(Tablets)

. .

 

: /

/ /

Systemic & Local action

  

 

 

 

 
1. 2. 3.

Die filling

Die filling

???

Tablet formation

???

Tablet ejection

(Single punch press) (Rotary press)

 

punch

punch 1 die

lower punch


200

punch die table

die 3 - 60 punch die

1.

Hopper

table 2. Feed frame die 3. : upper lower punch

4. die

 

  

 

 

(Wet granulation) (Dry granulation)

mass
  

+ Granulating fluid --> Wet --> Damp mass --> --> --> --> --> -->

Granulating fluid


  

Binding solution

 

granulating fluid : : Hydrolysis, Hydrolysis,

Organic solvent :

Slug Roller compactor

  

     

Shear granulator HighHigh-speed granulator FluidizedFluidized-bed granulator SpraySpray-driers Slugger Roller compactor

Shear granulator


granulating fluid Planetary mixer

 

Paddle Wet mass Damp mass

Planetary mixer

Planetary mixer

Shear granulator


Wet mass Oscillating granulator



Wet mass

Oscillating granulator

Oscillating granulator

Shear granulator


Tray drier  Fluidized-bed drier Fluidized

Tray drier

Shear granulator


Tray drier
 

granulating (Solute migration)

(186) 186)

fluid

Fluidized-bed drier Fluidized-

Shear granulator


Fluidized-bed drier Fluidized  

Solute migration

Shear granulator
 

  

High speed granulator

 

Impeller : Chopper :

High speed granulator

High speed granulator

High speed granulator

 

Impeller fluid granulating Wet mass chopper Wet

mass


High speed granulator

 

  

Fluidized-bed granulator Fluidized

Fluidized-bed granulator Fluidized-

Fluidized-bed granulator Fluidized

granulating fluid

granulating fluid


Fluidized-bed granulator Fluidized-

Fluidized-bed granulator Fluidized-

Fluidized-bed granulator Fluidized 

Fluidized-bed granulator Fluidized  

SpraySpray-driers


SpraySpray-driers

SpraySpray-driers

Slugger


Slug 25 mm 10 - 15 mm  Slug


Hammer mill

Roller compactor
 

Roller compactor

   

  

1. 2. 3. 4. 5. 6. 7. 8.

1. 2. 3. 4. 5. Slug

1. 2. -

magnesium stearate

1.

1.

(surface 2. 2. 3. 3. active agent)

1. 2.

1. 2.

lake dye lake

   

Compressibility Flow ability Wet ability Lubricity

Compressibility


(binder)

Flow ability

 

.....
--> -->

granule (glidant)

Wet ability
 

granule

Lubricity


 

(lubricant, lubricating agent)




 

 

pH

 

     




--> --> granulation


 

wet

or

dry

--> --> --> --> /




--> wet granulation -->




+ --> wet or dry granulation -->




--> direct --> compression --> --> granulation wet or dry

50 mg --> -->

   

 

     

(Hardness) (Friability) (Disintegration) (Dissolution) (Stability) /

dissolution 100% 100% in vivo Bioavailability & Bioequivalence

 

Active ingredient  Filler, Diluent  Binder  Disintegrant  Lubricant



Glidant  Antiadherant  Colorant  Flavor  Sweetener  Sorbent






Local effect




Systemic effect

:
  

: : :

(Filler, Diluent)


50 mg 3/16 --> -->

--> -->

   

Lactose
      

Lactose ***

crystalline  Crystalline form < 93. 5 rC 93 . monohydrate  > 93.5rC 93.  Amorphous form


amorphous

EF-anhydrous / sprayspray-dryer

Amorphous form


Crystalline lactose

  

Direct compression crystalline

Crystalline form --> wet granulation -->

Sucrose


+ sugar

3 % --> -->

Icing

  

 

Mannitol
 

Sorbitol
 

Optical isomer 65% 65%

Mannitol

Mannitol

Starch
 







hydrolysis

Cellulose


 

: Cellulose cellulose

Microcrystalline

Microcrystalline cellulose
Cellulose crystalline amorphous  Cellulose Spray drying  Crystalline cellulose
 

Avicel PH101 PH101 PH102  Avicel PH102  Direct compression & Wet granulation



Wet mass

Inorganic substance


Calcium sulphate, Dibasic calcium phosphate, Tribasic calcium phosphate

(Binder)
     




Slug


Starch
 

Starch paste 5-10% 10% 1 -5 %




Starch paste
2 -4 ...


water bath


glucose




dye migration


Lactose, Dibasic calcium sulphate



calcium

phosphate,

Sucrose
 

5050-85 %

 

Tribasic calcium phosphate

Gelatin
   

5-10% 10% gelatin

sucrose



Polyvinyl pyrrolidone, Povidone, PVP

 

: : PVP

PVP

3-15% 15%

sodium bicarbonate acid

citric

Methylcellulose
 

) (Methocel

1 -5 %

 

Lactose,

Mannitol

Ethylcellulose
  

) (Ethocel

0.5-2%

Enteric polymer

Hydroxypropyl methylcellulose (HPMC)

  

2-5% PVP, MC, EC




(Disintegrant)
 

 

 

--> -->

--> -->

 

......


.....


Extragranular addition
 

--> -->

Intragranular addition
  

--> -->

  

10

Modified starch and cellulose



Pregelatinized starch : Starch1500, Starch1500 Amijel Sodium starch glycolate : Explotab, Primogel Microcrystalline cellulose : Avicel PH101, PH102 PH101, PH102

CO2 generator


bicarbonate Tartaric acid



carbonate Citric acid, CO2

Effervescent tablets

(Lubricant)


    

Fluid lubrication


 

Liquid paraffin

Boundary lubrication


 

Stearic acid Magnesium stearate < 1%

***

 

 




2-5

(Glidant)


--> -->

Hopper


 

Talcum : 1-2% Colloidal silicon dioxide (Aerosil) : 0.2-1 % Magnesium stearate < 1%

     

(antiadherant)


 

--> -->

  

Food, drug and cosmetic (FD&C)  Drug and cosmetic (D&C)  External drug and cosmetic (Ext. D&C)


2
 

(Dye) (Lake) Lake) Aluminium hydroxide


 




Direct compression







 

Mannitol, Lactose Sucrose

Saccharin, Saccharin sodium

 

500

Sucrose NaCl 1

Aspartame
 

180 acid, Tartaric acid

Sucrose Ascorbic

(Absorbent)
Colloidal silicon dioxide, Microcrystalline cellulose


50% 50%


(Fluid extract)


Binding  Sticking, Picking, Filming  Capping, Laminating  Chipping, Cracking  Double impression  Drug migration, Dye migration  Weight variation  Hardness variation


Binding



-->

 

***

***

Binding


  

-->

Binding
 


--> --> --> -->

Binding

(Tapered die)

Binding


Sticking
Sticking


Sticking
 

2  Picking  Filming

Sticking
Picking


Filming


***

Sticking

 

Sticking


(Anti(Anti-adherent) Colloidal silicon dioxide

Sticking




: MCC, Aluminium hydroxide, Colloidal silicon dioxide

Sticking


--> -->

 

Sticking


Sticking


 

Isopropanol polysiloxane

Chromium 5% Mineral oil 5% Dimethyl Trichloroethylene

Sticking


A, B, O


Chromium

Capping, Laminating
Capping


Laminating


Capping, Laminating

Capping, Laminating

Capping, Laminating

elastic deform


Capping, Laminating


capping
 

prepre-compression

Capping, Laminating


elastic deform


Capping, Laminating



Capping, Laminating
1) Flat faced (r = g )

2) Shallow - concave (r = 22.2 mm)

3) Normal - concave (r = 15.9 mm)

4) Deep - concave (r = 7.9 mm)

5) Ball - shaped (r = 6.3 mm)

Capping, Laminating


Capping, Laminating


--> Capping -->

Capping, Laminating


Capping, Laminating


--> Capping -->



--> -->

Capping, Laminating


--> --> -> Capping



hygroscopic : Sorbitol / PEG 4000

Capping, Laminating


/ > Capping


--

Pregelatinized Sorbitol powder

starch,

Acacia,

Capping, Laminating



stearate
--> --> Capping


--> -->

--> --> --> Capping -->

Capping, Laminating


100100 -200

Capping, Laminating


Hopper
 

capping

Chipping, Cracking
Chipping


Chipping, Cracking
 

--> -->

Hopper

Chipping, Cracking
Cracking


capping

Double impression


--> --> / rotary



Drug migration, Dye migration



/ (solid-gas interface) solid/

Intragranular migration  Intergranular migration



Drug migration, Dye migration



Intragranular migration

Drug migration, Dye migration



Intergranular migration

Drug migration, Dye migration

 


  

Drug migration, Dye migration



Drug migration : Content uniformity Content potent drug  Dye migration : (Mottling)


Drug migration, Dye migration

Drug/Dye Drug/Dye migration


Tray dryer
 

Fluidized-bed dryer FluidizedTray dryer --> -->

Intragranular

Drug migration, Dye migration

 

4040-80rC

Drug migration, Dye migration



intragranular migration


lake

dye

lake

Weight variation
 

Weight variation

--> --> --> -->

Weight variation


--> -->
 

(Glidant)

Weight variation
 

rotary --> -->

Weight variation



binding

sticking
--> -->

Hardness variation

 

.....

weight variation --> hardness variation -->

The