上海交通大学：《药剂学》教学资源（课件讲义）Tablets 2

国卢生 图上人生 Adhesives ④Fillers/diluents ©PVP Fillers are used to arrive at a tablet of ®Starch paste reasonable size when a drug forms a small Cellulose and its derivatives portion of the formula. ·MC Depending on the physiological conditions and ·HPC formulation,one needs a tablet of around 100 ·HPMC mg for ease of handling and administration, ·EC and therefore,fillers are used to increase bulk. ©MCC 国丝生一 图生一 ©Diluents ©Disintegrants ·Lactose ·Added to tablet formulations to facilitate ·Starch disintegration of the tablet .Microcrystalline cellulose(MCC) when it contacts water. ·Dicalcium phosphate ·Mannitol 国丝生 国生 ©Binders Mechanism of Disintegrants bind small drug or excipient particles together to form ·Swelling a granulate of a designed size range help the tablet to remain intact after compression. ·Capillary action be added as solution or dry powders ·Gas release ©Moistening agents RCOOH +NaHCO;-RCOONa+CO:+H2O .moisten the powder and induce its stickiness Heat of wetting Water or alcohol ·Enzymes 1

1 Shanghai Jiao Tong University Fillers/diluents • Fillers are used to arrive at a tablet of reasonable size when a drug forms a small portion of the formula. • Depending on the physiological conditions and formulation, one needs a tablet of around 100 mg for ease of handling and administration, and therefore, fillers are used to increase bulk. Shanghai Jiao Tong University Diluents • Lactose • Starch • Microcrystalline cellulose (MCC) • Dicalcium phosphate • Mannitol Shanghai Jiao Tong University Binders • bind small drug or excipient particles together to form a granulate of a designed size range • help the tablet to remain intact after compression. • be added as solution or dry powders Moistening agents • moisten the powder and induce its stickiness • Water or alcohol Shanghai Jiao Tong University Adhesives PVP Starch paste Cellulose and its derivatives • MC • HPC • HPMC • EC MCC Shanghai Jiao Tong University Disintegrants • Added to tablet formulations to facilitate disintegration of the tablet when it contacts water. Shanghai Jiao Tong University Mechanism of Disintegrants • Swelling • Capillary action • Gas release • Heat of wetting • Enzymes

国生 Types of disintegrants 国生 Types of lubricants ®Dry starch ®Magnesium stearate Effervescent disintegrants Fumed silicon dioxides ©CMS-Na ©Talc ⊕CCNa ®L-HPC Hydrogenated vegetable oil 因PVPP ©PEG ®Surfactants Sodium lauryl sulfate 国生一 图上生 图Buffering agents Disintergrants adding method Control the microenviromental pH .Intragranular:be added during granulation ©Sweeteners Extragranular:be added after granulation Improve the taste of chewable tablets .Mixed mode:50-75%intragranular 圈Wetting agents 25~50%extragranular Improve the hydrophilicity 国垫生 生 ©Absorbents ④Lubricants retaining large quantities of liquids without becoming wet. Glidant promotes flow of the granules by reducing Colorants interparticulate friction. Product identification Die wall lubricant reduces friction between the tablet Production of a more elegant product surface and the die walls during and after compaction to enable easy ejection of the tablets ©Flavors Antiadherent reduces sticking of the tablet punch Usually limited to chewable tablets or other tablets intended to dissolve in mouth. surface and tablet punches. 2

2 Shanghai Jiao Tong University Types of disintegrants Dry starch Effervescent disintegrants CMS-Na CCNa L-HPC PVPP Surfactants Shanghai Jiao Tong University Disintergrants adding method • Intragranular: be added during granulation • Extragranular: be added after granulation • Mixed mode: 50~75% intragranular 25~50% extragranular Shanghai Jiao Tong University Lubricants • Glidant promotes flow of the granules by reducing interparticulate friction. • Die wall lubricant reduces friction between the tablet surface and the die walls during and after compaction to enable easy ejection of the tablets. • Antiadherent reduces sticking of the tablet punch surface and tablet punches. Shanghai Jiao Tong University Types of lubricants Magnesium stearate Fumed silicon dioxides Talc Hydrogenated vegetable oil PEG Sodium lauryl sulfate Shanghai Jiao Tong University Buffering agents • Control the microenviromental pH Sweeteners • Improve the taste of chewable tablets. Wetting agents • Improve the hydrophilicity Shanghai Jiao Tong University Absorbents • retaining large quantities of liquids without becoming wet. Colorants • Product identification • Production of a more elegant product Flavors • Usually limited to chewable tablets or other tablets intended to dissolve in mouth

图生 国生 Co-processed excipients Advantages of direct compression Coprocessed excipients are a"preblend"of two or more excipients that are commonly used in conjunction ·Simplicity with each other.(usually a diluent and binder, ·Economy sometimes a disintegrant) ·Improved stability Advantages to using coprocessed excipients Improved dissolution rate include Disadvantages of direct compression A reduction in the number of raw materials and processing time High requirement of flow and compaction properties .Improved batch-to-batch consistency Possibility of segregation Improved quality of products 国生一 Instruments for granulation High-shear granulator @@ Tablet manufacture ·Fluid Bed granulator ·Wet granulation Extrusion/Spheronization ·Dry granulation ·Roller compaction ·Direct compression 山的品 WET GRANULATION DRY GRANULATION DIRECT COMPRESSION Premixing drg with other Premixing dnug with other Premixing drug with ingredients other ingredients 2.Transferring the mixhure int 2. Transferring the miture 2.Adding a luhricant t Tablet apparatus a container into a roller compactor the granles Single punch press Milling/sieving of the 1 A binder solution is added under a mechanical shear resuting flakes or ribbons ·Rotary press 2 into granules 4. Adding lubricant and/oe d screen sin 5. 6 Dry sieving of granules Adding a lubricantand/or disintegrant to thed女y granules Compressing the granules 3

3 Shanghai Jiao Tong University Co-processed excipients • Coprocessed excipients are a “preblend” of two or more excipients that are commonly used in conjunction with each other. (usually a diluent and binder, sometimes a disintegrant) Advantages to using coprocessed excipients include • A reduction in the number of raw materials and processing time • Improved batch-to-batch consistency • Improved quality of products Shanghai Jiao Tong University Tablet manufacture • Wet granulation • Dry granulation • Direct compression WET GRANULATION DRY GRANULATION DIRECT COMPRESSION 1. Premixing drug with other ingredientss 1. Premixing drug with other ingredients 1. Premixing drug with other ingredients 2. Transferring the mixture into a container 2. Transferring the mixture into a roller compactor 2. Adding a lubricant to the granules 3. A binder solution is added under a mechanical shear 3. Milling/sieving of the resulting flakes or ribbons into granules 3. Compressing the granules 4. Wet sieving of granules through a desired screen size 4. Adding lubricant and/or disintegrant to granules 5. Drying of granules in a tray￾oven dryer 5. Compressing the granules into tablets 6. Dry sieving of granules 7. Adding a lubricantand/or disintegrant to the dry granules 8. Compressing the granules into tablets Shanghai Jiao Tong University Advantages of direct compression • Simplicity • Economy • Improved stability • Improved dissolution rate Disadvantages of direct compression • High requirement of flow and compaction properties • Possibility of segregation Instruments for granulation • High-shear granulator • Fluid Bed granulator • Extrusion/Spheronization • Roller compaction Shanghai Jiao Tong University Tablet apparatus • Single punch press • Rotary press