.
Lecturer – Dr. Cristina Ciobanu,
university assistant
Drug technology Department
EXTEMPORANEOUS
PHARMACEUTICAL TECHNOLOGY
PHARMACEUTICAL
SUSPENSIONS
State U i ersit of Medi i e a d Phar a Nicolae Testemitanu
DEFINITION:
SUSPENSIONS - ARE LIQUID PHARMACEUTICAL PREPARATIONS, CONSISTING OF ONE OR MORE INSOLUBLE ACTIVE SUBSTANCES SUSPENDED IN A LIQUID DISPERSION MEDIUM, FOR INTERNAL AND EXTERNAL ADMINISTRATION.
Lecturer – Cristina Ciobanu, PhD
CLASSIFICATION:
I. BASED ON GENERAL CLASSES
1. Oral suspension eg: antacids, Tetracycline HCl.
2. Externally applied suspension
II. BY THE METHOD OF PREPARATION AND PHYSICAL PROPERTIES:
1. Mixturae agitandae (agitating mixtures, turbide mixtures, coarse suspensions);
2. Mixturae turbidae (opalescent, fine suspensions).
III. BY THE PHYSICAL PROPERTIES OF ACTIVE SUBSTANCE
1. Suspensions of superficial hydrophilic substances;
2. Suspensions of superficial hydrophobic substances;
Lecturer – Cristina Ciobanu, PhD
Lecturer – Cristina Ciobanu, PhD
IV. BASED ON ELECTROKINETIC NATURE OF SOLID PARTICLES
1. Flocculated suspension
2. Deflocculated suspension
V. BY THE SIZE OF THE DISPERSED PHASE PARTICLES
1. Colloidal suspensions (< 1 micron) -Suspensions having particle sizes of suspended
solid less than about 1micron in size are called as colloidal suspensions.
2. Coarse suspensions (>1 micron) ¾Suspensions having particle sizes of greater than
about 1micron in diameter are called as coarse suspensions.
3. Nano suspensions (10 ng) Suspensions are the biphasic colloidal dispersions of
nanosized drug particles stabilized by surfactants.
VI. BY THE DISPERSION MEDIUM: PURIFIED WATER; ETHYL ALCOHOL; GLYCEROL;
AQUEOUS EXTRACTION SOLUTIONS;
ADVANTAGES:
They have larger pharmaceutical availability than powders;
The duration of action of medicinal substance is prolonged;
Sweeteners and flavorings (sugar and fruit syrup, volatile oils, aromatic waters) are added;
Preservatives (nipagin, nipasole, benzoic acid, sorbic acid, chlorobutanol hydrate) are added.
In suspentions-mixtures liquids containing volatile oils like pectoral elixir (licorice extract, ammonia solution, alcohol, purified water) and anisated ammonia liquor (anise oil, ammonia solution, ethanol) can be added.
Lecturer – Cristina Ciobanu, PhD
DISADVANTAGES:
They are unstable medicinal forms;
Possibility of hydrolytic degradation of medicinal substance;
Highly active substances (ex.: streptocide, chloramphenicol) may be prescribed only in amounts that do not exceed the maximum single dose.
Lecturer – Cristina Ciobanu, PhD
Lecturer – Cristina Ciobanu, PhD
SUSPENSIONS SHOULD HAVE:
• HIGH CONDENSATION RESISTANCE (the ability to withstand the coarsening of particles due to crystallization - the process is irreversible)
• HIGH AGGREGATIVE STABILITY (the ability to withstand clumping of particles,
the formation of aggregates – due to protective layer which coat the dispersed
particles’ surface; the process is reversible protective layer) Aggregation and condensation are generally interrelated and lead to sedimentation
• LOW SEDIMENTATION RATE of subsidence of particles, maintain a uniform
distribution of particles throughout the volume of the dispersed phase (settling of particles and the formation of sediment). The particles should settle so slowly that
the suspension can be accurately dosed at reception.
Lecturer – Cristina Ciobanu, PhD
DEFLOCCULATED SYSTEM FLOCCULATED SYSTEM
1. Pleasant appearance, because of
uniform dispersion of particles.
2. Supernatant remains cloudy.
3. Particles exist as separate entities
4. Rate of sedimentation is slow, as the
size of particles are small.
5. Particles settle independently and
separately
6. The sedimentation is closely packed
and form a hard cake.
7. The hard cake cannot be redispersed.
8. Bioavailability is higher due to large
specific surface area.
1. Somewhat unsightly sediment.
2. Supernatant is clear.
3. Particles form loose aggregates.
4. Rate is high, as flocs are the collection of
smaller particles having a larger size.
5. Particles settle as flocs.
6. Sediment is a loosely packed network
and hard cake cannot form.
7. The sediment is easy to redisperse.
8. Bioavailability is comparatively less due
to small specific surface area.
Lecturer – Cristina Ciobanu, PhD
HYDROPHILIC SUBSTANCES
ALUMINUM HYDROXIDE;
MAGNESIUM HYDROXIDE;
MAGNESIUM OXIDE;
ZINC OXIDE;
BASIC MAGNESIUM CARBONATE;
CALCIUM CARBONATE;
BISMUTH SUBNITRATE
1. ACTIVE SUBSTANCES
HYDROPHOBIC SUBSTANCES
Strongly pronounced hydrophobic character –
CAMPHOR;
MENTHOL;
THYMOL;
SULPHUR;
CHARCOAL
Less pronounced hydrophobic character -
PHENYL SALICYLATE;
SULFAMIDES.
Lecturer – Cristina Ciobanu, PhD
2. LIQUID DISPERSION MEDIUM
PURIFIED WATER;
ETHYL ALCOHOL;
GLYCEROL;
AQUEOUS EXTRACTION SOLUTIONS;
Requirements of the solvents used for preparing suspensions are: physical-chemical stability,
neutral reaction, antimicrobial stability and liquid consequence.
Lecturer – Cristina Ciobanu, PhD
Classification of Suspending Agents
1.POLYSACCHARIDES
Natural – gums, gelatosis, acacia, taragacanth,
sodium salt of alginic acid
Semi-synthetic – methylcellulose, hydroxyethyl
cellulose, sodium carboxymethylcellulose
1.INORGANIC AGENTS
Clays – bentonite, Magnesium Aluminum Silicate,
Aluminium hydroxide – Coloidal hidrated
Aluminium hydroxide, Aluminum Monostearate
1.SYNTETIC - carbomer, colloidal silicon dioxide.
Gelatosis (gelatos, zhelatoza) is a
product of incomplete gelatin
hydrolysis.
Description. Amorphous powder
of yellowish color with a peculiar
smell, slightly salty taste.
Solubility. Soluble in 10 parts of
water, insoluble in alcohol and
ether.
Storage. In well-sealed jars in a
cool place.
Lecturer – Cristina Ciobanu, PhD
Suspensions in pharmacy are prepared by 2 methods:
1. (particle reduction);
Mechanical dispersion – at 1.0 g of active susbstance - 0.4 - 0.6 ml liquid (Rebinder splitting effect).
In order to obtain an optimal dispersion of medicinal substances, it is recommended to add an
auxiliary liquid in the ratio of 1 : 2 .
For 1 g of substance – 0,5 ml of auxiliary liquid. – DERYAGIN RULE.
2. (particle enhancement).
• The liquid dispersion phase is constituted of liquid extracts and tinctures.
• Co de satio allo s to o tai suspe sio s i reasi g the i itial su sta e parti les, ei g either i ionic or molecular state.
• The o tai ed i tures are alled - opalescent.
PREPARATION OF PHARMACEUTICAL SUSPENSIONS:
Lecturer – Cristina Ciobanu, PhD
Suspensions with hydrophilic substance can be prepared by 2 ways:
• Common dispersion method
1. Medicinal substance is puted in a mortar, where,
2. It is well triturated with a humectant added according to
Deryagin’s rule (for 1 g of substance 0,5 ml of water).
3. The resulting paste is suspended with the rest of the liquid into
vial.
• Turbulence (medical substance is humidified with a humectant to
which a small amount of solvent is added, the mixture is shaken and then
left for a few minutes to sediment; the suspension is kept in a vial, the
operation is repeated until the whole precipitate turns into suspension).
Lecturer – Cristina Ciobanu, PhD
Rp.: Magnesii oxydi 2.0
Aquae purificatae 100 ml
M.D.S. Internally, 2 tablespoon after meals
and at bedtime as needed.
W.V.D.
Date Nr. of prescription
Magnesii oxydi 2.0
Aquae purificatae 100 ml
Total volume 100 ml Prepared by:
Checked by:
Dispensed by:
This medication is
used to treat the
symptoms of too
much stomach acid
such as stomach
upset, heartburn,
and acid
indigestion.
COMPOUNDING TECHNOLOGY: • Magnesii oxydi (white, light powder, insoluble in water but hydrophilic due to oxygen
atoms in its structure) is putted in a mortar. 1 ml of purified water is added (according to
Deryagin rule) and is well triturated for about 3-5 minutes.
• The resulting paste is suspended with the rest of purified water (99 ml) added in 3 - 4
portions and is introduced into a transparent delivering vial without filtering.
• The vial is labeled with mention “Shake before use”. • Shelf-life is 3 days.
Lecturer – Cristina Ciobanu, PhD
Natural suspending
agents
1:1
Semisynthetic agents
1 : 0.1
Natural suspending
agents
1:0,5
Semisynthetic agents
1 : 0,05
Strongly pronounced
Slightly pronounced
The quantity of suspending
agents added to suspentions
prepared from hydrophobic substances depends on:
1. Particularity of active
substance that can manifest
strongly pronounced
hydrophobic character (camphor) or less
pronounced hydrophobic character (phenilsalicilate).
2. Origin of suspending agent,
that can be natural
(gelatose) or semisynthetic (methylcellulose).
SUSPENSIONS PREPARED FROM HYDROPHOBIC SUBSTANCES:
Ex.: 1 g of Camphor requires 1 g of gelatosis or
0,1 of methylcellulose (dry powder)
Ex.: 1 g of Phenilsalicilate requires 0,5 g of gelatosis or
0,05 of methylcellulose (dry powder)
Lecturer – Cristina Ciobanu, PhD
W.V.D.
Date Nr.
Phenylii sallicilatis 2.0
Ap aethilici 95 % - 20 gtts
Gel Methylcellulose 5 % (1:20) - 2.0
Aquae menthae 100 ml
V tot 100 ml Prepared by:
Checked by:
Dispensed by:
CALCULATIONS
1 g Sub. --- 0.05 g Methylcellulose dry powder
2 g Sub. ------ 0.1 g Met.cel. dry powder
For example in compounding laboratory is present
Gel of methylcellulose of 5 %
Gel 5 % (1:20) = 0.1 * 20 = 2.0 of Gel
Rp.: Phenylii sallicilatis 2.0
Aquae menthae 100 ml
M.D.S. Internally, 1 table spoon 2 times a day
COMPOUNDING TECHNOLOGY:
2.0 of phenyl salicylate is grinded with 20
drops of alcohol of 95 %, till alcohol
evaporates. (for 1 g of subst. – 10 drops).
Then 2 g of gel of Methylcellulose is added.
The resulting paste is suspended with 100 ml of
peppermint water.
Lecturer – Cristina Ciobanu, PhD
SULFUR PRAECIPITATUM –
eng. Sulfur besieged. Yellow powder practically insoluble in
water and alcohol.
Effect Keratolytic, antiparasitic. Indications to use. Seborrhea, sycosis,
psoriasis, itch.
SULFUR DEPURATUM – eng. Sulphur cleared
A fine powder of lemon yellow color.
Soluble in water, slightly soluble in ether.
As an anthelmintic agent used for
enterobiosis.
It is also used sometimes as a mild
laxative (0, 5 - 1, 0 - 3, 0 g per reception).
The sulfur suspension is best stabilized with medicinal soap, which
increase its pharmacological activity; also sulfur is compatible with
mucilage 1% of methylcellulose and glycerol.
Sulfur
Lecturer – Cristina Ciobanu, PhD
Rp.: Sulfuris praecipitati 2,0 Glycerini 5,0 Aquae purificatae 100 ml M.D.S. For external use.
W.V.D.
Date Nr.
.
Sulfuris praecipitati 2.0
Glycerini 5,0
Aque purificatae 100 ml
V tot = 104 ml Prepared by:
Checked by:
Dispensed by:
CALCULATIONS Convert mass of glycerol in volume.
V = m / ρ V = 5 g / 1.225 g/cm3 = 4,0 ml
Total volume of suspension – 100 + 4 = 104 ml
COMPOUNDING
TECHNOLOGY: Sulfur is putted in a
mortar, is well triturated with 1
g of glycerol (Deryagin rule)
and, than all quantity of
glycerol is added and is all
mixed for about 3 minutes.
The resulting paste is
suspended with 100 ml of
water, added in 3 - 4
portions, suspention is
introduced into a transparent
delivering vial without
filtering.
The vial is labeled with
mention “Shake before use”. Shelf-life is 3 days.
Lecturer – Cristina Ciobanu, PhD
The redispersability (resuspension) process presents the uniform distribution
of particles in the liquid after agitation for 15-20 sec, 40-60 sec.
Quality control of suspensions