Dosage Forms I Exam 1 Flashcards
2A carboxylic acid with a pKa of 4.8 will be:
a) Partially ionized at pH 5.5
b) nearly completely ionized at pH 1
c) Nearly completely unionized at pH 1
d) a and c
e) a and b
d) a and c
partially ionized at pH 5.5 and nearly completely unionized at pH 1
The Ka for the dissociation of glibenclamide is 5.0119 x 10^-5. What is its pKa?
a) 9.7
b) 4.3
c) 9.9
d) 4.2
e) 3.85
b) 4.3
pKa is the negative log of the ionization constant of an acid
pKa= -logKa
Miconazole is an antifungal drug with a pKa = 6.7
At what pH will the concentration of the unionized and ionized species be equal?
a) pH 4.7
b) pH 8.7
c) pH 7.7
d) pH 5.7
e) pH 6.7
e) 6.7
concentrations of the ionized and unionized forms are the same at the pKa (6.7)
Micronazole pKa=6.7
When Micronazole is added to water the pH will:
a) Increase and then decrease
b) decrease
c) stay the same
d) increase
e) decrease and then increase
d) increase
pH will increase because miconazole is a weak base
miconazole pKa= 6.7
What fraction of miconazole is ionized in a buffer at pH 5.9?
a) 0.86
b) 0.14
c) 0.50
d) 0.76
e) 0.24
a) 0.86
equation for a weak base: pH-pKa = log B/BH+
5.9-6.7 = -0.8 = LogB/BH+
10^-0.8
B/BH+ = 0.158
Fraction of BH+ = 1/1.158 = 0.86
Omeprazole is sold as omeprazole magnesium in the tablet formulation. Omeprazole magnesium is:
a) The salt of the weakly acidic drug
b) The acid form of the drug
c) The neutral form
d) The salt of the weakly basic drug
e) the basic form of the drug
a) The salt of the weakly acidic drug
Magnesium is a positive ion, so it must be associated with a negative ion. A carboxylic acid or other acidic group would form a negative ion on salt formation, because of transferring a proton. Hence, omeprazole must be an acid.
What are the differences between druggability and developability?
Druggability- looks at binding as well as “drug-like” properties that are favorable for product translation.
-discovery stage, assess the ability of New Chemical Entities to bind to the drug target, in vivo models are used to assess (research conducted within the body)
Developability- included as a means to characterize if the new molecules can be formulated.
-refers drug product performance, incorporates factors like biorelevant solubility and dissolution, formulation factors related to ADME/T incorporated
What are the three main areas the control drug performance in patients?
Physiochemical properties of the API, Physiochemical properties and the composition of the formulation, Physiological barriers that influence the “targeted bioavailability” of the drug
What is drug performance?
The ability of a drug to elicit a therapeutic response; can stay in a safe therapeutic range during the dosing regimens; lack of toxic or non-efficacious response
Are excipients inert?
excipients are not inert!
Do partition coefficients accurately reflect absorption?
No. The GI tract has a diverse pH gradient that uses a buffer instead of water to see solubility which effect pKa. Solubility of water in octanol is about 4% while octanol is 0.4% soluble in water. Octanol looks nothing like the structure of cell membranes–many proteins, glycocalyx, lipids to consider.
The protein to lipid ratio in the GI tract is 1:7:1; thus, octanol:water partitioning is not an accurate predictor of physiological conditions
What is the partition coefficient?
ratio of concentrations in two immiscible solvents (octanol and water)
Ko/w = C(octanol)/C(water)
What is the pH-Partition hypothesis?
For drugs absorbed by a passive, transcellular mechanism across the lipid bilayer; permeability transport depends on the fraction of unionized drug at the intestinal pH
Compliance is a big part of patient acceptability. Name the senses that we try to appease for patients with formulations
Organoleptic Senses
-sight
-smell
-sound
-taste
-touch
Name the individual classes of excipients
binders - starches, sugars, cellulose, lactose, sugar alcohols
disintegrants - starches, sugars
fillers (diluents) - starches, sugars, cellulose
Lubricants - magnesium stearate, talc
Glidants (flow enhancers) - silicon dioxide, cellulose, titanium dioxide, talc
Compression aids - starches, sugars, lactose, cellulose
colors - titanium dioxide
sweeteners - sucrose, fructose, dextrose
preservatives - citric acid, sodium citrate, methyl paraben, propyl paraben
dispersing agents - gelatins, starches, gums, cellulose
film formers - polymers
flavors - sodium chloride, citric acid
printing inks
