Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

828 Dosage > Lecture 3: Formulation and API > Flashcards

Lecture 3: Formulation and API Flashcards

1
Q

Drug product performance

A

-ability of drug to elicit therapeutic response and stay in a safe range during dosage
-no toxic response
-described by pharmacokinetics and parmacodynamic processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Goal of Formulations

A

-transfer a new therapeutic compound
-develop reproducible dosage form

-release from dosage form must balance the way body processes medicine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

reproducible

A

-refers to each dosage form containing same amount of drug
-refers to same performance in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Drug blood level vs time graph

A
  1. Absorption: increase up to Cmax, Tmax (2hoursish)
  2. slow decrease through distribution, metabolism, excretion
    AUC= area under the curve
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Disposition phase of drug

A

distribution, metabolism, excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Elimination phase of drug

A

metabolism and excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Dosage form controls

A

-absorption, dissolution, degradation in intestinal tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Body controls

A

metabolism, distribution, excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Drug upon Administration

A

Intestinal tract (dosage form controls) –> portal vein –> liver (metabolism) –> blood –> peripheral tissues (distribution), perfused tissue, and urine (excretion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Absorption rate

A

-MUST BALANCE DISPOSITION
-begins declining as disposition starts to increase
-Kabs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Kabs defined by

A

-drug properties
-excipient/composition of formulation
-physiological barriers between GI tract and systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Margin of Safety

A

-goal of dosage form design
-area between pharma and toxicology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Drug discovery: Assessing translation

A

-finding chemistries that can mitigate disease
-driven by receptor binding
-druggability and developability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Druggability

A

-binding and “drug-like” properties favorable for product translation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Developability

A

assessment to characterize if new molecules can be formulated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Druggability stages

A
  1. discovery
  2. Assess ability to bind to drug target
  3. in vivo models used to assess
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Developability stages

A
  1. refers drug performance
  2. incorporates factors like solubility/dissolution
  3. incorporates formulation factors related to ADME/T
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Druggable genome

A

-genes that encode disease related proteins that can be modded by drugs
-includes differentially regulated drugs
-vary in intensity upon comparative analysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Healthy vs sick gene expression

A

-this contrast can yield genes that may serve as targets for drug design

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Druggable targets

A

mostly disease genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Druggable gene identification

A

via pharmacogenomic methods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Druggable proteins

A

-proteins that can bind drug-like compounds with affinity < 10mM
-compound must be able to modulate the protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Druggable proteins identification

A

-via genes of disease-related proteins that be modulated by drugs

24
Q

Druggable pharmacophore

A

-druggable genes converted to proteins via in silico methods

25
Druggable pharmacophore identification
binding cavities
26
Pharmaceutically tractable genome
-genes that encode proteins that can be targeted by smaller compounds, antibodies, and therapeutic proteins for pharmaceutical use
27
Drug candidate to tractable gene + protein associated with disease
= mitigated disease yay
28
Pharmacophore drug design
-proteins associated with disease modeled to find binding pockets -drugs fitting these pockets generated -chemicals can be made to optimize drug binding
29
Pharmacophore drug design applications
-virtual screening -de novo design
30
New chemical entities (NCE)
-generated to fit a pharmacophore -characterization to assess drugability
31
Good druggable entities
-do not equal a good potential to be translated
32
ADMET
T is toxicity
33
Developability
-centers on evaluating properties that will be used to generate a working formulation
34
Pharmacokinetics and pharmacodynamics
-main indicators of safe and efficacious use -do NOT vary across patient populations
35
Goal of Drug Delivery
Drug + vehicle -vehicle has selected properties to overcome barriers and transport it from administration site
36
Formulation design considerations (performance factors)
-physicochemical properties of the drug -properties and composition of formulation -biological factors (ADMET) -MUST be properly balanced
37
Performance
-drug response and therapeutic range -lack toxicity -function of the drug
38
Physicochemical Properties of the Drug that Affects Absorption
-solubility -drug stability in solution -lipophilicity -molecular size/shape -pKa of groups -physical state of drug -SLIDE 31
39
Solubility depends on
-molecular structure -physical state -composition of solvents -measurement methods
40
solid physical state
amorphous, crystalline, polymorphic
41
liquid physical state
predissolved in solvent
42
Composition of solvents
-types -cosolvent %s -solution components (salts, ions, lipids, ets) -pH and temp
43
Measurement Methods
-equilibration time -detection method
44
Partition Coefficient
-ratio of concentrations in two immiscible solvents (octanol and water) -Ko/w = Coct / Cwater
45
pH-partition hypothesis
-permeability transport depends on the fraction of unionized drug at intestinal pH -for drugs absorbed by passive, transcellular mechanism
46
solubility and partition coefficient
-as Ko/w increases, solubility decreases -formula SLIDE 34
47
pH and pKa
-important in determining absorption of weak acids vs weak bases
48
Cell membrane structure
-lipid bilayer with lipid and protein molecules
49
protein to lipid ratio in the GI tract
1:7 ?? -octanol:water partitioning not accurate predictor of physiological conditions
50
Organelle pH
-differences in extracellular and intracellular values affect transport -can trap molecule in a cell
51
Overcome effects of pH partition hypothesis
-functionalize the compound-change pKa -prodrug strategy -salt selection -drug delivery system
52
prodrug strategy
-modifiy charged moiety -modify molecule to be recognized by transporter
53
Salt selection
-ion pairing effective in improving permeation -form can alter unionized fraction
54
Polar Surface Area (PSA)
-solvent accessible surface area (SASA) provided by O, N, H -good estimate of H bond potential -does NOT account for charges
55
Poor absorption/permeation when:
-more than 5 H bond donors -more than 10 H bond acceptors -MW over 500 -MlogP over 4.15 (ClogP over 5)

828 Dosage (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions