CA test

1. Time 1800-1850 on January 28, 2013. 2. Close-book assessment. 3. Format: short questions.

Youtube video showed for lecture

Skin anatomy and biology: http://www.youtube.com/watch?v=yKAzVC0WcmI Transdermal electroporation http://www.youtube.com/watch?v=SElfH3e0fQ0 Transdermal laser http://www.youtube.com/watch?v=YInx_7w8Oqg Transderal ultrasonic http://www.youtube.com/watch?v=E-34gU_7jDY&feature=related Microneedle, drug coated; http://www.youtube.com/watch?v=2Pp4CE4F3jI Microneedle pretreatment; Then normal patches. http://www.youtube.com/watch?v=RVbY5nHPpnw&feature=related Microneedle hollow, for injection http://www.youtube.com/watch?v=6noG3gQBOyg Microneedle roller http://www.youtube.com/watch?v=Asj9q6jTBpo&feature=related

Short Questions
1. Describe the structure of epidermis and its relevance to the selection of drug candidates for transdermal and topical drug delivery. Epidermis consists of stratum corneum and the rest viable layers. The stratum corneum intercellular lipids are the major penetration pathway. Drugs need to partition from carrier to stratum corneum. Then drugs need to partition from stratum corneum to the hydrophilic regions of the viable epidermis. Drugs with high partition coefficients can easily partition into stratum corneum (lipid in nature) but have difficult partition into the hydrophilic regions of the viable epidermis. Therefore, a medium polarity (log P 1-3) is preferred for transdermal drug delivery. On the other hand, drugs of high lipophilicity can be good candidates for topical dosage forms as their targeting sites are skin. 2. Describe the sandwich model for transdermal drug delivery. The skin barrier is located in the outermost layer of the skin, the stratum corneum. This layer consists of keratin enriched cells embedded in lipid lamellae. These lamellae form the main passages for diffusion of substances through the skin. Drug can diffuse through the tortuous lipid regions where lipids are more loosely packed (liquid crystalline phase) than the densely packed (crystalline phase).The liquid crystalline phase consists of cholesterol and free fatty acids while the crystalline phase consists mainly of ceramides.

3. To deliver a hydrophilic drug through skin to treat bone cancer, what are potential semisolid dosage forms? To treat bone cancer, drug needs to be delivered into the blood circulation. So a transdermal dosage form is needed to deliver drug through skin into blood circulation. For a hydrophilic drug, hydrogel, emulsion and liposome can be potential dosage forms.

4. What are the functions of each ingredient in the following transdermal gel? Methyl Salicylate 5g (drug) Carbomer 0.1g (polymeric thickener) Farnesol 1g (enhancer) Methyl paraben 0.2g (preservative) Ethanol water to 100ml (solvents) 5. The oral dose of a drug is 10 mg per day. Its flux in a transdermal patch was determined to be 100 g/(hcm2). What should be the patch size? Assume the bioavailability of this drug is 100% for both oral and transdermal drug delivery. So 10 mg need to be delivered in 24 hours. In 24 hours, 2400 g of drug can be delivered per cm2. To deliver 10 mg, or 10000 g, the patch size needs to be 10000/2400 = 4.17 cm2. (You can also assume the bioavailability to be 40%, 70%...and calculate accordingly)

Long Question
6. A protein molecule (5k Dalton) shows therapeutic effect when its plasma concentration reaches 1 ng / ml. An in vitro skin permeation study needs to be carried out to test the drug permeation rate through skin.
1)

Hand-draw a schematic diagram of a flow-through cell for in vitro skin permeation study.

2)

Describe a method to prepare the epidermal membrane from a piece of human skin sample. Dermatome; hot water at 60 C for 2 minutes; or extract skin cells to engineer skin if the skin is still viable.

3)

If the size of a transdermal patch is 10 cm2 and the plasma clearance of the drug is 1 litre/hour, calculate the permeation rate needed for the drug to reach its effective plasma concentration. J = Clp*Css/A = (1000 ml/hour) * (10-3 g/ml) / 10 cm2 = 0.1 g/hour/cm2