国生 Mixing 国生 Wet Granulation 国生一 Factors which affect the mixing Widely employed method for the production of 1.Milling and mixing of drugs ad evcipieres Properties of ingredients Proportion ofeach ingrediest Milling and mixing of dngs and excipients 2 Preparaticn of binder soltioe .Preparic ofbinder soluice Density and Hthe dnm wabetnces is affected by water wc a nosagucoun hindo ·Cobesive and charge the wet mass granules. 金支Wet massing byiofbinderotion 间inaddedt te roda mittane Drying of the wet granules .Eutectie mixture Overudting cama gaues that ae too baod 。Underweing e i bc a业 ·Apparatuses ·Operations .Lubrication and blending. ·Compressiontt 国生一_strfor 通Estoder 5.Drying of the wet granules 角Ramg 9.Tableting Eld Bedgrnulor 6.Screenng of dry gsamlles e Comples mode ‘ a。the e cty SphencalCosallsation h ©生Mechanism of wet granution ©生Drying of the wet granules 国生Drying of the wet granules ®Property of wet air 0 ·We bulb temperature漫球度 兰末母汽化 ·ldha ·Humidity混度 Meaniolieldinhn H-a62。 ,Relative humidity相对度 1010 Shanghai Jiao Tong University Mixing Factors which affect the mixing • Properties of ingredients • Proportion of each ingredient • Density and particle size • Cohesive and charge • Liquid or hygroscopic material • Eutectic mixture • Apparatuses • Operations Shanghai Jiao Tong University Wet Granulation Widely employed method for the production of compressed tablets • Milling and mixing of drugs and excipients • Preparation of binder solution • Wet massing by addition of binder solution • Screening the wet mass into granules. • Drying of the wet granules • Screening of dry granules • Add disintegrants • Lubrication and blending. • Compression of tablet Shanghai Jiao Tong University 1. Milling and mixing of drugs and excipients • The active ingredient and excipients are milled and weighed, then mixed thoroughly. 2. Preparation of binder solution • The adhesives are solved in suitable solvent to make binder solution • If the drug substances is affected by water use a nonaqueous binder 3. Wet massing by addition of binder solution • A binder solution is added to the powder mixture • Overwetting causes granules that are too hard • Underwetting results in tablets that are too soft and friable Shanghai Jiao Tong University 4. Screening the wet mass into granules • Pass the wet mass through a sieve or screen, wet granules are obtained. 5. Drying of the wet granules • Temperature • Residual moisture content • Instruments 6. Screening of dry granules • After the granules are dried, pass through a screen of smaller size than the one used for the wet mass. This process is necessary to select granules of uniform size to allow even fill in the die cavity. Shanghai Jiao Tong University 7. Add disintegrants • Add (a part of) disintegrants into the dry granules. 8. Lubrication and blending • A dry lubricant, antiadherent and glidant are added to the granules. 9. Tableting • Content of the drug in the mixture is determined and tablet weight is calculated • Wtablet=labeled dose/Cgranule • The granule/lubricant mix is fed through a hopper in the die cavity and then compressed between a lower and an upper punch. Shanghai Jiao Tong University Instruments for granulation Extruder Roll granulator High-shear granulator Fluid Bed granulator Complex mode Spray-dryer Spherical Crystallization Shanghai Jiao Tong University Mechanism of wet granulation Interparticulate bonds • Attractive forces between solid particles • Interfacial forces and capillary pressure at freely movable liquid surfaces • Adhesion forces caused by the immobile liquid films • Solid bridges • Mechanical interlocking bonds Shanghai Jiao Tong University Drying of the wet granules Shanghai Jiao Tong University Drying of the wet granules Property of wet air • Dry bulb temperature干球温度 • Wet bulb temperature湿球温度 • Humidity湿度 • Relative humidity相对湿度 P p p H   0.622