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