Procedures for Quality Testing of Pharmaceutical Products
Session 11: Procedures for Quality Testing of
Pharmaceutical Products
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
monographs
forms (Hardness, smell, colour, texture, thickness, diameter, friability, disintegration etc.)
dosage forms (pH, smell, colour, conductivity, osmolarity etc.)
products (sterility tests, etc.)
reaction, dissolution test etc.)
Resources Needed:
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
SESSION OVERVIEW
Activity/
Step Time Content
Method
1 05 minutes Presentation Introduction, Learning Tasks
15 minutes Methods Commonly Used for Quality
Presentation
2 Testing of Pharmaceutical Products from
Buzzing
Monographs
20 minutes Procedures for Carrying Out Physical
Presentation and
3 Quality Tests for Solid Pharmaceutical
Brainstorming
Dosage Forms
Procedures for Carrying Out Physical
4 20 minutes Presentation Quality Tests for Liquid Pharmaceutical
Dosage Forms
15 minutes Procedures for Carrying Out
5 Presentation Microbiological Quality Tests for
Pharmaceutical Products
15 minutes Presentation Procedures for Carrying Out Chemical
6
Qualitative Tests
20 minutes Presentation Procedures for Carrying Out
7
Chromatographic Quality Tests
8 05 minutes Presentation Key Points
9 05 minutes Presentation Evaluation
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning objectives and clarify
ASK students if they have any questions before continuing.
STEP 2: Methods Commonly Used for Quality Testing of
Pharmaceutical Products from Monographs (15 minutes)
Activity: Buzzing (5minutes)
ASK students to pair up and buzz on the following questions for 2 minutes
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
includes
o Hardness,
o Smell,
o Colour,
o Texture,
o Thickness,
o Diameter,
o Friability test,
o Disintegration test
o Thin layer chromatography method-TLC
o High-performance liquid chromatography (HPLC
o Gas chromatography (GC)
o Paper chromatography
o pH,
o Smell,
o Colour,
o Conductivity,
o Osmolarity
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
o Sterility tests for pharmaceutical products
o Chemical qualitative tests includes Volumetric analysis
o Colour reaction, Dissolution test
STEP 3: Procedures for Carrying out Physical Quality Tests for Solid
Pharmaceutical Dosage Forms (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
parts or lose intactness or solidness and break up into particle or constituent under
specified conditions
specified size (or smaller) under carefully specified conditions.
capsules, pessaries and suppositories disintegrate within a prescribed time when placed in
a liquid medium under the prescribed experimental conditions.
For the purpose of this test, disintegration does not imply complete solution of the dosage
unit or even of its active constituent.
o A basket-rack assembly,
o A 1-litre beaker,
o A thermostatic arrangement for heating the fluid
o Mechanical device for raising and lowering the basket in the immersion fluid at
a constant frequency rate
o 6 tablets from each batch are taken and subjected to the disintegration test.
o One tablet is placed in the mesh screen at the bottom end of each of the 6 glass tubes,
o Tap water is used as disintegration medium. Simulated gastric fluid.
o The apparatus is maintained at a temperature of 37 ± 2°C.
o Glass tube maintains up and down movement in and out of the basket containing
1000mls distilled water. the basket move through a distance of 5-6cm at a frequency
of 28 to 32 cycles per minutes as specified by U.S.P
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
o Disintegration time of the each tablet is noted by means of a stopwatch and recorded.
o Disintegration time does differ depending on the nature of the tablets e.g. uncoated,
coated. Uncoated USP tablets have disintegration time as low as 5 minutes but
majority have maximum disintegration time of 30 minutes. Disintegration test we start
with 6 tablets if one or two tablets failed to disintegrate completely test should be
repeated for additional 12 tablets the requirement met if not less than 16 of the total
18 are disintegrated.
o Content-especially the quality and quantity of the Disintergrants and lubricant.
o Hardness .amount of binder, compression force.
o Design of granulation procedure which will affect the physical properties of the
granules
o Friability is the tendency for a tablet to chip, crumble or break following compression.
o This tendency is normally confined to uncoated tablets and surfaces during handling or
subsequent storage.
o It can be caused by a number of factors including poor tablet design too sharp edges, low
moisture content, insufficient binder.
o For obvious reasons, tablets need to be hard enough such that they do not break up in the
bottle but friable enough that they disintegrate in the gastrointestinal tract
the durability of tablets during transit. This testing involves repeatedly dropping a sample
of tablets over a fixed time, using a rotating wheel with a baffle. The result is inspected
for broken tablets, and the percentage of tablet mass lost through chipping
o 10 tablets from each batch are carefully de-dusted prior to testing.
o Accurately weighed and their weight recorded,
o placed in the drum of the friabilator and the drum rotated at 100 times in four
minutes,
o After 100 revolutions, tablets are removed,
o Loose dusts are removed from the tablets, and accurately weighed again.
o Note A maximum weight loss (obtained from a single test should be not more than
1.0%. If the tablet cracked, cleaved, or get broken after tumbling, the sample fails the
test
o Factors that affect the friability of tablets include tablet design such as too sharp
edges, moisture content, and binder being used.
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
STEP 4: Procedures for Carrying Out Physical Quality Tests for Liquid
Pharmaceutical Dosage Forms (20 minutes)
o PH of the oral liquid preparations must be Optimum as they are administered. The pH
value conventionally represents the acidity or alkalinity of an aqueous solution.
o In the pharmacopoeia, standards and limits of pH have been provided for those
pharmacopoeia substances in which pH as a measure of the hydrogen ion activity is
important from the standpoint of stability or physiological suitability.
o The determination is carried out at a temperature of 25±2°C, unless otherwise
specified in the individual monograph.
o The pH value of a solution is determined potentiometrically by means of a glass
electrode, a reference electrode and a PH meter either of digital or analogue.
o Conductivity may be measured by applying an alternating electrical current (I) to two
electrodes immersed in a solution and measuring the resulting voltage (V).
o During this process, the cations migrate to the negative electrode, the anions to the
positive electrode and the solution acts as an electrical conductor
STEP 5: Procedures for Carrying Out Microbiological Quality Tests for
Pharmaceutical Products (15 minutes)
o Are a crucial requirement across many industries worldwide where products,
processes and human health are at risk of being negatively affected by the presence
and breeding of micro-organisms such as specific pathogens, bacteria, yeast and
moulds.
o This test establishes the ability of new lots of medium to support growth when the
inoculums contain a small number of microorganisms.
o Sterility testing of pharmaceutical products is required during the sterilization
validation process as well as for routine release testing. USP requirements employ
sterility testing as an official test to determine suitability of a lot.
STEP 6: Procedures for Carrying Out Chemical Qualitative Tests
(15minutes)
Qualitative tests carried out include the following Volumetric analysis, Colour reaction, and
Dissolution test
o Is routinely used to provide critical in vitro drug release information for both quality
control purposes. It is used to assess batch-to-batch consistency of solid oral dosage
forms such as tablets, and drug development to predict in vivo drug release profiles
o Analytical data from drug dissolution testing are sufficient in many cases to
establish safety and efficacy of a drug product without in vivo tests, following minor
formulation and manufacturing changes
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
o The general procedure for a dissolution involves a liquid known as Dissolution
Medium which is placed in the vessels of a dissolution unit
o The drug is placed within the medium in the vessels after it has reached sufficient
temperature and then the dissolution apparatus is operated
o Sample solutions collected from dissolution testing are commonly analyzed
by HPLC or Ultraviolet–visible spectroscopy
o For most dosage forms to be efficacious, the API(s) must be absorbed into the
systemic circulation so that it can be transported to its site of activity.
o This process contributes to the bioavailability of the drug substance and involves two
steps: namely dissolution and absorption (or permeability).
o Dissolution is the process of extracting the API out of the dosage form solid-state
matrix into solution within the gastrointestinal tract.
o Absorption is the process of transporting the drug substance from the gastrointestinal
lumen into the systemic circulation
o Six tablets Weighed X mg are placed into each vessel of the dissolution apparatus
containing 900mls of 0.1M Hcl,
o Paddles are rotated at 75 revolutions per minute,
o iii. the apparatus is maintained at 37 degree centigrade
o After 30minutes a certain volume from each of the vessels is withdrawn and filtered
o then a certain volume of the filtrate from each tablet is poured into flask and made
up to volume using 0.1M NaoH
o Absorbance of all six tablets is obtained using UV-spectrophotometer and 0.1M
sodium hydroxide was used as blank.
o Absorptivity for each tablet is recorded
o The percentage absorbance of the tablet is obtained by taking percentage absorbance
of the test sample divide by that of reference standard
o Pka
o Stability
o Solubility as a function of pH/surfactant concentration
o Particle size
o The dosage unit, including dosage form type (tablet, capsule)
o Polymorphism
o Nature of excipients such as lubricants, Disintergrants.
o Moisture content, surface coating
STEP 7: Procedures for Carrying Out Chromatographic Quality Tests.
(20 minutes)
o Is the collective term for a set of separation techniques that operate based on the
differential partitioning of mixture components between a mobile and a stationary PH
The mobile phase (a liquid or a gas) travels through the stationary phase (a liquid or a
solid) in a defined direction.
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
o The distribution of components between the two phases depends on adsorption, ionic
interactions, diffusion, and solubility or, in the case of affinity chromatography,
specific interactions.
o The following are examples of chromatographic techniques used in quality test of
pharmaceutical products
Thin layer chromatography method-TLC
High-performance liquid chromatography (HPLC
Gas chromatography (GC)
Paper chromatography
o Is a chromatography technique used to separate non-volatile mixtures.
o Thin-layer chromatography is performed on a sheet of glass, plastic, or aluminium
foil, which is coated with a thin layer of adsorbent material, usually silica gel,
aluminium oxide (alumina), or cellulose
Figure; TLC-plate
Source: research gate (2012).
o After the sample has been applied on the plate, a solvent or solvent mixture (known as
the mobile phase) is drawn up the plate via capillary action.
o Because different analyte ascend the TLC plate at different rates, separation is
achieved
o For example, with silica gel which is a very polar substance, a non-polar mobile
phases such as heptanes are used
o After the experiment, the spots are visualized. Often this can be done simply by
projecting ultraviolet light onto the sheet
o The sheets are treated with a phosphor, and dark spots appear on the sheet where
compounds absorb the light impinging on a certain area.
o Also Chemical processes can also be used to visualize spots for example
anisaldehyde forms colored adducts with many compounds, and sulfuric acid will
char most organic compounds, leaving a dark spot on the sheet
o To quantify the results, the distance travelled by the substance being considered is
divided by the total distance travelled by the mobile phase.
o This ratio is called the retardation factor (R f )
o The mobile phase must not be allowed to reach the end of the stationary phase.
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
o Thin-layer chromatography can be used to monitor the progress of a reaction, identify
compounds present in a given mixture, and determine the purity of a substance
o To run a thin layer chromatography plate, the following procedure is carried out
o A small spot of solution containing the sample is applied to a plate, about 1.5
centimetres from the bottom edge.
o The solvent is allowed to completely evaporate off to prevent it from interfering with
sample's interactions with the mobile phase in the next step starting point
o If a non-volatile solvent was used to apply the sample, the plate needs to be dried in a
vacuum chamber.
o This step is often repeated to ensure there is enough analyte at the starting spot on the
plate to obtain a visible result
o Different samples can be placed in a row of spots the same distance from the bottom
edge, each of which will move in its own adjacent lane from its own
o A small amount of an appropriate solvent is poured into a glass beaker or any other
suitable transparent container (separation chamber) to a depth of less than 1
centimetre.
o A strip of filter paper is put into the chamber so that its bottom touches the solvent
and the paper lies on the chamber wall and reaches almost to the top of the container
o The container is closed with a cover glass or any other lid and is left for a few minutes
to let the solvent vapours‟ ascend the filter paper and saturate the air in the chamber.
o Failure to saturate the chamber will result in poor separation and non-reproducible
results
o The TLC plate is then placed in the chamber so that the spot(s) of the sample do not
touch the surface of the eluent in the chamber, and the lid is closed.
o The solvent moves up the plate by capillary action, meets the sample mixture and
carries it up the plate (elutes the sample).
o The plate should be removed from the chamber before the solvent front reaches the
top of the stationary phase (continuation of the elution will give a misleading result)
and dried.
o Without delay, the solvent front, the furthest extent of solvent up the plate, is marked
o The plate is visualized.
As some plates are pre-coated with a phosphor such as zinc sulphide, allowing
many compounds to be visualized by using ultraviolet light;
Dark spots appear where the compounds block the UV light from striking the
plate.
o Uses of TLC
Purity identification of any sample Identification of compounds Examination of
reactions
Biochemical analysis One of the most important applications of TLC is in
separation of multi-component pharmaceutical formulations. For example In food
and cosmetic industry, TLC method is used for separation and identification of
colours e.g. preservatives, sweetening agent, and various cosmetic products.
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
STEP 8: Key Points ( 5 minutes)
STEP 9: Evaluation (5 minutes)
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
References
Abdelelah, A. (2015, March 13). Disintegration and dissolution tests. Retrieved from
https://www.slideshare.net/ameraabdelelah/disintegration-and-dissolution-tests
Uddin, M., Mamun, A., Akter, N., Sarwar, M., Rashid, M., & Amran, M. (2016).
Pharmacopoeial Standards and Specifications for Pharmaceutical Oral Liquid
Preparations. Archives of Current Research International,
Formulation of pharmaceutical solid-dosage forms. (2018). Pharmaceutical, Cosmetic and
Personal Care Formulations,143-158. doi:10.1515/9783110587982-008
Djuris, J., Ibric, S., & Djuric, Z. (2013). Chemometric methods application in pharmaceutical
products and processes analysis and control. Computer-Aided Applications in
Pharmaceutical Technology,57-90. doi:10.1533/9781908818324.57
Pharmaceutical Sterility Testing. (n.d.). Retrieved from
https://www.contractpharma.com/issues/2008-03/view_features/pharmaceutical-
sterility-testing
The pharmaceutical codex: Incorporating the British pharmaceutical codex. (1979). London:
Royal Pharmaceutical Society of Great Britain.
Harrod, D. C., & Barnbrough, W. E. (1893). The British pharmacopoeia. London:
Spottiswoode &.
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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2
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