Skin Absorption Strategies Quiz

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Questions and Answers

What is the primary function of the stratum corneum in skin absorption?

To allow all active ingredients to pass through freely

To serve as a barrier against UV filters

To increase the absorption of active ingredients

To retain water and block external materials (correct)

Which of the following molecules typically has the highest skin absorption rate?

UV filters which are absorbed at 2-4% (correct)

Retinoids at around 1%

Lightening actives that target melanocytes

Humectants that cannot penetrate the skin

Which strategy is classified as an active approach to increase delivery of actives?

Increasing the thermodynamic activity

Utilizing penetration enhancers

Use of liposomes in formulation

Application of microneedles (correct)

What is a characteristic of the intercellular route for molecules passing through the skin?

It consists of alternating aqueous and lipid domains Signup and view all the answers

Which method is NOT considered a passive strategy to enhance active delivery?

Iontophoresis Signup and view all the answers

What role do penetration enhancers like DMSO play in a formulation?

They facilitate the delivery of active ingredients Signup and view all the answers

In terms of skin absorption, which of the following factors affects whether active ingredients can penetrate?

The ionization of the active ingredient Signup and view all the answers

Which formulation type is most likely to improve active delivery through increased thermodynamic activity?

Nanoemulsions Signup and view all the answers

What is the significance of the sphere in Hansen's solubility model?

It indicates whether two substances will be miscible based on their SP values. Signup and view all the answers

Which parameter is NOT a component of Hansen's Solubility Parameters?

Thermal energy Signup and view all the answers

What does a distance (Ra) greater than the radius of interaction imply for two substances?

They are not likely to be miscible. Signup and view all the answers

What is the accepted SI unit for solubility parameters as mentioned in the content?

MPa1/2 Signup and view all the answers

Which software models are mentioned for calculating solubility parameters?

Hansen and Van Krevelen and Hoftyzer Signup and view all the answers

What is attributed to a solubility parameter value of ±10 (cal/cm3)1/2?

Simple carbohydrates Signup and view all the answers

Which of the following substances is mentioned as an example of a Type II solubilizer?

Transcutol® Signup and view all the answers

Why is it important to stick with one approach when calculating solubility parameters?

To maintain consistency in results. Signup and view all the answers

Why is it important to determine how much of an active ingredient partitions into the skin for cosmetic formulations?

To optimize the formulation for desired outcomes Signup and view all the answers

What is a primary characteristic of the active ingredients used in topical cosmetic formulations?

They need to be in solution to partition effectively Signup and view all the answers

What principle do solubility parameters operate on?

Like dissolves like Signup and view all the answers

What does the Hildebrand solubility parameter value indicate?

The cohesive energy density and solvent interactions Signup and view all the answers

What does Hansen's approach to solubility parameter analysis involve?

Three components: hydrogen bonding, dipole-dipole, and van der Waals forces Signup and view all the answers

If a formulation contains a high concentration of active but only a small amount partitions, what might a cosmetic formulator need to do?

Increase the concentration of the active in the formulation Signup and view all the answers

What does the heat of vaporization relate to in the context of Hildebrand solubility parameters?

It provides a measure of intermolecular forces Signup and view all the answers

What might happen if the solubility parameter values for a solute and solvent are significantly different?

The solute will not dissolve well in the solvent Signup and view all the answers

What is the solubility parameter of EA?

15.4 (cal/cm³)^(1/2) Signup and view all the answers

Which parameter has the greatest influence on the movement of the active from the formulation into the skin?

Partition coefficient Signup and view all the answers

In Fick's 1st law of diffusion, what is implied about the skin?

It is the rate controlling barrier. Signup and view all the answers

What determines the movement of the active from a formulation into the skin according to Higuchi?

The thermodynamic activity difference Signup and view all the answers

What is the typical attributed value of thermodynamic activity (α) for a solute in a saturated solution?

1 Signup and view all the answers

What is the saturated solubility of caffeine in solvent A?

0.2 mg/mL Signup and view all the answers

According to Higuchi, how should the activity in the skin (γ) generally be characterized?

Less than 1 Signup and view all the answers

What does the partition coefficient (K) primarily determine in the context of absorption?

The partitioning from formulation into the skin Signup and view all the answers

What is the solubility parameter (cal/cm³)¹/² of ethyl acetate (EA)?

15.4 Signup and view all the answers

Which solvent has the highest solubility parameter value according to the data?

Glycerin (Gly) Signup and view all the answers

What effect do binary and ternary solvent combinations have on saturated solubility?

Decrease the saturated solubility Signup and view all the answers

What is the maximum y-axis value for single solvents concerning permeation amounts?

10 µg/cm² Signup and view all the answers

In a binary solvent system, what is the maximum y-axis value reported for permeation amounts?

40 µg/cm² Signup and view all the answers

Which solvent has a solubility parameter closest to that of EA?

Propylene glycol (PG) Signup and view all the answers

What is the solubility parameter of propylene glycol (PG)?

14.07 Signup and view all the answers

What general trend is observed in permeation amounts with increased solvent combinations?

Permeation amounts increase despite concentration decreases Signup and view all the answers

What does a high affinity between an active ingredient and a vehicle indicate?

High solubility and concentration in the vehicle Signup and view all the answers

What is the implication of having a larger percentage of an active ingredient partition from one solvent relative to another?

Concentration balance between activity and solvent is necessary Signup and view all the answers

If caffeine in solvent A shows high activity and in solvent B shows low activity when both are at 0.2 mg/mL, what conclusion can be drawn?

Solvent A has a higher affinity for caffeine than solvent B Signup and view all the answers

Why are solutes held firmly by the vehicle said to have low activity coefficients?

They exhibit lower thermodynamic activity Signup and view all the answers

Which property of the active ingredient influences its penetration speed into the skin?

Affinity for the vehicle Signup and view all the answers

To increase the likelihood of delivering an active ingredient to the skin, one should focus on solvents with what characteristic?

High affinity for the active ingredient Signup and view all the answers

What is the main consequence of formulating at maximum solubility of an active ingredient?

Potential instability of the formulation Signup and view all the answers

Which solvent is an example of a vehicle that might be selected due to its high affinity for active ingredients?

Isopropyl alcohol Signup and view all the answers

Study Notes

Formulation Strategies: Part 1

Formulation strategies are concerned with increasing the delivery of actives.
A cosmetic active is a substance intended for topical application to the skin, intended to change, improve or correct the body's appearance.
No legal definition for cosmetic active, interpretation differs.
Example criteria for an active: "Those materials for which it is possible to carry out controlled experiments in which a baseline cosmetic effect is measurably enhanced by the addition of the active in a defined concentration."
Active delivery is determined through intrinsic molecular activity and the delivery to targeted locations.

Overview

Active ingredients require specific biological models for testing.
Key tests for active include:
- In vitro tests (e.g., with cells)
- In vivo tests (e.g., on skin), using diffusion cells, tape stripping, confocal raman spectroscopy
Product efficacy testing provides indirect measures. Tools for this include a corneometer and a cutometer.
Important factors include Fick's law, physicochemical characteristics (e.g., solubility, molecular weight) and parameters (e.g., Higuchi).

What Are Cosmetic Actives?

No legal definition.
Interpretation varies.
Glycerol is not always considered an active.
Definition: A definition that applies strict criteria (materials that can be used in controlled experiments to determine the baseline cosmetic effect of a compound, considering the compound's specific concentration.).

Is the Active Working?

Active efficacy is determined by intrinsic activity, delivery to the action site, and assessment through indirect means like product efficacy testing.

Where Are We Delivering To?

External parts of human body: epidermis
Possible locations:
- Skin surface (e.g., for UV filters)
- Stratum corneum (e.g., for humectants)
- Melanocytes (e.g., for lightening)
- Viable epidermis (e.g., for antiaging actives)
- Dermis (e.g., for antiaging)

Delivery of the Active

Skin absorption is generally low (2-4%, around 1% in the case of retinoids).
Barrier characteristics of stratum corneum have varying effects, based on material size (greater than 500 Da).
Ionized molecules often have a more difficult time entering the skin.
Formulation and active properties affect absorption.

What Can We Do to Increase Delivery of the Active?

Active: This approach uses physical methods to enhance penetration. Examples include iontophoresis, phonophoresis, microneedles, and physical occlusion (patches).
Passive: This approach improves delivery by modifying formulation characteristics.

Passive Strategies: Formulation

Penetration enhancers (e.g., fatty acids, urea, alcohol, DMSO, Azone, terpenes).
Specific formulation types (e.g., emulsions, nano or microemulsions, micelles, liposomes).
Ion pairing, supersaturation, and optimization of formulation.
Concentration of active.
Thermodynamic activity of the active.

How Do Molecules Pass Through the SC?

Molecules can pass through the skin through three key pathways:
- Intercellular (dominant)
- Transcellular
- Appendageal pathways (hair follicles, sebaceous glands, sweat glands)

Intercellular Route

The dominant pathway.
Contains alternating aqueous and lipid domains.
The active must partition into alternating lipid and aqueous domains for the molecule to pass through the skin.

Fick's Laws of Diffusion

The movement of compounds through the skin follows Fick's laws.
1st step: partition into stratum corneum
2nd step: diffusion.
Repeated partitioning and diffusion across alternating domains is integral.

When Formulating, Consider These Active Characteristics

Molecular weight (MW)
Melting point
Partition coefficient
Solubility
Potency
Active's ability to leave the formulation and partition into the skin

Physicochemical Characteristics

Ideal MW: less than 500 Daltons.
Compounds with lower melting points often have higher skin partitioning.
Ideal log P: 1-3; to balance partitioning between aqueous and lipid phases.

Potency of the Active

LD50 (Lethal dose 50) is a toxicity measure for assessing the potency of compounds.
Comparing LD50 values of a compound with other molecules can provide insights into its relative potency.
For effective topical use of actives small amounts of the compound are required.

Solubility of the Active

Topically applied actives require solubility in a formulation.
High concentration of active may be needed in the formulation if significant skin partitioning is needed.
Selection tool to determine the suitability of a solvent: solubility parameters can be used to determine a solvent's compatibility.

Solubility Parameters (SP)

Numerical values indicating a solute-solvent's relative solvency behavior.
Determine compatibility using the concept that similar components dissolve each other. Values are associated with cohesive energy density for molecular interaction
Hildebrand's SPs, based on van der Waals' forces.
Hansen's SPs, which distinguish hydrogen bonding, dipole-dipole, and van der Waal's interactions.

Higuchi: Percutaneous Absorption

The rate is determined by the partition coefficient of the active passing through the skin.
Partition from the formulation into the skin is a crucial first step. (the active to pass the outer skin layers).
The partition coefficient is related to molecular structure and size.

Higuchi 1 and 2 (Activity)

Thermodynamic activity of the active, in relation to the formulation and skin, is a key concept
Activity is the driving force for the movement of an active from the formulation to the skin rather than concentration. Activity is less than 1 for most.

Higuchi 3 (Solubility & Affinity)

High solubility in a suitable solvent is a sign of high affinity rather than maximum solubility.
Understanding an active's affinity for the vehicle and skin is crucial.

Higuchi 4 (High Affinity)

High affinity can be identified by high solubility and concentration in the vehicle.
If an active has differing activity in different vehicles, the difference will affect how quickly it permeates.

Practical Implications of Thermodynamic Activity

Active concentration and activity must be balanced.
Solubility parameters to select solvents, noting high affinity for active and low affinity balancing.

Conclusion

Optimizing conditions for active release within the skin and to stratum corneum is needed for effective delivery.

References

Higuchi (1960), Physical chemical analysis of percutaneous absorption process from creams and ointments (The reference is directly found in the provided data)

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Description

Test your knowledge on the primary functions and mechanisms of skin absorption. This quiz covers topics including the stratum corneum, absorption rates of molecules, and strategies for delivering active ingredients through the skin. Ideal for students in dermatology or cosmetic science.