Dissolution ; Bulk Density ; Particle size, % in formula. EXAMPLE: 60% L 30% MCC 0.5% MS
CHOOSE DC BLEND Select A, B, or C
from table above
Fine Tune
Lactose type - (fine/coarse) MCC type pH 101/102 Lubricant package CHOOSE Tablet weight & Shape ± 120 - 1-5% Active ± 200 - 10% Active ± 300 - 20% Active Flat bevelled or Biconvex
(compare active dissolution) + compare reference drug)
Optimise
Dry blend mix
OPTIMIZATION
Unlubricated blend - UoC lubricated blend - UoC Lubrication range (0.5 - 1.0%) Tablet Weight Uniformity
Bromhexine Amitriphyline 8 mg 10 mg
LACTOSE
Active Material
MIX Y-cone Mill
Where necessary 0.6 -0.8 mm
Lubricant and Glidant
FLUSH
SIEVE
50 MESH
MICROCRYSTALLINE CELLULOSE SUPER DISINTEGRANTS
MIX Y-cone
20 - 25 min
Lubricant coats final blend in Y-Cone directly for a short period (3-5 min)
During Development
Content Uniformity of unlubricated blend to establish mixing time
LACTOSE
(65%)
Lubricant
(1%)
MIX Y-cone
20 - 25 min
Aerosil mixed with either starch (4), lactose (1+3) or lubricant (2)
SIEVE
50 MESH
Sieve
(Where necessary)
0.8 mm
Choose higher or lower % lubricant
Based on above active properties
EVALUATE
FORMULATE Development Batches A, B & C Weight uniformity Content Uniformity Hardness & Dissolution Profile
FINE TUNE A, B & C Adjust D & E
Repeat tests
OPTIMIZATION Formula & Process Fine tune D & E Tablet Hardness Qualification (low & High) with Dissolution Profile
BLEND STEP
rpm + time
IPQC
ID
Assay Content Uniformity
COMPRESS
AQUEOUS FILM COAT
Roller mixer
QC
Weight uniformity Thickness Hardness Disintegration
RELEASE To printing
Lubricant(s) MS
D Fine Tuning (Dissolution) SSG / CC / XP
E Fine Tuning Glidant / lubrication Talc / SA / CSD
Evaluate Active material
DIRECT COMPRESSION
Development Flowchart
Excipient Blend Decision Table
A DC Filler e.g. SDL/L KEY
CC CSD L MS MCC SA SDL SSG XP Croscarmellose Colloidal Silicon Dioxide Lactose monohydrate Magnesium stearate Microcrystalline cellulose Stearic Acid Spray dried lactose Sodium starch glycolate Crospovidone
PROCESS QUALIFICATION
To Pivotal
DIRECT COMPRESSION
Manufacturing Flowchart [I]
SDL(30%) - MCC(60%)
SUITABILITY:
Glibenclamide 5 mg Selegiline 5 mg Famotidine 10/20/40 mg
RELEASE To printing
COATED DC TABLETS
[Product suitable for either Wet or Dry Granulation]
ID Assay Content Uniformity Dissolution
SUITABILITY:
1. Buspirone 2. Tamoxifen 5/10 mg 10/20/40 mg -
BLEND Y-cone
5 min
IPQC
ID
Assay Content Uniformity
COMPRESS
AQUEOUS FILM COAT
QC
Weight uniformity Thickness Hardness Disintegration
Roller mixer
(See Chapter 11)
rpm + time
MIX
MIX Y-cone
Lubricant coats the lactose providing greater control over final blending stage
Development
Content Uniformity on unlubricated blend to establish mixing time
COATED DC TABLETS
ID Assay Content Uniformity Dissolution
DIRECT COMPRESSION
Manufacturing Flowchart [II]
SDL(60%) - MCC(30%)
Active Material (10%)
35%
MICROCRYSTALLINE CELLULOSE (15%) SODIUM STARCH GLYCOLATE (2%) AEROSIL (0.5%) STARCH (6%)