Dosage Forms Exam 2 Flashcards
What are the key ingredients for controlling drug delivery?
excipients
-Coatings (control diffusion rates)
-Disintegrants (control regions of release)
-Lubricants (slow dissolution)
-Internal excipients
What are coatings?
-applied to outside of dosage form
-used to: protect agent from air; mask taste; special drug release; aesthetics; prevent inadvertent contact with drug
What are enteric coatings?
-used on dosage forms to prevent the early release of API in an area where it can undergo chemical or metabolic breakdown
What is the difference between sustained and controlled release?
sustained release- onset of pharmacologic action is delayed, but its therapeutic effect has a sustained duration
controlled release- allows for us to maintain a narrow drug plasma concentration-steady state
ex. coated beads, granules, microspheres, multitablet system, microencapsulated
What are some physiological factors affecting absorption?
-Permeability/Perfusion (functional and molecular characteristics of transporters and metabolism)
What factors are important to consider with the composition of Biological membranes?
-cell membrane is semi-permeable
-cellular lipid composition is POLARIZED (cationic-get in better; anionic-not get in as well)
What does membrane and Cell-based assays utilize?
Permeability Coefficient
PAMPA
Caco-2
What are some drug transporters?
Nutrient and Xenobiotic transporters: Solute Carrier, ATP-binding cassettes
What are some differences between Passive Paracellular Permeation and Facilitative/Active Transcellular Permeation?
Passive Paracellular exhibits hydrophilicity, depends on molecular size, pKa, increase concentration—->increases permeability, utilizes adjuvants
Facilitative/Active Transcellular uses affinity and capacity properties, concentration dependent, expression level, function and is excipient dependent
What are some general considerations for Oral absorption?
-disintegration/Deaggregation
Crystalline (low solubility) vs. Amorphous (Increased solubility)
-food, protein binding, pH
-Intestinal flora, Bile, Nucleate
-Mucus, glycocalyx
What are some factors influencing drug solubility?
-buffer capacity
-bile salts
-Regional fluids
-other drugs
-endogenous substrates
What is ADMET?
A-absorption
D-Disposition (distribution and elimination)
M-Metabolism
E-Excretion
T-Toxicity
What is bioavailability?
refers to the rate and extent of drug absorption
What is absolute bioavailability?
the AUC of a given dosage form compared with the AUC of the same dose injected intravenously
What is Tmax and Cmax?
Tmax: time to reach the maximum blood/plasma concentration from a dosage form
Cmax: The maximum blood/plasma concentration from a dosage form
What is relative bioavailability?
refers to the AUC of a given dosage form compared to an arbitrary reference standard
T or F: Bioavailability is the fraction of an administered dose that reaches the systemic circulation intact
True
T or F: Dosage forms are designed to convey performance by balancing the composition of the excipients, the drug’s physiochemical properties and to overcome the physiological barriers required for a safe and efficacious response
True
T or F: When blinding clinical trials, it is often important to mask the organoleptic properties of the comparator and the drug being tested. These senses include sight, smell, taste, touch and sound
True
T or F: The stomach has a significantly increased surface area due to villi, folds of Keckring, and microvilli
False
Which is NOT included in the acronym of ADMET?
A) Excretion
B) Toxicity
C) Metabolism
D) Dissolution
E) Distribution
D) Dissolution
T or F: The microenvironmental pH at the membrane surface may be different than the lumen based on the fact that the mucus and the gylcocalyx have buffering effects
True
T or F: Drug levels observed in the therapeutic window can be governed in part by transporters and metabolism, based on the compound being studied. Therefore, transporters and enzymes do not play an important role in drug product performance
False
All of the following can reduce the bioavailability of an orally administered drug except:
a) Poor dissolution in the GI tract
b) Poor penetration of the blood-brain barrier
c) Chemical degradation in the GI tract
d) poor solubility in the GI fluids
e) Poor absorption across the GI mucosa
b) Poor penetration of the blood-brain barrier
What are the phases of drug metabolism?
Phase 1: CYP (oxidation and reduction reactions)
Phase 2: Conjugation
Transporters
