AKSON COLLEGE OF PHARMACY

SUBJECT PHARMACUTICAL
QUALITY MANAGEMENT
TOPIC SYRUPS AND THEIR QUALITY
CONTROL TESTS
SUBMITTED BY FAHAD WADOOD
JAVED IQBAL
ROLL NO SP18-DOP-028
SP18-DOP-003
SUBMITTED TO MAM HUSNA
SUBMISSION DATE 04-JAN-2022
 TABLE OF CONTENT

Sr# Page no# Sub-topics

1- 03 Introduction

2- 04 Types of syrup

3- 13 Advantages of syrup

4- 22 Method of preparation

5- 27 Comprehensive Pharmacokinetics model flow scheme

6- 28 References
 SYRUPS AND THEIR QUALITY CONTROL TESTS

Introduction
The syrup is a concentrated or nearly saturated viscous aqueous solution of sucrose/sugar
substitute with or without flavor/medicinal substances in purified water.

Syrups are viscous and sweet preparations

 According to B.P

Concentration of sucrose in water is 66.7%w/w

 According to USP

Concentration of sucrose is 85% w/v

Types of syrups
There are three types of syrups
 Simple syrup
 Medicated syrup
 Flavored syrup

Simple syrup
When Purified Water alone is used in making the solution of sucrose, the preparation is known
as “syrup,” or “simple syrup.

Medicated syrup
When Syrup contains medicinal substance  is know as medicated syrup
Examples:
Cough syrups
 Ambroxol
 Amoxicillin

Flavored syrup
Syrup containing aromatic or flavored substance is called flavored syrup .
They are mostly used to improve the taste of salty, bitter, or otherwise unpleasant mixture.
(Nitin.S 2021)

Advantages of syrups
 Syrup retards oxidation because it is partly hydrolyzed into its reducing sugar such as
laevulose and dextrose.
 It prevents the decomposition of vegetable substances. The syrup has a high concentration of
sugar having high osmotic pressure which prevents the growth of bacteria, fungi, microbes. It
acts as a self-preservative.
 They are palatable due to the sweetness of sugar. It is a valuable vehicle for the
administration of nauseous and bitter substances.
 Syrups are good demulcents and soothing agents and hence they are of special value in cough
syrup.
 Syrups have good patient compliance.(smith 2021)

Methods of preparation
 Hot process
 This method is a suitable preparation method, if the constituents are not volatile or degraded
by heat. Purified water is heated to 80–85°C, and then removed from its heat source. Sucrose
is added with vigorous agitation. Then, other required heat-stable components are added to
the hot syrup, the mixture is allowed to cool, and its volume is adjusted to the proper level by
the addition of purified water. In instances in which heat-labile agents or volatile substances,
 such as flavors and alcohol, are added, they are incorporated into the syrup after cooling to
room temperature.
 Invert sugar: When heat is used in the preparation of syrups, inversion of a slight portion of
the sucrose (a disaccharide) into monosaccharides, dextrose (glucose), and fructose
(levulose) by hydroxylation process. This hydrolytic reaction is referred to as “inversion,”
and the combination of the two monosaccharide products is “invert sugar.” Sucrose
solutions are dextrorotary, but, as hydrolysis proceeds, the optical rotation decreases and
becomes negative when the reaction is complete. The rate of inversion is increased greatly by
the presence of acids; the hydrogen ion acts as a catalyst in this hydrolytic reaction. Fructose
is responsible for the darkening of syrup. Invert sugar is more readily fermentable than
sucrose and tends to be darker in color. But, its two reducing sugars prevent the oxidation of
other substances.

 Agitation without heat

Procedure for heat-labile constituents

 Sucrose and other ingredients are weighed properly.

 Dissolved in purified water.
 Kept in a bottle of about twice the volume of syrup followed by continuous agitation.
 Prepared syrup volume is made up to q.s.

 Percolation
In this procedure, purified water or an aqueous solution is permitted to pass slowly through a bed
of crystalline sucrose packed in a percolator, thus dissolving it and forming syrup.
A piece of cotton is placed in the neck of the percolator to prevent the passage of un-dissolved
sucrose.
To be successful in this process:
The percolator should be cylindrical with a short conical base.
Coarse crystalline sucrose must be used to avoid formation of compact mass through which the
liquid cannot pass.
The cotton must not be pressed too tight (slow flow) or too loose (fast flow).
Syrup USP is an example of Syrup prepared by percolation.
Preservation of syrup

 Addition of sucrose in to medicated / flavored liued

Occasionally, a medicate liquid (tincture or fluid extract) is the source of medication in the
preparation of the syrup.

Tinctures and fluid extracts contain alcohols soluble ingredients.

Addition of tincture or extracts to syrup may cause precipitation of the alcohol soluble
components.

If the alcoholic components are not desired or unnecessary for the corresponding syrup, they are
generally
removed by mixing the tincture or extract with water, allowing the mixture to stand until
separation of the water insoluble agent is completed., and filtering them from the mixture. The
filtrate then is the medicated liquid to which the sucrose is added in preparation of syrup.

If the alcohol soluble components are required to be medicinal part of the syrup, some means of
rendering them water soluble is employed.
In some cases, tinctures or extracts is miscible with the aqueous preparation, it may be added
directly to simple syrup to medicate it.(Mistry 2021)

Formulation of syrup
o Vehicle: Syrups are prepared by using purified water.
o Adjuncts: The following adjuncts are generally added to improve the formulation of
syrup.
o Chemical Stabilizer: Glycerin, sorbitol, propylene glycol is added in small quantity to
syrup to prevent the crystallization.
o Coloring agent: Many syrups are attractively coloured with coal tar dyes such as
amaranth, compound tartrazine and Green S.
o Flavoring agents:
o Tinctures: Lemon and ginger tincture
 o Fruit juice: Cherry, Raspberry
o Essence: Vanilla, orange

Quality Control Test for Syrups

Physical Stability of Syrups:

The syrups must be stable physically e.g.

 Its appearance (no crystallization and microbial growth)
 Color must be completely soluble with other ingredients.
 Odor and taste (palatable)
 Solid material is completely miscible in liquid.

Visual inspection:
With the visual inspection, the ingredient & the final product are carefully examined for purity &
for appearance. Physical appearance of product for patient adherence &compliance is critical so
that it should be good looking & elegance in appearance.
Light Transmittance Meter:
A light transmittance meter is a tool i.e. used to check the syrup’s color. In a light transmittance
meter a syrup sample is check for color by passing the light to the sample. The %age of light
transmittance is compared to light transmittance rates set for different grades. When using one,
you should be sure that there is no finger prints on syrup test bottle, and that the syrup sample
has no bubbles or cloudiness. Any of these conditions may diminish the light i.e. transmitted
through the sample & therefore lower the grades of sample.

Content Uniformity:-
For oral solutions, suspensions, and syrup in single-unit containers, conduct the
Assay on the amount of well-mixed material that drains from an individual container in not more
than 5 seconds, and express the results as delivered dose. Where the amount of active ingredient
in a single dosage unit differs from that required in the Assay, adjust the degree of dilution of the
solutions and/or the volume of aliquots so that the concentration of the active ingredients in the
final solution is of the same order as that obtained in the Assay procedure; or, in the case of a
titrimetric assay, use a titrant of a different concentration, if necessary, so that an adequate
volume of titrant is required.
Content Uniformity (Acceptance Criteria)
Unless otherwise specified in the individual monograph, the requirements for dosage uniformity
are met if the amount of the active ingredient in each of the 10 dosage units as determined from
the Weight Variation or the Content Uniformity method lies within the range of 85.0% to
115.0% of the label claim and the Relative standard Deviation is less than or equal to 6.0%.
If 1 unit is outside the range of 85.0% to 115.0% of label claim and no units outside the range of
75.0% to 125.0% of label claim, or if the Relative standard deviation is greater than 6.0%, or if
both condition prevail, test 20 additional units. The requirements are met if not more than 1 unit
of the 30 is outside the range 85.0% to 115.0% of label claim and no unit is outside the range of
75.0% to 125.0% of label claim and the Relative standard deviation of the 30 dosage units does
not exceed 7.8%.

pH measurement:
The measurement & maintenance of pH is very important step in quality control testing.
Generally there are 2 different types of methods use in the measurement of pH;
Methods for pH measurement:

1. pH paper: The simplest & cheapest method is to dip a piece of pH paper into the sample.
The sample is impregnated with chemicals that change the color & color may be compare
to a chart supplied with the paper to give the pH of the sample.
2. pH meter: If greater accuracy is required a pH meter should be use. A typical pH meter
consist of special measuring glass electrode connected to an electronic meter that
measures & display the pH reading.

Optical rotation:

Range is 50°-60°. Syrup should not be less than 50° & not more than 60°. It is to check the
inversion of syrup.
Method: A simple polarimeter was built by using a light bulb, color filters, polarizing filters, and
a sample cell. Then prepared 100 – 200mm long columns of water solutions of sugars (sucrose,
fructose, dextrose, and lactose). Then measured the optical rotation of the sugars in solution by
rotating the analyzer in the polarimeter until no light was transmitted.
Specific gravity:

Specific gravity of syrup either 66.7% w/w or 85% w/v should be 1.313.
Method:

Wash pycnometer thoroughly with water. Then rinse with acetone and let it be air dried. Weigh
the empty pycnometer with stopper. Fill the pycnometer with water and weigh it. Subtract weigh
of empty pycnometer from this reading to find the weight of water. Now fill the pycnometer with
all assigned liquids one by one and weigh. Subtract weigh of empty pycnometer from reading to
find the weight of each liquid. Determine the specific gravity of each liquid by using formula:
𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑔𝑟𝑎𝑣𝑖𝑡𝑦= (𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑠𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒)/(𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑒𝑞𝑢𝑎𝑙 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟)

Sucrose concentration/Assay of active ingredient:

The determination of sucrose concentration is also very important in quality control testing of
syrups. If the concentration of sucrose in the syrup is very high it may crystallize the syrup &
less concentration give favor for the microbial growth. There is no specific method for the
determination of sucrose in syrup we use HPLC & U.V spectroscopy for this purpose.
By using HPLC

HPLC technique is used for both qualitative & quantitative analysis of sucrose.For qualitative
analysis or to confirm the presence of sucrose we compare the peaks obtained after running
HPLC with standards & specific peaks of sucrose. For quantitative analysis we measure the area
under curve (AUC) that will tell us about the concentration of sucrose present in given sample.
By using U.V spectrophotometer:

It can be used for quantitative analysis, by using Beer’s lambert law. The concentration of single
absorbing species in a solution can be readily determined. The absorptivity’s of many substances
at specified wavelength are available in literature. However, if any absorbance is not available it
can be determined by measuring the absorbance of a solution of known concentration of the
substance concerned, using Beer’s lamberts law.
Specification:

 B.P = 66.7 % w/w

 USP = 85 % w/v

Viscosity:
“It is a property of liquid that is directly related to resistance to flow”.
Viscosity measurement is very important quality control test in case of syrups & elixirs.
Viscosity & consistency directly relates with stability of solutions.

Types:-

Viscosity is of following types;

Absolute Viscosity:

It measures when all specification & parameters are defined.

Relative Viscosity:

It measures when we take any standard & make comparison.

Dynamic Viscosity:

The resistance to flow encored when 1 layer or plane of fluid attempts to move over another
identical layer or plane of fluid at a given speed. It is also called as absolute viscosity.

Kinematic Viscosity:

Addition & deletion of force is known as kinematic viscosity.

Determination of Viscosity:

Viscosity can be determined by following instruments;

 Ostwald’s Viscometer
 Falling Sphere Viscometer
 Cone & Plate Viscometer
 Cup & Bob Viscometer

1. Brook field Viscometer

Viscosity of syrup is determined by following apparatus;

 Falling sphere viscometer

 Rotational viscometer
a) Cup & Bob Viscometer
b) Cone & Plate Viscometer

1. Falling Sphere Viscometer

Principle:

o The principle of this instrument is based on stock’s law which state’s that “when a body
falls through a viscous medium it experiences a resistance or viscous drag which opposes the
motion of body”.

o At initial state body experiences acceleration due to gravity but soon this acceleration is
balanced by viscous drag & body falls with a uniform terminal velocity.

Construction & working:

 It consist on a tube having 2 marking A & B on the outer surface.

 The tube is filled with liquid whose viscosity is to be determined.
 The tube is clamped vertically inside a constant temperature bath & significant time is
allowed or equilibrium of temperature & removal of air bubble from the liquid.
 A ball (glass-steel) is allowed to fall through tube.
 Time taken by ball to fall from point A to B is noted & terminal velocity is calculated.
 This is obtained by dividing distance between the 2 points with time.

2. Rotational Viscometer

It Works on the viscous drag in the body when it is retained in the fluid whose viscosity is to be
determined, wide range of shear rate can be determined.

1. Cup &Bob Viscometer:

 It consists of 2 conical cylinder of different diameter.

 The outer cylinder forms the cup into which the inner cylinder or bob is fixed centrally.
 The sample to be analyzed is sheared in the space between the outer wall of the bob& the
inner wall of the cup.
 Torque setup in the bob is due to the rotation of the outer cup or due to rotation of bob itself
(Searne type viscometer).

3. Cone & Plate Viscometer:

1. It consists of flat circular plate with a wide angle cone placed centrally above it.
2. During operation the sample is placed at the center of plate which is then raised into position
under the cone.
3. The cone is driven by variable speed motor & sample is sheared in the narrow gap between
stationary plate & rotational cone.
4. The rate of shear is rpm & is increased or decreased & torque produced is measured.

Method:
Wash apparatus thoroughly with water. Then rinse with acetone and let it be air dried.
Determine the density of water and assigned liquids with help of pycnometer. Fill the viscometer
with water and suck up to upper mark A. Allow water to fall and record time of flow from mark
A to B with the help of stop watch. Repeat the same procedure with all assigned liquids.
Calculate viscosity by using formula;

REFRENCES:
 Mistry, S. (2021). "Syrup-Methord of prepration." n.t. Retrieved 1-jan-2022, 2021.

 Nitin.S (2021). "Syrup, Types & Preparation of Syrup: Pharmaceutics." Retrieved 1-jan, 2021,
from https://thepharmapedia.com/pharmaceusyrup-types-preparation-of-syrup/pharmacy-
notes/.
 smith, J. (2021). "pharmaceutical-drugs." from http://www.pharmaceutical-drug-
manufacturers.com/pharmaceutical-drugs/syrups.html.