Topical And Transdermal Delivery Workshop

Question 1

Scenario : Your company has developed a new drug called lucamine bromide, which works on nicotine receptors in brain and could help with smoking cessation. The goal is to create a topical formulation for this drug.

What is the difference between systemic and local treatment? Which type is required for lucamine bromide in this case?

Answer 1

The difference between systemic and local treatment lies in how and where a treatment is applied and how it acts within the body:

1. Systemic Treatment:
   • Definition: Systemic treatments affect the entire body, meaning the drug or treatment circulates through the bloodstream and reaches cells or tissues throughout the body.
   • Application: Systemic treatments are typically administered orally (pills or liquids), through injections, or intravenously (IV).
2. Local Treatment:
   • Definition: Local treatments target a specific area of the body, and their effect is generally limited to that area without affecting the entire system.
   • Application: These treatments can be topical (applied directly to the skin), surgical, or delivered via radiation aimed at a specific site.

Question 2

What problems might arise when trying to deliver lucamine bromide through the skin? Include a discussion on how drugs penetrate the skin.

Answer 2

1. Molecular Size and Weight:
   • Smaller, low molecular weight compounds tend = more easily absorbed into the bloodstream and more likely to be used for systemic delivery.
   • Larger molecules or those with high molecular weight, have limited ability to penetrate tissue barriers, and thus might be used for local delivery
2. Lipophilicity (Fat Solubility):
   • Lipophilic (fat-soluble) drugs are more likely to cross cell membranes - can therefore be absorbed into the bloodstream for systemic
   • Hydrophilic (water-soluble) drugs may stay in local environments - often used in formulation designed for local
3. Charge/Polarity:
   • Highly charged/polar molecules have difficulty crossing cell membranes and the blood-brain barrier, so used more for local applications
   • Neutral/less charged molecules are generally more likely to penetrate tissues and reach the bloodstream for systemic
4. Formulation/Excipients:
   • How the drug is formulated often determines whether it is for local or systemic delivery. For example, topical creams are typically local, while oral tablets/injections are systemic.
   • Some drugs can be formulated in a way that modifies their absorption. For example, encapsulating a drug in a nanoparticle might allow systemic delivery even for larger or hydrophilic molecules.
5. Route of Administration:
   • Drugs designed for oral ingestion, intravenous (IV), intramuscular (IM), or subcutaneous (SC) injections are usually intended for systemic delivery.
   • Drugs for topical application, nasal sprays, inhalers, or local injections (such as dental anesthesia) are typically designed for local delivery.
6. Stability and Metabolism:
   • Some drugs may be designed for local delivery if they are rapidly metabolized or degraded in the body, making them less suitable for systemic use.

Question 3

Higher the molecular weight ….

Answer 3

More hydrophobic

Question 4

Describe the relationship between the log K (octanol/water) value and skin
permeability for lucinesters

Answer 4

important factor in understanding how substances like lucinesters permeate the skin.

The octanol/water partition coefficient, often represented as log
K
ow
K
ow
​
, measures a substance’s relative solubility in a lipophilic (octanol) versus a hydrophilic (water) environment. A higher log kow value indicates greater lipophilicity, meaning the substance is more soluble in lipid environments like cell membranes.

Skin permeability typically increases with higher log
K
ow
K
ow
​
values, as more lipophilic substances pass more easily through the lipid-rich layers of the skin. However, if the log
Kow is too high, the substance may become too lipophilic and preferentially remain in the stratum corneum (outer skin layer) rather than moving into deeper layers.

Question 5

Why is it important to consider the par«on coefficient (P) when designing transdermal drug delivery systems? How would this affect the formula<on of different lucinesters?

Answer 5

The partition coefficient is a key factor in determining how a drug interacts with the skin, how well it penetrates the skin barrier, and how effectively it reaches systemic circulation or the target tissues.
Here are the main reasons why the partition coefficient is crucial in transdermal drug design:
1. Skin Barrier Penetration:
• The skin’s outer layer is primarily lipophilic (fat-loving), and the partition coefficient helps predict how well a drug will move from the formulation into the skin.

2. Balance of Lipophilicity and Hydrophilicity:
   • Log P helps balance lipophilicity and hydrophilicity (water solubility). Drugs that are too lipophilic (high log P) may get trapped in the stratum corneum, leading to poor diffusion into deeper skin layers or systemic circulation. On the other hand, drugs that are too hydrophilic (low log P) may struggle to penetrate the lipophilic skin barrier and remain on the surface or in the vehicle.
   • Therefore, the partition coefficient helps ensure that the drug has the right balance to pass through both lipophilic and aqueous regions of the skin.
3. Drug Retention and Release:
   • A drug’s partition coefficient influences its ability to be released from the delivery vehicle (e.g., a patch or gel) and absorbed into the skin.
   • If the log P is too high, the drug may have poor solubility in the vehicle and will not be released efficiently. Conversely, if the log P is too low, the drug may not leave the vehicle or penetrate the skin effectively.
4. Systemic Absorption:
   • The goal of transdermal drug delivery is often to achieve systemic absorption by bypassing first-pass metabolism in the liver. For this to happen, the drug must cross multiple skin layers and enter the bloodstream.
   • Drugs with an optimal log P value (1-3) tend to diffuse well through the skin and into systemic circulation. This helps achieve the desired therapeutic effect without the complications of oral administration.

Question 6

Given the absorption rates (0.25 μg/cm2/hour for ointment and 0.04 μg/cm2/hour for cream), why is the absorption higher for the ointment? Which formulation would be more appropriate?

Answer 6

Ointment as is oily base -> prevent occlusive layer, hydrate skin and is permeable and will work faster