Ipqc tests for suspension & emulsion ppt
- 1. IN PROCESS QUALITY CONTROL OF SUSPENSIONS AND EMULSIONS QUALITY CONTROL AND QUALITY ASSURANCE 1
- 2. CONTENTS IN PROCESS QUALITY CONTROL PURPOSE IMPORTANCE USFDA -CGMP GUIDELINES IPQC OF SUSPENSIONS IPQC OF EMULSIONS CONCLUSION REFERENCES
- 3. IN PROCESS QUALITY CONTROL ▪ IPQC stands for IN PROCESS QUALITY CONTROL . ▪ These are checks that are carried out before the manufacturing process is completed. ▪ IPQC means controlling the procedures involved in manufacturing of the dosage form starting from raw material purchase to dispatch of the quality product in ideal packaging. ▪ Evaluates & monitors products flaws for quality. ▪ Activity performed between QA/QC . 3
- 4. PURPOSE ▪ To ensure detectable and significant human errors. ▪ To minimize inter batch and intra batch variability. ▪ To ensure quality of final product. ▪ To ensure continuous monitoring of process variables which are going to affect the quality of product. 4
- 5. IMPORTANCE ▪ Provide accurate, specific and definite description of the procedure to be employed. ▪ It is a planned system to identify the materials, equipment, processes, and operators. ▪ It is to detect the errors if and when it does occurs. ▪ Is to enforce the flow of manufacturing and packing operation according to established rules and practice. 5
- 6. USFDA-CGMP GUIDELINES ▪ To assure batch uniformity and integrity of drug product, written procedures shall be established and followed. ▪ Valid in process specification for such characteristics shall be constituent with drug product. ▪ In process material shall be tested for identity, strength, quality and purity. 6
- 7. SUSPENSIONS ▪ It is a biphasic type of system. ▪ Pharmaceutical suspension can be defined as class of dispersed system in which a finely divided solid is dispersed uniformly in a liquid dispersion medium. ▪ The insoluble solid may have size range from 10 to 1000 µm. 7
- 8. IPQC TESTS OF SUSPENSIONS ▪ Appearance ▪ Photo microscopic examination ▪ Colour, odour and taste ▪ Density ▪ pH value ▪ Clarity testing ▪ Pourability ▪ Viscosity ▪ Rheology 8
- 9. ▪ Zeta potential measurement ▪ Drug content uniformity ▪ Particle size measurement ▪ Sedimentation rate and sedimentation volume ▪ Redispersibility ▪ Potency test ▪ Preservative effectiveness ▪ Compatibility with primary container-closure system 9
- 10. APPEARANCE ▪ It must appear uniform and elegant . ▪ Particles of suspension should be well distributed. ▪ No hard cake formation of particles 10
- 11. PHOTO MICROSCOPIC EXAMINATION ▪ The suspension is examined for particles size distribution and crystal habit under the microscope with camera. ▪ It is mainly used for distinguish between flocculated and non- flocculated particles and to determine changes in the physical properties. 11
- 12. COLOUR, ODOUR AND TASTE ▪ Features like these especially important in orally administered suspensions. Variation in colour often indicates poor distribution and/or differences in particle size. Variation in taste, especially of active constituents can often be attributed to changes in particle size, crystal habit and subsequent particle dissolution. ▪ Change in colour, odour and taste can also indicates chemical instability. 12
- 13. DENSITY ▪ Density of the suspension is an important parameter. Decrease in density indicates the presence of entrapped air with in the structure of the suspension. ▪ Hydrometers are used to measure the density 13
- 14. PH VALUE ▪ pH of the phases of suspension also contribute to stability and characteristics of formulations. So pH of the different vehicles, phases of suspension before mixing and after mixing are monitored and recorded time to time to ensure optimum pH environment being maintained. ▪ Different types of methods are used in the measurement of pH. a)Dip a piece of pH paper into the sample. b)pH meter 14
- 15. CLARITY TESTING ▪ Clarity testing is carried out to check the particulate matter in the sample. 15
- 16. POURABILITY ▪ This test is carried out on the phases of suspension after mixing to ensure that the final preparation is pourable and will not cause any problem during filling and during handling by patient 16
- 17. VISCOSITY ▪ Stability of a suspension is solely dependant on the sedimentation rate of dispersed phase which is dependant on the viscosity of the dispersion medium. So this test is carried out to ensure optimum viscosity of the medium so a stable, redispersible suspension can be formed. ▪ The viscosity of the dispersion medium is measured before mixing with dispersed phase and also viscosity after mixing is determined using Brook field viscometer. ▪ The calculated values are compared with standard values and if any difference is found necessary corrective action is taken to get optimized viscosity. 17
- 18. VISCOSITY MEASUREMENT ▪ The viscosity can be measured by; a)cup and bob viscometer b)cone and plate viscometer 18
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- 20. PARTICLE SIZE ▪ As the particle size is reduced they tend to exhibit Brownian movement. ▪ So it is necessary to choose the optimum particle size for maximum stability. 20
- 21. DRUG CONTENT UNIFORMITY ▪ For proper dosing of the dosage form it is necessary that the active ingredient is uniformly distributed throughout the dosage form.so samples are withdrawn from the dispersed phase after micronization and after mixing with dispersion medium, assayed to find out degree of homogeneity. ▪ If any discrepancy is found out it is suitably corrected by monitoring the mixing step to ensure a reliable dosage formulation. 21
- 22. EMULSIONS ▪ It is also a type of biphasic system. ▪ Emulsions can be defined as a dispersion of at least two immiscible liquids, one of which is dispersed as droplets in the other liquid, and stabilized by an emulsifying agent. ▪ The globule diameter may range from 0.1 to 100 µm. ▪ Emulsions are thermodynamically unstable systems. 22
- 23. IPQC TESTS FOR EMULSIONS ▪ Appearance ▪ Clarity testing ▪ pH value ▪ Viscosity ▪ Rheology ▪ Drug content uniformity ▪ Particle size distribution ▪ Densities of phases ▪ Phase volume ratio ▪ Charge of electrical double layer 23
- 24. ▪ Physical properties of interface ▪ Temperature fluctuations ▪ Quality control of water ▪ Breaking or cracking ▪ Compatibility of product with container-closure system 24
- 25. CREAMING ▪ Creaming is the concentration of globules at the top or bottom of the emulsion. ▪ The floccules move either upward or downward leading to creaming. ▪ It can be observed by a difference in colour shade of the layers. ▪ Creaming is influenced by a)globule size b)viscosity of the dispersion medium c)differences in the densities of dispersed phase and dispersion medium 25
- 26. COALESCENCE ▪ Coalescence is followed by creaming stage. ▪ In this process the emulsifier film around the globules is destroyed to a certain extent. ▪ This step can be recognised by increased globule size and reduced number of globules. ▪ Coalescence is observed due to a)insufficient amount of the emulsifying agent b)altered partitioning of the emulsifying agent c)incompatibilities between emulsifying agents 26
- 27. BREAKING ▪ This is indicated by complete separation of oil and aqueous phases. ▪ It is an irreversible process that is simple mixing fails to resuspend the globules into an uniform emulsion. ▪ In breaking the protective sheath around the globules is completely destroyed. 27
- 28. PHASE INVERSION ▪ This involves the change of emulsion type from o/w to w/o or vice versa. ▪ When we intend to prepare one type of emulsion say o/w and if the final emulsion turns out to be w/o it can be termed as a sign of instability 28
- 29. Fig; instability in emulsion29
- 30. PARTICLE SIZE DISTRIBUTION ▪ Globules of uniform size impart maximum stability. ▪ In such emulsions globules pack loosely and globule to globule contact is less. ▪ Globule distribution is effected by viscosity, phase volume ratio, density of phases etc. ▪ An optimum degree of size distribution range should be chosen to achieve maximum physical stability. 30
- 31. CHARGE OF ELECTRICAL DOUBLE LAYER ▪ When ionic type of emulsifier is employed, the electrical double layer(interface between oil and water)possesses charge. ▪ The repulsive forces, due to like charges on the surface of the globules prevent the flocculation of globules. 31
- 32. PHASE INVERSION ▪ The emulsion is checked for phase inversion. ▪ Phase inversion means a change of emulsion type from o/w to w/o or vice versa. 32
- 33. Fig; phase inversion in w/o emulsion. 33
- 34. TEMPERATURE FLUCTUATIONS ▪ Elevated temperatures alter the partition characteristics of the emulsifiers and preservatives results in instability. ▪ Temperature also enhances the chemical degradation of drugs and other ingredients. ▪ At lower temperature the aqueous phase may contain ice crystals which rupture the interfacial film and break the emulsion. ▪ So care should be taken to prevent temperature fluctuations during manufacture and storage. 34
- 35. CONCLUSION ▪ IPQC tests are carried out during the manufacturing to ensure stable, safe and quality product. 35
- 36. REFERENCES 1. Tangri P , Mamgain P, Shaffi , ML Verma , Lakshmayya, IN PROCESS QUALITY CONTROL: A REVIEW, Int. J of Industrial Pharmacy and Bio Sciences 2014. 2. Leon lachman, Herbert liberman, Joseph L. kanig , The theory and practice of industrial pharmacy , 3rd Edition , Indian Edition, Varghese publishing house , Mumbai . 36
- 37. 37 THANK YOU