5. Biphasic Liquid Dosage Forms-Suspension - Copy.pptx

Pharmaceutics II

1. Pharmaceutics II (0811) Chapter – 6. Prof. Vaishali P. Argade Lecturer in PRES, Institute of Pharmacy, Loni Email:[email protected] Mobile:[phone] Biphasic Liquid Dosage Form Suspension

2. Learning Outcomes After completion of this chapter, you will be able to: Define the Suspension as biphasic liquid dosage form. Understand q ualities & need of good suspension 3. Understand the Classification, formulation, container & storage condition required for biphasic liquid dosage forms Suspension.

3. Introduction Suspensions are heterogeneous biphasic systems consisting of two phases . The C ontinuous/External phase /Dispersion medium is generally a liquid or semisolid. The Discontinuous / Internal phase/ Dispersed phase is made up of particulate matter that is essentially insoluble, but dispersed throughout the continuous phase.

4. Definition: Suspension are heterogeneous, biphasic, thermodynamically unstable liquid system in which insoluble solid particles (Discontinuous/dispersed /Internal phase) is uniformly distributed in liquid phase (continuous/external phase /Dispersion medium). The range of solid particles in suspension from 0.5 to 5.0 micron. Suspensions are used in orally, parentally and also externally.

5. Why suspension?  If patient has a difficulty of swallowing solid dosage forms (a need for oral liquid dosage form). Faster rate of dissolution and oral absorption than solid dosage forms, yet slower than solutions. Drugs that have very low solubility are usefully formulated as suspensions. Drugs that have an unpleasant taste in their soluble forms e.g., chloramphenicol Suspension should settle slowly & should be readily redispersed upon shaking of the container. The suspension is pourable. Chemically inert Suspended particle should not form a hard cake. Particles in suspension are small and relatively uniform in size. so that the product is free from a gritty particle Qualities of good suspension

6. Classification of Suspension Oral suspension: Given oral route Contain flavoring agent & sweetening agent Ex : Antibiotic , paracetamol suspension 2. Parenteral suspension Given by parenteral route Sterilize Easily pass through the needle of syringe 3. Ophthalmic suspension Commonly not use. Use if drug is insoluble in solvent. Sterilize Isotonic Proper viscosity 4. Suspension for external use Use as protective Ex. Lotion, Inhalation, ear drop.

7. Types of suspension: Sr. No. Flocculated Suspension Sr. No. Deflocculated / Non flocculated Suspension 1 Particle form loose aggregate & forms network like structure. 1 particle are exist as separate entities . 2 Rate of sedimentation is high. 2 Rate of sedimentation is low. 3 Sediment is rapidly form 3 Sediment is slowly form 4 Sediment is loosely packed & does not form a hard cake 4 Sediment is tightly packed & form the cake 5 When shaking it can be redisperse easily & reform the original suspension. 5 When shaking it can not be redisperse easily 6 floccules remaining sticking to the side of the bottle. 6 floccules does not sticking to the side of the bottle. 7 Supernatant liquid is clear 7 Supernatant liquid is not clear 8 They does not have pleasing appearance 8 They have pleasing appearance

8. Drug: Stable, Good wettability Vehicle: Purified water Wetting agent : Some insoluble drug do not wet easily with vehicle. The lumps of drug float on the surface of the liquid until the layer of air is displaced completely. The use of wetting agent allows removing this air from the surface and to easy penetration of the vehicle into the pores. e.g . Alcohol in tragacanth mucilage, glycerin or glycol in sodium alginate etc . Excessive amount wetting agent lead to foaming or undesirable taste or odour to suspension. Formulation of suspension:

9. 4. Suspending Agent/ thickening agent : They increases the viscosity of the continuous phase so that the particles remain suspended for a sufficient long time . These structured vehicles entrapped the particle and reduces the sedimentation of particles. They form protective coat over an individual particle. Classification of suspending agent: 1. Natural Polysaccharide   a. Acacia: Form protective coat over individual particle. Combine with tragacanth Need preservatives Contain peroxidase enzyme

10. b. Tragacanth : Better thickening agent than acacia Free from peroxidase enzyme Needs preservatives 6 % mucilage is used c. Starch: 2.5% solution used d. sodium alginate e. Clays Ex. Bentonite : 5%, Hectorite , veggum . 2. Semisynthetic suspending agent: a. Methyl cellulose Soluble in cold water & insoluble in hot water. Non ionic & stable pH 3-11. resistant to bacterial attack use in 0.5 – 2% conc.

11. b . Sodium carboxy ethyl cellulose Soluble in cold & hot water It is anionic & stable at 5 to 10 pH 0.25 – 1% concentration. c . Hydroxy ethyl cellulose d . Microcrystalline cellulose 3. Synthetic Suspending Agent Carbomer Carboxy vinyl polymer Water soluble& stable at pH 6-11 Use in 0.1-0.4% conc. b. Colloidal silicondioxide White non gritty powder Use in 1.5-4& conc.

12. 5 . Flocculating agent or surfactant : They reduces the interfacial tension.  They act like, surfactant with negative charge are adsorbed on the particles, minimize flocculation in the presence of positive ions because of natural repulsion of like charge. 6. Preservative : Ex. Benzoic acid, Methyl paraben , Propyl paraben , Sodium benzoate 7. Organoleptic additives: Coloring, flavoring, sweetening agent

13. Method of Dispensing of Suspension Suspension Containing Diffusible Solid Suspension Containing Indiffusible Solid Suspension Containing Precipitate Forming Liquids Suspension Produce by Chemical Reaction.

14. 1. Suspension containing diffusible solid Diffusible solid are insoluble in water but get evenly distributed on shaking throughout the liquid for sufficient long time . Eg : Magnessium carbonate, Calcium carbonate, magnesium trisilicate , light kaolin, rhubarb powder etc. Follow method A for ppt yielding interaction Rx Bismuth carbonate 1g Sodium bicarbonate 0.7g Tincture belladonna 0.4ml Water q.s . 30ml Make a mixture Label: SHAKE WELL BEFORE USE

15. 2. Suspension containing indiffusible solid Indiffusible Soilds are insoluble in water but do not get evenly distributed on shaking throughout the liquid for sufficient long time, So Suspending agents are incorporated . Ex. Chalk powder, Acetyl salicylic Acid, Phenacetin , Zinc Oxide, calamine, Hydrocartisone & Calamine etc . Follow method B for ppt yielding interaction Rx Bismuth carbonate 1g Prepared chalk 1g Kaolin 4g ticture catechu 2ml Water q.s . 30ml Make a mixture Label: SHAKE WELL BEFORE USE

16. 3. Suspension containing precipitate forming liquids Some liquid preparation may precipitated on addition of water. Ex. Comp. benzoin tincture, myrrh tincture, tolu tincture When tincture containing resinous matter is added in water , resins agglomerated forming in diffusible precipitate.so suspending agents are added. Example. Rx Compound benzoin tincture Benzoin tincture Myrrh tincture Tolu tincture

17. 4. Suspension produce by chemical reaction . If highly diluted samples are mixed together they form very fine ppt. that can be easily redisperse by shaking is form diffusible ppt. Hence no needs to add suspending agent. Rx Sulphorated potassh 5g Zinc sulphat 5g Conc. Camphor water 2.5 ml Water q.s . 100ml Make a mixture Label: SHAKE WELL BEFORE USE

18. Stability of Suspension The flocculated suspension are more stable because, they form loose cake and can be redispersed easily after shaking. The non flocculated suspension can be made stable by decreasing the particle size of dispersed phase or by increasing the viscosity of vehicle. Evaluation of stability of suspension  T he following methods are used for evaluating the physical stability of the suspension Sedimentation method Rheological method Electrokinetic method Micromeritic method

19.   1. Sedimentation method I n this method sedimentation volume is determine. Sedimentation volume (F) is the ratio of ultimate height and initial height. F= Hu /Ho = ultimate height / initial height The ultimate height is determined by keeping the measured  volume of the suspension in graduated cylinder in an undisturbed position for a definite period and sedimentation volume can be determined. 2. Rheological method The viscosity of suspension is studied at different time interval by using viscometer.

20. 3. Electro kinetic method The determination of surface electric charge or Zeta potential of suspension is important in stability . Zeta potential produced more stable suspension that can be calculated by electrophoretic method . 4. Micromeritic method The stability depends on particle size.   The size of particle may grow and form lumps or cake so this can be studied by microscopy and coulter counter method.

21. Containers & Storage : It should be packed in wide mouth bottle to permit easy removal. Suspension should be store in cool place. Do not freez .

22. Questions????? Sr.no. Questions 1 Define the term suspension. Write the qualities of an ideal suspension? 2 Differentiate between flocculated and deflocculated suspension. 3 Write a note on stability of suspension. 4 Differentiate between emulsion & suspension. 5 Give an brief account on formulation of suspension.

23. References Pharmaceutics II By R. M. Mehata , Vallabh Prakashan , Third edition, 2010. Pharmaceutics-2 (Dispensing Pharmacy) By Dr. G.K.Jani , B.S.shah Prakashan , 10 th edition, 2011-2012. Introduction to Pharmaceutics-II By A.K.Gupta & S.S. Bajaj, CBS Publishers & Distributors, 4 th edition,2000. MSBTE board Annual question paper, https ://msbte.org.in 24 By- Ms. Argade V.P.

24. Thank you………..