The document discusses characterization techniques for pharmaceutical granules and compacts. It describes methods for analyzing granule particle size, shape, density, moisture content, flow properties, and friability. It also covers techniques for evaluating tablet properties like weight variation, disintegration, dissolution, hardness and thickness. The purpose is to ensure granules and tablets meet specifications for content uniformity, drug release and stability.

1. SVERI's COP,PANDHARPUR.

2. CHARACTERIZATION OF GRANULES & COMPACTS Presented By:- Phakatkar Vinayak Balasaheb Dept.of Pharmaceutics, M.Pharm I-Year. SVERI’s college of Pharmacy,Pandharpur. SVERI's COP,PANDHARPUR.

3. CONTENTS Introduction to granules. Characterization of granules. *Particle size & Shape determination. *Surface area. *Density & Packing. *Granule strength & Friability. * Flow properties. *Moisture content. *Percentage fines(% fines). SVERI's COP,PANDHARPUR.

4. CONTENTS Characterization of Compacts. *Weight of tablet. *Weight variation. *Disintegration test. *Dissolution test. *Friability. *Hardness. *Thickness. SVERI's COP,PANDHARPUR.

5. WHAT ARE GRANULES? Granules are the multiparticle entities in which primary powder particles are made to adhere to form larger particle. Granule size range- between 0.2 to 4 mm. In tablets & capsules granules are the intermediate product & having size of 0.2 to 0.5 mm. SVERI's COP,PANDHARPUR.

6. HOW GRANULES ARE PREPARED? Granules are prepared by two methods- 1)Dry granulation a)Slugging b)Roller Compaction 2)Wet granulation. SVERI's COP,PANDHARPUR.

7. NEED FOR GRANULATION Improve flow Densify materials Improve content uniformity Improve compression characteristics Control the rate of drug release Facilitate metering or volume dispensing Decrease dust generation and reduce employee exposure to drug product Improve the appearance of the tablet SVERI's COP,PANDHARPUR.

8. CHARACTERIZATION OF GRANULES 1). PARTICLE SIZE & SHAPE DETERMINATION :- Size affects the average weight of tablet, DT, wt.variation,friability,flowability & drying rate. The size & shape depends upon processing requirements & during granulation. The methods for determining size & shape are 1.Sieving 2.Sedimentation rate. 3.Microscopy(SEM) 4.By light scattering SVERI's COP,PANDHARPUR.

9. 2. SURFACE AREA It is not commonly used for granules but generally used for drug substances. If required particle size is measured & from this surface area is measured. Most method used is gas absorption & air permeability. SVERI's COP,PANDHARPUR.

10. Continued….. In gas absorption, gas is absorbed as monolayer on particles this is in term of calculated & converted to surface area. In air permeability method the rate of air permeates a bed of powder ,is used to calculate surface area of powder sample. SVERI's COP,PANDHARPUR.

11. 3. DENSITY Density may influence compressability,tablet porosity & dissolution. Dense hard granules may require higher load to produce cohesive compact to reduce free granules seen on the surface of tablets. ↑ compressibility ↑ DT, Dissolution, if DT is slower dissolution is indirectly hampered. Dense granules have less friability but cause a problem in releasing the drug. SVERI's COP,PANDHARPUR.

12. Methods to determine density:- 1. Pycnometer :- Liquids used-Mercury -Any solvent of low surface tension e.g. Benzene Liquids should not masks granules solubilies in it, & having property to penetrate the pores. Density is then determine from volume of intrusion fluid displaced in pycnometer by giving mass of granulation SVERI's COP,PANDHARPUR.

13. Continued….. Density (D)=M/ V p -V i V p -Total volume of pycnometer V i -vol. of intrusion fluid containing mass(M) req. to fill pycnometer. 2. Bulk Density :- Bulk density is given by equation ρ b = M/ V b More compressible bed of particulate less flowable powder or granules. If less dense compressible more flowable granules SVERI's COP,PANDHARPUR.

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17. GRANULE STRENGTH & FRIABILITY They are important because they affect:- 1.changes in particle size distributions of granulations 2.compressibility into cohesive tablets. Granule strength & friability are measured by:- 1.Compressive Strength 2.Using Friability measurements SVERI's COP,PANDHARPUR.

18. FLOW PROPERTIES It is an ability of the granule to flow from hopper to die cavity for tablet uniformity. Flow property of granule are not uniform we are not getting tablet of uniform size. Flow property of material results from many forces 1.Frictional force 2.Surface tension force 3.Mechanical force caused by interlocking of irregular shape particles 4.Electrostatic forces 5.Cohesive/ vander Waals forces SVERI's COP,PANDHARPUR.

19. Continued….. Forces also affect granule property such as particle size, particle size distribution, particle shape, surface texture, roughness & surface area. If particle size of powder is ≤ 150µm the magnitude of frictional & vander waals force predominate. When particle size↑ mechanical & physical properties become more important with packing properties. SVERI's COP,PANDHARPUR.

20. SVERI's COP,PANDHARPUR. Continued… Fig(1) Fixed height Fig(2) fixed base cone Fig (3) Tilting angle Fig (4) Rotating cylinder

21. Continued… In fig.(1) height is constant & powder is added through the hopper until powder reaches tip of funnel. In fig.(2) height is varied & base cone is fixed, powder is added until height reaches at max. In fig.(3) rectangle box is filled with powder & tipped until content begins to slide. In fig.(4) revolving cylinder with transparent end is made to revolve horizontally when half filled with powder. The max. angle that the plane of powder makes with horizontal surface on rotation is taken as the angle of repose. SVERI's COP,PANDHARPUR.

22. continued… (1),(2) & (3) gives static angle of repose. While (4) gives kinetic or dynamic angle of repose. SVERI's COP,PANDHARPUR.

23. HOPPER FLOW RATE It has been used as method of assessing flowability. It monitors the flow of material out of conical hopper on to a recording balance device. Instrumentation is simple & results are easy to interpret. SVERI's COP,PANDHARPUR.

24. MOISTURE CONTENT The amount of moisture present in the granule is called moisture content. Generally the granules contain 2% moisture. It is required for the binding of the powder or granules during compression in die cavity. Percentage of moisture is calculated by using “moisture Balance” or “IR Balance”. IR Balance consist of simple balance which is placed I to the casing in which the IR bulb is attached which produce heat inside the chamber SVERI's COP,PANDHARPUR.

25. SAROTORIOUS MA-100 MOISTURE ANALYZER VARIOUS INSTRUMENTS OF IR BALANCES SVERI's COP,PANDHARPUR.

26. continued… The small amount of sample taken from oven to measure moisture content & place in the moisture balance. Initial reading should be note down after that we are initiated the IR Bulb as IR bulb is initiated the moisture is removed from the granules via heating after that note down the reading. % of moisture is calculated by, % moisture content = Initial wt.- Final wt. SVERI's COP,PANDHARPUR.

27. continued… For e.g. suppose initial weight is 100 gm. after heating by IR Bulb weight is reduced to 94 gm,then 100-94=6 gm i.e. % moisture is 6%. In this way we calculate the moisture content. SVERI's COP,PANDHARPUR.

28. PERCENTAGE FINES ( % FINES ) % fines means amount of powder remain in the granule. Generally the amount is 15% of fines. It is necessary for the tablet compression because if we are using 100% granules then it is difficult to maintain hardness of tablet because they having free space in the die cavity after compression the tablet is crack due to air. % fine can be calculated by using sieve method. %fine should not be more than 15%. SVERI's COP,PANDHARPUR.

29. EVALUATION OF TABLETS It contains following parameters:- General appearance Weight variation Disintegration test Dissolution test Friability Hardness Thickness. SVERI's COP,PANDHARPUR.

30. GENERAL APPEARANCE The general appearance of a tablet is essential for consumer acceptance, for control lot-to-lot uniformity & tablet-to-tablet uniformity and for monitoring trouble-free manufacturing. It involves the measurement of a number of attributes such as tablet size, shape, color, presence or absence of an odour,taste,surface texture, consistency and identifying markings . SVERI's COP,PANDHARPUR.

31. WEIGHT VARIATION Weight variation is an official test . perform to check the weight variation in the tablet manufacture. For this test,20 tablets are weighed & total weight of 20 tablets are averaged. The average wt. of the tablet is considered for further calculation. The % wt. variation is given in the following table…… SVERI's COP,PANDHARPUR.

32. WEIGHT VARIATION TOLERANCES FOR UNCOATED TABLETS USP XX NF- STANDARDS To pass the weight variation test not more than 2 tablets should cross the limits. SVERI's COP,PANDHARPUR. Sr. No Average wt. of tablet(mg) Max. % difference allowed 1 130 or Less 10% 2 130-324 7.5% 3 More than 324 5%

33. DISINTEGRATION TEST Disintegration test is an official test . It is performed to identify the disintegration of tablet in particular time period. Disintegration test is not performed for controlled & sustained release tablets. SVERI's COP,PANDHARPUR.

34. VARIOUS INSTRUMENTS OF DISINTEGRATION TEST APPARATUS SVERI's COP,PANDHARPUR.

35. DISSOLUTION TEST Dissolution is an official test . Dissolution is performed to check the percentage release from the dosage forms.i.e.tablet. Tablet breaks down into small particles which offers a greater surface area to the dissolving media. Disintegration test does not give assurance that particles will release drug in solution at an appropriate rate, that’s why dissolution tests & it’s specifications developed for all tablet products. SVERI's COP,PANDHARPUR.

36. The rate of drug absorption Acidic drug moiety absorbed high in GI tract Determined by rate of drug dissolution from the tablet. SVERI's COP,PANDHARPUR.

37. Various instruments of Dissolution test apparatus SVERI's COP,PANDHARPUR.

38. FRIABILITY Friability is an unofficial test . It is performed using a friability test apparatus It has been done to check the intactness of the tablet before coating of tablet & packing. E.g. Roche type friabilator. SVERI's COP,PANDHARPUR.

39. Various instruments of Roche’s friabilator SVERI's COP,PANDHARPUR.

40. HARDNESS Hardness is an unofficial test . Hardness evaluation of the tablet is performed to check whether tablet maintain its integrity(intactness) during transportation & handling. Hardness is low tablet fails to maintain its integrity. Hardness is high problems of dissolution & disintegration may occur. Hardness is measured by:-1)Monsanto tester. 2)Pfizer. SVERI's COP,PANDHARPUR.

41. TYPES OF HARDNESS TESTER Electro mechanical tester-C53 Monsanto tester. Pfizer. Strong-Cobb tester(1950) Brinell Rockwell Vickers Knoop Digital tablet hardness tester SVERI's COP,PANDHARPUR.

42. Monsanto hardness tester Pfizer hardness tester SVERI's COP,PANDHARPUR.

43. THICKNESS Thickness is an unofficial test . Thickness of the tablet is inversely proportional to hardness i.e. increase in Hardness decrease the thickness & vice versa. Thickness of tablet is measured by vernier caliper. SVERI's COP,PANDHARPUR.

44. VARIOUS INSTRUMENTS OF VERNIER CALIPER SVERI's COP,PANDHARPUR.

45. REFERENCE Leon Lachman, The theory and practice of Industrial pharmacy,3 rd edition, Varghese publishing house, page no.67-68,77-78,315-317,296-303. Indian Pharmacopoeia-2007,Govt.Of India ministry of health & family welfare,5 th edition, page no.177,179. www.pharmainfo.net www.blog.cencophysics.com, www.indiamart.com . www.alibaba.com , www.galaxylabequip.tradeindia.com . www.starlabs.co.in , www.magicardindia.com . www.hellotrade.com , www.coslabindia.com. www.tradeindia.com , www.labscientificequipments.com . SVERI's COP,PANDHARPUR.

46. QUESTIONS ASKED IN PREVIOUS EXAMS 1)Write note on characterization of granules? (10 marks)(2005)(2007) 2)Write a note on characterization of solid compact? (10 marks)(2008) 3)Explain various means adopted for characterization of granule? (10 marks)(2009) 4) Write various methods of granule characterization? (5 marks)(2010) SVERI's COP,PANDHARPUR.

47. THANK YOU SVERI's COP,PANDHARPUR.