Exam 2- Lecture 7 (Part II of Dosage Form Design: Biopharmaceutical Considerations) Flashcards
What is the rate limiting step for absorption?
Dissolution
What is dissolution?
Amount of substance that goes into solution per unit time under standard conditions of liquid solid interface: temperature and solvent
The solvent of oral formulations?
Gastric fluid
How does temperature affect dissolution?
As temperature increases the rate of dissolution increases because high temps break bonds and the drug is available at a faster rate.
Noyes Whitney equation is used to determine what?
Drug concentration with respect to time
What physiological factors affect dissolution?
Solubility
pKa
Size
Excipients
Viscosity of medium
Temperature
pH of medium
What are the formulation factors that affect dissolution?
Diluent: what the solute is being dissolved in
Disintegrating agents: high concentration of these agents will break down the drug before you want it to
Lubricants: hydrophobic, too much lubricant can prevent breaking of tablet. Has low water solubility
What are the processing factors that affect dissolution?
- Method of granulation: wet vs. dry. Wet is preferred
- Compression force: too much force can cause the tablet to be too hard. Result in dense cake
How do particle size, surface area, and rate of disassociation relate to one another?
Decrease particle size:
increase surface area
increase the rate of dissolution.
Which is more soluble the amorphous form or crystallation form?
Amorphous form
With time the rate of dissolution increases or decreases?
Decreases, once you reach peak, rate decreases because there is more drug in the bulk layer than the stagnant layer.
How does hydration, food, pH of GI tract, absorption, drug interactions and aging affect dissolution?
Hydration:
- anhydrous forms have higher solubility than hydrate form
Food:
- affects how quickly the drug can pass through stomach, food can decrease the rate of dissolution
pH:
- increase or decrease
Absorption:
- reduces absorption because molecules can absorb to insoluble materials
Drug interactions:
- some molecules reduce absorption when bound to certain drugs
Aging:
- physiological changes as you age
- pH, SA of endostein, and body response to a drug changes
What is bioavailability?
- Rate and extent of active drug that is absorbed from drug product and becomes available at site of action
- How fast and how much of the drug is going into the systemic circulation
What is bioequivalence?
Comparing bioavailability of different formulations, drug products, or different batches of the same drug product
- A generic drug and brand drug are bioequivalent when there is no statistically significant difference between rate and extent of absorption
What is bioavilabiity used to determine?
- Amount drug absorbed from dosage form
- Rate drug is absorbed
- Duration of drug’s presence in body
- Relationship between blood levels and efficacy of drug
What is MEC?
Minimum effective concentration:
- minimum amount of drug concentration to be considered effective. (below won’t be effective)
What is MTC?
Minimum toxic concentration:
- minimum amount of drug concentration that can be considered toxic (side effects can happen)
Brands are cheaper than generics?
False, generics don’t have to go through the same pre-clinical and clinical stages that brand products have to go through
Similarity in Generic and Brand Drugs
- mechanism of action
- active ingredients
- efficacy
- Formulation (recipe- exact quantities)
- route of administration
- dosage form
- strength
- conditions of use
The only difference between brand and generic is the in-active ingredients? (excipients)
True
- Differences in inactive ingredietns results in some side effects to patients if they are susceptible to certain inactive ingredients
Generic drugs are only required to do bioequivalence and bioavailability testing.
True
FDA can give drug exclusivity for 6 months to 7 years
True
US trade mark and US patent gives patent protection for 20 years.
True
What if a new indication arises for the drug?
Will have to do some small trials to verify. Doesn’t have to go through whole process again. After that, the new indication will be able to be added to the label
