Evaluation of Ophthalmic Preparations

Evaluation of Ophthalmic Suspension:

Tests for Physical Stability (include the General Test):

(a) Sedimentation rate:

• The rate at which the suspension particles settle in the vehicle is called sedimentation rate.
• The ratio of the sedimentation volume to time gives the sedimentation rate.
• Different samples of the suspension are taken and sedimentation volumes are determined graph plotted between the sedimentation volume (on the y-axis).
• Time (on the x-axis)-horizontal curve and slope of the graph gives the sedimentation rate.
• The sedimentation rate should be low to facilitate the installation of a uniform dose each time.

(b) Redispersibility:

• The sediment formed during storage of the suspension should be easily dispersible by normal shaking to provide a uniform dose at all times.
• Redispersibility depends on the surface tension of a suspension.
• Different samples are collected and the surface tension of each is determined.
• The lesser the surface tension of a sample, the more dispersible it is.

(c) Viscosity:

• Using Brookfield viscometer, the viscosity of different samples is determined.
• More is the viscosity of a sample, less is the rate of setting of particles and more is the stability.

(d) Particle size:

• Smaller particles settle at a slow rate and implicate the stability of a suspension
• Using colter counter apparatus or photomicroscopy.
• The particle size of the different samples is determined.
• Out of the 50 particles tested, 20 are not more than 25 µ, 10 are not more than 50 µ and no particle is more than 100 µ in size.

Evaluation of Ophthalmic Ointment:

(a) Test for Minimum Fall:

• Nearly five ointment tubes are selected at random.
• The net weight of the ointment in each tube is determined.
• The result should match with the quantity specified on the label of the tubes.
• This test is to be as certain that each tube is filled with the minimum specified quantity.

(b) Test for Metal Particles:

•  This test is to be certain that the ointment is not contaminated by the particles of the packaging material which can irritate the ocular tissue.
• Different samples are collected from ten ointment tubes.
• Each sample is melted using heat.
• Then examined under a microscope for metal particles.
• The particles identified are counted and their size is measured with the help of an eyepiece micrometer.
• For the total samples, the total number of metal particles (sized 10 µm or more) is more than 50 and only one sample contains more than 8 particles.

(C) Squeesability:

• Represent the product output and the minimum amount to be expelled out.

Evaluation of Ophthalmic Emulsion:

The quality of the emulsion can be determined by:

• Globule size
• Globule size distribution
• Physical appearance
• Spreadability

Evaluation of Ophthalmic Gels:

• Viscosity
• Clarity
• Spreadability
• Residence time

Evaluation of Ophthalmic In-situ Gel:

 (i) Gelling time:

• The time taken by the gel-forming solution to transform into the gel phase is called gelling time.
• The gelling time should be less so that the onset of action will be fast.

(ii) Viscosity:

• It is checked at both room temperature and body temperature.

Evaluation of Ophthalmic Injection:

1. Test for Pyrogens: Ophthalmic injections are tested for the presence of pyrogen.

• Pyrogens are endotoxins that are produced by gram-negative bacteria.
• The test for pyrogens is carried out on aqueous preparation also.
• Rabbits are the test animals that are considered for test for pyrogen of quick response and it should be around 1.5 kg.

(a) Selection of rabbit /animal: condition:

• The weight of the rabbit is 1.5 kg – 2.5 kg and it should be constant.
• It should be free from disease.
• The washout period should be a minimum of 2 weeks to be considered.

Procedure:

• The rabbit should have a normal temperature (body temperature of 38.3o C- 39.4o C (101o F -103o F).
• A body temperature greater than 49.8 oC should not be selected for the test.
• If any rabbit has been used for the positive test during the last 2 weeks or negative test during 2 days should not be selected again for the test.
• Syringes or needles or glass was used in this procedure should be free from pyrogen
• It can be sterilized by heat.
• The animal has to fast for 12 hours before the test and then be injected into the ear vein.
• Observe the changes.
• Once after injection, the temperature has to be observed after 1-2 hours.
• The different initial and final temperature readings should not excess 1-4o C (for average animals) and should not exceed 0.6o C (for individual animals).

(b) LAL test (Limulus amoebocyte lysate test):

• For identification of gram-positive bacteria.
• An enzyme is produced by a horseshoe crab.
• Test for particulate matter

To identify particulate matter, four different methods are used:

• Visual method
• Light blockage method
• Filtration method
• Coulter counter method

(i) Visual methods: The sample is filled in the container and is carried out to identified the foreign particles against a black and white background in presence of light. In the case of a colorless solution, white background is used and for a colored solution, black background is used.

(ii) Light blockage method: Instrument consists of the bright white light source and photodiode sensor.

• The sample to be tested is allowed to pass through the instrument.
• The stream of the sample solution passes between the light source and the photodiode sensor.
• The instrument measures the cross-sectional area of the particles and the size of the particles can be easily determined by the method is employed for hydraulic oils.

(iii) Filtration method: The samples are filtered through a membranes filter with a pore size of 0.02 µm.

• The particle should be microscopy (to know the particle size and weight) if the particle is higher it has to be discarded.

(iv) Coulter counter method: The colter counter is an electrical method to determine the particle size.

• It consists of two electrodes and an orifice.
• Electrodes are connected to an amplifier.
• When a particle passes through the orifice, increased electrical retention is observed.
• This is because the particle displaces its volume of the electrolyte, hence particle size is determined.
• The determined particle size of diameter below 0.1 mm.

2. Packaging Test /Test for Packaging:

(i) Leakage test: The test is carried out in ampoules.

• This method is employed to see whether the ampoules which are sealed by the fusion method are intact or not.
• In the vacuum chamber, vacuum is applied and ampoules are dipped in 1% sodium methylene blue solution.
• After releasing the vacuum, the ampoules are checked for leakage if any evaluation is done by examining whether the dye enters the ampoules or not.
• If the preparation becomes colored it indicates there is leakage in the container, hence the particular batch will be rejected.

(ii) Spark detector method: This is also a method of determination of leakage in the container carried out if the pot present in the ampoules is thermolabile (e.g. vaccine).

• The ampoule contains an inert gas and the sample is introduced into the spark detector, the gas inside the impulse gloves.
• This indicates that the container is intact and free from any leakage.

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