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suspensi. Suspension Dispersed phase (internal fasea ) Continuous phase ( eksternal fase ). Advantages:. 1- Used for insoluble drug or poorly soluble drugs
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SuspensionDispersed phase (internal fasea) • Continuous phase • (eksternalfase)
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 formulate 4 Uniform and accurate dose can not be achieved unless suspension are packed in unit dosage form
Classification of suspensions 1- Based On General Classes Oral suspension e.g. antacid, antibiotic Externally applied suspension Parenteralsuspension Ophthalmic suspension 2- Based On Proportion Of Solid Particles Dilute suspension (2 to10% w/v solid) Concentrated suspension (50% w/v solid) 3- Based On Electrokinetic Nature Of Solid Particles Flocculated suspension Deflocculated suspension
FACTORS TO BE CONSIDERED 1. Particle size control 2.Wetting of the particles wetting agents include: 1) Surfactants Disadvantages 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.
Surfactant classification • A. Ionic Anionic – e.g. sodium stearate, sodium laurylsulphate CH3(CH2)11 OSO3 Na Cationic – e.g. quaternary ammonium compounds, hexadecyltrimethyl ammonium bromide (cetrimide). • B. Nonionic – e.g. polyethylene oxide, Sorbitan mono-oleate (Span), Polyoxyethylene (CH3CH2O) Sorbitanmonooleate
Wetting Agents Include… (2. Hydrophilic Colloids e.g. acacia, tragacanth, alginates, gelatin, wool fat, egg yolk, bentonite, Veegum, Methylcellulose etc.
FACTORS TO BE CONSIDERED… 3. Sedimentation (hukum stokes) V= d2 (ρs ρo ) g 18 Sedimentation Parameters 1) Sedimentation volume (F) or height (H) For flocculated suspensions 2) Degree of flocculation (β)
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
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 derwaals 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 Movement 5. Electrokinetic Properties (zeta potensial) The zeta potential is defined as the difference in potential between the surface of the tightly bound layer (shear plane) and electro-neutral region of the solution.
FACTORS TO BE CONSIDERED…6. Deflocculation and flocculation
FACTORS TO BE CONSIDERED… 7.Viscosity Of Suspensions Advantages • 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, methylcellulose), clays(bentonite), sugars (glucose, fructose) • 2- Co-solvents Some solvents which themselves have high viscosityare used as co-solvents to enhance the viscosity of dispersion medium.
Pembuatansuspensi • Bagaimanasuspensi yang ideal ? • Alat: mikropulverisator Jet milling/mikronizer Spray drier Perhatikankarakteristikfaseterdisperse Perlukah wetting agent?
Suspension preparation • 1. presipitation method • pH change • Organic solvent • Double dissociation • 2. dispersion method
Quality Control of Suspensions 1. 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 measurement 5. Sedimentation volume 6. Redispersibility and Centrifugation tests 7. Rheological measurement 8. PH 9. Freeze-Thaw temperature cycling 10. Compatibility with container and cap liner