Table |: Major technical challenges for immediate-release (IR) and Cee eae Major technical challenge API %| API %| Potential process technologies High-shear granulation Sen Fluid-bed granulation High shear granulation Compactibilty Fluid-bed granulation Highly compressible excipient Follar compaction Flowabilty High-shear granulation Free-flowing excipient Tablet matrix-containing : polymers Dissolution are Coated beads Prt ln esheets Preliminary study Factors Responses DOE approaches % API Uniformity Plackeit Burhman Major fillers Compaetibility Fractional factorial Binders Flowabllity Disintearants Dissolution Glidants Stability Lubricants ‘Optimization study Factors Responses DOE approaches % API Uniformity Factorial % fillor(s) Compactibility Fractional factorial % binder Flowability Central composite % disintegrant Dissolution Mixture % glidant Stability D-optimal % lubricant Box-Behinkenet uy API level and excipient choice 510% Diluent Wicrocystaline cellulose, lactose, or starch Disintogrant | Crospovidono or sodium starch glycolato Lubricant | Magnesium stearate or stearic acid Table IV: An example ofa final formulation system fora simple tablet formulation. Factors API level and excipient choice API 510% Diluent Microcrystalline cellulose and lactose. Disintegrant | Crospovidone Lubricant | Magnesium stearate DEA cee ME Cu UOC e SCL Li [econ [aw sro] Ho = 10 Microcrystalline cellulose 30, Lactose Crospovidone Magnesium stearate Factors API Diluent Disintegrant Lubricant so ZeTable VI:A design-of experiments example fora tablet formulation FU ‘APL % | Diluent 5 | ucc* 5 | mcc 5 | McC 5 | mcc 5 | Lactose 5 | Lactose 5 | Lactose 5 | Lactose 5 | Starcn 5 | Starch 5 | Starch 421] 5 | Starch | wee 14 | 10 | cc 15 | 10 | mcc 16] 10 | moc iz | 10 | Lactose 48] 10 | Lactose 19 | 10 | Lactose 20} 10 | Lactose 21} 10 | Starch 22} 10 | Starch 22} 10 | Starch 24} 10 | Starch Disintearant Crospovidone Crospovidone Sodium starch glycolate Sodium starch alycolaie Crospovidone Crospovidone Sodium starch glycolate Sodium starch glycolate Crospovidone Crospovidone Sodium starch alycolate Sodium starch glycolate Crospovidone Crospovidone Sodium starch alycolate Sodium starch glycolate Crospovidone Crospovidone Sodium starch glycolate Sodium starch glycolate Crospovidone Crespovilone Sodium starch glycolate Sodium starch glycolate * MCC denotes microcrystalline cellulose. Lubricant Magnesium stearate Stearic acid Magnesium stearate Stearic acid Magnesium stearate Stearic acid Magnesium stearate Stearic acid Magnesium stearate Stearic acid Magnesium stearate Stearic avid Magnesium stearate Stearic acid Magnesium stearate Stearic avid Magnesium stearate Stearic acid Magnesium stearate Stearic acid Magnesium stearate Stearic acid Magnesium stearate Stearic acidTable VIE Adesign-of-experiments example fora tablet optimization study.Table VIli:An example ofa tablet-manufacturing process flow. Factors Varlables Preblending Blending time Load size Load size Grenulating Total water ‘Water addition rate Ai flow Drying Moisiure level Drying temperature Load size Blonding and sizing | Blending timo ‘Mesh size Lubricating Blanding time Tablet press speed Tableting Force feeder speed Compression force Coating colution Coating Rate of spray Responses Content uniformity Content uniformity. Sieve analysis Compression force profile Sieve analysis Bulkdensty Moisture content profile Content uniformity Siovo analysie Compressibilty Compression characteristios Powder homogeneity Ejection force Compression foree protila Friability Disintegration time Dissolution. Dosage form uniformity Frabilty of fim Dissolution Disintegration time Moisture content Stability