Physical Pharmacy, Lab

Lesson Outline
1. Orders of Reaction
● Factors affecting reaction
● Zero-order process
● First order process
2. Half life
3. Shelf- Life and Expiration Dating
4. Assay of Chloramphenicol Oral Solution

REACTION KINETICS
Study of rates at which reaction takes place.

RATE OF REACTION
● The velocity with which a reactant/s undergo Remember:
chemical change Ø Concentration vs time: CURVE
Ø ln concentration vs time: Straight
● Applications:
1. Production of more stable drug preparation SHELF-LIFE (t90)
2. Prediction of Shelf-Life - Time required for 10% of a drug to degrade with 90%
3. Optimum storage condition of the intact drug remaining
- Time required for loss of 10% of the original
● Factors affecting the rate of reaction: concentration
1. Concentration - Time required for concentration to decrease to 90%
2. Temperature of the original concentration
3. Catalyst - USE FOR EXPIRATION
4. Light
5. pH Formulas:
𝟎. 𝟏𝟎𝟓
𝒕𝟗𝟎 =
CHEMICAL KINETICS 𝒌𝟏
- Deals with the stability of drugs and mode of 𝑲𝟏𝒕
𝒍𝒐𝒈 (𝑫) = 𝐥𝐨𝐠[𝑫] 𝟎 −
action of their degradation through the 𝟐. 𝟑𝟎𝟑
examination of rates of reaction and reaction
mechanism. 𝑬𝒙𝒑𝒊𝒓𝒂𝒕𝒊𝒐𝒏 𝒅𝒂𝒕𝒆 = 𝒔𝒉𝒆𝒍𝒇 − 𝒍𝒊𝒇𝒆 + 𝒅𝒂𝒕𝒆 𝒐𝒇 𝒎𝒂𝒏𝒖𝒇𝒂𝒄𝒕𝒖𝒓𝒆

COMMON DRUG DEGREDATION REACTIONS In some pharmaceutical firms:

à SOLVOLYSIS Expiration date =

Splitting of a drug via solvent-molecule hydrolysis 𝑺𝒉𝒆𝒍𝒇 − 𝒍𝒊𝒇𝒆
(predominant solvolysis reaction) + 𝒅𝒂𝒕𝒆 𝒐𝒇𝒂𝒑𝒑𝒓𝒐𝒗𝒂𝒍 𝒐𝒓 𝒓𝒆𝒍𝒆𝒂𝒔𝒆 𝒇𝒓𝒐𝒎 𝒍𝒂𝒃𝒐𝒓𝒂𝒕𝒐𝒓𝒚
à OXIDATION
Occurs simultaneously with reduction reactions (REDOX)
HALF-LIFE (t50) (t1/2)
à PHOTOLYSIS - The time necessary for the original concentration to
be reduced by one- half
ORDER OF REACTIONS - USE FOR DOSING
1. FIRST ORDER REACTION
● Rate of reaction is directly proportional to the Formula:
𝟎. 𝟔𝟗𝟑
concentration of one of the reactants. 𝒕𝟓𝟎 =
● The speed of reaction is affected by the first 𝒌𝟏
power concentration of a single reaction
substance. 2. SECOND-ORDER REACTION
● A → products ● Rate of reaction is affected by the concentration
● Symbol: k1 of 2 reacting species
● Unit: time-1 (1/time) ● A + B → products
● A + A → products
● 2A → products
Symbol: k2
● Unit: concentration-1 x time-1 (1/conc x time)

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Physical Pharmacy, Lab

APPARENT OR PSEUDO-ORDER RXN REFRACTIVE INDEX (n)

- Higher order reaction appears to be a lower-order Ø A material property that describes how the material
reaction because one or more reactant affects the speed of light travelling through it.
concentrations are constant or in great excess Ø Ratio of velocity of light in air to its velocity in a
compared to another reactant material under the same condition.
- Describes a situation where one of the reactants is
present in large excess or do not affect the overall
reaction & be held constant

Solutions: pseudo-first-order reaction

Suspensions: pseudo-zero-order reaction

3. THIRD-ORDER REACTION
● Rate of reaction is affected by the
concentration of 3 reacting species
● A + B + C→ products
● 2A + B → products
● 3A → products
IMPORTANCE OF REFRACTICE INDEX
4. ZERO-ORDER REACTION 1. Physical constant to identify volatile oil
● Rate of reaction is not affected by the 2. Detection of impurity in volatile oil
concentration of the reacting substance but by 3. To determine the concentration of the substance
other factors (solubility).
● Symbol: k0 MOLAR REFRACTION (RM)
● Unit: conc x time-1 (conc/time) Ø Sum of atomic, group, and bond refraction in a
molecule
Shelf-Life (t90)
𝟎. 𝟏 [𝑫]𝟎 𝑹𝑴 = 𝒔𝒑𝒆𝒄𝒊𝒇𝒊𝒄 𝒓𝒆𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏 (𝒓𝒅)𝒙 𝑴𝑾
𝒕𝟗𝟎 = [(𝒏𝟐 − 𝟏)] 𝟏
𝒌𝟎
𝒓𝒅 = 𝒙
Half-Life (t50) (t1/2) [(𝒏𝟐 + 𝟐)] 𝛒
𝟎. 𝟓 [𝑫]𝟎 Where:
𝒕𝟗𝟎 =
𝒌𝟎 n = refractive index (no unit)
ρ = density (g/mL)
rd = specific refraction (g/n)
MW = Molecular weight
RM = Molar refraction

Therefore;
[(𝒏𝟐 − 𝟏)] 𝑴𝑾
𝑹𝑴 = 𝒙
[(𝒏𝟐 + 𝟐)] 𝛒
§ Experimental RM
§ Theoretical RM (chemical structure)
MOLAR REFRACTION Atomic refraction value
Ø C= 2.418
REFRACTION Ø H= 1.100
- Bending of light rays as they pass obliquely from one Ø O in OH (hydroxyl group)= 1.525
medium into another of different optical density. Ø O in OR (ester group)= 1.643
Ø O in double bond= 2.211
Ø Structural double bond= 1.733
Ø Structural triple bond= 2.398

REFRACTOMETER

Hand Refractometer

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Physical Pharmacy, Lab

Baush & Lomb Refractometer OPTICAL ACTIVITY

Expressed as:
1. Optical Rotation – for liquid
2. Specific Rotation – for solid/substance in solution
• Importance:
1. For identification
2. Index of purity
3. Indication of therapeutic value

ANGULAR ROTATION
• The product of the property of a substance to
rotate when a plane of polarized light is passed
through it.

Abbe Refractometer

SPECIFIC ROTATION
● For solids in a solution
● Angle through which the plane of polarization of
light is rotated when the polarized light passes
through a 1dm layer of a liquid at a specific
temperature.

OPTICAL ACTIVITY
• The property of substance to rotate the plane of
polarization of the polarized light.
• Conditions for molecules to show optical
activity:
1. Molecules should be dissymetric MOLAR ROTATION
> Should not be superimposable with mirror image.
𝒔𝒑𝒆𝒄𝒊𝒇𝒊𝒄 𝒓𝒐𝒕𝒂𝒕𝒊𝒐𝒏 𝒙 𝑴𝑾
2. Molecules of Chiral Carbon 𝛉=
> Carbon bonded to 4 different groups. 𝟏𝟎𝟎

POLARIMETER
• Measure the extent of rotation of the plane of
polarized light.
• PARTS:
1. Source of light – Sodium D Line lamp
2. Polarizer – with polarimeter tube 2dm
3. Analyzer
4. Eye piece
5. ADS (Angular Degree Scale)
6. ISS (International Sugar Scale)

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Physical Pharmacy, Lab

𝟎. 𝟏𝟎𝟓
𝒌𝟏 =
Solve the following: 𝒕𝟗𝟎
1. A reconstituted suspension loses 20.00% of its potency 𝟎. 𝟏𝟎𝟓
𝒌𝟏 = = 𝟎. 𝟎𝟏𝟑𝟏/𝒉𝒓
after 8 days in a refrigerator. Give the expiry date if you 𝟖
were to prepare in on January 9, 2021. Pseudo-zero-order
reaction. 𝑲𝟏𝒕
𝒍𝒐𝒈 (𝑫) = 𝐥𝐨𝐠[𝑫] 𝟎 −
𝟐. 𝟑𝟎𝟑
Given:
20% - lost potency (concentration) (𝟎. 𝟎𝟏𝟑𝟏)(𝟏𝟐)
𝒍𝒐𝒈 (𝑫) = 𝐥𝐨𝐠[𝟏𝟎𝟎] − = 𝟏. 𝟗𝟑
8- days (time) 𝟐. 𝟑𝟎𝟑
January 9, 2021
Required: Expiry date 10&.() = 85.11%

10 𝑚𝐿 𝑥𝑚𝐿
Formula: (for zero order) =
𝟎. 𝟏 [𝑫]𝟎 85.11 100
𝒕𝟗𝟎 =
𝒌𝟎 10 𝑚𝐿 (100)
= 𝟏𝟏. 𝟕𝟓 𝒎𝑳
85.11
Solution:
First, let’s find k0 3. The refractive index of benzoic acid (122g/n) at 25.0˚C
is 1.223, and the density is 0.872g/mL. Calculate its molar
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 refraction.
𝑘0 =
𝑡𝑖𝑚𝑒
Given:
20 122 g/n -molecular weight
𝑘0 = = 2.5 1.223 – refractive index
8
0.872 g/mL- density
Required: Molar refraction
𝟎. 𝟏 [𝑫]𝟎
𝒕𝟗𝟎 = Formula:
𝒌𝟎
for Experimental RM
𝟎. 𝟏 (𝟏𝟎𝟎) [(𝒏𝟐 − 𝟏)] 𝑴𝑾
𝒕𝟗𝟎 = =𝟒 𝑹𝑴 = 𝒙
𝟐. 𝟓 [(𝒏𝟐 + 𝟐)] 𝛒

January 9 + 4 days = January 13, 2021(expiry date) Solution:

Experimental RM
2. A solution that when prepared has a shelf-life of 8hr is [(𝟏. 𝟐𝟐𝟑𝟐 − 𝟏)] 𝟏𝟐𝟐
kept for 12hr. The original dose is 10.00mL. What dose in 𝑹𝑴 = 𝒙 = 𝟏𝟗. 𝟖𝟒 𝒎𝑳/𝒎𝒐𝒍
[(𝟏. 𝟐𝟐𝟑 + 𝟐)] 𝟎. 𝟖𝟕𝟐
𝟐
mL would be required to give a 100.0% label dose after
12hr? Consider it as a first-order reaction. Theoretical RM
Remember:
Given: Atomic refraction value
t90- 8 hr---- was kept for 12 hr Ø C= 2.418
Original dose- 10.00 mL Ø H= 1.100
Required: dose in mL after 12 hr Ø O in OH (hydroxyl group)= 1.525
Ø O in OR (ester group)= 1.643
Formula: Ø O in double bond= 2.211
(Shelf-life first order) Ø Structural double bond= 1.733
𝟎. 𝟏𝟎𝟓 Ø Structural triple bond= 2.398
𝒕𝟗𝟎 =
𝒌𝟏
𝑲𝟏𝒕 Molecular Formula of benzoic acid: C6H5COOH
𝒍𝒐𝒈 (𝑫) = 𝐥𝐨𝐠[𝑫] 𝟎 −
𝟐. 𝟑𝟎𝟑
Solution:
Since given yung t90, let’s compute for k1

𝟎. 𝟏𝟎𝟓
𝒕𝟗𝟎 =
𝒌𝟏

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Physical Pharmacy, Lab

C 7 x 2.418= 16.926 ü Used for rickettsial disease & drug of choice for
O (double bond) 1 x 2.211= 2.211 typhoid fever
H 5 x 1.100= 5.5
O (hydroxyl group) 1 x 1.525= 1.525 BEER LAMBERT’S LAW
double bond 3 x 1.733= 5.199 • Combination of Beer’s &Lambert’s Law
TOTAL 31.361 • Relates the power of incident & transmitted
radiant thickness & concentration of solution
4. Compute for the molar refraction of Acetone (58g/n). containing the absorbing chemical species

Since there are no given values, we use the Theoretical

RM.

Molecular formula of Acetone: C3H6O

Where:
Ø A = absorbance
Ø I* = Incident light
Ø I = Transmitted light
Ø Ɛ = specific rotation (A of 1% w/v solution in 1cm
cuvette)
Ø C = concentration of solution
Ø l = length of light path/thickness
Remember:
Atomic refraction value
BEER’S LAW
Ø C= 2.418
● States that the power of transmitted radiant
Ø H= 1.100
beam decrease exponentially as the
Ø O in OH (hydroxyl group)= 1.525
concentration of the solution containing the
Ø O in OR (ester group)= 1.643
absorbing chemical species increases
Ø O in double bond= 2.211
arithmetically.
Ø Structural double bond= 1.733
● Decrease transmitted light = Increase
Ø Structural triple bond= 2.398
concentration
C 3 x 2.418= 7.254
LAMBERTS’S LAW
H 6 x 1.100= 6.6
● States that the power of transmitted radiant
O (double bond) 1 x 2.211= 2.211
beam decrease exponentially as the thickness of
TOTAL 16.065 the solution containing the absorbing chemical
species increases arithmetically.
ASSAY OF CHLORAMPHENICOL ORAL SUSPENSION ● Decrease transmitted light = Increase thickness of
Ø Test procedure that determines the amount of solution
active ingredient in a dosage form.
Ø Test potency and strength SPECTROPHOTOMETER
PRINCIPLE:
CHLORAMPHENICOL • From the source of light to pass through your
sample and it could emit electromagnetic
radiation at a specific wavelength, the reading is
taken using 1cm path length

ASSAY OF CHLORAMPHENICOL ORAL SUSP.

ü Molecular Formula: C11H12Cl2N2O5
ü Acetamide, 2,2 dichloro -N-[2-hydroxy–(-
(hydroxymethyl)- 2- (4 nitrophenyl)ethyl)]
ü Has wide spectrum of antibacterial activity

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