国生 国生一 Concepts Concepts ④Micromeritics粉体学：science and Micromeritics technology of small particles ·Powdert粉：<100um Second peoperties ·Particles粒：>100um ·Primary particle一级粒子 ·Second particle二级粒子 国生三 Particle size Characteristics:compare with solid,liquid and gas Knowledge and control of particle sine is very There are many types of analyses for +Flowability南动性 important in pharmacy. particle characterization.Each method will result in a unique measure of particle size and distribution,since a real sample ·Anti女rmablity抗变形往 exhibits a range of shapes and size.It is ·Tble片剂 important to distinguish between different ·Suspension匹混巷剂 methods,and to use the same type of analysis when comparing lots of raw material. 国生 Particle size Particle size Particle size Ge 几何学较子径 m三径 (Stoke's dimndet,EBed diander) ④Sieving diameter筛分径 ,Fee dumde定方向接线径D, ·(a,+b) ,边in dunder定方内等分径D K定方最大 D=ab D,=4+6 ·ywood dumde等权面面积同相当竖O 2 wdt6缸女等表到积相当径， 1
1 Micromeritics School of Pharmacy Chen Jian 2012.2 chenjian@sjtu.edu.cn Shanghai Jiao Tong University Concepts Primary properties • Particle size and size distribution • Morphology and specific surface area Second properties • Density and porosity • Flowability and packability • Moisture absorption and wetting • Adhesion and cohesion • Compact characterization Shanghai Jiao Tong University Concepts Micromeritics粉体学: science and technology of small particles • Powder粉: ＜100μm • Particles粒:＞100μm • Primary particle一级粒子 • Second particle 二级粒子 Shanghai Jiao Tong University Characteristics: compare with solid, liquid and gas • Flowability 流动性 • Compressibility 可压缩性 • Anti-deformability 抗变形性 Shanghai Jiao Tong University Knowledge and control of particle size is very important in pharmacy. • Powders散剂 • Capsules胶囊 • Tablets片剂 • Suspensions混悬剂 Shanghai Jiao Tong University Particle size There are many types of analyses for particle characterization. Each method will result in a unique measure of particle size and distribution, since a real sample exhibits a range of shapes and size. It is important to distinguish between different methods, and to use the same type of analysis when comparing lots of raw material. Shanghai Jiao Tong University Geometric diameter 几何学粒子径 • Diameter of the three dimensions三轴径 • Projected diameter投影径 • Feret diameter定方向接线径DF • Martin diameter定方向等分径DM • Krummbein diameter定方向最大径DK • Heywood diameter 等投影面积圆相当径DH • Equivalent perimeter diameter等投影面周长圆相当径DL • Equivalent volume diameter 等体积球相当径DV • Equivalent surface diameter 等表面积相当径DS • Equivalent specific surface diameter 等比表面积相当径DSV Particle size Shanghai Jiao Tong University Settling velocity diameter 沉降速度相当径 (Stoke’s diameter, Effect diameter) Particle size t h g D p l stk ( ) 18 Shanghai Jiao Tong University Particle size Sieving diameter筛分径 • (-a, +b) D a b A D ab A 2
©t生Particle size distribution ④生Particle size distrbution 国a生Particle size distrbution Particle size distribution Particle size distribution Particle size distribution ·Fre问uency size distribution频率分布 ·Normal distribution正态分布 ·Count basis个数基准 ·Cumulative size distrbution累积分布 ·Log-normal distributon对数正态分布 Mass basis 质量基准 ·Surface basis面积基准 ·Volume basis体积基准 ·Length basis长度基准 ,Undersize distribution痛上分布 ·Oversize distribution暗下分布 国生一 Morphology Mean diameter 式 Methods used to determine particle size ∑d1∑n ·3 icrcopic method是微镜法 The shape affects the flow and packing ,Co点r coumer ethod库尔特计数法 properties of a powder,as well as having 烟验录多的龄子直登 ·mchd态光射法 ·mem沉法 some influence on the surface area. 紧积中饲值《D) ·Specificsuface ea mcthod此表面积法 ∑dI∑ 围Shape index形状指数 面积长皮平尚轻 ·Sieving methodi游分法 ·动日 ∑nd1∑u 国Shape factor}形状系数 ∑nd1∑m Specific surface area ©t生Specific surface area 图Specific surface area 象Volume specific surface area体积比表面积 象Gas adsorption method气体吸附法 ©Gas permeability method气体透过法 S.=42400602x100 14AP.1c2 ④Weight specific surface area重量比表面积 pVn-L·Q1-s)2 1,C-1.卫 6 V(P-P)V.C+V 2
2 Shanghai Jiao Tong University Particle size distribution Particle size distribution • Frequency size distribution频率分布 • Cumulative size distribution累积分布 • Undersize distribution筛上分布 • Oversize distribution筛下分布 频率百分数 % Shanghai Jiao Tong University Particle size distribution Particle size distribution • Normal distribution 正态分布 • Log-normal distribution 对数正态分布 Shanghai Jiao Tong University Particle size distribution Particle size distribution • Count basis 个数基准 • Mass basis 质量基准 • Surface basis 面积基准 • Volume basis 体积基准 • Length basis 长度基准 Shanghai Jiao Tong University 名称 公式 算术平均径 Arithmetic mean diameter 众数径 Mode diameter 频数最多的粒子直径 中位径 Medium diameter 累积中间值（D50） 面积-长度平均径 Surface length mean diameter 体面积平均径 Volume surface mean diameter 重量平均径 Weight mean diameter nd nd 2 / nd nd 4 3 / nd nd 3 2 / nd n / Mean diameter Shanghai Jiao Tong University Methods used to determine particle size • Microscopic method显微镜法 • Coulter counter method库尔特计数法 • Photon correlation spectroscopy method动态光散射法 • Sedimentation method沉降法 • Specific surface area method比表面积法 • Sieving method筛分法 • Mush目 Shanghai Jiao Tong University Morphology The shape affects the flow and packing properties of a powder, as well as having some influence on the surface area. Shape index形状指数 Shape factor形状系数 Shanghai Jiao Tong University Specific surface area Volume specific surface area体积比表面积 Weight specific surface area 重量比表面积 S s v d n d n d v 2 3 6 6 S s w d n d n d w 2 3 6 6 Shanghai Jiao Tong University Specific surface area Gas adsorption method气体吸附法 23 6.02 10 22400 m w V S A 0 0 1 1 ( ) p p V C V p p V C p m m Shanghai Jiao Tong University Specific surface area Gas permeability method气体透过法 2 2 (1 ) 14 L Q A P t Sw
国生 Density 国生 Density 国生 Density Methods to determine true density and Methods to determine density ©True density 真密度 granule density ·Liquid immersion method液浸法 ·Liquid immersion method液浸法 ©Granule density颗粒密度 ·Gas pressure method乐力比较法 且 (%-%A ©Bulk density松密度 Methods to determine bulk density P= ·Tapping method轻薇法 (m-%)-(m-m) 丝_Density ©a生_Density 国生一 Porosity Methods to determine density Methods to determine bulk density ●Porosity空豫率 ·Gasp四essure method压力比较法 ·Tapping method轻敲法 内=1-巳 5m=1-巳 Pe 58=1-巳 Flowability Flowability Flowability ©Angle of repose休止角 ©Flow velocity流出速度 @Compressibility压缩度 电@ c=P-Pex1o0(%) 3
3 Shanghai Jiao Tong University Density True density 真密度 Granule density 颗粒密度 Bulk density 松密度 Shanghai Jiao Tong University Density Methods to determine true density and granule density • Liquid immersion method液浸法 • Gas pressure method压力比较法 Methods to determine bulk density • Tapping method轻敲法 Shanghai Jiao Tong University Density Methods to determine density • Liquid immersion method液浸法 ( ) ( ) ( ) 0 0 L aL S S l t m m m m m m Shanghai Jiao Tong University Density Methods to determine density • Gas pressure method压力比较法 Shanghai Jiao Tong University Density Methods to determine bulk density • Tapping method轻敲法 Shanghai Jiao Tong University Porosity Porosity空隙率 t g 内 1 g b 间 1 t b 总 1 Shanghai Jiao Tong University Flowability Angle of repose休止角 Shanghai Jiao Tong University Flowability Flow velocity流出速度 Shanghai Jiao Tong University Flowability Compressibility压缩度 100(%) 0 f f c
国生 Flowability 国生 Packability(充填性) 国a生Moisture absorption Methods to improve flowability 和性导位发量)周本体裂 Increase particle size Smooth particle surface .Reduce moisture 空比 兰 ·Add glidant 体明真样装与后情之比 7777 ④4生Moisture absorption ®24线Moisture absorption 国生一Wetting润湿性 Water soluble materials ©Contact angle接触角 ,CRH:critical relative humidity在界相对漫度 ,Humidity湿度 ,Relative humidity相对湿度H办 ·CRH一CRH~CRH Water insoluble materials Water soluble drugs Water insoluble drugs 国生 Wetting ©Contact angle Adhesion粘附性： 体层 attract force between different kinds of molecules rYI COs0 t 2n 体吸入高度 需凝聚性： .attract force between se kind of molecules 4
4 Shanghai Jiao Tong University Flowability Methods to improve flowability • Increase particle size • Smooth particle surface • Reduce moisture • Add glidant Shanghai Jiao Tong University Packability(充填性) 松比容 Specific volume 粉体单位质量（1g）所占体积 ν=V/W 松密度 Bulk density 粉体单位体积（cm3）的质量 ρ=W/V 空隙率 Porosity 粉体的松体积中空隙所占体积比 ε=(V-Vt )/V 空隙比 Void ratio 空隙体积与粉体真体积之比 e=（V-Vt ）/Vt 充填率 Packing fraction 粉体的真体积与松体积之比 g=Vt /V=1-ε 配位数 Coordination number 一个粒子周围相邻的其它粒子个数 Shanghai Jiao Tong University Moisture absorption Shanghai Jiao Tong University Moisture absorption Water soluble materials • CRH: critical relative humidity临界相对湿度 • Humidity湿度 • Relative humidity相对湿度 RH=p/ps • CRHAB=CRHA·CRHB Water insoluble materials P p p H 0.622 Shanghai Jiao Tong University Moisture absorption Water soluble drugs Water insoluble drugs Shanghai Jiao Tong University Wetting润湿性 Contact angle接触角 S SL L cos Shanghai Jiao Tong University Wetting Contact angle t r h l 2 cos 2 Shanghai Jiao Tong University Adhesion粘附性: • attract force between different kinds of molecules Cohesion凝聚性: • attract force between same kind of molecules Shanghai Jiao Tong University Compact characterization Compressibility 可压缩性 Compactibility 可成型性 Tabletability 可压片性
®日stic deformation弹性变形 Upper punch force,u上冲力 Lower punch foree,Fi下冲力 Pas deforation塑性变形 画Radical force,Fa径向力 专Doe wall friction force,下a模壁摩候力 ®Brittle deformation脆性变形 图4生Learning Objectives 图丝一Learning Objectives Advantages and disadvantages ©Types specific surfce True density,Granule density, TABLETS Tablet excipients Hulk densiry,Angle of repose,Porosity,cntical relative humidity,Contactae Methods of preparation ®Evalution Packaging and Storage mmersion method,Gas pressure method Variables which effect quality Coating ®Tablet Types Oral tablets for ingestion ©Advantages eOr包tabletsfor s Standard compressed tablets 份Coued tahlets农片 h泡秀片 Tablesainsd by other routes Chewable tablets咀第片 Dispersible tablets分敢片 ©Disadvantages Release tablet缓释片 Unsuitable for those can't swallow ®Controlled Release tablets控释片 .Problems with biouvalabiliry @Multilayer tablets多层片 +Loos of vo山tile coe世pone 口聚速崩/速溶片 5
5 Shanghai Jiao Tong University Compact characterization Elastic deformation 弹性变形 Plastic deformation 塑性变形 Brittle deformation 脆性变形 Shanghai Jiao Tong University Compact characterization Upper punch force, FU 上冲力 Lower punch force, FL 下冲力 Radical force, FR 径向力 Die wall friction force, FD 模壁摩擦力 Ejection force, FE 推出力 Shanghai Jiao Tong University Compact characterization Compression cycle 压缩循环图 Shanghai Jiao Tong University Learning Objectives Frequency size distribution, Cumulative size distribution, Medium diameter, Volume specific surface area, Weight specific surface area , True density, Granule density, Bulk density, Angle of repose, Porosity, critical relative humidity, Contact angle Coulter counter method, Sedimentation method, Gas adsorption method, Gas permeability method, Liquid immersion method, Gas pressure method TABLETS School of Pharmacy Chen Jian 2012.2 chenjian@sjtu.edu.cn Shanghai Jiao Tong University Learning Objectives Advantages and disadvantages Types Tablet excipients Methods of preparation Evaluation Packaging and Storage Variables which effect quality Coating Shanghai Jiao Tong University Advantages • Accurate and uniform • Stable • Convenient • Suitable for large-scale production • Able to develop special release properties Disadvantages • Unsuitable for those can’t swallow • Problems with bioavailability • Loss of volatile component Shanghai Jiao Tong University Tablet Types Oral tablets for ingestion Tablets used in the oral cavity Tablets administered by other routes Shanghai Jiao Tong University Oral tablets for ingestion Standard compressed tablets Coated tablets包衣片 Effervescent tablets泡腾片 Chewable tablets咀嚼片 Dispersible tablets分散片 Sustained Release tablets缓释片 Controlled Release tablets控释片 Multilayer tablets 多层片 Orally disintegrating/dissolving tablets 口服速崩/速溶片