Topical formulation Workshop W5 Flashcards
Your company has developed a new drug, lucamine bromide, which shows excellent activity at nicotine receptors in the brain and may be used for smoking cessation. On that basis the company wants you to formulate the drug as a topical formulation.
What is the difference between systemic and local treatment? Which is required for lucamine bromide in this case?
Systemic = treatment that affects the whole body. Is absorbed into blood and carried to different organs and tissues
Local = affect only the area where administered
If it’s for the brain then it needs to reach the CNS. Can’t be local as cant inject into the brain. Topical may not be best either as it may not penetrate into the blood stream and would only affect the skin.
What problem can you immediately envisage as far as this drug is concerned?
Include in your answer a discussion of how drugs may penetrate through the barriers
of the skin.
if it’s formulated typically then the worry is how it gets through the skin a nd into the blood to get to the CNS. The skin is a barrier and so it needs to penetrate multiple layers. If the drug is not lipophillic enough then it may have troubles penetrating the skin layers. If it does manage to penetrate then t may have issues with having enough concentration needed for effective smoking cessation. It could cause skin irritation. Could make it into a patch instead with slow controlled releases
You choose to synthesise a number of lucamine derivatives containing long chain ester
groups (now called lucinester). Describe the relationship between log K and the skin permeability to lucamine esters.
Explain this relationship.
log K is the partition coefficient of a compound . The relationship between log K and skin permeability is crucial because it determines how well a drug can penetrate the skin barrier. Lucamine esters with a higher log K (more lipophilic) would likely have better skin permeability, allowing them to pass through the skin’s lipid-rich layers and potentially reach systemic circulation more efficiently. On the other hand, low log K (more hydrophilic) compounds would face challenges in crossing the skin and may need formulation strategies to enhance absorption.
Why is it important to consider the effect of partition coefficient between formulation
and skin (P) when designing transdermal drug delivery systems? How will this impact on the
formulation of different lucinesters?
The partition coefficient (P), which is the ratio of a drug’s concentration in a lipophilic (fat-soluble) phase to its concentration in a hydrophilic (water-soluble) phase, is a key factor in determining how well a drug will be able to penetrate the skin when used in transdermal drug delivery systems (TDDS). This coefficient has a direct impact on both the permeability of the drug through the skin and the efficacy of the delivery system.
To effectively pass through the SC, a drug must be able to dissolve in the lipid layers. A drug with a higher lipophilicity (i.e., a higher partition coefficient, P) is more likely to cross these lipid layers, as it will dissolve more easily in the skin’s fatty environment.
The P value also influences how the drug will be released from the formulation and absorbed through the skin. Drugs that are highly lipophilic (high P) tend to be released more slowly, but once they penetrate the skin, they may be absorbed more efficiently into the systemic circulation.
Describe the structure of a typical transdermal patch.
several layers:
- Baking layer - outermost for structural support
- Drug reservoir - contain the active drug and control its release
- Rate controlled membrane - regulated the rate at which the drug is released from patch
- Adhesive layer - ensure patch sticks and stays in place
- Linear layer - protective layer over the patch before it is applied
You obtain the following data for flux rates across the stratum corneum:
0.25g/cm2/hour for lucamine bromide from an ointment but 0.04g/cm2/hour from a
cream. Comment on these data. Would either of these formulations be appropriate?
flux is the amount of drug that passes through a given area of skin per unit of time
The ointment delivers more drug through the skin than the cream. Ointments typically have a greasier, more occlusive base, which helps to trap moisture and keep the skin hydrated, potentially aiding in better drug absorption through the stratum corneum
Glycopyrronium is a synthetic anticholinergic drug. It is a competitive antagonist at
muscarinic receptors that can counteract excessive cholinergic activation of eccrine sweat
glands.
Describe the challenges associated with the delivery of glycopyrronium bromide to
eccrine sweat glands of human skin.
the SC acts as a major skin babies and glycopyrronium is charged and so may have difficulty crossing and it is also hydrophilic so is less likely to penetrate the skin. Endocrine glands are deep in the skin and so the drug needs to penetrate the skin first.
Justify the use of iontophoresis for the delivery of glycopyrronium bromide for
treatment resistant palmoplantar hyperhidrosis.
Iontophoresis is a technique that uses a small electrical current to drive charged molecules (such as glycopyrronium bromide) through the skin. This method is particularly useful for conditions like palmoplantar hyperhidrosis, where excessive sweating on the palms and soles needs to be controlled.
Discuss the rationale for the use of microneedle-assisted delivery of glycopyrronium
Microneedles are tiny needles that can create microchannels in the skin, allowing drugs to bypass the stratum corneum and be delivered more effectively to deeper skin layers
