Transcript ophthalmic products

DEPT. OF PHARMACEUTICS,

CONTENTS:
1.INTRODUCTION.
i.
Definition.
ii.
ideal properties of ophthalmic preparation.
iii.
Types of ophthalmic dosage forms
2.MANUFACTURING OPERATION
i . Area requirement.
ii. Equipments as per schedule M.
iii. Packaging.
iv. Process flow chart.
3.FACTORS AFFECTING OPHTHALMIC STABILITY.
4. QUALITY CONTROL TESTS.
5. DOCUMENTATION.
6. REFERENCES
OPHTHALMICS PRODUCTS :
Ophthalmic preparation are sterile Product that are
intended to be applied to the eyelids or placed in the
space between the eyelids and the eyeball.
Ideal properties for ophthalmic
preparation.:

Sterility. (Avoidance of pyrogens )
 Preservation.
 Tissue compatibility.
 Suitable packaging.
 Must be isotonic with lacrymical fluids.
 should have P H approx 7.4.
 viscosity.
Types of ophthalmic dosage forms.:
1) SolutionsADVANTAGES
-convenience
DISADVANTAGES
- rapid corneal elimination.
- loss of drug by drainage.
- No sustained action
2) SuspensionsADVANTAGES
- patient compliance
- slow dissolution
DISADVANTAGES
- loss of both solution
& suspended solid.
3.EMULSIONS:
 Advantages:
prolonged release
 Disadvantages:
Patient non compliance.
Blurred vision.
4. OINTMENTS:
Advantages:
improved drug stability
Disadvantage:
poor patient compliance
5.GELS:
Advantages:
-comfortable
-less blurred vision than ointments.
Disadvantage:
-no rate control on diffusion.
6.Erodible inserts:
Advantages:
-effective
-need only to be introduced into eye,
and not removed.
Disadvantage:
-patient discomfort
-occasional product.
7.Non-erodible inserts:
Advantages:
-prolonged delivery
-controlled rate of release.
Disadvantage:
-tissue fibrosis
-patient discomfort
-irritation to eye.
FORMULATION
1. Vehicles:
There are two types of vehicles which are:
i. Aqueous vehicles:- e.g. Water is used as vehicle because water is
tolerated well by the body
ii. Non-aqueous vehicles:- e.g. Oils and Alcohols, such as, fixed oils, almond
oil,, ethyl alcohol, propylele glycol.
2. Adjuvants:
Thickening agents - methyl cellulose.
- carboxy methyl cellulose.
- polyvinyl alcohol.
- polyethylene glycol.
Buffers - Boric acid.
- Sodium acid phosphate.
- Sodium citrate.
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Anti-oxidants.:
They are added to provide protection from Oxidation.
e.g - Sodium metabisulphite
- Sodium thiosulphate
- Thiourea .
- ascorbic acid.
Wetting agents.
e.g. Polysorbate 20
Polysorbate 80
Commonly used tonicity adjusting agents are
Nacl , Kcl , buffer salts, dextrose,glycerin ,
propylene glycol and mannitol .
Preservatives.
- Benzalkonium chloride
- Phenylmercuric acetate
- Phenylemercuric nitrate
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VARIOUS FACTORS AFFECTING
STABILITY OF FORMULATIONS
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Temperature.
pH.
Excipients.
Oxidation.
Light.
packaging.
Manufacturing considerations:
 Manufacturing Environment:
 The environment should be sterile and particle-free
through:  Laminar-flow should be used throughout the
manufacturing area.
 Relative humidity controlled to between 40 and 60%.
 Walls, ceilings and floors should be constructed of
materials that are hard, non flaking, and non-affected
by surface cleaners or disinfectants.
Manufacturing Environment:
FLOW DIAGRAM SHOWING ARRANGEMENT OF
DIFFERENT AREA
PREPARATION
AREA
ASEPTIC
AREA
QUARANTINE
AREA
RAW
MATERIAL
STORAGE
AREA
CLEAN UP
AREA
STERILIZATTI
ON
PACKAGING
AREA
STERILIZATION
WFI
INGREDIENTS
VEHICLES
ADDITIVES
COMPOUNDING
EQUIPMENTS
PACKAGING
MATERIAL
FILTRATION
ASEPTIC
FILLING
AND
SEALING
INSPECTION
AND
INPROCESS
QC
PACKAGING
AND
LABELLING
CONTAINERS
EQUIPMENTS
CONTAINERS
CLOSURES
WASHING
STERILIZATION
FINISHED
PRODUCTS
STORAGE
PRODUCT
OUTPUT
PROCESS FLOW CHART
MANUFACTURING OPERATION
1) AREA REQUIREMENT
 Minimum of 10 m 2 → for ancillary area.
 Minimum of 25 m 2 → for basic installation.
 Areas must meet the requirements of class 1,00,000 space in
all areas where open containers and closures are not
exposed or filling and capping operations are not taking
place.
 Manufacturing & filling shall be carried out in air –conditioned
areas under aseptic condition (class 100).
 The rooms shall be further dehumidified as considered
necessary if preparation containing antibiotics are
manufactured .
 Equipments as per schedule M.:
For Ophthalmic solutions & suspensions
1) Jacketed kettle/stainless steel tanks(steam gases electrically heated).
2) Mixing & storage tanks of stainless steel/planetary mixer.
3) Sintered glass funnel.
4) Liquid filling equipments (semi automatic & automatic filling machine).
For Ophthalmic Ointments
1)Colloid mill/ointment mill.
2) Tube filling & crimping equipment(semi automatic & automatic filling
machine).
3) Tube cleaning equipments (air jet type).
4) Tube washing & drying equipments.
EQUIPMETNS
1)Thermostatically controlled Hot air oven. (preferably double ended)
2) Autoclave.
3) Air conditioning & dehumidification arrangement.
4) Laminar air flow units.
6) Automatic vial washing machine.
7) Vial drying oven.
8) Distillation unit.
9) Packaging & labelling.
10) Inspection machine.
Multicolumn distillation unit:
 Multicolumn distillation unit
specially designed columns .
(Principle inter stage heat exchange).
 stainless steal & Teflon.
 Spiral baffle system.
( centrifugal force)
SS Tank with Stirrer Manufacturing vessel:
-Available from
50 ltrs to 10,000 ltrs.
-With SS steam jacketed &
insulation with SS cladding.
-Different type of stirrer (paddle/
anchor/propeller) available.
-Electric heating also possible
for small scale.
Triple roller mill
-It’s used for grinding ointment,
pastes, paints, etc.
- Side scrappers moves up and
down with compression spring
and knob to secure appropriate
working pressure
-Tube holders are of spring loaded
type to take care of any tube
diameter variation.
- Fill accuracy : + 98.8 %.
-Useful in filling paste, lotion,
cream, gums, etc.
-Accurate tail cutting arrangement.
Audio alarm.
Output up to 50 - 55 Tubes/minute.
Can fill from 3 Grams to 500 Grams.
GMP model contact parts SS 304 / SS 316
(As per customer requirement).
Power consumption 0.75 HP,
230 Volts / 415 Volts.
- Overload c protection.
memory to indicate the number
of filled tubes.
Vial filling machine :
-Suitable for 2 ml to 30 ml vials
- Output Speed up to 120 VPM
STEAM STERILIZER or AUTOCLAVE:
PACKAGING:
Plastic containers → ease of use.
→ little breakage.
→ less spoilage.
 Large volume intraocular solutions of 250ml &500ml have
been packaged in glass.
Type 1 glass vials with appropriate stoppers are used for
intraocular ophthalmic products administered by injection.
 Different ophthalmic cap colour coding are given by the
FDA.
OPHTHALMIC CAP COLOR CODING :
color
Pharmaceutical class
Yellow or blue
Beta blockers
Gray
Colour
pink
Yellow or blue
Non steroidal
Pharmaceutical class
steroidal
Beta blockers
Gray
Pink
brown
Brown
orange
Orange
Turquoise
redRed
Green
green
Non steroidal
Steroidal
Anti infective
Anti infective
Carbonic anhydrase
Carbonic anhydrase inhibitors
inhibitors
Prostaglandins
mydriatics
Mydriatics
mitotic Mitotic
QUALITY CONTROL SPECIFICATION
 1) Raw material
- Description
- Moisture content
- Assay of ingredient
3) In process Product
a) Mixing
- Assay
- Grittiness
- Viscosity
- Density
- pH
2) packing material
- Compatibility
- Stability
- Purity
b) Filling
- weight variation
- content uniformity
4) Product Specification
a)Microbial specification.
- limit for total microbial count.
- Absence of specific microorganism as per pharmacopoeia.
b) Chemical specification.
- pH.
- Content uniformity.
- Chemical potency.
c) Physical specification.
- clarity.
- Particle size.
- Density.
- Viscosity.
Evaluation of final product:
 Evaluation is the test of the finished ophthlmic products are
free from of micro organism or not.
 Evaluation of the opthalmic products is done by following
tests.
1. Sterility test
2. Clarity test
3. Leaker test
4. Metal particles in ophthalmic ointments
Sterility Test:
 Two basic methods for sterility testing.
 Direct inoculation method : Involves the direct
introduction of product test samples in to culture media.
 Membrane filtration method: Involves filtering test
samples through membrane filter, washing the filter with
fluid to remove inhibitory property and transferring the
membrane aseptically to appropriate culture media.
Detection of contamination using two culture media A. Soybean- Casein digest medium incubated at 20o to 250C
B. Fluid thioglycollate medium incubate at 300 to 350C on 7
days
Clarity test:
 Ophthalmic solutions by definition contains no undissolved
ingredients and are essentially free from foreign particles.
 Visual inspection- under a good light , baffled against
reflection in to the eyes, and viewed against a black and
white background, with the content set in motion with a
swirling action .
 Instrumental method utilizing the principle of light
scattering, light absorption and electrical resistance to obtain
particle count and size distribution-destrution of product
units- only for quality control testing.
 Instrumental method utilizing video image projection
detects moving particles without destrution of product unitsused for inline detection.
Leaker test:
 Select 10tubes of the Ointment with seals applied when specified.
 Thoroughly clean and dry the exterior surfaces of each tube with
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an absorbent cloth.
Place the tubes in a horizontal position on a sheet of absorbent
blotting paper in an oven maintained at a temperature of
600±30for 8hours.
No significant leakage occurs during or at the completion of the
test.
If leakage is observed from one, but not more than one, of the
tubes, repeat the test with 20 additional tubes of the Ointment.
The requirement is met if no leakage is observed from the first 10
tubes tested, or if leakage is observed from not more than one of
30 tubes tested.
Metal particles in ophthalmic ointments
 Extrude, as completely as practicable,the contents of 10 tubes
individually into separate,clear,flat-bottom,60-mm Petri
dishes that are free from scratches.
 Cover the dishes, and heat at 85 for 2 hours, increasing the
temperature slightly if necessary to ensure that a fully fluid
state is obtained.
 Taking precautions against disturbing the melted sample,
allow each to cool to room temperature and to solidify.
 Remove the covers, and invert each Petri dish on the stage of
a suitable microscope adjusted to furnish 30 times
magnification and equipped with an eye-piece micrometer
disk that has been calibrated at the magnification being
used.
 Examine the entire bottom of the Petri dish for metal
particles.
 Count the number of metal particles that are 50µm or larger
in any dimension
The requirements are met if the total number of such
particles in all 10tubes does not exceed 50, and if not more
than 1tube is found to contain more than 8 such particles.
 If these results are not obtained, repeat the test on
20additional tubes:
The requirements are met if the total number of metal
particles that are 50µm or larger in any dimension does not
exceed 150in all 30tubes tested, and if not more than 3 of the
tubes are found to contain more than 8 such particles each.
Documentation:
 Master formula records.
 Batch formula records.
 Equipment & containers records.
 Filtration & filling records.
 Batch Packaging & Labeling Records.
Master formula records
Name of the product________________________________________
Name and Weight of API ____________________________________
Name and Weight of Ingredients _______________________________
Description of equipment ____________________________________
Statement of theoretical yield_________________________________
Process and packaging procedure_____________________________
A description of container____________________________________
Closure and packaging material _______________________________
In process control during processing ___________________________
In process control during packaging____________________________
Precaution to be taken______________________________________
Batch Manufacturing Records
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Name of the company:_________________________
Address:-_____________________
Name of the product___________________
Active pharmaceutical ingredient________________
M F R No. ___________________________________
Batch No._____________________
Batch size ____________________
Mfg. date _____________________
Date of expiry_________________
Requisition slip
Sr no Ingredients Item code Standards
ATR no Label
claim
Qty required
Qty issued
Equipment & containers records
 Description of containers _______________________________________
 Q/C report of container ________________________________________
 Date ________________________
 Equipment used__________________
 Cleaning agent used ______________________________________
 Cycle of washing: _____________________________________________
 Sign. Of officer______________________
If sterilized by dry heat or autoclave :
Articles
Date Time when
oven started
Desired temp.
attained
Temp.
Time when
oven switched
off
REFERENCES:
 Remington-The science and practice of pharmacy 21 st
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edition volume I.
Controlled drug delivery by N.K.Jain , Page
No.(82,85,86,92,94-96).
Indian pharmacopiea , 2007 . vol – 1.
Controlled drug delivery by Roop K.Khar & S.P.Vyas , Page
No.(384-397,399,403).
Modern pharmaceutics edited by Gilbert S. Banker.
THANQ