pharmaceutical suspensions - usmf

.

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;



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.


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.



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.


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.


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.


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.


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.


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:


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).


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.


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)


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.


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


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.


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

pharmaceutical suspensions - usmf

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