Pharmaceutical Statistics
* Capsule size with volume occupied:
000 size ⇨ 1.36 ml
00 size ⇨ 0.95 ml
0 size ⇨ 0.67 ml
1 size ⇨ 0.48 ml
2 size capsule ⇨ 0.37 ml
3 size capsue ⇨ 0.27 ml
4 size capsule ⇨ 0.20 ml
5 size capsule ⇨ 0.13 ml
* USP grade specifications for Purified water
1. TDS ⇨ 10 mg/L
2. Electrical conductivity ⇨ 1.3 microS/cm
3. pH ⇨ 5–7
4. TOC ⇨ 500 ppb
5. Chlorides ⇨ 500 ppb
6. Ammonia ⇨ 300 ppb
7. Bacteria alert (FDA)⇨ 100 cfu/ml [cfu⇨ colony forming unit]
8. Endotoxins ⇨0.25 EU/ml
9. Final purification process ⇨ Any
* USP grade specifications for WFI ( Water for Injection)
1. TDS ⇨ 10 mg/L
2. Electrical conductivity ⇨ 1.3 microS/cm
3. pH ⇨ 5-7
4. TOC ⇨ 500 ppb
5. Chlorides ⇨ 500 ppb
6. Ammonia ⇨ 300 ppb
7. Bacteria alert (FDA)⇨ 10 cfu/ml [cfu⇨ colony forming unit]
8. Endotoxins ⇨0.25 EU/ml
9. Final purification process ⇨ Distillation, Reverse Osmosis
* HLB Value (Hydrophilic–Lipophilic Balance):
HLB range/ Surfactant application
0-3 ⇨ Antifoaming agents
4-6 ⇨ w/O emulsifying agents
7-9 ⇨ Wetting agents
8-18 ⇨ O/W emulsifying agents
13-15 ⇨ Detergents
10-18 ⇨ Solubilizing agents
* Particle size ranges of Various compounds
Solutions ⇨ 1A° -10A°
Colloids ⇨ 10A° -2000A°
Suspension ⇨ 1-50 micrometer/ 2000 A°
Macromolucles ⇨ 10A°-10000A°
Emulsion ⇨ 100–600 nm
Elixir ⇨
Granules ⇨ 0.2–4 mm
Microcapsule ⇨ 200 micrometer
* Clean Room Classification according to Europe Economic community guidelines-EEC
Grade/Class
1. Grade A/ Class 100 ⇨ Particle count in air is not more than 100 per cubic foot of 0.5 micro meter & larger size particle.
2. Grade B/ Class 100 ⇨ Particle count in air is not more than 100 per cubic foot of 0.5 micro meter & larger size particle.
3. Grade C/ Class 10,000 ⇨ Particle count in air is not more than 10,000 per cubic foot of 0.5 micro meter & larger size particle
4. Grade D/ Class 1,00000 ⇨ Particle count in air is not more than 1,00000 per cubic foot of 0.5 micro meter & larger size particle.
* Clean Room Classification according to GMP EU
Grade/Class
1. Grade A/ Class 100/ISO 5 ⇨ Particle count in air is maximum 3520 per cubic meter of 0.5 micro meter & larger size particle in operation
2. Grade B/ Class 100/ISO 6 ⇨ Particle count in air is maximum 3,52000 per cubic meter of 0.5 micro meter & larger size particle in operation
3. Grade C/ Class 10,000/ ISO 7 ⇨ Particle count in air is maximum 35,20000 per cubic meter of 0.5 micro meter & larger size particle in operation
4. Grade D/ Class 1,0000/ ISO 8 ⇨ N/A
* Working area for Grade A cleanroom:
⇨ Filling
⇨ Sealing
⇨ Aseptic Manufacturing
⇨ Handling of sterile starting materials
⇨ Manufacturing ans filling of sterile creams, ointments
⇨ Emulsion and suspension preparation
* Working areas for Grade B Cleanroom
⇨
Efficiency of Various Filters
Filters
1.HEPA Filter (High efficiency Particulate Air)⇨ 99.997% Efficency
2.ULPA filter (Ultra Low penetration Air) ⇨ 99.999% Efficency
3. SULPA filter (Super ultra low penetration air) ⇨ 99.9999% efficency
Methods of Stability Study
1. Real time/ Long term stability study
2. Accelerated stability study
* Long term Stability testing conditions (ICH Stability zones)
Climate Zone/ Temperature/ Humidity/ Minimum duration
Frozen ⇨ (-15 +/- 5°C) ⇨ No humidity ⇨ minimum duration 12 months
Refrigerated ⇨ ( 5 +/- 3°C) ⇨ No humidity ⇨ minimum duration 12 months
Zone I (Temperate zone) ⇨ ( 21°C +/- 2°C) ⇨ (45% +/- 5% RH) ⇨ minimum duration 12 months
Zone II (Mediterranian/ Subtropical zone) ⇨ ( 25°C +/- 2°C) ⇨ (60% +/- 5% RH) ⇨ minimum duration 12 months
Zone III (Hot dry zone) ⇨ ( 30°C +/- 2°C) ⇨ (35% +/- 5% RH) ⇨ minimum duration 12 months
Zone IV (Hot humid zone/Tropical zone) ⇨ ( 30°C +/- 2°C) ⇨ (65% +/- 5% RH) ⇨ minimum duration 12 months
Zone IVb (ASEAN testing condition - Hot or higher humidity) ⇨ ( 30°C +/- 2°C) ⇨ (75% +/- 5% RH) ⇨ minimum duration 12 months
* Accelerated and Intermediate Stability Testing Conditions
Climate zone/ Temperature/Relative humidity/ Minimum duration
Accelerated frozen ⇨ ( 5 +/- 3°C) ⇨ No humidity
Accelerated Refrigerated ⇨ ( 25 +/- 2°C) ⇨ (60% +/- 5% RH)
Accelerated Ambient (পারিপার্শ্বিক) zone ⇨ ( 40 +/- 2°C) ⇨ (75% +/- 5% RH)
Intermediate zone ⇨ ( 30°C +/- 2°C) ⇨ (65% +/- 5% RH)
International Climate zones and Climate condition (WHO)
Zone
Mean annual temperature
Mean kinetic temperature
Mean annual relative humidity
Drived storage condition (for real time studies)
Zone
Mean annual temperature
Mean kinetic temperature
Mean annual relative humidity
Drived storage condition (for real time studies)
Zone
Mean annual temperature
Mean kinetic temperature
Mean annual relative humidity
Drived storage condition (for real time studies)
Zone
Mean annual temperature
Mean kinetic temperature
Mean annual relative humidity
Drived storage condition (for real time studies)
Carr's Index
Carr's Index (%)
5-15. ⇨ Excellent
18-21 ⇨ Fair to Passable
23-35. ⇨ Poor
35-38. ⇨ Very Poor
>40 ⇨ Extremely Poor
Hausner ratio
Hausner ratio
Less than 1.25 ⇨ Good flow
1.25-1.50 ⇨ Moderate flow
More than 1.50 ⇨ Poor flow
Angle of repose
Angle of repose (degree)
<25° ⇨ Excellent
25-30° ⇨ Good flow
30-40° ⇨ Passable
>40° ⇨ Very poor
Weight variation of Tablets
Weight variation of Tablets
Average weight ⇨ Maximum % Variation allowed
(According to BP)
</= 80 mg ⇨ maximum 10% variable allowed
80-150 mg ⇨ maximum 7.5% variation allowed
>150 mg ⇨ maximum 5% variation allowed
(According to USP)
<= 130 mg ⇨ maximum 10% va variation allowed
130-324 mg ⇨ maximum 7.5%variation allowed
>324 mg ⇨ maximum 5% variation allowed
* Official standards for Hardness of tablets
For common tablets ⇨ 5–8 kg
For sustainable & controlled release tablets ⇨ 8–12 kg
First reading indicate ⇨ Thickness of tablets
Second reading indicate ⇨ Diameter of tablets
Third reading reading indicate ⇨ Hardness of tablets
Dissolution test stages with acceptable range
Stages// number of tablets
Stage 1 // 6 tablets ⇨ Not less than 5%
Stage 2// 12 tablets ⇨ 15% (,but not more than 2 tablets)
Stage 3// 24 tablets ⇨ 5%
Stage 1 // 6 tablets ⇨ dissolved amount of each unit should not less than D+15%
Stage 2// 12 tablets ⇨ Average 12 units is eual to or greater than D and no unit should not be less than D-15%
Stage 3// 24 tablets ⇨ Average of 24 units is equal to or greater than D, not more than 2 units are less than D-15% and no unit is less than D-25%
[D= Dissolved active ingredient specified in the individual monograph)
Pressures durimg slugging/tablet press
Pressure during slugging⇨ 15 tones
Pressure during tablet press⇨ 4 tones or less
Compression Machine Tooling
Types of tooling
Punch Barrel Diameter (mm)
Die outer Diameter (mm)
Punch length (mm)
Maximum tablet size (mm)
Types of tooling
Punch Barrel Diameter (mm)
Die outer Diameter (mm)
Punch length (mm)
Maximum tablet size (mm)
Types of tooling
Punch Barrel Diameter (mm)
Die outer Diameter (mm)
Punch length (mm)
Maximum tablet size (mm)
Types of tooling
Punch Barrel Diameter (mm)
Die outer Diameter (mm)
Punch length (mm)
Maximum tablet size (mm)
Sterilization Conditions
Dry heat sterilization
Temperature: 120-170°C/ 160-180°C
Pressure: 100 MPa
Moist heat sterilization
Temperature: 100-121°C
Pressure: 1200 MPa
Methods
Ultra high pressure
Moist Heat sterilization
Dry heat sterilization
Limits of Microbiological Contamination (Bioburden Test)
Grade (Critical asceptic processing area)
Air sample (CFU/m3)
Settle plates-90 mm diameter (CFU/4hr)
Contact Plates-55 mm diameter ((CFU/plate)
Glove print-5 fingers (CFU/Glove)
Grade (Asceptic processing areas)
Air sample (CFU/m3)
Settle plates-90 mm diameter (CFU/4hr)
Contact Plates-55 mm diameter ((CFU/plate)
Glove print-5 fingers (CFU/Glove)
Grade (Non-critical area)
Air sample (CFU/m3)
Settle plates-90 mm diameter (CFU/4hr)
Contact Plates-55 mm diameter ((CFU/plate)
Glove print-5 fingers (CFU/Glove)
Grade (Non-critical support area for production activities)
Air sample (CFU/m3)
Settle plates-90 mm diameter (CFU/4hr)
Contact Plates-55 mm diameter ((CFU/plate)
Glove print-5 fingers (CFU/Glove)
Scale up process test requirement
Batch
Batch design
For Solid or Semisolid
For Tablets or Capsules
For Liquids
Batch
Batch design
For Solid or Semisolid
For Tablets or Capsules
For Liquids
Batch
Batch design
For Solid or Semisolid
For Tablets or Capsules
For Liquids
Process Scale -Up according to FDA
Batch name
Lab (Process development)
Pilot (Exhibit)
Commercial (Proposed)
Sampling plans for starting materials
Name of sampling plan
Number of container less than 5
Number of containers more than 5
Raw material
Solvents
Name of sampling plan
Number of container less than 5
Number of containers more than 5
Raw material
Solvents
Name of sampling plan
Number of container less than 5
Number of containers more than 5
Raw material
Solvents
* Friability limits
⇨ According to B.P, Percentage of friability should not be more than 0.8%
⇨ According to USP, Percentage of friability should not be more than 1%
* Disintegration time for various tablets according to USP-NF
For Uncoated tablet ⇨ 15 minutes
For Film coated tablets ⇨ 30 minutes
For Hard gelatin capsules ⇨ 30 minutes
For Enteric coated tablets ⇨ 60 minutes
For Sugar coated tablets ⇨ 60 minutes
Disintegration test requirement
Number of Glass tube ⇨ 6 pices
Glass tube length⇨ 3" long
mesh size ⇨ 10 mesh screen
Temperature ⇨ 37 +/- 2°C
Rotation⇨ 28 to 32 cycles per minute
Particle size after disintegration ⇨ less than 2 mm diameter
Particle size after deaggregation ⇨ less than 0.25 mm diameter
Dissolution occur when particle size range become ⇨ less than 0.25 mm diameter
* Number of Batches of various process validation
For Prospective validation ⇨ 3 consequitive batches
For Concurrent validation ⇨ 3 consequitive batches
For Retrospective validation ⇨ 10-25 batches
For Revalidation ⇨ Depends upon risk snalysis
Acid-Base Indicators
Indicator/ Colour in acidic condition/ Colour in basic candition/ pH range
Color of Methyl orange in acidic condition ⇨ Red
Color of Methyl orange in basic condition ⇨ Yellow
pH range of Methy orange ⇨ 3.1-4. 4
Color of Methyl red in acidic condition ⇨ Red
Color of Methyl red in basic condition ⇨ Yellow
pH range of Methy orange ⇨ 3.1-4. 4
Color of Methyl orange in acidic condition ⇨ Red
Color of Methyl orange in basic condition ⇨ Yellow
pH range of Methy orange ⇨ 3.1-4. 4
Color of Methyl orange in acidic condition ⇨ Red
Color of Methyl orange in basic condition ⇨ Yellow
pH range of Methy orange ⇨ 3.1-4. 4
Methyl red/ red/yellow/ 4.4-6.3
Litmus/ red/ blue/ 5-8
Bromothymol blue/ Yellow/ blue/ 6-7.6
Phenolphthalein/ Colourless/ Pink/ 8.3-10
Choice of suitable Indicator for various acid-base titration
1. Strong acid/strong base titration ⇨ Methyl orange & Phenolphthalein
2. Strong acid/weak base titration ⇨ Methyl orange & methyl red
3. Weak acid/ Strong base titration ⇨ Phenolphthalein
4. Weak acid/ Weak base titration ⇨ No indicator is suitable
pH
pH of tear ⇨ 7.4
pH of Blood⇨ 7.35-7.45
pH of Bile acid ⇨ 6-8.5
pH of Saliva ⇨ 5.5- 7.5
pH of Skin ⇨ 5.5
pH of Urine ⇨ 4.5-8.00
pH of Gastric juice ⇨ 1.5-3.5
pH of HCl ⇨ 1.2-1.4
* Temperature Condition according to BP
For Deep freeze⇨ below - 15°C
For Refrigerator ⇨ 2-8° C
For Cold/Cool ⇨ 8-15° C
For Room temperature ⇨ 15-25° C
Solubility range according to BP
1. Very soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : Less than 1
2. Freely soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 1 to 10
3. Soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 10 to 30
4. Sparingly soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 30 to 100
5. Slightly soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 100 to 1000
6.Very slightly soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : 1000 to 10,000
7. Partially insoluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : More than 10,000
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