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 Pharmaceutical Dosage Forms and Drug
Delivery Systems, 9th edition, Chap. 13
 Remington: the Science and Practice of
Pharmacy, 2013, Chap. 39
§ Introduction
 Syrups are concentrated, viscous, aqueous
preparations of a sugar or sugar-substitute with
or without flavors and medical substances.

Nonmedicated syrups (vehicles)

To serve:
As pleasant-tasting vehicles for medicinal
substances to be added in the extemporaneous
compounding of preparations
In the preparation of a standard formula for a
medicated syrups

For children and elderly people, those who
are unable to swallow a solid dosage form.
Any water-soluble drugs stable in an
aqueous solution may be added to flavored
syrup, but must ensure the compatibility.
Should consider drug solubility, stability, and
bioavailability case by case.

 Medicated Syrups
It is usually commercially prepared from the
starting materials, i.e., combining each of
individual components.
Most frequently found medicated syrups are
antitussive agents and antihistamines.

Table 39-5. Examples of Commercial Medicated Syrups
Active Ingredient and
Product Name Manufacturer Indication
2 mg
Chlor- Schering- Allergic
Trimeton Plough rhinitus
maleate/5 mL
12.5 mg
Children's Allergic
Pfizer diphenhydramine
Benadryl rhinitus
HCl/5 mL
Demerol 50 mg meperidine Narcotic
Syrup HCl/5 mL analgesic
Ditropan 5 mg Oxybutynin Overactive
Syrup chloride/5 mL bladder
12.5 mg
Dramamine Pfizer Antiemetic
dimenhydrinate/5 mL
Phenergan 25 mg promethazine
Wyeth-Ayerst Antiemetic
Syrup HCl/5 mL
Symmetrel 50 mg amantadine
6 Endo Antiviral
Syrup HCl/5 mL
§ Components of Syrups

1) Purified water
2) Any medicinal agents
3) The sugar – sucrose or sugar substitutes to
provide sweetness and viscosity
4) Antimicrobial preservatives
5) Flavorants
6) Colorants

Sucrose and Non-sucrose Based Syrups
Sucrose is the sugar most frequently
employed in syrups; it may be replaced
by other sugars, such as dextrose, or
non-sugars polyols such as sorbitol,
glycerin, and propylene glycol.
In some instances, all glycogenetic
substances* are replaced by non-
glycogenetic substances.

* Glycogenetic substances: materials converted to

glucose in the body.
 Non-glycogenetic substances such as
methylcellulose and hydroxyethylcellulose
are used for diabetic patients or others,
those who need diet controlled.
These cellulosic derivatives can generate a
viscosity very much like sucrose syrup.
 Then, the addition of one or more artificial
sweeteners usually produces a facsimile of
true syrup.

Proper viscosity attained by syrups
together with the sweeteners or flavorants
to mask the taste of added medicinal
When the syrup is swallowed, only a
portion of dissolved drug actually makes
contact with the taste buds.
E.g. for antitussive syrups, thick sweet
syrups has a soothing effect on the
irritated tissues of the throat.

Most syrup contain high conc. of sucrose
(60-80%) – not only for sweetness and
viscosity but also for it’s inhered stability.
 Dilute sucrose solutions – an efficient
nutrient medium for the growth of
microorganisms (molds and yeast)
 Concentrated sucrose solutions – are
resistant to microbial growth
(∵unavailability of the water required for
the growth of microorganisms).
Syrup NF (Simple Syrup, 單糖漿)
 85 g sucrose dissolved in enough purified water
to make 100 mL syrup.
 Required no additional preservative.
 No preservative is allowed in this official syrup.
 The official syrup is stable and resistant to
crystallization as well as microbial growth.
 Simple Syrup has a specific gravity about 1.313
 100 mL syrups weighed 131.3 g  have 46.3
g (mL) of purified water existed in 100 mL syrup.
 Solubility of sucrose in water is 1 g in 0.5 mL
water; 85 g sucrose needs 42.5 mL water to
dissolve. A very slightly excess of water (about
3.8 mL per 100 mL syrup) exists in syrup.
 Why not prepare a fully saturated syrup?

If the syrup is completely saturated with sucrose,

sucrose might crystallize from solution under
some conditions (e.g. cool storage condition) 
result in the separation of an amount of sucrose
 Many other official syrups have no near
saturated sucrose, need to add preservative.
 A solution of polyol, as sorbitol, or a mixture of
polyols, as sorbitol and glycerin, are commonly
used to prepare non-sucrose based syrups.

Antimicrobial Preservative
The amount of preservative required depends on the
proportion of water available for growth.
Commonly used preservative in syrups are: benzoic
acid (0.1~0.2%), sodium benzoate (0.1~0.2%),
various combinations of methyl-, propyl-, and butyl-
parabens (total about 0.1%), glycerin, and alcohol.
Alcohol is a good solubilizing aid vehicle, but it is
usually not containing to a concentration higher
enough (15-20%) to have adequate preservative

Synthetic flavorants, Volatile oils, Vanillin, &
Sometimes a small amount of alcohol is added to
ensure the continued solution of a poorly water-
soluble flavorant.

 Colorant
Flavorant and Colorant: Green with mint; brown
with chocolate
Characteristics: Water-soluble; Nonreactive;
color-stable at the pH range and under the
intensity of light; etc.
Preservation of Syrups
Syrups can be preserved by
1) storage at low temperature
2) adding preservatives such as glycerin, benzoic
acid, sodium benzoate, methyl paraben or alcohol
in the formulation
3) maintaining a high concentration of sucrose as a
part of the formulation.
High sucrose concentration is able to protect oral
liquids from the growth of most microorganisms.

In syrups, if it is needed to add other
ingredients in syrups, it may result in a
decrease in sucrose concentration  then it
may cause a loss of the preservative
effectiveness of the sucrose.  Preservative
will be required in the formulation
How to calculate the quantity of a preservative
(e.g. alcohol) required to the formula to
maintain preservative effectiveness:
Free-water Method

EXAMPLE- Free-water Method
Rx Active drug 5 mL volume occupied
Other drug solids 3 mL volume occupied
Glycerin 15 mL
Sucrose 25 g
Ethanol 95 % q.s.
Purified water q.s. 100 mL
How much alcohol would be required to preserve
this prescription? Use the free-water method to
calculate the quantity of alcohol required.
Simple syrup contains 85g sucrose per 100 mL of
solution, which weight 131.1g (specific gravity,
1.313). It takes 46.3 mL water to prepare the
solution (131.3-85=46.3), and the sucrose
occupies a volume of (100-46.3=53.7) 53.7mL.
1. Since this solution is preserved, 85g of sucrose
preserve 46.3 mL of water, and 1 g of sucrose
preserves 0.54 mL of water. With 25 g of
sucrose present, the amount of water
preserved is 25 × 0.54=13.5 mL
2. Since 85 g of sucrose occupies a volume of 53.7
mL, 1 g of sucrose will occupy a volume of 0.63
mL. The volume occupied by the sucrose in this
prescription is 25 × 0.63=15.75 mL
3. The active drug and other solids occupy 8 mL
(5+3) volume.
4. Each mL of glycerin can preserve an equivalent
quantity of volume (2×15=30), so 30 mL would
be preserved.
5. The volume taken care of so far is
13.5+15.75+8+30= 67.25 mL. The quantity of
free water remaining is
100-67.25=32.75 mL
6. Since it requires about 18% alcohol to preserve
the water, 0.18 × 32.75=5.9 mL of alcohol (100%)
would be required.
7. If 95% ethanol is used, 5.9/0.95=6.21 mL would
be required.
To prepare the prescription, about 6.21 mL of 95%
ethanol can be added with sufficient purified
water to make 100mL of the final solution.

§Preparation of Syrups
Solution with the Aid of Heat
 It is good for syrups to be prepared quickly if
syrups’ components are not damaged or
volatilized by heat.
 General procedure: sugar adds to purified water
 apply heat until the solution is effected  add
other required heat-stable components to hot
syrup  cool  then add additional purified water
to the volume
 For syrups have heat-labile agents or alcohol or
volatile agent, add these components to hot syrup,
and then cool the syrup rapidly.
 Sucrose, a disaccharide, may be hydrolyzed by heat
into dextrose (glucose) and fructose (levulose).
 This hydrolyzed reaction is referred to as
“inversion” and the combination of the two
monosaccharide products is “invert sugar”.
 The rate of inversion is increased greatly by the
presence of acids. (hydrogen ion acts like a
catalyst to the reaction).

 Invert sugar is more readily fermentable than
sucrose and tends to be darker in color.
 It is suggested to use boiled purified water in
preparation and add preservatives if allowed.
 The fructose formed during inversion is sweeter
than sucrose, thus, the resulting syrup is sweeter
than the original syrup.
 The relative sweetness of fructose, sucrose, and
dextrose is in the ratio of 173:100:74. Thus, invert
sugar is 1/100 (173 + 74)1/2 = 1.23 times as
sweet as sucrose.
 Fructose is responsible for the darkening of syrup,
as it is amber in color. If the syrup is significantly
overheated, sucrose carmelizes and becomes
Solution by Agitation without the Aid of
 This process is more time consuming, but the
product has maximum stability.
 When add other solid agents, dissolve them in
a minimum amount of purified water and then
incorporate the resulting solution into the
 If directly add other solids to syrup, it may
dissolve very slowly due to the viscous
character of syrup.

Addition of Sucrose to a Medicated
Liquid or to a Flavored Liquid
 Medicated liquids such as a tincture or
fluidextract may be employed as the source of
medication syrup. Such tincture or fluidextract
contains alcohol-soluble constituents.
 If the alcohol-soluble components are desired
in syrup, then mix them.
 If the alcohol-soluble components are
undesired in syrup then removed them by
mixing the tincture or fluidextract with water 
stand until the separation of water-insoluble
component completely  filter them.
 If the tincture or fluidextract is water soluble,
25 then add to syrup directly.
Percolation (滲漉)
In some cases need two separate procedures:
1) preparation of the extractive of the drug, and
2) preparation of the syrup.

For example: ipecac syrup (吐根糖漿)

Ipecac powder under percolation to extract active
alkaloids  extractive  add glycerin and syrup
Ipecac syrup is prepared by percolation by adding
glycerin and syrup to an extractive of powdered
ipecac obtained by percolation.

Ipecac Syrup (吐根糖漿)
Mechanism of Actions
The actions of Ipecac are mainly coming from its major
alkaloids, emetine (methylcephaeline) and cephaeline.
They both act locally by irritating the gastric mucosa and
centrally by stimulating the medullary chemoreceptor
trigger zone to induce vomiting.
Poison Treatment
The commercial preparation of ipecac consists of 1/14th of
fluidextract of ipecac root. The rest is composed of glycerin
and sugar syrup. Ipecac root itself is a poison but due to
the normal strengths used and the inability of the patient
to keep the solution ingested it is seldom fatal.
Ipecac was used in cough mixtures as an expectorant or
an emetic from the 18th until the early 20th century.
Ipecac syrup is still used to induce vomiting, though it is
no longer widely recommended.
Simple Syrup
製 法:本品製造時所用之原料及其用量如下:
蔗糖 850 g
蒸餾水 適量
共製 1000 mL
本品亦可用下列方法製之:取蒸餾水450mL 煮沸後,加入蔗糖,
到達100˚ 為止。然後用精製棉或其他適當之濾器過濾,另取適量
性 狀:本品之比重約為1.313(通則1005)。
貯 藏 法:本品應置於緊密容器內,於25 ˚C 以下貯之。
29 用途分類:製劑輔助劑(矯味劑)。
Orange Syrup
別 名:柑皮糖漿
注 意:本品如有類似松節油之臭或味,或呈其他變質徵象時,即不可再
製 法:本品製造時所用原料及其用量如下:
甜橙皮酊 50 mL
檸檬酸 5g
滑石粉 15 g
蔗糖 820 g
蒸餾水 適 量
共製 1000 mL
貯 藏 法:本品應置於緊密容器內,於25 ˚C以下貯之。
Medication Syrups
Ferrous Sulfate Syrup Amantadine Hydrochloride Syrup
Ferrous Sulfate 40.0 g 10.0 g
Citric Acid 2.1 g
Artificial Raspberry
Citric Acid 2.1 g 2 mL
2 mL Methyl paraben 2 g
Sucrose 825 g Propyl paraben 0.5 g
Purified Water Sorbitol Solution to
1000.0 mL 1000 mL
to make make

(4011) 糖漿劑 (中華藥典第七版第68頁)