上海交通大学：《药剂学》教学资源（课件讲义）Tablets 1

国生 圈生 Oral solid dosage forms Micromeritics ©Tablets Capsules Tablets ⑧Coating ®capsules 国生一 国话生一 国Micromeritics粉体学 Characteristics:compare with solid,liquid and gas -science and technology of small particles ·Anti-deformability抗变形性 ·Flowability流动性 国Powder粉：l00um 国生一 Particle Size Distribution Measurement 围Size reduction ·Sieving method ·Mortar and pestle ·Ball mill ·Microscopic method ·Impact mill .Coulter counter method ·Jet Mil Sedimentation method Us= 2(Pp-P1gR 9 1

1 Shanghai Jiao Tong University Oral solid dosage forms Tablets Capsules Shanghai Jiao Tong University Micromeritics Tablets Coating capsules Shanghai Jiao Tong University Micromeritics 粉体学 -science and technology of small particles Powder粉: ＜100μm Particles粒:＞100μm Shanghai Jiao Tong University Characteristics: compare with solid, liquid and gas • Anti-deformability 抗变形性 • Flowability 流动性 • Compressibility 可压缩性 Shanghai Jiao Tong University Size reduction • Mortar and pestle • Ball mill • Impact mill • Jet Mill Shanghai Jiao Tong University Particle Size Distribution Measurement • Sieving method • Microscopic method • Coulter counter method • Sedimentation method

国生一 国生一 Density ©Density ·True density Methods to determine true density and -True particle density is when the volume measured excludes both granule density open and closed pores ·Granule density ·Gas pressure method -The volume includes both the particulate volume and the pore Liquid immersion method volume. ·Bulk density Methods to determine bulk density -The total volume includes particle volume,inter-particle void ·Tapping method volume and intemal pore volume 国生一 国话生一 圈Flow of powders Three types of interparticle force Good flow properties are a prerequisite forces due to electrostatic charging for the successful manufacture of both tablets and powder-filled hard gelatin ·van der Waals forces capsules. forces due to moisture 国线 国生 圈Two types of flow Core flow and mass flow in hopper flow from powder hoppers flow through orifices Hoppe die wall lower punch 2

2 Shanghai Jiao Tong University Density • True density -True particle density is when the volume measured excludes both open and closed pores. • Granule density -The volume includes both the particulate volume and the pore volume. • Bulk density -The total volume includes particle volume, inter-particle void volume and internal pore volume Shanghai Jiao Tong University Density Methods to determine true density and granule density • Gas pressure method • Liquid immersion method Methods to determine bulk density • Tapping method Shanghai Jiao Tong University Flow of powders • Good flow properties are a prerequisite for the successful manufacture of both tablets and powder-filled hard gelatin capsules. Shanghai Jiao Tong University Three types of interparticle force • forces due to electrostatic charging • van der Waals forces • forces due to moisture Shanghai Jiao Tong University Two types of flow • flow from powder hoppers • flow through orifices Shanghai Jiao Tong University Core flow and mass flow in hopper

国生一 国生 Powder flow into orifices Measuring powder flow properties Changes in bulk density Hausner ratio= tapped bulk density poured bulk density ·Angle of repose 国生一 国话生一 ④Mixing of powder Segregation ·Random mixture Most pharmaceutical powders consist of ·Ordered mixture mixtures of materials with differing 888A ●0 的 properties.This leads to segregation, where particles of similar properties tend 888 58 的 to collect together in part of the powder. 国生一 国秋生 Compaction of powders ©Heckel plots ·Elastic deformation Inp]=K.P+A Plastic deformation D=Pgz ·Brittle deformation Pia -tue of me poder(same as the dersty of the 3

3 Shanghai Jiao Tong University Powder flow into orifices Shanghai Jiao Tong University Measuring powder flow properties • Changes in bulk density • Angle of repose Shanghai Jiao Tong University Mixing of powder • Random mixture • Ordered mixture Shanghai Jiao Tong University Segregation • Most pharmaceutical powders consist of mixtures of materials with differing properties. This leads to segregation, where particles of similar properties tend to collect together in part of the powder. Shanghai Jiao Tong University Compaction of powders • Elastic deformation • Plastic deformation • Brittle deformation Shanghai Jiao Tong University Heckel plots P

国生 Advantages of tablets ·Ease to use TABLETS The highest output efficiency chool of Phar ·The most economical Chen Jian 2013.3 chenjian/situ.cdu.cn ©Challenges Drug molecules show various differences in physical and chemical properties Fulfill the requirement of high bioavailability, stability and mechanical strength 国生一 国生 国Category of tablets 。 1.Simple uncoated tablets Desirable properties of raw materials 2.Film-Coated tablets ·Particle size 3.Effervescent tablets ·Moisture content 4.Buccal and sublingual tablets ·Crystalline form 5.Chewable tablets Hiestand tableting indices 6.Multilayered tablets ·Variability 7.Sugarcoated tablets ·Purity 8.Fast-disintegrating tablets ·Compatibility 9.Vaginal tablets 10.Controlled-release tablets 国生一 国秋生 圈Particle size 围Moisture content Act as an internal lubricant and affect the ·Mixture mechanical strength of tablets ·Dissolution Accelerate aging and crystal transformation ·Mechanic property rate 4

4 TABLETS School of Pharmacy Chen Jian 2013.3 chenjian@sjtu.edu.cn Shanghai Jiao Tong University Advantages of tablets • Ease to use • The highest output efficiency • The most economical Challenges • Drug molecules show various differences in physical and chemical properties • Fulfill the requirement of high bioavailability, stability and mechanical strength Shanghai Jiao Tong University Category of tablets • 1. Simple uncoated tablets • 2. Film-Coated tablets • 3. Effervescent tablets • 4. Buccal and sublingual tablets • 5. Chewable tablets • 6. Multilayered tablets • 7. Sugarcoated tablets • 8. Fast-disintegrating tablets • 9. Vaginal tablets • 10. Controlled-release tablets Shanghai Jiao Tong University Desirable properties of raw materials • Particle size • Moisture content • Crystalline form • Hiestand tableting indices • Variability • Purity • Compatibility Shanghai Jiao Tong University Particle size • Mixture • Dissolution • Mechanic property Shanghai Jiao Tong University Moisture content • Act as an internal lubricant and affect the mechanical strength of tablets • Accelerate aging and crystal transformation rate

国生一 国生 ©Crystalline form Polymorphism of active ingredients Hiestand tableting indices Polymorphism of excipients ·Strain index Polymorphic transformation during manufacturing ·Bonding index Brittle fracture index 国生一 国生 圈Variability ©Purity It is necessary to test the raw materials including Impurity may influence the tablet quality active ingredients and excipients to ensure uniformity 1与 of final product. 、7-13t-0492-n Table 3 Average Particle Data for Different Sources of 叫 Magnsium Stearate Size Surface Pore radius Source (m) area (m/g) United States 1.532 13.4 50 Great Britain 2152 12.2 Germany 4.1-6.9 7.4 61 Avoid the microbiological contamination of raw materials Italy 5591 4.6 36 国生一 ©Tablet excipients ·L.Fillers/diluents .2.Binders 圈Compatibility .3.Disintegrants ·4.Lubricants An incompatibility may be defined as an ·5.Glidants undesirable drug interaction with one or ·6.Buffering agents more components of a formulation, ·7.Sweeteners 。8.Wetting agents resulting in changes in physical, ·9.Absorbents chemical,microbiological or therapeutic ·10.Colorants ·11.Flavors properties of the dosage form. ·12.Coating agents 13.Matrix formers 5

5 Shanghai Jiao Tong University Crystalline form • Polymorphism of active ingredients • Polymorphism of excipients • Polymorphic transformation during manufacturing Shanghai Jiao Tong University Hiestand tableting indices • Strain index • Bonding index • Brittle fracture index Shanghai Jiao Tong University Variability • It is necessary to test the raw materials including active ingredients and excipients to ensure uniformity of final product. Shanghai Jiao Tong University Purity • Impurity may influence the tablet quality • Avoid the microbiological contamination of raw materials Shanghai Jiao Tong University Compatibility • An incompatibility may be defined as an undesirable drug interaction with one or more components of a formulation, resulting in changes in physical, chemical, microbiological or therapeutic properties of the dosage form. Tablet excipients • 1. Fillers/diluents • 2. Binders • 3. Disintegrants • 4. Lubricants • 5. Glidants • 6. Buffering agents • 7. Sweeteners • 8. Wetting agents • 9. Absorbents • 10. Colorants • 11. Flavors • 12. Coating agents • 13. Matrix formers