Ionization of Water and the pH phenomenon Lewis acids are electrophiles (electron loving)

• Hydronium Ion- combination of two water they attract electron. Positively charge (cations)
molecule which produce hydronium ion and such as copper, iron. Metal ions are acid except
hydroxide ion. The hydronium ion alkali group.
concentration is 1.0 x 10-7 at 25 deg C. Lewis base are nucleophilic (proton loving) they
H2O + H2O – H3O+ + OH- attack positively charge electrons through their
The ionization can be computed by lone pair.
(𝐻3 𝑂+ )(𝑂𝐻 −) Dissociation Constant
K= (𝐻2 𝑂)
Definition:
Equilibrium constant can be computed as:
• It is a measure of the strength of an acid or a
𝑝𝑟𝑜𝑑𝑢𝑐𝑡 (𝐻3 𝑂+ )(𝑂𝐻 − )
K= 𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡 = base.
(𝐻2 𝑂)2
(𝐻3𝑂+)(𝐴−)
Since the concentration of hydronium ion and For acid: 𝑘𝑎 = (𝐻𝐴)
hydroxide ion are very much small than the (𝐵𝐻+)(𝑂𝐻)
For base: 𝑘𝑎 =
concentration of water molecule, the water (𝐵)
molecule concentration is held constant. WEAK ACID (pKa= -log (ka)) Ka= antilog (-pka)
Therefore, the formula is A. Weak Acid Ka pKa
𝑝𝑟𝑜𝑑𝑢𝑐𝑡 (𝐻3 𝑂+ )(𝑂𝐻 − ) (Functional
K=𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡 = ) = H3O+ + OH-
(𝐻2 𝑂)2 Groups)
Kw = H3O+ + OH-
pH= -log (H3O+) Acetaminophen 3.09 x 10-10 9.51
POH= -log (OH-) (Aromatic
Pkw= pH + POH =14 Alcohol)
-arrhenius theory about acid and bases, any ASA (-COOH) 3.27 x 10-4 3.49
substance that gives hydrogen ions are acid and Phenobarbital 3.9 x 10-8 7.41
substances that gives hydroxide ions are bases. (cyclic ureide)
-not all acid and bases had hydroxide and Phenytoin 7.9 x 10-9 8.1
hydronium ion or hydrogen ion. (imide)
Acetic acid (- 1.75 x 10-5 4.75
• Ionization of water
COOH)
Chemical Theories on Acids and Bases
Boric acid 5.8 x 10-10 9.24
• Bronsted-Lowry Acid-Base Theory
Increase ka, decrease pKa and vice versa
BL acid= donate proton (+)
Ka is directly proportional to hydronium ions. If
BL base= accepts proton
ka decreases therefore the concentration of
Ammonia is a basic solution.
hydronium ion. When the concentration of
• Lewis Acids and Bases
hydronium ion decreases, the acidity decreases.
o Less than a full octet of electrons
B. Weak Base Kb pKb pKa of
o Metal ions except those of the alkali
(Functional conjug
group Groups) ate
o Compounds having double bonds acid
Acid and base when react they produce Atropine 4.5 x 10-5 4.35 9.65
coordinate covalent bond. Type of covalent (tertiary
bond in which one of reactant give its electron amine)
pair. Erythromycin 6.3 x 10-6 5.2 8.8
Lewis base= donates e- (tertiary
Lewis acid= accepts e- amine)
 Papaverine 8 x 10-9 8.1 5.9 equilibrium and able to neutralize small amount
(pyridine)) of acid and bases
Tolbutamide 2.0 x 10-9 8.70 5.30
(Sulfonylurea) What are the Uses?
Ammonia 4.1 x 10-14 13.39 0.61 -Buffers can neutralize small amount of acid and
Pkw (14) = Pka + pkb bases in a solution. Therefore, it can maintain
Pka + pkb =14 the ph of the solution making the solution
Pka = 14 – pkb relatively stable. Examples of processes that
requires specific stable ph is assay.
1. The dissociation constant of acetic acid (acid) • Preparation of such dosage of injections and
is 1.75 x 10-5 at 25˚C. Calculate its pKa and pKb ophthalmic solutions.
value • For product stability.
Pka = -log (ka) • Pharmaceutical tests and assays requiring
-log (1.75 x 10-5) = 4.75 adjustment or maintenance of a specific pH
Pkb
Pkw= pka + pkb Henderson-Hasselbach Equation
Pkb = 14 – 4.75 = 9.25 𝑠𝑎𝑙𝑡
2. The dissociation constant of ammonia is 1.80 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
𝑏𝑎𝑠𝑒
x 10-5 at 25˚C. Calculate its pKa value. 𝑏𝑎𝑠𝑒
𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + 𝑙𝑜𝑔
pKb = -log (1.80 x 10-5) =4.74 𝑠𝑎𝑙𝑡
Pka= 14 – pkb 1. What is the pH of a buffer solution prepared
14 – 4.74 = 9.26 with 0.05 M sodium borate & 0.005 M boric
acid? The Ka of boric acid is 6.4 x 10-10
3. The pKa value listed for the conjugate acid of 𝑠𝑎𝑙𝑡
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
ephedrine is 9.36. Calculate the pKb and the 𝑎𝑐𝑖𝑑
0.05 𝑀
basicity constant for this drug. 𝑝𝐻 = − log (6.4 𝑥 10−10 ) + 𝑙𝑜𝑔
0.005 𝑀
Pkb= 14 – pka
= 10.19
14 – 9.36 = 4.64 2. What is the pH of a buffer solution containing
Kb= Antilog (pkb) HAc & NaAc after enough NaAc has been added
= 10-4.64 = 2.29 x 10-5 to make solution of 0.1 M with respect to HAc?
The Ka of boric acid is 1.75 x 10-5
Buffers 𝑠𝑎𝑙𝑡
• Mixture of compounds that, by their presence 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
𝑎𝑐𝑖𝑑
in solution, resist changes in pH upon the 0.1
addition of an acid or alkali. 𝑝𝐻 = − log (1.75 𝑥 10−5 ) + 𝑙𝑜𝑔 = 4.76
0.1
-Maintenance of ph is buffer action
• Why use Buffer? 3. What is the pH of a buffer solution prepared
• Components of Buffer? with 0.05 M Ammonia (base) & 0.05 M
Weak acid + conjugate base Ammonium Chloride? The Kb of ammonia is 1.8
Weak base + conjugate acid x 10-5
• How do they work? 𝑏𝑎𝑠𝑒
𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + 𝑙𝑜𝑔
Able to resist the ph change because the 2 𝑠𝑎𝑙𝑡
components in conjugate acid and base are 0.05
𝑝𝐻 = 14 − [− log(1.8 𝑥 10−5 )] + 𝑙𝑜𝑔
both present in appreciable amount at 0.05
= 9.26
4. What is the pH of a solution containing 0.1M Example:
ephedrine & 0.01 M of ephedrine HCl? The pKb 1. Calculate the change in pH after adding
of ephedrine is 4.64. 0.04M of NaOH to a liter of a buffer solution
𝑏𝑎𝑠𝑒 containing 0.2M concentrations of NaAc and
𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + 𝑙𝑜𝑔
𝑠𝑎𝑙𝑡 HAc. pKa of acetic acid is 4.76.
0.1 (𝑠𝑎𝑙𝑡) + (𝑏𝑎𝑠𝑒)
𝑝𝐻 = 14 − 4.64 + 𝑙𝑜𝑔 = 10.36 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
0.01 (𝑎𝑐𝑖𝑑) − (𝑏𝑎𝑠𝑒)
(0.2) + (0.04)
𝑝𝐻 = 4.76 + 𝑙𝑜𝑔 = 4.94
(0.2) − (0.04)
Buffer Equation
Pka is equal to pH.
Molar ratio of Salt/Acid for a buffer system of
Change in ph= final – initial
desired pH.
4.94 – 4.76 = 0.18
𝑠𝑎𝑙𝑡
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
𝑎𝑐𝑖𝑑
Buffer Capacity
-Buffer is a solutions containing weak acid and
Examples:
conjugate base or weak base and conjugate
1. What molar ratio of salt/acid is required to
acid. In a particular solution it can maintain the
prepare a sodium acetate-acetic acid buffer
pH of particular solution
solution with a pH of 5.76? The pKa of acetic
• It is the measure of the magnitude of the
acid is 4.76.
𝑠𝑎𝑙𝑡 buffer action of the buffer system.
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔 - It is the measure of the magnitude of the
𝑎𝑐𝑖𝑑
𝑠𝑎𝑙𝑡 resistance of a buffer to pH changes.
5.76 = 4.76 + 𝑙𝑜𝑔 • It is the amount in g/L of SA or SB required to
𝑎𝑐𝑖𝑑
𝑠𝑎𝑙𝑡 𝑠𝑎𝑙𝑡 be added to a solution to change in pH by 1 unit
5.76 − 4.76 = 𝑙𝑜𝑔 = 1 = 𝑙𝑜𝑔 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑆𝐴 𝑜𝑟 𝑆𝐵
𝑎𝑐𝑖𝑑 𝑎𝑐𝑖𝑑 𝐵= ΔpH= final ph-initial ph
(1) 10 ΔpH
Antilog = 10 = 10 or 1 = 10:1
2.3 𝑥 𝐶 𝑥 𝐾𝑎 𝑥 (𝐻3 𝑂+ )
𝐵=
(𝐾𝑎 + (𝐻3 𝑂+ )2
2. What is the molar ratio of salt/acid is
required to prepare an acetate buffer solution 2.303
with a pH of 5? 𝐵𝑚𝑎𝑥 = 𝐶
4
Pka of acetate
𝑠𝑎𝑙𝑡 If acid = base the pH is equal to pKa
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
𝑎𝑐𝑖𝑑
𝑠𝑎𝑙𝑡 𝑠𝑎𝑙𝑡
5 − 4.76 = 𝑙𝑜𝑔 = 0.24 = 𝑙𝑜𝑔 Sample Problem
𝑎𝑐𝑖𝑑 𝑎𝑐𝑖𝑑 • At a [H3O+] of 1.75 X 10-5 (pH = 4.76), what is
Antilog = 10(0.24)
1.74 the buffer capacity containing 1 mole each of
= HAc & NaAc per liter of solution. Ka = 1.75 X 10-
1
1
If the given is acid/salt the answer is 1.74 5?
2.3 𝑥 𝐶 𝑥 𝐾𝑎 𝑥 (𝐻3 𝑂+ )
𝐵=
Change in pH with the addition of an acid or a (𝐾𝑎 + [(𝐻3 𝑂+ )]2
2.303 𝑥 2𝑀 𝑥 1.75 𝑥 10−5 𝑥 1.75 𝑥 10−5
base. 𝐵= = 1.152M
(1.75 𝑥 10−5+ [1.75 𝑥 10−5)]2
(𝑠𝑎𝑙𝑡) + (𝑏𝑎𝑠𝑒)
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔 Or
(𝑎𝑐𝑖𝑑) − (𝑏𝑎𝑠𝑒) 2.303
𝐵𝑚𝑎𝑥 = 𝐶
4
 2.303 Ph is 7.4 or ranging 7-8
𝐵𝑚𝑎𝑥 = 𝑐 = 0.576 𝐶 = 0.576 𝑥 2𝑀
4 • Urine
𝑀 -Average urine is pH 6
= 1.152
𝑝𝐻 𝑢𝑛𝑖𝑡 o It can be as low as 4.5 or as high as
7.8.
• Calculate the buffer capacity of a solution o Physiological pH balance.
containing 0.10 M acetic acid and 0.10 M -When the pH of urine goes below normal
acetate. Find the pH change when you add values, the kidneys excrete hydrogen ion. High
NaOH so that the solution becomes 0.005M in concentration of hydrogen ion it means acidic.
NaOH. -When the pH goes above the normal, kidneys
2.303
𝐵𝑚𝑎𝑥 = 𝐶 retain hydrogen ion. When hydrogen ions
4 retain, it accumulates which mean it increases
0.10 + 0.10 = 0.20M
2.303 hydrogen ion and cause increase acidity (the ph
𝐵𝑚𝑎𝑥 = 𝐶 = 0.575 𝑥 0.20𝑀 will decrease)
4
𝑀 • Pharmaceutical buffers:
= 0.1152 -Pharmaceutical buffers are used in the
𝑝ℎ 𝑢𝑛𝑖𝑡
• What is the maximum buffer capacity of an preparation of different dosage form like
acetate buffer with a total concentration of 0.02 parenteral product. The pH of the blood should
mole/L? be maintain. It can increase the stability of
2.303 formulation because some drugs are pH
𝐵𝑚𝑎𝑥 = 𝐶 dependent.
4
2.303 -Also used in assay.
𝐵𝑚𝑎𝑥 = 𝐶 = 0.576 𝑥 0.02𝑀
4 o Phosphate buffer System:
𝑀 o Sorensen buffer
= 0.01152
𝑝ℎ 𝑢𝑛𝑖𝑡 o It is a mixture of salts of
Sodium Phosphate for buffer
Importance of Buffer Systems solutions of pH (6.8).
In-vivo biological buffer systems o Sodium Chloride is added to
• Blood buffer systems: (pH =7.4) (pH of the make it isotonic.
blood is 7-7.8) • Borate Buffer Systems:
• Primary Buffers: (seen in our plasma) • Gifford Buffer
Plasma are acid in the blood and tend to bind • It contains Boric acid and Sodium
with bases, neutralizing the blood. Plasma Carbonate
protein can act as buffers in the blood. • It is used as a buffer for solutions with
o Carbonic Acid/Bicarbonate (has 2 pH of 5-9.
acidity dissociation constant. It has 2 hydrogen • Feldman’s Buffer
ion that can donate. K1 and K2) • It contains boric acid and sodium
o Acid or Alkali Na salts of phosphoric borate
acids • Sodium Chloride is added.
• Plasma CHONS (acid) • It is used as a buffer for solutions with
• Secondary Buffers: (seen in rbc / erythrocytes) pH of 7-8.2.
o Hemoglobin/Oxyhemoglobin • Atkins & Pantin Buffer
o Acid/Alkali potassium salts of • It contains Boric acid & Sodium
phosphoric acids Carbonate.
• Lacrimal Fluid
 • Sodium Chloride is added. o Sodium chloride equivalent ( compute for the
• It is used as buffer for solutions with amount of NaCl that is required to adjust the
pH of 7.6-11. tonicity of solution)
• Class 2: (thee tonicity adjustment involves
- Phosphate buffer Saline Solution- phosphate addition of water to prepare isotonic solution)
buffer that contain sodium chloride -It finds the volume of the solution
- To be isotonic sodium chloride is used. Aside o Sprowl’s Method
from sodium chloride it can also use potassium v = 0.3 x e x111.1
chloride, potassium biphosphate. Calcium o White Vincent Method
chloride, and magnesium sulfate. v = weight of drug x e value x 111.1
• Class 3:
Isotonic and Buffer Solutions o Liso value (molal freezing point of water
• Osmosis considering the ionization of electrolytes)
o The movement of solvent from a region of Liso
Δtf =
MW
low solute concentration to a region of a high 𝐿𝑖𝑠𝑜
E value = 17 x 𝑀𝑊
solute concentration through a semi-permeable
membrane. o Cryoscopic Method (-0.52 deg c =0.9% NaCl)
o And the pressure responsible is called
Osmotic Pressure 1. Zinc sulfate is a 2-ion electrolyte, dissociating
o Premises: 40% in a certain concentration. Calculate the I
§ If the solute is non-electrolyte, it will factor.
contain only molecules and osmotic pressure
will vary only with the concentration of solute. 2. Zinc chloride is a 3-ion electrolyte,
§ If the solute is electrolyte, it will dissociating 80%.
contain ions and the osmotic pressure will vary
with the solute concentration but also with the 3. Estimate the E value for a solute with an MW
degree of dissociation of solute. of 340 g/mole and an L iso value of 3.4
𝐿𝑖𝑠𝑜
Premises: 17 𝑥
• Osmotic pressure will depend on the number 𝑀𝑊
of particles in solution. 3.4
• Solutions to be administered should be 17 𝑥 = 0.17
340 𝑔/𝑚𝑜𝑙𝑒
isosmotic with the body fluids, for greater
comforter, efficacy and safety. 4. A 500 mL solution of drug (E = 0.21) contains
• A solution with the same osmotic pressure is 3 g of the drug. How much sodium chloride is
said to be isotonic with the body fluid. needed to render the solution isotonic?
• In most cases, preparations are isotonic, to 3g x 0.21 = 0.63
have homeostasis with the body’s intracellular 500 mL x 0.9% (isotonic NaCl)
0.9 𝑔 𝑁𝑎𝐶𝑙
fluids but not most of the time. 500 mL x = 4.5𝑔 𝑁𝑎𝐶𝑙
100 𝑚𝐿
4.5 NaCl – 0.63 g = 8.87 NaCl
Preparation of Isotonic solutions: you need to add 8.87 g of NaCl to the solution
• Class 1: to be isotonic.
o Hemolytic Method (rbc and add different
solution and observe the appearance of rbc. Sample Problems
Shrink (hypertonic) swell
1. How many g of NaCl should be used in Drug to NaCl (multiply)
compounding the following Rx? NaCl to drug (divide)
Pilocarpine nitrate (MW = 271.27) 0.3 g
NaCl qs 3. Chloramphenicol (MW = 323.13, Liso = 2) 1g
Pur. Water 30 mL Sterile water for injection q.s. ad. 100 mL
M ft. isotonic solution
Solution: According to White Vincent method, compute
Missing e value for the volume of an isotonic solution of the
𝐿𝑖𝑠𝑜 drug.
E value = 17 x 𝑀𝑊
3.4 V = W x E x 111.1
E value = 17 x 271.27 = 0.21 2
E value = 17 x 323.13 = 0.12
V = 1g x 0.12 x 11.1 =13.33 mL
Pilocarpine nitrate 0.3 g x 0.21 = 0.063g NaCl
NaCl qs Answer: 0.207g
0.9𝑔 4. Acyclovir (MW = 248.21, Liso = 3.4) 0.5 g
Pur. Water 30 mL 30mL x 100 𝑚𝐿 = 0.27𝑔 𝑁𝑎𝐶𝑙
Sterile water for injection q.s. ad. 10 mL
According to Sprowl’s method, what is the
0.27g – 0.063g = 0.207g NaCl volume of an isotonic solution that can be
prepared?
2. How many g of Boric acid should be used in
compounding the following Rx? V = 0.3g x e value x 111.1
Phenacaine HCl (MW = 334.84) 1% 𝐿𝑖𝑠𝑜
E value = 17 x 𝑀𝑊
Chlorobutanol (MW = 175.5) 0.5% 3.4
Boric acid qs E value = 17 x 248.21 = 0.23
Pur. Water qs 60 ml V = 0.3g x 0.23 x 111.1 = 7.67mL

Solution: 5. Estimate the E value and freezing point

Phenacaine HCl (Liso = 3.4) depression of chloramphenicol and acyclovir in
3.4 the previous problems.
E value = 17 x 334.84 = 0.173
Chlorobutanol (Liso = 2.5) Chloramphenicol
2.5 Liso
E value = 17 x = 0.24 Δtf =
175.5 MW
2
Δtf = = 6.19 𝑥 10−3 𝑜𝑟 0.00619 deg 𝑐
Phenacaine HCl 1% =
1𝑔
𝑥 60 𝑚𝐿 = 323.13
100 𝑚𝐿
0.6𝑔 𝑥 0.173 = 𝟎. 𝟏𝟎𝒈 Acyclovir
0.5 𝑔
Chlorobutanol 0.5% = 𝑥 60 𝑚𝐿 = 3.4
100 𝑚𝐿 Δtf = = 0.014 deg 𝑐
0.3𝑔 𝑥 0.24 = 𝟎. 𝟎𝟕𝟐𝒈 248.21

0.9𝑔
60 mL x 100 𝑚𝐿 = 0.54 𝑔 𝑁𝑎𝐶𝑙
0.54g NaCl – (0.01 + 0.072) = 0.37g NaCl Isotonic and Buffer Solutions
Physical/Chemical considerations in the
Boric acid (e value 0.50) = = preparation of Isotonic Solutions.
1𝑔 𝑥
𝑥 = 0.74𝑔 𝐵𝑜𝑟𝑖𝑐 𝑎𝑐𝑖𝑑 • Colligative properties maybe used for
0.5𝑔 𝑁𝑎𝐶𝑙 0.37𝑔 𝑁𝑎𝐶𝑙
Or
0.37𝑔 𝑁𝑎𝐶𝑙
= 0.74𝑔 determining tonicity.
0.5
• The freezing point of blood serum and
lacrimal fluid is – 0.52 deg C.
• When 1 g molecular weight of any
nonelectrolyte, such as boric acid (MW = 61.8)
is dissolved in 1000 g of water, the freezing
point of the solution is about 1.86 deg C below
the freezing point of pure water.
• For electrolytes, example is Sodium chloride
(MW = 58.5). If we assume that sodium chloride
in weak solutions is about 80% dissociated, then
each 100 molecules yields 180 particles, or 1.8
times as many particles as are yielded by 100
molecules of a non-electrolyte. This dissociation
factor, commonly symbolized by the letter i,
must be included in the proportion.
Dissociation factors varies from the type of
substance.
• Non electrolytes = 1
• Substances that dissociates into 2 ions = 1.8
• Substances that dissociates into 3 ions = 2.6
• Substances that dissociates into 4 ions = 3.4
• Substances that dissociates into 5 ions = 4.2
Example Calculations of the I factor:
• Zinc sulfate is a 2-ion electrolyte, dissociating
40% in a certain concentration. Calculate the I
factor.
• Zinc chloride is a 3-ion electrolyte, dissociating
80%
Measurement of isotonicity:
• Hemolytic Method
• Based on Osmotic pressure
Using Liso value
• Based on Freezing point Depression
• ∆Tf of blood and tears = 0.52˚C
• Isotonic Solutions = 0.9% NaCl
1. Compute for ∆Tf of 1% Ascorbic acid solution
with Liso value of 1.9 ˚C/M. MW = 176.12 g/mol
2. Compute for isotonic concentration for
phenylephrine using its Liso value of 3.5 ˚C/M
∆Tf =0.18˚C.
Interfacial Phenomenon
Interface
- Affects the absorption of the drug onto solid
adjunct in solid forms and it can affect the
penetration of molecule through biologic
membrane and production of emulsion, its
stability and dispersion of insoluble particles in
liquid media to form suspension.
• Boundary between two phases
• Boundaries of solids, liquids, or gases with
other solids, liquids or gases.
Surface
• Boundaries of solids or liquids with air
Surface tension
- Is used when one of the phases is in contact
with air.
• Force that pulls the molecules at the interface
together, which results to the contraction of the
surface.
• It is the force per unit length that must be
applied parallel to the surface so as to
counterbalance the net inward pull.
- The forces of attraction between molecule like
w/w is called force of cohesion and forces of
attraction between unlike molecule like water
and air, water and glass, water in olive oil is
called forces of adhesion. Like molecule is
cohesion and unlike molecule is adhesion.
• Dynes/cm or N/m
Interfacial tension
• Force per unit length existing at the interface
between two immiscible liquid phases.
• Attractive forces between immiscible liquids
 2. Calculate the surface tension of a 2% (w/v)
solution of a wetting agent that has a density of
1.008 g/cm3 and that rises 6.6 cm in a capillary
tube having an inside radius of 0.02 cm.
γ = ½ hgrρ
½ (6.6 cm) (981 cm/sec2) (0.02 cm) (1.008
g/cm3)
= 65.26 dynes/cm

3. The surface tension of benzene at 20°C is

28.85 dynes/cm. In a capillary apparatus, the
liquid rose to a height of 1.832 cm. The density
of benzene is 0.8756. Calculate the diameter of
Surface Tension the capillary tube
Measurement of Surface tension γ = ½ hgrρ
2𝑦
• Capillary rise: γ = ½ hgrρ r = ℎ𝑔𝑝
Y = surface tension 𝑑𝑦𝑛𝑒𝑠
2(28.85 𝑐𝑚
R = inner radius r= 𝑐𝑚 𝑔 = 0.037
(1.832 𝑐𝑚)(981 ) (0.8756𝑐𝑚3)
𝑠𝑒𝑐2
H = height
P= density
Diameter is twice the radius
G= gravity (981 cm/sec2)
2 x 0.037 = 0.074 cm

Interfacial Phenomenon
Sample Problem
Surface Active Agents
1. A sample of chloroform rose to a height of
- Called amphiphiles.
3.67 cm at 20°C in a capillary tube having an
• Molecules or ions that are adsorbed at
inside radium of 0.01 cm. What is the surface
interfaces.
tension of chloroform? Ρ = 1.476 g/cm3
• It has a certain affinity for both polar and
nonpolar solvents, depending on the number
γ = ½ hgrρ
and nature of the polar and nonpolar groups
½ (3.67 cm) (981 cm/sec2) (0.01 cm) (1.476
present,
g/cm0)
• Maybe predominantly hydrophilic (water
Cmo to cancel cm
loving group), lipophilic (oil loving group) or
=26.57 g/sec2
reasonably well-balanced between these two
But the unit must be in dynes/cm or n/M
extremes
g/sec2 is same as dynes/cm

𝑔 1 𝑑𝑦𝑛𝑒
Types of Surfactants
𝑥 Cancellation • Anionic Surfactants
𝑠𝑒𝑐 2 1𝑔−𝑐𝑚/𝑠𝑒𝑐2
• Cationic Surfactants
• Non-ionic surfactant
• Zwitterionic Surfactants

Anionic surfactants
• In solution, the head is negatively charged.
• These surfactants are the most widely used
type of surfactant for preparing shampoos
because of its excellent cleaning properties and
high hair conditioning effects.
• But they have unpleasant taste and have skin
irritation potential.
• They are incompatible with cationic
surfactants but compatible with other type of
surfactants.
• Anionic surfactants are particularly effective
at oil cleaning and oil/clay suspension.
- Examples: carboxylate, sulfonate, or sulfate
group. Sodium stearate, sodium dodecyl
sulfate, sodium lowryl sulfate.
Cationic surfactants
• are quaternary ammonium compounds and
they are mostly used for their disinfectant and
preservative properties as they have good
bactericidal properties.
• They are used on skin for cleansing wounds or
burns.
• They are also used as hair conditioners and
fabric conditioners.
• They are also electrolytes like anionic
surfactants and that are incompatible with
anionic surfactants.
- Examples: cetrimide, benzal konium chloride,
cety pyridinium chloride.
Non-Ionic Surfactants
• Those surfactants do not have any electrical
charge, which makes them resistant to water
hardness deactivation.
• They are not affected by presence of salts or
changes in pH.
• They are less irritant than other anionic or
cationic surfactants.
- Examples: spans (sorbitan esters),
tweens (polysorbates),
pluronics (poloxamer)
Amphoteric/Zwitterionic Surfactants
• They are mainly used as cosurfactants.
• These surfactants are very mild, making them
particularly suited for use in personal care
preparations over sensitive skins.
• They can be anionic (negatively charged),
cationic (positively charged) or non-ionic (no
charge) in solution, depending on the acidity or
pH of the water. Hence surfactants have
excellent dermatological properties.
• They are frequently used in shampoos and
other cosmetic products, and also in hand
dishwashing liquids because of their high
foaming properties
- contain carboxylates, or phosphate groups
(anions).
And have amino or quaternary ammonium
(cations).
Carboxylate and amino group Called
polypeptides or proteins. Phosphate group and
quaternary ammonium called lecithins and
cephalins.
Applications:
• Improve drug dissolution rate in solid dosage
forms.
• They act as lubricants or glidants.
• Suppository base
• Solubilizing agents to aid in solubility.
(Vitamins like a, e, k when add polysorbates 20
or 80) (Nonionic surfactants they have been
used as solubilization of wide variety of
hydrophobic drug such as anesthetic,
photosensitizers, sedative, anticancer drugs)
• Preparation of mouthwashes.
• Cerumenolytic (ear wax (cerumen) hydrogen
peroxide and combination of hydrogen
peroxide and urea)
• In cosmetics, improve penetration and
cleaning purposes.
• Biologically important.
- used for antibacterial and other protective
agents.
Sample Problem
• What is the HLB of a mixture of 40% of Span
60 (4.7) and 60% of Tween 60 (14.9)?
4.7 x 40% = 1.88
14.9 x 60% = 8.94
10.82
Dispersed Systems
Pharmaceutical Dispersions
• They are systems where one substance is
dispersed within another substance.
• It includes homogenous dispersions and
heterogenous (true solutions, combine a liquid
and liquid solid or gases you see one phase)
dispersions.
• Components:
o Internal / Noncontinuous / Dispersed phase
components
o External / Continuous / Dispersion medium

• What is the HLB of an emulsifier blend

consisting of 25% of Span 20 (8.6) and 75% of
Tween 80 (15)?
8.6 x 25% = 2.15
15 x 75% = 11.25
13.4

• Calculate the HLB of a mixture of 45 g of Span

80 (4.3) and 55 g of Tween 80 (15).

45g + 55g = 100g

4.3 x 45% = 1.935
15 x 55% = 8.25
10.185
Colloidal Dispersions
• What is the HLB of an emulsifier blend
Colloids or Colloidal Systems Dispersions
consisting of 20% of Span 60 (4.7), 20% of Span
- Glue like substances
80 (4.3) and 60% of Tween 60 (14.9)?
• Systems in which the size of the dispersed
4.7 x 20% = 0.94
phase is 1nm – 500 nm (5 micrometer) or from
4.3 x 20% = 0.86
the previous slide.
14.9 x 60% = 8.94
• The dispersion medium can be liquid, solid or
10.74
gas.
Types of Colloids:
• Lyophilic Colloids- lyo “solvent” philic “loving
=solvent loving
• Lyophobic Colloids – solvent hating
• Association Colloids- amphiphilic
Lyophilic Colloids
• It can Hydrophilic or Lipophilic colloidal
dispersions
• Examples:
• Hydrophilic Colloidal Dispersions
• Lipophilic Colloidal Dispersions
- Example: true solution (acacia and
povidone), Gelled solution (gelatin), particulate
dispersion (bentonite magma), Magnesium or
aluminum stearate in cotton seed oil
Hydrophilic Colloidal Dispersions
• They have Polar Regions that enable them to
become hydrated in contact with aqueous
environments.
• Examples:
• Macromolecules – such as proteins (albumin
and gelatin) and polysaccharides (natural gums
and semisynthetic cellulose derivatives)
o They are true solutions , since they are
solvated by their medium but their size makes
them in the colloidal size ranges
o They are sometimes referred to as colloid
solutions, to distinguish
them from crystalloid solutions
o Usage: Plasma Volume expansion
Lipophilic Colloidal Dispersions
• They don’t have sufficient surface
hydrophilicity to enable them to interact well
with water.
• They have the tendency to form aggregates.
• Examples:
o Milk
o Lipid emulsions
o Nanocrystal suspensions
Lyophobic Colloidal System (solvent hating)
• Colloidal systems in which the dispersed
phase has little affinity towards the dispersed
medium.
• They require more time to prepare than
lyophilic colloidal systems because the
dispersion process is not spontaneous.
• Examples:
o Hydrophobic polymers,
o Ethylcellulose
o Inorganic particles such as gold, silver and
sulfur.
Preparation: deduce the course particles,
condensation method, milling and grinding,
supersaturation, chemical reactions
Properties of Colloids:
• Optical Properties:
-colloidal particles shows interaction of light
and a beam of light is strike in colloidal particles
it causes polarization of atom and molecules
and induce dipole moment.
-weaker light in same wavelength incidence
light appears. The emitted light propagates in
all direction and its phenomena is knows as
light scattering.
-the bigger the particle the more light
scattering.
o Faraday-Tyndall Effect
§ The formation of a highly visible cone of light
when a strong beam of light is allowed to pass
through a colloidal sol.
-the bigger the particle the more light
scattering.
-can be seen clearly against in a dark
background.
o Turbidity
§ Fractional decrease in the intensity of light
due to scattering as the incident light passes
through 1 cm of the dispersion.
- spectrophotometer – nephelometer
Properties of Colloids
Kinetic Properties:
1. Brownian movement - Robert brown. Erratic
motion of colloidal particles caused by the
bombardment of molecules in dispersion
medium. Zigzag motion.
2. Sedimentation – movement of the particles
downward due to the gravity which promotes
mixing.
3. Viscosity – expression of the resistance to
flow of the system under applied particles.
Method of Preparing Colloids:
1. Dispersion method
• coarse particles are reduced in size achieved
by using mechanical disintegration devices.
-breakdown the larger particles into particles of
colloidal dimension through milling and
ultrasonic.
2. Peptization (defloculation)
• This is the breaking up of aggregates or
secondary particles into smaller aggregates in
the colloidal size range.
- process of formation of converting precipitate
or aggregates into colloids by shaking an
electrolytes.
3. Condensation method
• colloidal dispersion is achieved by allowing
materials of subcolloidal dimensions to
aggregate into particles within colloidal size
range
-making larger particle.
Method of Separation
1. Ultrafiltration
• a method which uses negative pressure
through the dialysis membrane thus separating
colloidal particles from the filtrate.
-collodions - filter paper that are soaked
previously with nitrocellulose. (ultrafilters)
2. Dialysis
• a technique of separation where semi-
permeable membrane will prevent the passage
if colloidal particles yet will permit small
molecules and ions to pass through.
3. Electrodialysis
• a dialysis and ultrafiltration method which
makes use of an electric potential to hasten the
removal of ionic contaminants.
- the diffusion of ions or electrolytes is carried
out by applications of electrodes.
Stability of Colloids
• The presence or absence of charge on a
colloidal particle may affect the stability of the
system. For stabilization to be accomplished,
we may provide the dispersed particles with an
electric charge and surround the particle with a
protective sheath to prevent the adhesion of
particles as they due to Brownian movement.
Stability of Colloids
• Lyophilic colloids are stable, forms a true
solution, addition of small amount of electrolyte
may not result in precipitation of the colloid but
this may be possible at higher electrolyte
concentration.
• Hofmeister series – lyotropic series, lists of
cations and anions in their rank as precipitant of
hydrophilic sols (decreasing order)
o Citrate, tartrate, sulfate, acetate, Cl, NO3, Br, I
o Li, Na, NH4, K, Rb, Cs
• Alcohols and other semi polar solvents may
decrease solubility of hydrophilic colloids thus
increasing possibility of precipitation.
Gold number
• usual expression for the protective property
of colloid.
• Minimum weight in mg of the protective
colloid (dry weight) required o prevent a color
change from red to blue in 10 mL of gold sol on
the addition of 1 mL of a 10% solution of
sodium chloride.
• Examples:
• Gum Arabic and Egg albumin – 0.15 – 0.25
• Gelatin – 0.005 – 0.01
• Starch – 25
• Hemoglobin – 0.03
• Caseinate – 0.01 Physical Pharmacy Lab
• Sodium oleate – 0.4 Buffers
• Dextrin - 6 -20 ▹ Solution that resist change to pH
▹ It is made of a weak acid and its weak
Association colloids
conjugate base present in similar amounts.
These are colloids formed by the association of
dissolved molecules of a substance to create The effect of adding acid or base to an
particles of colloidal dimensions, most unbuffered solution. There is a great increase or
commonly termed as micelles. decrease in pH of the solution.
Classification:
• Surfactant micelle: 2 – 5 nm in diameter
• Microemulsion: 10 – 100 nm in diameter
• Liposome: 50 – 100 nm

Coarse Dispersions
• They contain larger particles than colloidal
dispersions (1 – 200 um) The effect of adding acid or base to a buffered
• They include emulsions and suspensions. solution. There is minimal changes in the pH
• Emulsions
• They are mixtures of immiscible liquids in
which one phase is dispersed as droplets within
the other phase

How a Buffer Works: Le Chatelier’s Principle

When you add acid or base to a solution with

buffer system, this causes a shift either to the
left or right of the reaction maintaining the
equilibrium. The shift causes an increase in the
concentration of the buffer. However the
increase in concentration to the weak acid and
weak base is sort of negligible, there’s a slight
changes in pH.
Buffers In Nature: Blood 𝑛
𝐵𝑂𝐴𝑐 =
Most organisms survive in a narrow pH range. △ pH (final − initial)
Humans require pH ~7.4 5 𝑥 10−5
𝐵𝐻𝐶𝑙 = = 1.67 𝑥 10−3 𝑚/𝑢𝑛𝑖𝑡𝑝𝐻
Solution: Use buffer with pKa ~7.4 4.73 − 4.70
H2CO3 + H2O HCO3 - + H3O+ pKa = 6.1
(close enough)
▹ Calculate the pH of a buffer that is 0.020 M in
Buffer Capacity NH3 and 0.030 M inNH4Cl.
Kb= 1.8 x 10−5
▹ Buffer resistance to change 𝑏𝑎𝑠𝑒
▹ Buffer concentration ↑, Buffer capacity ↑ pH = pkw –pkb + log 𝑠𝑎𝑙𝑡
▹ pH closer to pKa, Buffer capacity ↑ pKb = -log (kb) = -log (1.8 x 10−5 ) = 4.74
- bmax – pH = pKa
0.020 𝑀
14 – 4.74 + log = 9.08
0.030 𝑀
Buffer Capacity
▹ Formula:
𝑛 ▹ What is the change in pH on adding 0.02 mol
𝐵=
ΔpH of NaOH to a liter of a buffer solution
Where: containing 0.5 M of NaOAc and 0.5 M HOAc?
b= buffer capacity
The pKa value of acetic acid is 4.76 at 25°C.
n = number of moles of acid or base per Liter 𝑠𝑎𝑙𝑡+𝑏𝑎𝑠𝑒
added pH = pKa + log 𝑎𝑐𝑖𝑑−𝑏𝑎𝑠𝑒
△pH = change in pH
0.5 +0.02
Bmax = 0.576 C = 4.76 + log = 4.79
0.5−0.02
C= total concentration of buffer system
pKa= pH
Problem Set
△ pH = final – initial
▹ Compare the buffer capacity of HCl and a 4.79 – 4.76 = 0.03
HOAc/NaOAc buffer solution if the initial pH of
4.70 increased to 9.89 and 4.73, respectively, Other method
after adding 10 drops of 0.1 M NaOH. Bmax =0.576 C (total conc. Of weak acid)
C 0.5 + 0.5 = 1M
𝑛
𝐵𝐻𝐶𝑙 =
△ pH (final − initial)
𝑛 0.576 x 1M = 0.576
Moles = 𝐿 𝑜𝑓 𝑎𝑐𝑖𝑑/𝑏𝑎𝑠𝑒 𝑛
B= ΔpH

N= Moles x Liter of acid or base 𝑛

10 drops to liters ΔpH =
𝐵
1 𝑚𝐿 0.5 𝑚𝐿 0.02
10 drops x 20 𝑑𝑟𝑜𝑝𝑠 = 0.5 𝑚𝐿 = = ΔpH = = 0.03
1000
0.576
0.0005

0.01M x 0.0005 = 5 x 10-5 or 0.00005 moles

5 𝑥 10−5
𝐵𝐻𝐶𝑙 = 9.98−4.70 = 9.63 x 10 −6 m/unit pH