SUSPENSIONS

1. SUSPENSIONS

2. CONTENTS • Definition. • Classification. • Advantages &disadvantages. • Applications. • Theoretic consideration ofsuspensions. • Sedimentation • Brownianmovement • Electrokineticproperties

3. Formulation ofsuspensions • Packing ofsuspensions • Storagerequirement &labelling • Evaluation ofsuspension

5. DISPERSESYSTEM • The term "Disperse System" refers to a system in which one substance (The Dispersed Phase) is distributed, in discrete units, throughout a second substance (the continuous Phase ). • Each phase can exist in solid, liquid, or gaseous state. • Suspensions are heterogenous system consisting of 2 phases.

6. A solidinliquiddispersionin which theparticles are of colloidalsize. DISPERSESYSTEM DISPERSEDMEDIUM DISPERSEDPHASE oAqueous oilyliquid oInsolublesolid

7. Definition • A Pharmaceutical suspensionis a coarse dispersion in whichinternal phase (therapeutically active ingredient)is dispersed uniformly throughout the externalphase.

8. The internal phase consisting of insoluble solid particles having a range of size(0.5 to 5 microns) which is maintained uniformly through out the suspendingvehicle with aid of single or combination of suspendingagent. • The external phase (suspending medium) isgenerally aqueous in some instance, may be an organic or oily liquid for non oraluse.

9. The reasons for the formulation of apharmaceutical suspension: -- when the drug is insoluble in the deliveryvehicle. –To mask the bitter taste of thedrug. –To increase drugstability. –To achieve controlled/sustained drugrelease.

10. SOME PHARMACEUTICALSUSPENSIONS • 1. Antacid oralsuspensions • 2. Antibacterial oralsuspension • 3. Dry powders for oral suspension(antibiotic) • 4. Analgesic oralsuspension • 5. Anthelmentic oralsuspension • 6. Anticonvulsant oralsuspension • 7. Antifungal oralsuspension

11. Classification • Based On GeneralClasses • Oralsuspension • eg: Paracetamol suspension antacids, TetracyclineHCl. • Externally appliedsuspension eg :Calaminelotion. • Parenteralsuspension • eg: Procaine penicillinG Insulin ZincSuspension

12. Based on Proportion of SolidParticles • Dilute suspension (2 to10%w/vsolid) • Eg: cortisone acetate, predinisoloneacetate • Concentrated suspension (50%w/vsolid) Eg: zinc oxidesuspension

13. Based on Electrokinetic Nature of SolidParticles • Flocculatedsuspension • Deflocculatedsuspension

14. Based on Size of SolidParticles • Colloidal suspensions (< 1micron) • -Suspensions having particle sizes of suspended solid lessthan about 1micron in size are called as colloidalsuspensions.

15. Coarse suspensions (>1micron) • Suspensions having particle sizes of greater thanabout 1micron in diameter are called as coarsesuspensions. • Coarse dispersion Bariumsulphate • Nano suspensions (10ng) • Suspensions are the biphasic colloidal dispersionsof nanosized drug particles stabilized bysurfactants. • Size of the drug particles is less than1mm.

16. Advantages AndDisadvantages • Advantages • .Suspension can improve chemical stability of certaindrug. • E.g. Procaine penicillinG. • Drug in suspension exhibits higher rate of bioavailability than other dosageforms. • Solution > Suspension > Capsule > Compressed Tablet > Coatedtablet • Duration and onset of action can becontrolled. • E.g. Protamine Zinc-Insulinsuspension. • Suspension can mask the unpleasant/ bitter taste ofdrug. • E.g.Chloramphenicol

17. Disadvantages • Physical stability , sedimentation and compaction cancauses problems. • It is bulky sufficient care must be taken during handlingand transport. • It is difficult toformulate. • Uniform and accurate dose can not be achieved unless suspensionare packed in unit dosage form.

18. Applications • Suspension is usually applicable for drug which is insoluble (or) poorlysoluble. • E.g. Prednisolonesuspension • To prevent degradation of drug or to improve stability of drug. • E.g. Oxy tetracyclinesuspension • To mask the taste of bitter of unpleasant drug. • E.g. Chloramphenicol palmitatesuspension • Suspension of drug can be formulated for topicalapplication • e.g. Calaminelotion

19. Suspension can be formulated for parentral application in orderto • control rate of drug absorption. E.g. penicillinprocaine • Vaccines as a immunizing agent are often formulated assuspension. • E.g. Choleravaccine • X-ray contrast agent are also formulated as suspension. eg: Barium sulphate for examination of alimentarytract.

20. Features Desired In PharmaceuticalSuspensions • The suspended particles should not settle rapidly and sediment produced, must be easily re-suspended by the use of moderate amount ofshaking. • It should be easy to pour yet not watery and nogrittiness. • It should have pleasing odour , colour andpalatability. • Goodsyringeability. • It should be physically,chemically and microbiologicallystable. • Parenteral /Ophthalmic suspension should besterilizable.

21. THEORITIC CONSIDERATION OFSUSPENSIONS • A knowledge of the theoretic considerations pertaining to suspension s technology ultimately help formulator to select ingredients thatare • Appropriateforsuspension preparation • That available formilling • Mixing equipment

22. Some theoretic considerations are: • Particle sizecontrol. • Wetting • Sedimentation • Brownianmovement • Electokinetic • Aggregation

23. Particle sizecontrol: • - Particle size of any suspension is critical and must be reduced within the range. • -Too large or too small particles should beavoided. • Larger particleswill: • settle faster at the bottom of thecontainer • particles > 5 um impart a gritty texture to the product and also cause irritation if injected or instilled to theeye • particles > 25 um may block theneedle • -Too fine particles will easily form hard cake at the bottom of thecontainer.

24. Wetting of theparticles • Hydrophilic materials (talc, ZnO, Mg2CO3) areeasily • wetted by water while hydrophobic materials (sulphur ,charcoal) are not due to the layer of adsorbed air on thesurface. • Thus, the particles, even high density, float on the surface ofthe liquid until the layer of air is displacedcompletely. • The use of wetting agent allows removing this airfrom • the surface and to easy penetration of the vehicle into thepores. • However hydrophobic materials are easily wettedby non-polarliquids.

25. THEORY OFSEDIMENTATION SEDIMENTATION: Sedimentation means settlingofparticle (or) flocculesoccur under gravitational force in liquid dosageform.

26. 2.1. Velocity of sedimentation expressed by Stoke’s equation Where, d = Diameterofparticle r = radius ofparticle vsed.= sedimentation velocity in cm /sec ρ s= density of dispersephase ρ o= density of dispersemedia g = acceleration due togravity ηo = viscosity of disperse medium in poise

27. Limitation Of Stoke’s Equation. • Stoke's equation applies onlyto: • Spherical particles in a very dilute suspension (0.5 to 2 gmper • 100 ml) • Particles which freely settle without collision. • Particles with no physical or chemicalattraction.

28. Sedimentation volume (F) or height (H)for flocculatedsuspensions: SedimentationParameters Definition: Sedimentation volume is a ratio of the ultimate volumeof sediment (Vu) to the original volume of sediment (VO) beforesettling. F = V u /VO Where, Vu = final or ultimate volume of sediment VO = original volume of suspension beforesettling

29. F has values ranging from less than one to greater thanone. When F< 1 Vu <Vo WhenF=1 Vu = Vo The system is in flocculated equilibrium and show noclear supernatant onstanding. When F> 1 Vu >Vo Sediment volume is greater than the original volumedue to the network of flocs formed in the suspension and so loose and fluffysediment

30. The sedimentation volume gives only a qualitative account of flocculation. Fig : Suspensions quantified by sedimentation volume(f)

31. Degree of flocculation(β) It is the ratio of the sedimentation volume of the flocculated suspension ,F , to the sedimentationvolume of the deflocculated suspension,F∞ • ß = F /F∞ • (Vu/Vo) flocculated ß =-------------------- • (Vu/Vo)deflocculated • The minimum value of ß is 1,when flocculated suspension sedimentation volume is equal to the sedimentation volume of deflocculatedsuspension.

32. . 2.Brownian Movement (Drunkenwalk) • Brownian movement of particle prevents sedimentation by keeping the dispersed material in randommotion. • Brownian movement depends on the density of dispersed phase and the density and viscosity of the dispersemedium. • The kinetic bombardment of the particles by the molecules of the suspending medium will keep the particles suspending, providedthat their size is below critical radius(r).

33. Brownian movement can beobserved, • If particle size is about 2 to5mm, • Whenthedensityofparticle&viscosityofmedium are favorable.

34. Brownian motion is given byequation: Where, R = gasconstant T = temp. in degreeKelvin N = Avogadro’s number η = viscosity ofmedium t =time r = radius of theparticle

35. 3.Electro kineticProperties ZetaPotential The zeta potential is defined as the difference in potential betweenthe surface of the tightly bound layer (shear plane) and electro-neutral region of thesolution.

36. As the potential drops off rapibdly atfirst,followed moregradual decrease as the distance from the surfaceincreases. • This is because the counter ions close to the surface acts asa screen that reduce the electrostatic attraction betweenthe • charged surface and those counter ions further away fromthe surface.

37. Zeta potential has practical application in stability ofsystems • containing dispersed particles. • Since this potential, rather than the Nernst potential, governsthe degree of repulsion between the adjacent, similarly charged, dispersedparticles. • If the zeta potential is reduced below a certain value , theattractive forces exceed the repulsive forces, and the particles cometogether. • This phenomenon is known asflocculation.

38. The flocculated suspension is one in which zeta potentialof particle is -20 to +20mV. • Thus the phenomenon of flocculation and de flocculation depends on zeta potential carried byparticles.

39. Deflocculation andflocculation • FlocculatedSuspensions • In flocculated suspension, formed flocs (loose aggregates) willcause increase in sedimentation rate due to increase in size of sedimenting particles. • Hence, flocculated suspensions sediment morerapidly. • Here, the sedimentation depends not only on the size of the flocs but also on the porosity offlocs.

40. Deflocculatedsuspensions • In deflocculated suspension, individual particlesare settling. • Rate of sedimentation is slow , which prevents entrapping of liquid medium which makes it difficultto re-disperse byagitation. • This phenomenon called ‘caking’ or‘claying’. • In deflocculated suspension larger particles settlefast and smaller remain in supernatant liquid so supernatant appears cloudy.

41. FORMULATION OFSUSPENSIONS • The formulation ofa suspension depends on whetherthe suspension is flocculated ordeflocculated. • Three approaches are commonlyinvolved • Use of structuredvehicle • Use of controlledflocculation • Combination of both of themethods

42. Flow chart of formulation ofsuspension

43. Structuredvehicle • Structured vehicles called also thickening orsuspending agents. • They are aqueous solutions of natural and syntheticgums. • These are used to increase the viscosity of thesuspension. • It is applicable only to deflocculatedsuspensions. • E.g. methyl cellulose, sodium carboxy methylcellulose, acacia, gelatin andtragacanth.

44. These structured vehicles entrapped the particleand reduces the sedimentation ofparticles. • Thus, the use of deflocculated particles in a structurevehicle may form solid hard cake upon longstorage.

45. Too high viscosity is not desirableas: • It causes difficulty in pouring andadministration. • It may affect drug absorption since they adsorb onthe surface of particle and suppress the dissolutionrate. • Structured vehicle is not useful for Parenteral suspension because they may create problem in syringeability due tohigh viscosity.

46. Controlledflocculation Controlled flocculation of particles is obtained by adding flocculating agents, whichare: electrolytes surfactants polymers

47. Flocculation in structuredvehicles • Sometimes suspending agents can be addedto flocculated suspension to retardsedimentation • Examples of these agentsare: • Carboxymethylcellulose(CMC), • Carbopol934, • Veegum, and bentonite

48. INGREDIENTSFOR FORMULATION OFSUSPENSIONS

49. .

50. Suspendingagents • Suspending agent are also known as hydrophilic colloids which form colloidal dispersion with Water and increasethe viscosity of the continousphase. • Suspending agent form film around particle anddecrease interparticleattraction. • Most suspending agents perform twofunctions • i.e. besides acting as a suspendingagent • they also imparts viscosity to thesolution.