Experiment 6 to 9

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Post Lab
Discussion
Experiment 6
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Liquid Dosage
Forms: Solution
and Syrup
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Solution

 Solution is a dosage form that delivers the highest

bioavailability because of the already available
active drug.

 In a manufacturing firm the Quality control assures

the delivery of the correct amount.
 The product labeling includes statement of the net
content or the total quantity of the dosage form in a
certain container
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Quality Test for Solutions and Liquids

 Deliverable volume

 Appearance
 Visual inspection
 Organoleptic test

 Stability
 Chemical
 Physical

 Identification test
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1. Deliverable Volume

 A test designed to provide assurance that oral

solutions and suspensions packaged in multiple-
unit containers will, when transferred from the
original container, deliver the volume of dosage
form as stated on the label of the article.
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Deliverable or Fill Volume

 Pour the content of each container (10 containers)

into a separate dry graduated cylinder.

 Measure the volume of each solution/mixture.

 Specification: nlt 100% and no bottle has a volume
<95%

 Compute for the mean and standard deviation.

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Mean and SD
 Mean
 The average (center) of the values in the given
dataset.

 Standard Deviation
 How spread out the values are around the mean in a
given dataset.
 The higher the SD the more spread the values are in
the sample.
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Control Charts

 A control chart consists of several parts. It has two 

control limits and an average line.
 The bottom dashed line is called the 
lower control limit (LCL). 
 The solid middle line is the average of the statistic
being plotted.
 The top dashed line is the upper control limit (UCL).

 Control charts provides you a guide to what is

really happening in your process.
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Control Limits
 The control limit is calculated from the data that is
plotted on the control chart.
 It is placed 3 sigma (of the data being plotted) away
from the average line.
 UCL – 3 above the average
 LCL – 3 below the average
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68-95-99.7 Rule
 Also known as empirical rule or sigma
rule.

 Used to remember the percentage of

values in a given data set lie within an
interval estimate in a normal
distribution.
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Chart Analysis
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Bottl Volume measured

Sample Charting
e no. (60mL label claimed)
1 63.34 mL  UCL = 84.96 mL
2 60.05 mL
3 57.78 mL
 LCL = 37.93 mL
4 59.95 mL  +1SD = 64.55
5 65.44 mL
 +2SD = 67.65
6 59.33 mL
7 66.52 mL  +3SD = 70.75
8 64.09 mL
 -1SD = 58.35
9 61.24 mL
10 56.80 mL  -2SD = 55.25
Mean 61.45 mL
 -3SD = 52.15
SD 3.10
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2. Appearance

 Parameters are set by the manufacturer according

to their specific monograph or reference.
 Visual inspection
 Cap/closure problems
 Labelling
 Presence of particulate matter
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 Organoleptic test
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3. Stability

 Defined as the ability of a particular formulation in a

specific container or closure system to remain with
in its physical, chemical, microbiological,
therapeutic and toxicological specifications

 Nlt 90% of the labelled potency

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Shelf Life

 Refers to the duration of time during which a drug

preparation will remain physically, chemically,
therapeutically, toxicology, and microbiology stable
(possessing NLT 90% of the labeled potency)

 It also indicates the period when the formulation is

expected to remain “fit for use” under ordinary
conditions of handling and storage in the
environment such as warehouse, home, hospital
and pharmacy shelf
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Product Stability Evaluation
 Chemical
 Degradation products
 Reduction/Oxidation/Hydrolysis

 Potency
 Shelf-life

 Dosage strength
 Underdose/overdose

 Physical
 pH, viscosity, color, taste, clarity, odor
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Types of Stability Studies

 Short term/Accelerated SS
 Involves use of exaggerated conditions of
temperature, light, moisture, pH and humidity.
 Duration: 3 months = 2 years expiry
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Types of Stability Studies

 Long term/Real Time SS

 Conducted under the usual/normal conditions of
environment, transport and storage expected during
product distribution
 Duration: 2 years = 4 to 5 years expiry
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Types of Stability Studies

 Stress Test
 Done in API
 Involves the use of elevated temperatures in 10
degrees increments higher than those in ASS.
 Performed until the total physical and chemical
degradation of the product is reached.
 Duration: 6-12 months
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 Physical Test
 Viscosity
 pH
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Unit of Measurement
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4. Identification Test

 Chemical Test and Assay

 Different test and procedures for identification and
assay of active pharmaceutical ingredient can be
found in their specific monographs.
 Assay

 Instrumentation
 Chromatography

 Spectrophotometry
Experiment 7
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Powders and
Granules
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Powders and Granules

 Conventional solid dosage forms includes

powders, granules, capsules, and tablets.
Powder is a mixture of finely divided drugs
and /or chemicals in dry form.
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 Powders properties relevant to pharmaceutical formulations are

single particle properties, bulk properties, particle-particle
interactions, powder morphology, and mixing and blending
properties.

 It is also important for preparing powder formulations.

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Quality Test for Powders and Granules

 Particle Size Distribution

 Sieving
 Hausner Ratio

 Optical and Electron Microscopy  Moisture Content

 Sedimentation  Content Uniformity
 Light Scattering Technique
 Shape
 Angle of Repose

 Bulk and Tapped Density

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Particle Size Distribtion
 1. Sieving
 Analytical test sieves are constructed from a
woven-wire mesh.
 The basic analytical method involves stacking
the sieves on top of one another in ascending
degrees of coarseness, and then placing the
test powder on the top sieve.
 Sample needed: 25-100g for powders having
200mm diameter depending on bulk density.
 The larger the BD the lower the sx needed.

 Smaller diameter (<75mm) may require smaller

amount (10-25g) since it may clog the mesh.
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 The nest of sieves is subjected to a standardized

period of agitation, and then the weight of material
retained on each sieve is accurately determined.

 The test gives the weight percentage of powder in

each sieve size range.

 This sieving process for estimating the particle size

distribution of a single pharmaceutical powder is
generally intended for use where at least 80% of
the particles are larger than 75 µm.
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How to Determine the Particle Size
Using Sieve?

 The test sieving analysis is complete when the

mass on any of the sieve does not change by more
than 5%.

 NMT 10% in powders with diameter size of 75mm

below.
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Course Determination
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Microscopy

 Sufficient quantity is needed (10-100mg)

to be suspended in 10mL solvent which
the powder does not dissolve.

 Examine under microscope and count the

number of particles having dimension
greater than the prescribed limit.
 The size limit and the number of particles
exceeding to prescribed limit are defined
for each substance.
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Sedimentation
 Sedimentation test or gravitational
sedimentation can be done by
transferring suitable amount of powder in
a 100mL solvent which the powder does
not dissolve.

 Transfer the suspension in a 100mL

graduated cylinder then stand for 24
hours.

 The amount of sediments are measured.

 Larger (and denser) particles, therefore
settle out more quickly than do smaller
particles.
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Dynamic Light Scattering
 Measures “Brownian motion”.
 Random movement of particles
which results from their collision with
solvent molecules.
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Angle of Repose

 Measure the frictional force present in

loose powder or the index of flowability.
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Bulk and Tapped Density

 The bulk density of a material is the ratio of

the mass to the volume (including the inter-
particulate void volume) of an untapped
powder sample.

 Tapped density of a powder is the ratio of

the mass of the powder to the volume
occupied by the powder after it has
been tapped for a defined period of time.
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Hausner’s Ratio/Compressibility or
Carr’s Index

 Inter-particulate interaction influencing the

bulking properties of a powder are also
interaction that interfere the powder flow.

 Comparison of the bulk and tapped densities

can give a measure of the relative
importance of these interaction in a given
powder.
 It measures the powder’s ability to settle and
to flow
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Interpretation
Experiment 8
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Solid Dosage
Forms: Tablet
and Capsules
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Quality Test for Tablets and Capsules

 Tablets
 Hardness  Capsules Refer to our
lecture
 Friability  Disintegration discussions!
 Thickness  Dissolution
 Disintegration  Thickness
 Dissolution  Uniformity of Dosage Units
 Uniformity of Dosage Units
Experiment 9
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Disintegration
Test
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Tablet Disintegration
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Disintegration Testing
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END.

 Thank you!