Novel Formulations for CNS Drug Delivery (Snow Stolnik) Flashcards
What is an Exelon Patch? What are some of the formulation perks?
Rivastigmine; treatment for Parkinson’s disease (An acetylcholinesterase inhibitor)
24 hour treatment improves compliance, overcomes problems with swallowing pills, reduced side effects compared to oral formulation.
Which layers of the Exelon patch does the drug diffuse through?
Adhesive layer and adhesive contact layer into the skin over 24h
What four layers make up the Exelon patch?
Layer 1: backing layer
Layer 2: drug in adhesive layer
Layer 3: contact adhesive layer
Layer 4: release liner (removed when applied)
What is the problem with rivastigmine in the patches?
Rivastigmine is susceptible to oxidation in the patch
How is the oxidation of rivastigmine overcome?
Novel patented packaging solutions:
- packaging prevents light and humidity that causes degradation
- possibly replace air with inert gas such as nitrogen.
Include an antioxidant, in Exelon, alpha-tocopherol (Vit E) is used.
What are the problems that face the use of methylphenidate for treatment of Attention Deficit Hyperactivity Disorder (ADHD/ADD)?
Immediate release formulations have to be given 2-3 times a day (school stigma)
Compliance issues or abuse potential.
Extended formulations are better as a single daily dose however behaviour is poorly controlled later in the day
How does an extended release formulation result in a sub therapeutic concentration by the end of the day?
Either the concentration of a drug declines at an earlier time but at a slower rate
OR the concentration of the drug remains constant for a satisfactory amount of time but then reduces dramatically.
How can the problems associated with original extended release formulations be rectified?
Extended release tablets that give ascending release using osmotic drug delivery.
How does an osmotic delivery system work?
- Initial release of an outside coating containing drug molecules.
- Water ingress is allowed through the semi-permeable membrane of the formulation.
- Swelling due to the hygroscopic tablet forces out drug particles from the laster drilled hole of the tablet
Water continues to enter the push layers of the tablet, causing further drug to be released
The tablet is not degraded, it uses the push system to control release.
What are the drawbacks to the ascending extended release via osmotic delivery system?
Children use this formulation; tablet not ideal
Tablet must be swallowed whole and not crushed or chewed. If so, could receive a bolus dose, overdose, toxicity.
What are some of the problems that are faced by Carmustine or BCNU?
Short plasma half life of 12 mins and also extremely toxic
Conventional injections require crossing the BBB to treat glioblastoma multiforme which is very difficult.
What is Carmustine a.k.a BCNU used to treat?
Glioblastoma multiforme (brain tumour), rapidly progresses, uniformly fatal disease, normall a year of survival with treatment.
What is the solution to the formulation problems associated with Carmustine and BCNU?
Biodegradable polymer (poly anhydride) wafer implant Wafer degrades by surface erosion Marketed as Gliadel
What is the biodegradable polymer used in Gliadel?
Polyanhydride
Erosion at the surface, breaks the links of this polymer.
What are the advantages to using the polyanhydride polymer?
Very labile group that degrades quickly and immediately in water
The monomer is hydrophobic and so slows down water penetration of the bulk wafer.
