream. This delivery svstem avoids the gastrointestinal tract, reducing potential side effects and ensure seaov olasma concentracions

Question 26

How to improve drug delivery and strategies

Answer 26

1) Increase Diffusion Coefficient (D)
The diffusion coefficient depends on the physicochemical properties of the drug (e.g., molecular size, solubility, and polarity) and the nature of the skin
B arrier
J = - D (AC(x,t)) / дх

Strategies:

Use of permeation enhancers: Chemicals like alcohols, fatty acids, or surfactants can disrupt the skin’s lipid structure and improve the fluidity of the stratum corneum (outermost skin layer), enhancing drug diffusion.

Lipid-based formulations: Liposomes and other vesicular systems can carry drugs through the skin’s lipid bilayer.

Nanoparticles: Nano-sized carriers (e.g., solid lipid nanoparticles, polymeric nanoparticles) can penetrate the skin more easily, improving drug transport.

2) Increase the concentration Gradient
• The driving force for diffusion is the concentration gradient, so increasing the drug concentration at the skin’s surface can improve delivery.

Strategies:
• Saturated formulations: Use formulations that maintain a high drug
concentration at the SurAce or SUStAined release over time

• Drug reservoirs: Use systems like transdermal patches that maintain a consistently high concentration over the application period.

• lontophoresis: Apply an electric current to increase drug movement by enhancing the concentration gradient

Question 27

Ointment mechanism of delivery

Answer 27

Localized Delivery:
Direct application to the skin or mucosa.
Useful for treating conditions like eczema, psoriasis, or fungal infections.

Systemic Delivery:
Through skin absorption into the bloodstream.
Effective for drugs with high skin permeability.

Question 28

Factors affecting ointment efficiency

Answer 28

Drug Penetration:
Molecular size and lipophilicity.
Formulation characteristics.

Skin Properties:
Hydration, temperature, and integrity of the skin.

Formulation:
Type of base used.
Concentration of active ingredients.

Question 29

How can the absorption of a formulation be improved?

Answer 29

mucosa - use water base gel (surface is already hydrated)

1. Enhancers

Fatty Acids: Disrupt lipid bilayers to increase permeability (e.g., oleic acid, linoleic acid).
Surfactants: Reduce surface tension for better penetration (e.g., sodium lauryl sulfate, polysorbate 80).

2. Formulation Adjustments

pH: Adjust to match skin’s pH (~5.5) for better stability and absorption.
Viscosity: Increase to prolong skin contact; excessive viscosity may hinder absorption.
Osmotic Pressure: Optimize to reduce irritation and enhance drug release.

3. Nanoparticles

Increased Surface Area: Smaller particles enhance skin contact and absorption.
Enhanced Penetration: Can bypass skin barriers for deeper delivery.
Controlled Release: Provide sustained therapeutic effects over time.

4. Microneedles

Microchannels: Create channels in the skin, bypassing the stratum corneum.
Deeper Penetration: Deliver drugs to dermal layers, reaching blood and lymphatic vessels.

5. Temperature

Increased Permeability: Mild heat enhances skin permeability.
Enhanced Blood Flow: Heat increases blood flow, improving drug uptake.

6. Drug Solubility and Stability

Solubility: Enhanced solubility improves absorption.
Stability: Prevents degradation of the drug in the formulation.

7. Patient Compliance

Formulations must be easy to apply and comfortable for regular use.

Question 30

Based on the comparison between gel and cream formulations, describe how these two formulations should be modified to target either the mucosa or the skin.

Answer 30

Thick (viscosity)
Skin contact for a long time
API solubility - ensure ingredient easily solubilised in chosen formulation to absorb into skin tissue
Penetration enhancers (for lipid based to enhance penetration efficacy)
PH - PH must align with natural environment of mucosa or skin surface
Moisturising barrier enhancers - improved hydration of skin to enhance drug delivery eg humectants attract water to skin. Moisturising properties help overcome skin barrier (stratum corneum).