School of Pharmacy

Physical Pharmacy (PHAR 420)

Fall 2019 - 2020
Instructor: Dr. Ruba Shdeed, Dr. Mohammad Hendaus, Dr. Tarek Jenani, Dr. Elise
Makhoul, Dr. Faten Hamed

Practice Problems –Chapter 5

Student Name: ID#:

1- Rx: Procaine HCL 2%
Ft. 30 ml

Knowing that the freezing point of 1% Procaine HCl = -0.122 C. Determine the
quantity in milligrams of NaCl required to make the solution isotonic.

Since the freezing point of 1% Procaine HCl is -0.122C, then the freezing point of 2%
is 2*-0.122=-0.244C
Grams of NaCl in 100 ml = 0.9 (0.52-Δt’f)/0.52
Where Δt’f = tfsolvent - tfsolution = 0 – (-0.244) = 0.244
Grams of NaCl in 100 ml = 0.9 (0.52-0.244)/0.52= 0.47769g%= 477.69 mg%

100ml-------------477.69mg
30ml--------------Xmg
X = 143.31 mg of NaCL are required for 30 ml of the formulation
2- What weight of Ascorbic acid (MW= 176.12) must be added to 1.00 L buffer
containing a total buffer concentration of 0.05M in order to change the pH from 3.5 to
3.9 (pKa = 4.1)?

= = = 0.251 1st Method:C = n/v (v = 1L) so n = C

[salt] = 0.251 [acid] and [salt] + [acid] = 0.05M
n 1 = m/Mw >> m1 = 0.010 x 176.12 = 1.76 g
[salt]1 = 0.010 M
n 2 = m/Mw >> m2 = 0.019 x 176.12 = 3.34 g
Added mass: m2 – m1 = 1.58 g
= = = 0.630
2nd Method:
[salt]2= 0.14 [acid] and [salt] + [acid] = 0.05M
Added mass= =
[salt]2 = 0.019 M
= 1.58 g

3- At what pH a sample of 60mg/5ml pseudoephedrine solution will precipitate.

Solubility of pseudoephedrine (So) is 2g/1000 ml.

MW = 165.23 g/mole for pseudoephedrine

MW = 201.69 g/mole for pseudoephedrine HCl
pKa = 10.3

So = = x = 0.0121 M
S = = x = 0.059 M
pHp = pKa+ log
pHp = 10.3+ log = 10.3 – 0.588 = 9.712
Therefore, above pH 9.712 saturated solution of pseudoephedrine would become
cloudy.

4- A pharmacist prepares a 3.0% solution of an antibiotic as an ophthalmic solution and

dispenses it to a patient. A few days later the patient returns the eye drops to the
pharmacist because the product contains a precipitate. The pharmacist, checking the pH
of the solution and finding it to be 6.0, reasons that the problem may be pH related. The
physicochemical information of interest on the antibiotic includes the following:
Volume 10mL
Molecular weight 285 (salt) 263 (free acid)
3.0% solution of the drug 0.1053 M solution
Acid form solubility (So) 3.1 mg/ml (0.0118 M)
Ka 5.86 × 10 –6
pKa = 5.23

a- Calculate the quantity of the antibiotic in solution at a pH of 6.0’

= = = 5.88

s = 0.0809 M
b- Calculate the amount of precipitated drug
= 0.064172 g = 64.17 mg
c- What is the pH where all the drug will remain in the solution originally prepared?

pHp = pKa + log = 6.135

5- How would you prepare a buffer solution of pH= 3.9 having a capacity of 0.6, using
lactic acid with pka 3.86? What is the new pH after addition of 1 g Eq of NaOH to 1 L of
the prepared buffer solution?

pH = pKa + log [salt]/[acid]

3.9 = 3.86 + log [salt]/[acid]
0.04 = log [salt]/[acid]
10 0.04 = [salt]/[acid]
1.096 = [salt]/[acid]

Step 3: the buffer capacity:

C = [Salt] + [acid]
β = 0.6 ;pKa = 4.1 ka = 1.38 x 10 -4
pH = 3.9 [H3O+] = 1 x 10-3.9 = 1.25 x 10 -4
β = 2.3 C x Ka [H3O+] / (Ka + [H3O+]) 2
0.6 = 2.3 * C * 1.38 x 10 -4 * 1.25 x 10 -4 / (1.38 x 10 -4 + 1.25 x 10 -4) 2
0.6 = 0.573 C C = 1.047mol/L
Step 4:
[Salt] = 1.096 [acid]
[Salt] + [acid] = 1.047mol/L
1.096 [acid] + [acid] = 1.047
 2.096 [acid] = 1.047 [acid] = 0.499mol/L
[Salt] = 0.548mol/L
b) β = Δ B / Δ pH
0.6 = 1 g Eq.L-1 / Δ pH
Δ pH = 1 / 0.6 = 1.66
New pH = pH of the buffer solution + Δ pH (plus since we added a strong base
pH will decrease) New PH = 3.9 +1.66= 5.56

6- Diflunisal is a nonsteroidal anti-inflammatory drug (NSAID) that is effective in

treating fever, pain, and inflammation in the body. Diflunisal has a pKa of 4.5

a) Using the above chemical structure, determine whether Diflunisal is an acidic,

basic or neutral compound. Explain your answer

Acidic since it has carboxylic acid function group

b) Calculate the ratio of ionized/unionized of the drug in the stomach where pH is 1.

pH of stomach = pKa of Diflunisal + log [ionized]/[unionized]
1 = 4.5 + log [ionized]/[unionized]
log [ionized]/[unionized] = 1-4.5
log [ionized]/[unionized] = -3.5
[ionized]/[unionized] = 0.000316 (Answer)
From the above value it means that for every 3 ionized molecules in the stomach
there are almost 10000 unionized molecules, suggesting that Diflunisal is largely
unionized in the stomach

c) Calculate the ratio of ionized/unionized in the intestine where pH is 6.

pH of the intestine = pKa of Diflunisal + log [ionized]/[unionized]
6 = 4.5 + log [ionized]/[unionized]
log [ionized]/[unionized]= 6 – 4.5
log [ionized]/[unionized] = 1.5
[ionized]/[unionized] = 31.62 (Answer)
 From the above value, it means that for 31.6 ionized molecules of Diflunisal in
the intestine there is only 1 unionized molecule, suggesting that Diflunisal is
largely ionized in the intestine

d) Based on these calculations where is Diflunisal absorbed within the body?

Based on the above calculations we can see that it is more unionized in the
stomach than in the intestine. Thus majority of the Diflunisal is absorbed via the
stomach under acidic pH.

7- A solution contains 20 g of Magnesium Chloride in a volume of 100 mL. What quantity

of sodium chloride must be added to make the solution isotonic? How much dextrose
would be required for this purpose?

The quantity of the drug is multiplied by its sodium chloride equivalent. E, giving 1he
weight of sodium chloride to which the quantity of drug is equivalent in osmotic
pressure:
Mg Chloride: 20g x 0.03 = 0.6g
Mg chloride has contributed a weight of material osmotically equivalent to 0.6 g of
sodium chloride.
Because a total of 0.9 g of sodium chloride is required for isotonicity, 0.3 g (0.90 - 0.6 g)
of NaCl must be added.
If one desired to use dextrose instead of sodium chloride to adjust the tonicity, the
quantity would be estimated by setting up the following proportion.
Because the sodium chloride equivalent of dextrose is 0.16.

= X= 1.87 g of dextrose

8- Consider the following prescription:

Rx:
Ephedrine Sulfate (MW= 428.54 g/mol; Liso = 5.8) 0.5 g
Boric Acid (MW= 61.83 g/mol; Liso = 1.9) 0.2 g
Ammonium Chloride (MW= 53.49 g/mol; Liso = 3.4) 0.25 g
Purified Water ad 60.0 mL
M. ft. isotonic solution
a. Calculate the NaCl equivalent value of Ephedrine Sulfate, Boric Acid, and
Ammonium Chloride.
b. By applying the White-Vincent equation, how would you prepare the above
prescription?

a. E = 17 * Liso / MW (2pts)

E value of Ephedrine Sulfate = 17 * 5.8 / 428.54 = 0.23

E value of Boric Acid = 17 * 1.9 / 61.83 = 0.52
E value of Ammonium Chloride = 17 * 3.4/ 53.49 = 1.08

b. V = [Ʃ Wi * Ei ] * 111.1
V = [ (0.5 * 0.23) + (0.2 * 0.52) + (0.25 * 1.08) ] * 111.11
V = 0.489 * 111.11 = 54.3 mL volume of isotonic solution that can be prepared
In order to prepare isotonic solution, the three ingredients are dissolved in
purified water to make 54.3 mL of an isotonic solution, and the preparation is
adjusted to a volume of 60 mL by adding isotonic vehicle (like NaCl 0.9%).

9- A pharmacist is asked to prepare a buffer solution having a pH=5 and a buffer

capacity = 0.04

Weak acid pKa

Salicylic acid 3

Propanoic acid 4.81

Acetic acid 4.76

a. How would you prepare the requested buffer solution?

Step 1: Select a weak acid whose pKa is approximately equal to the pH since
desired pH = 5 Select propanoic acid PKa=4.81
Step 2: apply the Henderson-Hasselbalch equation to calculate the ratio of
quantities of salt and weak acid
pH = pKa + log [salt]/[acid]
5= 4.81 + log [salt]/[acid]
0.19 = log [salt]/[acid] 10 0.19 = [salt]/[acid] 1.5 = [salt]/[acid]
 Step 3: From the buffer capacity equation:
C = [Salt] + [acid]
β = 0.04 ;pKa = 4.81 ka = 1.54 x 10 -5
pH = 5 [H3O+] = 10-5
β = 2.303 C x Ka [H3O+] / (Ka + [H3O+]) 2
0.04 = 2.303 * C * 1.54 x 10 -5 * 10 -5 / (1.54x 10 -5 + 10 -5) 2
C = 0.07mol/L

Step 4:
[Salt] = 1.5 [acid]
[Salt] + [acid] = 0.07mol/L
1.5 [acid] + [acid] = 0.07
2.5 [acid] = 0.07 [acid] = 0.07 / 2.5 = 0.028mol/L
[Salt] = 0.07 – 0.028 = 0.042mol/L

b. What is the maximum buffer capacity, of HA/A- buffer, when the total
concentration of this solution is 0.4 mol/L?

βmax = 0.576 C = 0.576 * 0.4 = 0.23