Process validation of Tablets and Lquids
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The document discusses the process validation of tablets and liquids, emphasizing the importance of establishing documented procedures that ensure product quality and consistency. It details the critical steps involved in tablet manufacturing, including mixing, granulation, drying, and coating, as well as the validation tests necessary for liquid formulations. Overall, it highlights the need for careful consideration of various parameters to enhance manufacturing efficiency and product safety.
![By A.R.T 35
• Sindhur N, Gouthami B, Madhuri L, Lavanya RV,
Krishnaveni N, Meyyanathan SN et al. The concept of
process validation in tablet manufacturing:Review. J
Pharm Res 2012;5(2): 1264-67.
• Lakshmana PS, Suriyaprakash TNK, Ruckmani K,
Thirumurugan R. Concepts of process validation in
solid dosage form [tablet] – an overview. SAJ Pharm
Pharmacol 2014; 1(1): 1-12.
• Sharma C, Rana AC, Bala R, Seth N. An overview of
industrial process validation of tablets. J Drug Delv
Therapeu 2013; 3(3): 175-183.
• Goyal A, Priyambada P.Process Validation of
pharmaceutical dosages form: a review. Biomed J Sci &
Tech Res 2017;1(5):1-9.](https://image.slidesharecdn.com/raheemppt-180406052455/85/Process-validation-of-Tablets-and-Lquids-35-320.jpg)
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Process validation of Tablets and Lquids
- 1. Process Validation of Tablets and Liquids Prepared By: Abdul Raheem. T 2nd Sem. M.pharm Bapuji Pharmacy College, Davangere 1By A.R.T
- 2. INTRODUCTION By A.R.T 2 PROCESS VALIDATION : Is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications & quality characteristics. WHY? • Application of process validation results in fewer product recalls & trouble shooting assignment in manufacturing processes. • To produce economically & technically sound products & their manufacturing process.
- 3. Newly developed manufacturing procedure Write & approve process procedure Write and approve validation protocol Equipment installation, trial runs & debugging Modifications (if necessary ) to meet process requirements Selection of process equipment Qualify equipment & personnel Schematic diagram for VALIDATION OF NEW PROCESS 3By A.R.T
- 4. . Modify procedure or equipment Validate process Impact is minor Impact is minor Impact is major Impact is major Implement monitoring and change control procedure Successful Unsuccessful Procedure change required Equipment change required By A.R.T 4
- 5. PROCESS VALIDATION OF SOLID DOSAGE FORM : TABLETS • A tablet is a most known solid pharmaceutical dosages form and comprises of a mixture of active substances and suitable excipients. • The knowledge of stepwise manufacturing process of any dosages form is a must for validating any process. • It helps in determining the critical areas which need special consideration in terms of causing problems during the process. By A.R.T 5
- 6. PROCESS EVALUATION AND SELECTION: Mixing Or Blending : Mixing is one of the most critical step and used at various stages during manufacturing of tablets. parameters to be considered in mixing process are: a) Mixing Or Blending Technique: - • The techniques like Diffusion (tumble), convection (planetary or high intensity), or pneumatic (fluid bed) are used to mix or blend materials. • The choice of technique depends on whether the drug and excipients are mixed for a direct compression formulation or for granulation. 6By A.R.T
- 7. b) Mixing or Blending Speed:- • Mixing the drug and excipient requires more intense mixing than adding the lubricant to the final blend. c) Mixing or blending time: - • It will be dependent on the mixing or blending technique and speed. d) Drug uniformity: - • The test for content uniformity is usually performed to estimate the uniformity of drug throughout the mix or blend. e) Excipient uniformity: - • Two key excipients are: 1- Lubricant . 2- colorants By A.R.T 7
- 8. By A.R.T 8 f) Equipment capacity/load: - • The bulk density of materials or granules will affect the capacity of the equipment. Undercharging or overcharging a blender can result in poor drug or tablet lubricant distribution. Wet Granulation : • Wet granulation parameters to be considered during development and validation are: a) Binder Addition: - • Adding the binder dry avoids the need to determine the optimal binder concentration and a separate manufacture for the binder solution.
- 9. By A.R.T 9 b) Binder Concentration: - • The optimal binder concentration will need to be determined for the formulation. If the binder is to be sprayed, the binder solution needs to be dilute enough so that it can be pumped through the spray nozzle. It should also be sufficiently concentrated to form granules without over wetting the materials. c) Amount of Binder Solution/Granulating Solvent:- • Too much binder or solvent solution will over wet the materials and prolong the drying time. The amount of binder solution is related to the binder concentration.
- 10. By A.R.T 10 d) Binder Solution/Granulating Solvent Addition Rate: • The rate or rate range at which the binder solution or granulating solvent can be added to the materials should be defined properly. e) Mixing Time: • Granulations that are not mixed long enough can form incomplete or weak granules. These granules may have poor flow and compression properties. On the other hand, over mixing the granulation can lead to harder granules and a lower dissolution rate.
- 11. By A.R.T 11 Wet Milling : Sometimes wet milling of granules is needed before subjecting it for drying to efficiently dry them. • Factors to consider are: a) Equipment Size And Capacity:- • The mill should be large enough to carry the entire batch within a reasonable time period to minimize manufacturing time and prevent the material from drying during this operation. b) Feed Rate:- • The feed rate of the wet granulation is interrelated to screen size, mill size and speed.
- 12. By A.R.T 12 c) Screen Size:- • The screen needs to be small enough to carry the material, but not too small to cause excessive heating of the mill, resulting in drying of the granulation. c) Mill Speed:- • The speed should be sufficient to efficiently reduce size of the material without straining the equipment. Drying: • The type of drying technique (e.g., tray, fluid bed, and microwave) required for the formulation needs to be determined and justified. The type of technique may be dependent on such factors as drug or formulation properties and equipment availability. Changing dryer techniques could affect such tablet properties as hardness, disintegration, dissolution, and stability.
- 13. By A.R.T 13 • The optimal moisture content of the dried granulation needs to be determined. i. High moisture content can result in a) Tablet picking or sticking to tablet punch surfaces and b) Poor chemical stability as a result of hydrolysis. ii. An over dried granulation could result in poor hardness and friability.
- 14. By A.R.T 14 Parameters to consider are: a) Inlet/Outlet Temperature: - • The inlet temperature is the temperature of the incoming air to the dryer, while the outlet temperature is the temperature leaving the unit. The inlet temperature is critical to the drying efficiency of the granulation and should be set high enough to maximize drying without affecting the chemical/physical stability of the granulation. The outlet temperature is an indicator of the granulation temperature and will increase toward the inlet temperature as the moisture content of the granulation decreases (evaporisation rate).
- 15. By A.R.T 15 b) Airflow:- • There should be sufficient airflow to ensure removal of moisture air from the wet granulation. Insufficient air flow could prolong drying and affect the chemical stability of the drug. c) Moisture Uniformity:- The moisture content could vary within the granulation d) Equipment Capability/Capacity:- The load that can be efficiently dried within the unit needs to be known.
- 16. By A.R.T 16 Dry Milling: • The milling operation will reduce the particle size of the dried granulation. The resultant particle size distribution will affect such material properties as flow, compressibility, disintegration, and dissolution. An optimal particle size/size distribution for the formulation will need to be determined. Factors to consider in dry milling are same as that of wet milling.
- 17. By A.R.T 17 Lubrication: Lubricants are added in order to remove the problem of sticking and picking in the tablets. a) Selection of Lubricant: - • Grade of the lubricant used and compatibility with other ingredients should be studied thoroughly and then the appropriate one must be chosen. b) Amount of Lubricant Added:- • How much lubricant is required? Too much lubricant will form hydrophobic layer on the tablet resulting in dissolution problems.
- 18. By A.R.T 18 c) Mixing Time: - • The optimum mixing time must be decided on proper trial of batches because if not mixed long enough, form problems like chipping, capping, etc. Tablet Compression: Compression is a critical step in the production of a tablet dosage form. As for the compressibility properties of the formulation, it should be examined on an instrumented tablet press. Factors to consider during compression are as follows: a) Tooling:- • The shape, size, and concavity of the tooling should be examined based on the formulation properties and commercial specifications.
- 19. By A.R.T 19 b) Compression speed: - • The formulation should be compressed at a wide range of compression speeds to determine the operating range of the compressor. c) Compression/ejection force: - • The compression profile for the tablet formulation will need to be determined to establish the optimal compression force to obtain the desired tablet hardness. The following in-process tests should be examined during the compression stage: I. Appearance II. Hardness III. Tablet weight IV. Friability V. Disintegration VI. Weight uniformity VII. Tablet Coating
- 20. By A.R.T 20 Tablet coating can occur by different techniques (e.g., sugar, film, or compression): • Film coating has been the most common technique over recent years and will be the focus of this section. Key areas to consider for tablet coating include the following: a. Tablet Properties:- • Tablet properties such as hardness and shape are important to obtain a good film-coated tablet. The tablet needs to be hard enough to withstand the coating process
- 21. By A.R.T 21 c) Coater Load:- • A large pan load can cause attrition of the tablets because of the overall tablet weight in the coater. • In the case of a fluid bed coater, there may not be sufficient airflow to fluidize the tablets. d) Pan Speed:- • This will be interrelated to other coating parameters, such as inlet temperature, spray rate and flow rate. e) Spray Guns:- • The number and types of guns should be determined in order to efficiently coat the tablets.
- 22. By A.R.T 22 f) Application/Spray Rate:- • The optimal application/spray rate should be determined. Spraying too fast will cause the tablets to become over wet, resulting in clumping of tablets and possible dissolution of the tablet surface. Spraying too slowly will cause the coating materials to dry prior to adhesion to the tablets. This will result a rough tablet surface and poor coating efficiency. g) Tablet Flow:- • The flow or movement of the tablets in the coater should be examined to ensure proper flow. The addition of baffles may be required to provide adequate movement of tablets for tablet coating.
- 23. By A.R.T 23 h) Inlet/Outlet Temperature and Airflow:- • These parameters are interrelated and should be set to ensure that the atomized coating solution reaches the tablet surface and then is quickly dried. i) Coating Solution:- • The concentration and viscosity of the coating solution will need to be determined. The solution will need to be sufficiently diluted in order to spray the material on the tablets.
- 24. By A.R.T 24 j) Coating Weight:- • A minimum and maximum coating weight should be established for the tablet. k) Residual Solvent Level:- • If solvents are used for tablet coating, the residual solvent level will need to be determined
- 25. By A.R.T 25 Summary table including steps, control variable and critical parameters to be checked in manufacturing of tablets.
- 26. By A.R.T 26 Process Validation Of Liquids • They are liquid preparation in which the drugs are dissolved, suspended or disperse in a suitable vehicle and generally several doses are contained in the bottle. • Types Of Oral Liquids 1. Syrups 2. Solutions 3. Suspension 4. Eye drops 5. Nasal drops etc
- 27. By A.R.T 27 Validation Includes Mainly Following Tests : a. Particle size and size distribution b. Particle shape or morphology c. Microbial count d. Rheology of solvent or vehicle e. PH of the solvent or vehicle
- 28. By A.R.T 28 Monitoring outputs : Some outputs to be monitored are a. Appearance b. pH c. Viscosity d. Specific gravity e. Microbial count f. Content uniformity g. Dissolution testing
- 29. By A.R.T 29 • Appearance of the final product indicates the signs of instability and degradation. For e.g. settling of solid particles in case of suspension and turbidity in case of emulsion. • Time for mixing or agitation and temperature of process can affect the appearance greatly.
- 30. By A.R.T 30 • Viscosity affects the settling rate of suspended particles in suspension and coalescence of globules of internal phase in emulsions and also in case of oral solutions it affects the overall appearance of the final product so it must be measured and validated properly. • A decrease in specific gravity of the product like suspensions indicates the presence of air within the structure of the formulation.
- 31. By A.R.T 31 • Microbial count for the final product is essential to validate because by performing microbial count we can select the preservative for the final product storage. • Content uniformity affects the dose uniformity in case of multi dose formulations and also affects the homogeneity of the drug within solvent system
- 32. By A.R.T 32 • PH of aqueous oral formulations should be taken at a given temperature and only after equilibrium has been reached in order to minimize the PH drift. • Microbial count for the final product is essential to validate because by performing microbial count we can select the preservative for the final product storage. There are specifications for each liquid oral product for the bio burden content.
- 33. By A.R.T 33 Summary table for validation of liquid dosages form
- 34. By A.R.T 34 References : • Ira RB, Robert AN, Pharmaceutical process validation. 2nd ed. Newyork: Marcel dekker; 1993. p.167-88. • Frederick JC, James PA, Validation of pharmaceutical processes. Newyork: Marcel dekker; 1999. p.703-20. • Nitish M, Saroj J, Satish S. Process validation of liquid lyophillized formulation: a review. J Adv Pharm Edu Res 2013; 3(2): 46-58. • Warkad PR, Joshi AM, Wagdarikar M, Kakad S, Nadendla S. Process validation of sterile product. Int J Pharmac Res Sch 2014; 3(3): 369-86.
- 35. By A.R.T 35 • Sindhur N, Gouthami B, Madhuri L, Lavanya RV, Krishnaveni N, Meyyanathan SN et al. The concept of process validation in tablet manufacturing:Review. J Pharm Res 2012;5(2): 1264-67. • Lakshmana PS, Suriyaprakash TNK, Ruckmani K, Thirumurugan R. Concepts of process validation in solid dosage form [tablet] – an overview. SAJ Pharm Pharmacol 2014; 1(1): 1-12. • Sharma C, Rana AC, Bala R, Seth N. An overview of industrial process validation of tablets. J Drug Delv Therapeu 2013; 3(3): 175-183. • Goyal A, Priyambada P.Process Validation of pharmaceutical dosages form: a review. Biomed J Sci & Tech Res 2017;1(5):1-9.
- 36. By A.R.T 36 THANK YOU…