MN 552 MIDTERM QUETIONS AND ANSWERS
What is Modified Release? - Answer- The term modified-release is used to describe dosage forms that alter the timing and/or the rate of release of a conventional drug product/dosage form
- FDA does define this
Some Modified Release Systems - Answer- - some of these have overlap 1. Delayed release
2. Repeated Release or Repeat Action
4. Extended, Sustained, Long-Acting, Prolonged, Controlled Release 5. Targeted Release
Delayed-release - Answer- - dosage forms release the drug at a later time than an immediate dose system
- Delayed-release can include enteric-coated tablets, where timed release is achieved by a barrier coating
- takes more time to release drug; doesn't start dissolving until a certain point of time
Repeat-release - Answer- - multiple doses of immediate release drug units with intermittent dosing
- Such as repeat-action tablets and capsules
Extended, Sustained, Long-Acting, Prolonged, Controlled Release - Answer- - Extended, Sustained-release systems slowly release the drug over an extended period of time
- Rate and duration are not always designed to a particular profile
- If the system can maintain predictable levels of drug in the target tissue or cells, it is considered controlled- release. (Examples: XL,SR,CR) - Controlled release systems are also called extended or sustained (prolonged) release
- dissolves and continues dissolving for a longer time
Targeted Release - Answer- - Site-specific or targeting refers to concentrated drug release at a certain site such as a tissue, organ, receptor, or cell - A form of controlled release
- very difficult to achieve - trying to control distribution of drug to target area
What is Controlled Release? - Answer- - Controlled Drug Delivery attempts to deliver the precise amount of a therapeutic agent (drug), to a specific site (site of action), for a specific time (duraterm-5tion of treatment) - OR Achieve both spatial (targeted) and/or temporal "control" of the drug
- a lot of prediction involved, very precise, and targeted - The Drug Delivery System attempts to control the drug concentration at the target tissue Disadvantages of Conventional Delivery - Answer- - Inconvenient because pt can forget
to take dose
- Difficult to monitor - Overdosing possible
- Large amounts of drug can be "lost" when it does not get to the target organ because has to distribute to the whole body
- Drug goes to non-target cells and can cause damage
- Expensive (using more drug than necessary)
The Goal of Modified Drug Delivery - Answer- To Alter and Control
- Absorption - Distribution - includes Cellular Uptake - Metabolism (reduce it so more drug available) - Elimination (reduce how fast eliminated to prolong effect of drug) - Toxicity (reduce it)
What is Sustained Drug Action? - Answer- - ideal dosage form
- pt only has to take one time rather than multiple times
- minimize side effects by delivering API to site of action (target receptors, cells, tissues,
or area in the body) - re-patenting without new drug development.
Improving Patient Compliance - Answer- Minimize Plasma fluctuation
- Plasma Concentration vs Time
- Sustained Release: takes longer to be absorbed and in therapeutic range for longer but eventually eliminated
- Controlled: absorbed quickly and in therapeutic range for as long as necessary - the more times you have take a medication day, the lower pt compliance
Tries to Achieve: Site Specific Drug Delivery - Answer- Reduction of side effects
- Anticancer drugs
--> Cytosine arabinoside- Dpocyt®
- Anti-fertility Agents - Anti-inflammatory drugs
Site Specific Drug Action or Drug Targeting - Answer- - Targeting or Spatial Delivery
- exclusive drug delivery to specific organ, tissues, or cell types
- Still in development and difficult
- Designed to be directed to a specific organ, tissues, cell or cell compartment
- Targets include surface or compartment cell markers, proteins or even nucleic acids
- can locally put the drug through patches
Routes of Administration - Answer- a. Parenteral - Refers to injections and IV - Fast Absorption - No First pass
- Painful
- Inconvenient
b. Transdermal - Easy access
- Large surface area
- Avoid first pass metabolism
- Avoid GI incompatibility of drugs
- Good patient compliance
- Slow absorption
- Transport across skin can be a challenge
- Need lipophilic
- Low MW drugs
c. Ocular - Localized delivery for eye disorders
- Good absorption for many drugs
- Bypasses certain clearance routes
- Problems with loss of drug in tears
d. Nasal - Easy administration
- Local delivery of drugs
- Rapid absorption
- Can bypasses certain clearance routes
e. Pulmonary - Rapid absorption
- Large surface area for absorption
- Local delivery of drugs
- Can bypasses certain clearance routes when delivered systemically
- Particle size determines anatomic placement in respiratory tract
- Some drug may be swallowed
f. Buccal or Sublingual - No first pass, Thin mucous membrane with a rich blood supply, Good absorption, Mild pH ~6.0, Drug must be potent, Can be swallowed.
g. Rectal - Less worries about pH changes or enzymatic degradation as in oral, Good for patients who cannot swallow, Good for Local delivery of drug, Limited systemic absorption, Discomfort.
h. Oral -Most common route, Easy to formulate and manufacture, Patient compliance is generally good, Inexpensive dosage form, Tricky due to environment of GI tract because of: First pass, pH degradation, Enzymatic degradation, Intestinal motility - affects residence time, Single patient and patient-to-patient variations, Absorption limitations in stomach.
Stents, Implants, Inserts - Answer- a. Stents
- XIENCE PRIMETM coronary artery disease
b. Implants
- dental c. Inserts
- NuvaRing ® IUD Contraceptive
Variables to Consider - Answer- includes examples of controlled/sustained oral drug delivery systems because historically, the oral route of administration has been used the
most for both conventional and novel drug delivery systems
- The types of release systems employed for oral administration include virtually every currently known theoretical mechanism
Variables to Consider when designing an Oral Modified/Sustained Drug Delivery System - Answer- a. Physiochemical & Drug Properties
pKa, Solubility, Log P, Permeability, Stability, Dose size
b. Biological
- Half-Life (time for 50% of drug to be eliminated) - GI Environment: Absorption, Metabolism, Target site
c. Others
- Route of delivery
- Disease state-acute vs. chronic
Physiochemical and Drug Properties Variables to Consider - Answer- - pKa, Solubility: Must now also consider delivery system *> 0.01mg/mL Lower Limit* (pH 1-7.8)
- Log P: Must now also consider delivery/carrier system
--> if drug is sticks to carrier, it won't release as well
- Stability: Drugs that are unstable in the small intestine may have decreased bioavailability in sustained release forms
- metabolism increases if enzymes not saturated - Dose size: 1 gram oral, I.M. 2mL
--> most people don't like to swallow bigger tablets
If a drug must be taken 3 times daily and 325 mg per dose is required, what is the estimated sustained/controlled dose if the Duration of Action needed is 24 hours? - Answer- 3 * 325mg = 975 mg (the total dosage size is small enough, under 1 g)
Biological Variables to Consider - Answer- - short half-life is ideal because
