Lecture 22 transdermal drug delivery Flashcards
Describe the concept pro-drugs in transdermal drug and how they are designed to enhance skin partitioning.
Prougs are inactive compounds that are chemically into active metabolites after administration. They are designed to increase the lipophilicity of the parent drug, typically by linking an active drug with an inactive moiety via an ester bond. Skin esterases cleave the active drug from the inactive moiety, which should be non-toxic and easily eliminated. Pro-drugs require additional regulatory steps for approval.
Explain the ion pair strategy in drug modification for transdermal delivery and how it enhances skin permeation.
Ionised drugs have poor skin permeation due to their charge. The ion pair strategy involves adding oppositely charged species to a charged drug to neutralize the charges, enhancing lipophilicity. The ion pair diffuses through the stratum corneum, dissociates in the viable epidermis, and releases the active drug. No covalent bonds are formed in this process.
How do eutectic mixtures work in transdermal drug delivery to reduce the melting point of a drug?
Eutectic mixtures lower the melting point of a drug by inhibiting each other’s crystallization at specific ratios. This results in a system with a lower melting point than either component alone. The reduced melting point enhances solubility, including in the intercellular lipids of the stratum corneum, improving drug absorption.
Discuss the role of eutectic mixtures in enhancing the solubility of drugs in transdermal formulations.
Eutectic mixtures reduce the melting point of drugs, leading to enhanced solubility. By inhibiting each other’s crystallization, the components form a system with improved solubility, including within the intercellular lipids of the stratum corneum. This allows for maximal thermodynamic activity in the donor phase.
How are pro-drugs designed to optimize the physicochemical characteristics of drugs in transdermal delivery?
Pro-drugs are chemically modified inactive compounds that are transformed into active metabolites post-administration. They are designed to increase the lipophilicity of the parent drug by linking it with an inactive moiety via an ester bond. Skin esterases cleave the active drug from the inactive moiety, which is non-toxic and easily eliminated.
Explain the concept of ion pairs in drug modification for transdermal delivery and how they aid in enhancing skin permeation.
Ion pairs involve adding oppositely charged species to a charged drug to neutralize the charges, enhancing lipophilicity. This strategy allows the ion pair to diffuse through the stratum corneum, dissociate in the viable epidermis, and release the active drug without forming covalent bonds.
Describe the process electroporation in contrast to iontopis.
roporation uses high pulses (10 – 1000 V) for short to create aqueous in lipid bilayers facilitating drug transport. In contrast, iontophoresis uses small voltages (<10 V) for drug delivery.
How does sonophoresis enhance drug delivery using ultrasound?
Sonophoresis uses ultrasound waves (>20 KHz) to enhance drug delivery by inducing permeation at low frequencies (<100 kHz). Ultrasound can be applied before drug delivery or simultaneously with the formulation.
Define jet injection and its application in drug delivery.
Jet injection delivers drugs at high pressure (>100 m/s) to pierce the skin without needles. It can be powered by compressed air or springs, targeting specific skin layers to avoid needle stick injuries.
Explain the significance of miniaturization in electroporation devices.
Miniaturization of electroporation devices is crucial for patient use, allowing routine application. More clinical studies are needed to ensure long-term safety and understand the mechanism of action.
What are the two types of jet injectors and how do they differ?
The two types of jet injectors are liquid jet injectors and powder jet injectors. They differ in the form of the substance delivered, with liquid jet injectors delivering liquid drugs and powder jet injectors delivering powdered drugs.
How do the effects of ultrasound on the skin during sonophoresis differ between thermal and non-thermal mechanisms?
Ultrasound effects on the skin during sonophoresis can be thermal or non-thermal. Thermal effects involve heat generation, while non-thermal effects induce changes without raising skin temperature.
Describe some physical methods used in microneedle technology.
Physical methods in microneedle technology include hydration, thermal ablation, suction ablation, laser ablation, tape-stripping, and microscissioning.
How are high-loading dissolving microneedles designed and what factors influence their performance?
High-loading dissolving microneedles are designed with 50% w/w drug loading, using biodegradable or low MW polymers. Factors like film formation, dissolution characteristics, and patch design influence their performance.
What are the characteristics and advantages of hydrogel-forming microneedles in drug delivery
Hydrogel-forming microneedles do not contain drugs but have a separate reservoir. They are chemically crosslinked, allowing rapid uptake of skin fluid. They offer potential for higher doses and prolonged drug delivery.
