aseptic process technology

1. 1
• PRESENTD BY :-
• PATIL PRANJAY SADASHIV.
• FIRST YEAR M.PHARM.
• DEPARTMENT OF QUALITY
ASSURANCE.
ASEPTIC PROCESS TECHNOLOGY

2. Introduction
The production of sterile drug products by bringing
together the product, container, and closure that have been
subjected to different sterilization methods separately. To
assembled them is required extremely high quality
environment by skilled personnel using the right tools.
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3. Manufacturing
 Manufacturing is the making of goods by hand or by
machine that upon completion the business sells to a
customer.
Items used in manufacture may be raw materials or
component parts of a larger product.
The manufacturing usually happens on a large-scale
production line of machinery and skilled labor.
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4. 4
Clean Area Classification
FS209
Cleanroom
classification
ISO 14644-1
Cleanroom
classification
≥0.5um
particles/m3
Viable Microbes
(cfu/m3)
Ave Airflow
Velocity
(fpm)
Air changes/hr
1 0 0 ,0 0 0 8 3 ,5 2 0 ,0 0 0 1 0 0 5 -1 0 5 -4 8
1 0 ,0 0 0 7 3 5 2 ,0 0 0 1 0 1 0 -1 5 6 0 -9 0
1 0 0 0 6 3 5 ,2 0 0 7 2 5 -4 0 1 5 0 -2 4 0
1 0 0 5 3 ,5 2 0 1 4 0 -8 0 2 4 0 -4 8 0

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 A semisolid preparation usually containing medicinal
substances and intended for external application
 A semisolid preparation for external application to the
skin or mucous membranes.
Ointment

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Manufacturing of Ointment

7. Punam patil 7

8. IPQC test for ointment
1 Content uniformity of drug
2 Penetration
3 Draize test
4 Consistency test
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9. 1)Content uniformity of drug
A known weight of ointment is taken and assayed for amount of the
drug.
2)Penetration
A weighed quantity of ointment is rubbed over skin for a given period of time and
unabsorbed ointment is collected and weighed.
The Differences in weights represent the amount absorbed.
In vitro skin Penetration
1. Flow through cell
2. Franz diffusion cell
Diffusion cells mainly have two compartments
1)Donor
2)Receptor
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10. 3) Draize Test
Draize skin irritation test:
A known amount of test substance is introduced under a one square inch
gauge patch ,
The patch is applied to skin of 12albino rabbits ,(6 with intact skin)and(6
with abraded skin),
The patch is secured in place with adhesive tape and the entire trunk of the
animals wrapped with an impervious material for a 24 hour period,
After 24 hours the patches are remove and resulting reaction evaluated For
erythema and edema formation.
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11. The reaction is again scored at the end of 72 hours and two readings are
averaged.
A known amount of test material is placed is one eye of each of 6 albino
rabbits the other eye remains untreated, serving as a control.
The eyes are not washed after installation and are examine at 24,48 and 72
hours for ocular reaction.
The test is considered positive if ulceration, inflammation of the iris,
swelling of the conjunctiva occurs.
A substance is an eye irritant if,
4 of six rabbits score positive.
It is considered a non-irritant if none or only one of the 6 animals exhibit
irritation.
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12. 4) Consistency test
PENETROMETRY:
PROCEDURE:
Preparation of test sample: 3 methods (A,B,C)
A: Carefully and completely fill three containers without forming air
bubbles .
B: Apply a suitable shear to the samples for 5 min carefully and completely
fill three containers without forming air bubbles.
C: Melt 3 samples carefully and completely fill three containers without
forming air bubbles .
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13. Suspension:
 A suspension is a heterogeneous mixture that contains solid particles
sufficiently large for sedimentation.
The particles may be visible to the naked eye, usually must be larger than 1
micrometer, and will eventually settle.
 A suspension is a heterogeneous mixture in which the solute particles do not
dissolve, but get suspended throughout the bulk of the solvent, left floating
around freely in the medium.
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14. Manufacturing
of suspension

15. IPQC test for suspension
1. Appearance
2. Color, Odor, taste
3. Determination of particle size
4. Uniformity of volume
5. Viscosity
6. Density
7. Particle size measurement
8. Extent of sedimentation
9. Re disprsibility
10. Determination of zeta potential
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16. 1) Appearance
The appearance of the suspension is noted and determine the uniformity of
sedimentation and also determined the breaks or air pockets in the sediment.
Photo microscopic Examination:
The microscope can be used to distinguish between flocculated and non-
flocculated particles and to determine changes in the physical properties and
stability.
2) Color, Odor and Taste
These characteristics are especially important in orally administered
suspensions .
Variation in color photomicrograph of a flocculated steroid suspension
indicates poor distribution and /or differences in particle size .
Taste can also indicate chemical instability.
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17. 3) Determination of particle size
1) Coulter counters method:
2) Microscopic count method or membrane filtration method:
1)Coulter counters method:
This electronic method is used to detect the particles and also determine to
particle size. The sample solution is added to an electrolyte solution. The solution
is drawn through a small orifice of the device. Positive and negative electrodes are
present one on either side of an orifice.
2)Microscopic count method:
A measured sample solution is filtered through a membrane filter. The
collected particles on the surface of the filter are then counted with the help of a
microscope at 100x magnification. The is whole method is carried out under
aseptic conditions , it is time consuming process .
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18. 4)Uniformity of volume
5) Viscosity
6)Density
7)Particle size measurement
Method:-
I. Light-scattering methods for particle size determination called photon
correlation spectroscopy
II. Single particle optical sensing
III. laser diffraction
IV. Ultrasound attenuation
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19. 8) Re- dispersibility
Re- dispersibility can be estimated by shaking the suspension with hands or by some
mechanical device which is stimulated with motion of human arm. Suspension is placed
in 100ml graduated cylinder.
After storage and sedimentation ,cylinder is rotated through 360 t 20 rpm. The end
point is taken When base of cylinder is clear as sediment ,
The time required/ no of revolution is noted. The shorter the time/power the no of
revolutions, greater or faster re- despersibility.
9) Determination of zeta potential
This can be determined by using ‘zeta meter’ which determines by measuring
electrophoretic mobility of particles in suspension
Z = 4πnv/Εe
Where, n = viscosity of suspension
E = applied electric field
ε = dielectrical constant
V = velocity of particle
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20. 20
Emulsion
 A mixture of two immiscible liquids, one being dispersed throughout
the other in small droplets; a colloid system in which both the
dispersed phase and the dispersion medium are liquids.
 Margarine, cold cream, and various medicated ointments are
emulsions.
 In some emulsions the suspended particles tend to join together and
settle out; hence the container must be shaken each time the
emulsion is used.

21. Manufacturing of emulsion
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22. IPQC test for Emulsion
1. Appearance
2. Color, Odor, Taste method
3. Miscibility Emulsion
4. Determination of zeta potential
5. Determination of globule size
6. Rheological method
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23. 1) Appearance
2) Colour, odour and taste method
3) Miscibility emulsion
Staining evaluation method: For evaluation of emulsion the staining test is
performed. A dry filter paper impregnated with cobalt chloride turns from blue to pin
exposure to stable o/w emulsion .
4)Determination of Zeta Potential
This can be determined by using ‘zeta meter’ which determines by
Measuring electrophoretic mobility of particles in suspension.
Z = 4πnV/Εe
Where, n = viscosity of suspension
E = applied electric field
e = di electrical constant
V = velocity of particle
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24. List of zeta potential and stability behaviour
Zeta potential (mV) Stability behaviour
0 to ±5 Rapid coagulation / flocculation
±10 to ±30 incipient stability
±30 to ±40 Moderate stability
±40 to ±60 Good stability
> ±61 excellent stability
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25. 5) Determination of globule size
Size of globule is increased over long storage period i.e. it causes
coalescence. So to prevent it, globule size should be small. Globule
size is determined by:-
a) Coulter counter method:
b) Microscopic method:
c) Laser diffraction sizing method:
6) Rheological method
This method ensures flow property of emulsion so as to ensure its
stability. Low viscosity of emulsions causes increase in rate of creaming
leading to instability. Determination of viscosity is done by using brook
field viscometer.
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Sterile solution (SVP & LVP)
 Small volume parenteral (SVP) solutions are usually 100 ml or less
and are packaged in different ways depending on the intended use.
 Large volume parenetral or LVPs (sometimes called large volume
injections) are aqueous solutions usually supplied in volumes of at
least 100 ml with sizes of 250 ml, 500 ml, 1000 ml, 3000 ml, and 5000
ml most common.

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28. IPQC test for sterile solution (SVP and LVP)
1. Uniformity of content
2. Clarity test for (particulate matter method)
3. Leakage test
4. Extractable volume
5. Sterility testing
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29. 1) Uniformity of content
2) Clarity test for (particulate matter method)
Particulate matter is defined as presence of unintentional undesirable
extraneous , mobile and undissolved substances (other than gas bubbles)
within the parenteral preparations. Presence of particulate matter could make
the user to conclude that it is of inferior quality. It has been suggested that as
erythrocytes have a diameter of approximately 4.5µm, particles of more than
5µ should be the basis of evaluation Permissible limits(Maximum limits) for
particulate matter According to IP
Particle size(µm) (Maximum no of particles/ml)
10 50
25 5
50 Nil
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30. I. Light obscuration method
II. counter method Microscopic count method (membrane filtration
method)
3) Leakage test
Ampoules are subjected to leakage test because ampoules are sealed by fusion.
Therefore, there is a chance for a incomplete sealing or for microspores to exist,
allowing the contents to leak or microorganisms and other contaminants to enter the
ampoules.
4) Extractable volume
Where the nominal volume does not exceed 5 ml, the containers comply with the
Requirements of
Method :
5) Sterility testing
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Powder
 Pharmaceutical powder is a solid dosage form comprising of a
large number of finely divided solid particles of drugs or
mixture of drugs and excipients.
 Size of particles ranges from 10mm (1cm) in diameter to 1um
or less

32. IPQC TEST FOR DRY POWDER
1. Appearance
2. Size and shape
3. Bulk density and Tapped density
4. Angle of repose
5. Moisture content
6. Compressibility index
7. Hauser's ratio
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33. 1)Appearance
2) Size and Shape
Sieving
Particle having the size range between 50 and150 m are estimated by this
method. In this method the size is expressed as d sieve which describes the di
meter of a sphere that passes through the sieve aperture as the asymmetric
article .The method directly gives the weigh determination
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34. 3) Bulk Density and Tapped Density
Bulk Density:
Bulk Density=Mass of Powder/Bulk Volume
Tap Density:
Tap Density=Mass of Powder/Tap Volume
4)angle of Repose (θ)
θ = Tan-1
(H/r)
h = height of pile
r = Radius of the base of pile
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35. Shows Angle of Repose Angle of repose Powder flow
25-30 Good
30-40 Passable
> 40 Very poor
5) compressibility Index
it demonstrates the relation between the flow and compressibility of powder
%compressibility=Mass of Powder(tapped density-poured density)/tapped density
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36. Compressibility Index Type of Flow
5-15 Excellent
12-16 Good
18-21 Fair
23-25 Poor
33-38 Very poor
>40 extremely poor
6) Hausner Ratio
Hauser's predict the flow property of powder by using inter particle
friction
Hauser's ratio=tapped density/powder density
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37. Reference
1) Leon Lachman, Herbert A. Lieberman the theory and practice of industrial
pharmacy page no.479-502.
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