SUSPENSI

Suspension Dispersed phase (internal fasea)

Continuous phase (eksternal fase)

ADVANTAGES:

1- Used for insoluble drug or poorly soluble drugs

2. To over come the instability of certain drug in aqueous solution (phenoxymethypencillin/ coconut oil and tetracycline HCL/ oil)

3. Drug in suspension exhibits higher rate of bioavailability than several dosage forms. bioavailability is in following order,Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

4- Suspension can mask the unpleasant/ bitter taste of drug.

DISADVANTAGES

1. Physical stability, sedimentation and compaction can causes problems.

2 It is bulky, sufficient care must be taken during handling and transport.

3 It is difficult to formulate4 Uniform and accurate dose can not be

achieved unless suspension are packed in unit dosage form

CLASSIFICATION OF SUSPENSIONS1- Based On General Classes

Oral suspension e.g. antacid, antibioticExternally applied suspensionParenteral suspensionOphthalmic suspension

2- Based On Proportion Of Solid ParticlesDilute suspension (2 to10% w/v solid)Concentrated suspension (50% w/v solid)

3- Based On Electrokinetic Nature Of SolidParticlesFlocculated suspensionDeflocculated suspension

FACTORS TO BE CONSIDERED1. Particle size control2. Wetting of the particles

wetting agents include:1) SurfactantsDisadvantages of surfactants are:a. that they have foaming tendencies.b. they are bitter in taste.c. Some surfactants such as polysorbate 80 interact with preservatives such as methyl paraben and reduce antimicrobial activity.

SURFAKTAN

SURFACTANT CLASSIFICATION

A. IonicAnionic – e.g. sodium stearate, sodium lauryl sulphate CH3(CH2)11 OSO3 Na

Cationic – e.g. quaternary ammoniumcompounds, hexadecyl trimethyl ammonium bromide (cetrimide).

B. Nonionic – e.g. polyethylene oxide, Sorbitan mono-oleate (Span), Polyoxyethylene (CH3CH2O) Sorbitan monooleate

Wetting Agents Include…(2. Hydrophilic Colloidse.g. acacia, tragacanth, alginates, gelatin, wool fat, egg yolk,

bentonite, Veegum, Methylcellulose etc.

FACTORS TO BE CONSIDERED…3. Sedimentation (hukum stokes) V= d2 (ρs ρ o ) g

18Sedimentation Parameters1) Sedimentation volume (F) or

height (H) For flocculated suspensions

2) Degree of flocculation (β)

VOL. SEDIMENTASI DAN DERAJAT FLOKULASI

FLOCCULATING AGENTS:

1. Electrolytes (e.g. Nacl, sulfate, citrates, phosphates

salts) reduce the zeta potential surrounding

the solid particles. This leads to decrease in repulsion

potential and makes the particle come together to from loosely arrange structure (floccules).

- The flocculating power increases with the valency of the ions.

As for example, calcium ions are more powerful than sodium ions because the velency of calcium is two whereas sodium has valency of one.

EX: bismuth subnitrate with KH2PO4

CAKING DIAGRAM

CAKING DIAGRAM

FLOCCULATING AGENTS…2.Surfactants Both ionic and non-ionic surfactants can be

used to bring about flocculation of suspended particles.

Ionic surfactants: cause neutralization of the charge on each particle. The particles are then attracted towards to each other by van der waals forces and forms loose agglomerates.

Non-ionic surfactant: they are adsorbed on to more than one particle thus forming a loose flocculated structure.

FLOCCULATING AGENTS… 3. Polymers (e.g. alginate, starch,

cellulose derivatives) Polymers possess long chain in their

structures. The part of the long chain is adsorbed on the surface of the particles and remaining part projecting out into the dispersed medium. Bridging between these later portions, also leads to the formation of flocs.

FACTORS TO BE CONSIDERED…4. Brownian Movement5. Electrokinetic Properties (zeta potensial)The zeta potential is defined as thedifference in potential between the surface of the tightly bound layer (shear plane) andelectro-neutral region of the solution.

0

FACTORS TO BE CONSIDERED…6. DEFLOCCULATION AND FLOCCULATION

FACTORS TO BE CONSIDERED…

7.Viscosity Of SuspensionsAdvantages High viscosity inhibits the crystal growth. High viscosity prevents the transformation of

metastable crystal to stable crystal. High viscosity enhances the physical stability.

Disadvantages High viscosity hinders the re-dispersibility of the

sediments High viscosity retards the absorption of the drug. High viscosity creates problems in handling of the

material during manufacturing

DIFFERENT APPROACHES TO INCREASE THE VISCOSITY OF SUSPENSIONS 1-Viscosity Enhancers / Structured

vehicles Some natural gums (acacia, tragacanth),polymers, cellulose derivatives (sodium CMC, methyl cellulose),clays(bentonite), sugars (glucose, fructose)

2- Co-solventsSome solvents which themselves have high viscosity are used as co-solvents to enhance the viscosity of dispersion medium.

ADDITIVE IN SUSPENSIONS

PEMBUATAN SUSPENSI Bagaimana suspensi yang ideal ? Alat: mikropulverisator

Jet milling/mikronizerSpray drier

Perhatikan karakteristik fase terdispersePerlukah wetting agent?

SUSPENSION PREPARATION 1. presipitation method pH change Organic solvent Double dissociation

2. dispersion method

QUALITY CONTROL OF SUSPENSIONS1. Appearance Color, odor and taste 2. Physical characteristics such as particle size

determination and microscopic photography for crystal growth

3. Sedimentation rate 4. Zeta Potential measurement5. Sedimentation volume 6. Redispersibility and Centrifugation tests 7. Rheological measurement 8. PH9. Freeze-Thaw temperature cycling10. Compatibility with container and cap liner