Biopharmaceutics and Pharmacokinetics

Lab Manual

Fall 2021-2022

Faculty of Pharmacy BAU, MISSION STATEMENT

Faculty of Pharmacy, at BAU, is an academic institution founded in 1986 to provide high quality pharmacy
education and scientific research. The faculty educational program was designed and developed to prepare
competent pharmacists able to effectively participate in the advancement of pharmacy profession, nationally and
internationally. The faculty supports the role of its graduates as health care providers in the frame of professional
ethics. The faculty seeks to establish a well-built relation with peer institutions and the surrounding society. To
accomplish its mission, the faculty relies on qualified staff members, laboratory facilities and educational tools.
LABORATORY REGULATIONS

1- Students must avoid any unnecessary, unofficial presence in pharmaceutics lab,

especially in the absence of responsible staff members.
2- It is absolutely forbidden to eat, drink or smoke in the lab.
3- While being in the lab, white coats and safety glasses should be put on all the time and only
taken out after leaving of the lab.
4- Students must avoid smelling any material (or have to be very careful) to avoid shocks
when dealing with strong odorous materials!
5- Do not taste any material in the pharmaceutics lab even if you think that it is not
toxic!
6- Wearing loose clothes should be avoided, and long hair should be tied back.
7- Broken glass and sharp items should be disposed in special containers made for that
purpose.
8- The student must keep with him 2 cleaning towels all the time.
9- The student must keep his place clean and organized during and after finishing the
practical classes. Each place will be regularly checked by the lab staff members.
10- Check all glassware before using for the presence of any cracks!
11- On burning skin by some chemicals, wash with a large volume of running water and
then:
A- Burns caused by acid should be washed with 5%sodium bicarbonate or 5% borax
solution.
B- Burns caused by caustic alkalis should be washed with 5% acetic acid or boric acid
solution.
C- Burns caused by phenols should be treated with glycerol.
D- Eye injuries should be washed similarly with water and then consulting an optician.
12- Minor direct heat skin burns can be immediately treated with ice pieces.
13- Carefully deal with glassware to avoid their breaking, and make sure that every type of
glassware should be property used.
14- Students must be sufficiently spaced in the pharmaceutics lab, and they have to work
quietly, obeying all instructions and report any minor accident to the staff in charge.

WITH OUR BEST WISHES

 Lab 1

Improvement of Drug Dissolution by Solid Dispersion Techniques

(Preparation and evaluation of salicylic acid -urea coprecipitate)

Theoretical Background
Dissolution rate of drugs:
An equation which describes the process of dissolution is the Noyes- Whitney
equation. This equation describes the rate of dissolution of spherical drug particles
when the dissolution process is diffusion controlled and involves no chemical
reaction, may be written:
dm / dt  DA / hCs  C 

Where:
D: Diffusion coefficient of the drug in the dissolution medium. A:
Effective surface area of the drug particles.
h: Thickness of the diffusion layer.
Cs: Saturated solubility of the drug in the diffusion layer. C:
Concentration of the drug in the bulk of the solution.

What are the factors affecting the dissolution rate?

How to decrease the particle size:

a- Grinding (Milling).
b- Controlled precipitation in a fine state.

Problems of size reduction:

Simple size reduction may not produce the expected increase in dissolution
rate because the work done to decrease the particle size (increasing
the surface area) will increase the surface free energy. So the small, particles
will tend to decrease their high surface free energy to be more stable via aggregation
and clump formation leading to decrease in their surface area and hence their
dissolution rate.

How to overcome this Problem?

a- Using low concentration of a SAA (less than cmc) to increase the
wettability of particles and prevent their aggregation.
b- Incorporating a SAA in the crystalline structure of the drug through
crystallization from an aqueous solution of a SAA.
c- Using solid dispersion technique.

What is a solid dispersion?

It is a system in which the drug is homogeneously distributed in a solid carrier or
matrix. It is used either to increase the dissolution rate of poorly soluble drugs, or
to decrease the release of soluble ones.

Classification of solid dispersions according to the type of carrier

a- Water soluble carriers:
e.g. Urea, PVP, PEG, Cyclodextrins
The drug particles are surrounded by a layer of the carrier preventing their
aggregation, and increasing their wettability.

It could be:

i-Eutectic mixture:
it is a heterogeneous mixture of two pure crystalline components (drug
+ carrier) prepared by solidification of the molten drug-carrier mixture. The
melting point of the mixture is less than that of each component alone e.g.: Urea -
phenobarbitone
ii-solid solution:
It is a homogenous mixture of the drug and the carrier (the drug is dissolved in the
carrier -in a molecular state)
e.g: Urea- indomethacin
iii- glass dispersion
it is characterized by the glassy appearance of the carrier when melted than
solidified e.g.: citric acid, glucose

b- water insoluble Carrier:

e.g: aerosil
In this case the drug is dissolved in a solvent which dissolves the drug but not
the carrier which is suspended in the drug solution. Upon evaporation of the
solvent the drug will precipitate on the surface of the Carrier in a molecular
(minuscular) state i.e. particle size reduction without aggregation of the drug
particles. This type of solid dispersion is known as surface solid dispersion.

Which is the difference between aerosil, aerosol, Aerosol OT???

Methods of preparation of solid dispersion:

1- Fusion (melting) method.
2-Solvent method

Explain each method and comment on the advantages and disadvantages of each
one.

Factors affecting- dissolution rate from solid dispersion

1- Particle size of the drug.
The smaller the particle size, the faster the dissolution rate. Rapid cooling or
rapid evaporation of the solvent gives smaller particle size in melting and
solvent method respectively.
2- Type of the carrier:
The carrier may have an additional solublizing effect on the drug.
e.g. Urea has an additional solublizing effect on salicylic acid through
complexation, salting-in, and increasing the amount of free water.

3- Carrier-drug ratio:
The higher the ratio, the higher the dissolution rate. WHY??

4- Polymorphism of the drug:

During the preparation of solid dispersion, drug may crystallize in the metastable
form, which has a higher dissolution rate than the stable form of the drug.

Applications of solid dispersion in pharmacy:

1- To increase the dissolution rate of sparingly soluble drugs in an attempt
to increase their absorption and hence bioavailability.
2- To prepare a sustained release preparation where an insoluble matrix is used to
decrease and control the rate of drug release.
Preparation and evaluation of salicylic acid - urea coprecipitate
Practical procedure:
1- Weigh 200 mg salicylic acid and 200 mg urea.
2- Dissolve urea in 4 ml alcohol, then dissolve salicylic acid.
3- Evaporate the solvent on a water bath, then cool.
4- Scratch the formed solid dispersion, and grind it.
5- Weigh 200mg of the solid dispersion, put them in a conical flask
containing 100 ml distilled water as the dissolution medium.
6- Take 5 ml samples at time intervals (10, 20, 30,45 min).
7- Add drops of FeCl3, measure colorimetrically at max 540 nm.
8- Compare the dissolution rate with that of 100 mg salicylic acid alone.
9- Calculate the amount of salicylic acid dissolved and tabulate your results.
10- Plot mg% of salicylic acid dissolved versus time in minutes.
11- Write a full comment.

Calibration curve of salicylic acid at max 540 nm.

Concentration mg% 1 2 3 4 5

Absorbance 0.14 0.23 0.37 0.49 0.62