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QUALITY CONTROL TESTS TABLETS GRANULES / POWDERS & IPQC TEST Figure 27. Properties of Granules/Powders. hould be flowable S ○ QC Test: Angle of Repose Should compressible ○...
QUALITY CONTROL TESTS TABLETS GRANULES / POWDERS & IPQC TEST Figure 27. Properties of Granules/Powders. hould be flowable S ○ QC Test: Angle of Repose Should compressible ○ QC Test: Hausner Ratio and Compressibility Ratio ○ QC tests found in USP chapter for powder flow IPQCisperformedonthegranulesandtabletsatthestart of the compression process ○ granules - test it to see if it is appropriate for compression Figure 29. Machine for Bulk Density ○ requirement:beforetableting,thegranulesshouldbe flowable and compressible ethod 1: Graduated cylinder M compressible-thetabletneedstobeacompact ○ weigh a specific amount of material, and place it solid mass inside Method 2: Volumeter IPQC TESTS ○ has a baffle system, and can show the flowability Particle Size Distribution - (786) Bulk Density and Tapped Density - (616) ○ this is where the data for Hausner ratio and compressibility index is based on Powder Flow - (1174) Moisture Content ○ product = solid = should be dry ○ moisture should be minimal ○ can affect powder flow ○ can stick to the diff parts of the equipment ARTICLE SIZE DISTRIBUTION P Analytical Sieving ○ For particles >75um ○ Not for oily or cohesive particles Methods Figure 29. Volumeter Machine Illustration ○ mechanical sieving ○ air entrainment (air jet, sonic sifter) ethod 3: Vessel M Use of air current ○ volume is specified Endpoint determination: ○ sample receiving cup - has specificdimensionsand ○ Weight change in any test sieve ≤ 5% volume ○ If less than 5% of the total specimen weight is presentinasieve,weightchangeinanytestsieve≤ 20% ○ If more than 50% of the total specimen weight is present in a sieve, repeat test with an additional coarser sieve BULK AND TAPPED DENSITY ulk Density B Figure 30. Vessel Machine Illustration ○ ratioofthemassofuntappedpowderanditsvolume (m/𝑉 𝑜) apped Density T ○ attained after mechanically tapping a container containing the powder sample (m/V) bulk is higher than tapped RANS TEAM MEMBERS T 10 bit.ly/TransDatabase Compressibility (𝑉𝑂 −𝑉𝑓) 𝐶𝐼 = × 100 Index 𝑉𝑂 𝑉𝑂 Hausner Ratio 𝐻𝑅 = 𝑉𝑓 Table 2.Flow Property of Hausner Ratio and Carr’sIndex. CI (%) Flow Property HR ≤ 10 Excellent 1.00-1.11 11 - 15 Good 1.12-1.18 16 - 20 Fair - aid not 1.19-1.25 needed 21 - 25 Passable - may 1.26-1.34 Figure 31. Machine for Tapped Density hang up 26 - 31 Poor - must agitate, 1.35-1.45 ○ ethod 1: Graduated cylinder M vibrate ○ Method 2: Graduated Cylinder (different tap rate) itisdifferentfromMethod1duetothequalityof 32 - 37 Very poor 1.46-1.59 the powder >38 Very, very poor > 60 more intense, and bigger tap rate if the powder is fluffier, the force needs to be LOW THROUGH AN ORIFICE F greater Continuous monitoring of flow thesizeofthegraduatedcylinderdoesnotaffect ○ detects possible changes in flow rate the tapped density ○ Particle and process related factors affecting flow rate ○ Method 3: Vessel Only for free-flowing materials Mass per time POWDER FLOW ○ it could also be volume per time Relates to interparticulation ○ has no acceptance criteria, depends on theproduct and process NGLE OF REPOSE A Relatedtointerparticlefrictionorresistanceofmovement HEAR CELL METHODS S between particles Provides more extensiveDcharacterization of powderflow ○ Literally measure the angle of the powder flow ○ just insert the powder and an extensive list of measuretheradiusofthebaseandtheheightof characterization will be provided the powder cone ○ Ex. how will our powders perform under flow property based on the angle compression? mas mababa, mas okay yung flow MOISTURE CONTENT Formula for 𝑡𝑎𝑛(α) = ℎ 𝑟 Angle of Repose Table 1.Flow Property of Angle of Repose. Flow Property Angle of Repose (º) Excellent 25 - 30 Good 31 - 35 Fair - aid not needed 36 - 40 Passable - may hang up 41 - 45 Poor - must agitate, vibrate 46 - 55 Figure 32. Moisture Analyzer Illustration Very poor 56 - 65 oisture analyzer M Very, very poor >66 ○ Gravimetric method ○ iinitin yung powder and mababawasan yung weight HAUSNER RATIO AND COMPRESSIBILITY INDEX ○ difference in weight is the moisture content etermined from the bulk and tapped volume of D powders/granules Indirect measure of bulk density, size, shape, surface area, moisture content, and cohesiveness of materials RANS TEAM MEMBERS T 11 bit.ly/TransDatabase TABLET PROPERTIES & IPQC TEST tablets must be able to withstand the rigorsofhandling, rocessing, and transportation p ○ can be measure in kg or newtons ○ Mosanto hardness tester ○ Pfizer hardness tester ○ Schleuniger hardness tester Figure 33. Characteristics of a Good Tablet ust be sufficiently strong and resistant to shock m ○ Characteristics Tested:Hardness, Friability Figure 34. Machines Used for Testing Hardness/Tablet must be uniform in weight and drug content Breaking Forces of Tablets ○ Characteristics Tested: Weight Variation, Content Uniformity RIABILITY F ○ very important in clinical setting dahil dose ang Mechanical strength of compressed, uncoated tablets tinitignan natin for a patient ○ subjected to simulated test API must be bioavailable ○ Characteristics Tested:Disintegration, Dissolution ○ Even if the appropriate yung dose, can the API be released? must be elegant in appearnce ○ Characteristics Tested:Organoleptic Evaluation must retain all functional attributes ○ Characteristics Tested:Stability not a routine QC test performed in all batches to ensure the expiry date placed is right usually done at the start of development Figure 35. Friability Tester Machine retention samples are the ones being checked ○ during storage and shipping quipment: Friability Tester E ○ must retain the characteristics of the product ○ the tablet is inserted into the drum androtatedata specific speed ○ if the tablet isrotated,thereshouldbenochangein PQC TEST FOR TABLETS F weight or signs of breakage Organoleptic evaluation* Thickness BIOAVAILABILITY TESTS ○ it can impact the uniformity Hardness (Tablet Breaking Force) - DISINTEGRATION Friability - Bioavailability Testing ○ Disintegration ○ Dissolution - Uniformity of Dosage Units ○ Weight variation - ○ Content uniformity - Assay* ○ either titration or spectrophotometer ○ depends on the individual monograph *organoleptic evaluation, thicknessandweightarealsoIPQC tests THICKNESS Figure 36. Disintegration Tester Illustration ernier caliper V ○ there is also other equipment that is an all in one Determines if a tablet or capsule break or disintegrate ithin the prescribed time w ARDNESS/TABLET BREAKING FORCE H Not for troches, chewable tablets, or extended- or delayed-release dosage forms Mechanical strength of compressed, uncoated tablets ○ Exception for delayed-release tablet: Enteric-coated Tablets must be able towithstandtherigorsofhandling, tablets,sinceitneedstobedisintegratedinthesmall processing, and transportation mechanical strength of intestine compressed, uncoated tablets RANS TEAM MEMBERS T 12 bit.ly/TransDatabase Disintegration:anyresidueleftafterthetestisasoft For extended release - takes time before release ofthe ass having no palpably firm core m rug d ○ No palpably firm cree: wala ka nang makakapa; ○ you sample in multiple stage with its own specific should look like sand acceptance criteria ○ Apparatus: basket-rack assembly ○ Temperature: 37± 2ºC NIFORMITY OF DOSAGE SYSTEMS U ○ Time: Monograph-specified Degree of uniformity in the amount of drug substance ○ Medium: Water or monograph-specified among dosage units Acceptance criteria:Immediate-release dosage forms 2 methods ○ All 6 dosage units should disintegrate at the endof ○ Weight Variation the test time ○ Content Uniformity ○ If1or2tabletsfailtodisintegratecompletely,repeat the test on 12 additional tablets -> NLT 16 dosage CAPSULE PROPERTIES & TEST units out of 18 IPQC Tests Acceptance criteria: Delayed-release dosage forms ○ Powder Flow (enteric-coated) ○ Bulk and Tapped Density ○ Gastric fluid TS: After 1 hour, no tablet should FPQC Tests disintegrate ○ Uniformity of Dosage Units ○ Intestinal fluid TS: All tablets should disintegrate ○ Disintegration completely after the time specified ○ Dissolution DISSOLUTION PHARMACEUTICAL FACILITY pparatus A ayout L ○ Basket Control of cross contamination ○ Paddle Humidity / Temperature controls Water Pest control LAYOUT ontrols material flow C Separate released materials from quarantine or rejected materials Common layouts ○ Perimeter manufacturing, center warehouse wherein warehouse is in the center ○ Circular flow ○ Straight line flow Figure 37. Apparatuses for Dissolution Test PERIMETER MANUFACTURING/ CENTER WAREHOUSE emperature: 37± 0.5ºC T Medium: Specified in the monograph Rotation speed and run time: Specified in the monograph Acceptance criteria: %of drug dissolved after a certain time ○ you have to filter out because if not,thedissolution process continues Acceptance criteria: Immediate Release Dosage Table 3.Acceptance criteria: Immediate Reelase Dosage. Stage Number Acceptance Criteria Tested S1 6 Each unit is not less than S2 6 verage of 12 units (S1+S2) is equal A Figure 38. Perimeter Manufacturing Flow. to or greater than Q, and no unit less than Q - 15% The warehouse of approved materials is located in the S3 12 verage of 24 units (S1+S2+S3) is A c enter of the whole facility equal to or greater than Q, not more Advantage than 2 units are less than Q-15%, ○ Central Warehousing = materials are easily and no unit is less than Q-25% sourced/get by the personnel Disadvantage RANS TEAM MEMBERS T 13 bit.ly/TransDatabase Intersection = source of cross-contamination ○ ○ Sampling/weighing Flow: ○ warehouse -> dispensing -> tablet granulation -> in-process quarantine -> approved bulk materials-> packaging areas CIRCULAR FLOW the air flows from the ceiling (one direction) to the sampling area and weighing area this air cannot be mixed there is anexhaustsystemthatisabletodirect the airflow ○ Granulation Figure 38. Circular Flow. ircular pathway; pa-ikot C Advantage: ○ Easier Process ○ No Intersection = No cross contamination Disadvantage ○ Some areas are farther than other areas c an control dust thur pressure control when powder is beinghandled,thesetupshud STRAIGHT LINE FLOW be negative pressure (-) pressure -> pressure inside the rooms are lower compared to the main area Goal: dust does not get out of the main area ○ Compression Figure 39. Straight Line Flow. traight pathway S Advantage: ○ Less chance of cross-contamination Con: ○ the space requirement is big ○ can the company afford this s everal rooms divided by the main area CONTROL OF CROSS-CONTAMINATION HEPA filter air will go to the main area (-) AIR HANDLING SYSTEMS pressure Filtration systems Recirculation of air HUMIDITY AND TEMPERATURE CONTROL Positive and negative pressure areas roduct protection and employee comfort P Dust collection and exhaust systems Ensure little or no variation will be caused by external ambient temperatures DUST CONTROL Adequate ventilation (e.g. large roof fans for warehouse) Encountered in: install dehumidifier WATER SYSTEMS s upply of potable water must be free of defects or contamination ion-exchange treatment, reverse osmosis, distillation methods to obtain purified water waters used in solids manufacturing” RANS TEAM MEMBERS T 14 bit.ly/TransDatabase ○ ell water -> for non-manufacturing operations w ○ Potable/drinkingwater->forpersonnel;cleaningand sanitation purposes if they are non-sterile, purified water will be enough ○ Purified water RANS TEAM MEMBERS T 15 bit.ly/TransDatabase
