SYRUP & ELIXIR

Pharmaceutics department
Pharmacy study program faculty of medicine
Brawijaya university
 LEARNING OUTCOME

• Describe the definition, specification, principal of formulation

• Describe the preparation of syrup and elixir
• Ability to solve the problem of the formulation and manufacturing
• The precison of procedure and specification
• The suitability of the result with the specification
 SYRU
P
• concentrated aqueous preparations of a sugar or sugar substitute with or without
flavoring agents and medicinal substances.

• Syrups containing flavoring agents but not medicinal substances are called
nonmedicated or flavored vehicles (syrups)
COMPONENTS OF SYRUP

flavorants

Purified water + therapeutic agents

for medicated syrup
colorants

Sugar

preservative Other

Special solven,
solubilizing agents,
thickeners, stabilizers
SUGAR
Propylen
sorbitol glycol
Usually
SUCROSE replaced by

glycerin

viscosity

Sucrose
Glycogenetic
60-8 0 % substances

sweetness stability

• Syrup, NF, also called simple syrup. It is prepared by dissolving 85 g of sucrose in

enough purified water to make 100 mL of syrup.
 HOW ABOUT DIABETIC PATIENTS?

• Glycogenetic substances :materials converted to glucose in the body

• Nonglycogenetic substances :methylcellulose (MC) or hydroxyethylcellulose (HEC).
• They are not hydrolyzed and absorbed into the blood stream
• Other sugar :aspartam, saccharin, etc
• Look atADI
 THE IMPORTANT OF PROPER VISCOSITY

• Sucrose and other alternative agents  Taste masking

• When the syrup is swallowed, only a portion of the dissolved drug actually makes
contact with the taste buds, the remainder of the drug being carried past them and
down the throat in the viscous syrup.
• This type of physical concealment of the taste is not possible for a solution of a drug
in an unthickened, mobile aqueous preparation.
• In the case of antitussive syrups, the thick, sweet syrup has a soothing effect on the
irritated tissues of the throat as it passes over them.
 ANTIMICROBIAL PRESERVATIVE

• benzoic acid 0.1% to 0.2%

• sodium benzoate 0.1% to 0.2%
• various combinations of methylparabens, propylparabens, and butylparabens
totaling about 0.1%.
• Alcohol?
 PRESERVATION OF SYRUPS

(a)storage at low temperature

(b)adding preservatives such as glycerin, benzoic acid, sodium benzoate, methyl
paraben, or alcohol in the formulation

(c) by the maintenance of a high concentration of sucrose as a part of the formulation

 PREPARATION OF SYRUPS

• (a) solution of the ingredients with the aid of heat,

• (b) solution of the ingredients by agitation without the use of heat, or the simple
admixture of liquid components,

• (c) addition of sucrose to a prepared medicated liquid or to a flavored liquid, and

• (d) percolation of either the source of the medicating substance or the sucrose.
 SOLUTION WITH THE AID OF HEAT

• it is desired to prepare the syrup as quickly as possible

• the components are not damaged or volatilized by heat
• the sugar is generally added to the purified water, and heat is applied until the sugar
is dissolved. Then, other 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.
• heat-labile agents or volatile substances,such as volatile fl avoring oils and
alcohol,after the solution is rapidly cooled to room temperature

Beware of overheated!
 SOLUTION BY AGITATION WITHOUT
THE AID OF HEAT
• sucrose and other formulative agents may be dissolved in purified water by placing
the ingredients in a vessel larger than the volume of syrup to be prepared, permitting
thorough agitation of themixture

• more time consuming than the use of heat, but maximum stability
 THE PROBLEMS

Solubility
• Low solubility
• Acid and alkali

• pH optimization
• Co-solvents
• Surfactant
• Heat
Stability • Sedimentation
• Crystalization
• Degradation of API
• Incompatibility
• Bacterial conatmination
• Heat instability of API
• Buffer pH
• No heat
• Effective preservative
 EVALUATION
Parameter Specification IPC PackagingIPC Stability

Pemerian Hijau bau menthol rasa mint √ √

pH 4.0 – 6.0 √ √
Berat Jenis 1.180 – 1.220 g/mL √ √

Viskositas √ √
Kadar Zat Aktif √ √
• Paracetamol 90 % - 110 %
Mikrobiologi √
• MPN Bakteri < 300 cfu/mL
Volume kemasan √
Cap seal, Kebocoran √
 ELIXIRS

• clear, sweetened hydroalcoholic solutions intended for oral use and are usually
flavored to enhance theirpalatability

• Nonmedicated & medicated

• elixirs are usually less sweet and less viscous because they contain a lower
proportion of sugar and consequently are less effective than syrups in masking the
taste of medicinal substances
• elixirs should be stored in tight, light-resistant containers and protected from
excessive heat.
COMPONENTS OF ELIXIRS

Poly-ol cosolvent

Purified water + therapeutic agents

for medicated syrup
Colorants, flavour

Alcohol

preservative Other

Buffer pH,solubilizing
agents, thickeners,
stabilizers
 PREPARATION OF ELIXIRS

• simple solution with agitation and/or by admixture of two or more liquid ingredients
 PREPARATION

Cosolvency approach
1) Making the mixtures (cosolvency approach)  total
volume needed
2) Add the solute into the mixtures
3) Stir until dissolve
Dissolve in the appropriate solvent
• Alcohol-soluble and water-soluble components are generally dissolved
separately in alcohol and in purified water, respectively
• the aqueous solution is added to the alcoholic solution, to maintain the
highest possible alcoholic strength at all times so that minimal separation
of the alcohol-soluble components occurs
• Frequently, the fi nal mixture will be cloudy, principally because of
separation of some of the flavoring oils by the reduced alcoholic
concentration
PROBLEMS

Solubility

Stability
 EVALUATION
Parameter Spesifikasi Prosedur Interpretas
i Hasil
Pemerian
pH
Berat Jenis
Kejernihan
Kadar Zat Aktif

Kadar Etanol
Volume
Terpindahkan
THANK YOU
 Formulasi Eliksir

KONSTANTA DIELEKTRIK (δ)

Indeks yang menunjukkan polaritas bahan.
δ rendah non-polar
δ tinggi  polar
 Dielectric Dielectric
Compound Compound
constant, δ constant, δ
Polyethylene glycol
N-methylformamide 190 12.4
400
Water 80 Chloroform 5
Sorbitol Solution USP (7 0 % w/w) 62 Castor oil 4.6
Syrup USP 56 Ethyl ether 4.3
Glycerol (glycerin) 46 Sucrose 3.3
Methanol 33 Olive oil 3.1
Propylene glycol 32.1 Sesame oil 3.1
Ethanol 25 Benzene 2.2
n-Propyl alcohol 22 Carbon tetrachloride 2.2
Acetone 21 Octane 1.9

polar (δ > 50), semi-polar (δ = 20 - 50), non-polar (δ = 1 -20)

 Formulasi Eliksir

Contoh
Akan dibuat eliksir Paracetamol menggunakan pelarut
campur etanol, propilen glikol, dan air. Berapa volume
masing-masing air, propilen glikol dan etanol?

Polaritas pelarut yang dibutuhkan (=polaritas zat yang

akan dilarutkan)?

Polaritas pelarut yang akan digunakan?

Konstanta Dielektrik Konstanta Dielektrik

Pelarut Campur Zat Terlarut
 Formulasi Eliksir
Rumus Onsager-Kirkwood
Konstanta
Konstanta Dielektrik Pelarut Campur = Dielektrik Zat
Terlarut
(fA x δA) + (fB x δB) + (fC x δC) = Konstanta
+ …. Dielektrik yang
Diperlukan
fA adalah Fraksi Volume Pelarut A
δA adalah Konstanta dielektrik pelarut A
SOAL:
Akan dibuat eliksir Paracetamol. Pelarut: Etanol, propilen glikol, dan Air.
Diketahui:
-- δ Alkohol = 25
-- δ Propilen glikol = 32,1
-- δ Air = 80
Step 1. Polaritas pelarut campur yang dibutuhkan berapa?
1 bagian Pct dapat larut dalam 7 bagian Alkohol (FI III).
Berarti, misalnya dalam 10 ml larutan Pct, komponen alkohol 7 0 % dan
air 30%.
Maka dapat diprediksikan δ pelarut campur untuk melarutkan Pct.
Hitung pakai rumus Onsager-Kirkwood: δ = (fAlk x δAlk) + (fAir x
δAir)
 Formulasi Eliksir
Penyelesaian
δ = (fAlk x δAlk) + (fAir x δAir)
= (0,7 x 25) + (0,3 x 80)
= 41,5 --- δ yang diperlukan.

Step 2. Menghitung komponen pelarut supaya menghasilkan

δ 41,5.
(fAlk x δAlk) + (fAir x δAir) + (fPg x δPg) = δ Zat terlarut
(fA x δA) + (fB x δB) + (fC x δC) = 41,5

--”buat pemisalan untuk menyeimbangkan persamaan”---

 Formulasi Eliksir
Penyelesaian
Misalnya akan dipakai (total 100%):
--Alkohol 1 0 %
--Air Y %
--Propilen glikol ( 9 0 % - Y)
(fA x δA) + (fB x δB) + (fC x δC) = 41,5
(0,1 x 25) + (Y x 80) + (0,9-Y) x (32,1) = 41,5

“Complete yourself”