Problem Statement :-

A sterile ophthalmic suspension of a micronized steroidal drug was developed using

the formula mentioned below. After the serial addition of all the ingredients in the
manufacturing vessel, the batch was mixed at 150-200 RPM. After 10 mins of
mixing under a vacuum of -0.5 bars, the content uniformity in the manufacturing
vessel was assessed by sampling from the top, middle, and bottom of the
manufacturing vessel and was subjected to HPLC analysis. The assay of the top
sample was found to be 120%, the middle sample was 105% and that of the bottom
sample was found to be 85%. What changes would you recommend?
Formula:
Steroidal drug (micronized)- 1%
Polysorbate 40- 10%
Sodium chloride- 0.9%
Sodium citrate- 0.9%
Disodium EDTA – 0.05%
Benzalkonium Chloride – 0.01%
Sterile water- - qs to 100

Group code:- UG08

Solution:
The composition of the formulation is as follows :-
1. Steroidal Drug: The concentration (1%) is within safe and effective ranges for ophthalmic
administration.

2. Polysorbate 40: Commonly used as a surfactant and emulsifier in ophthalmic formulations to

improve solubility and stability. The concentration (10%) appears to be appropriate for this purpose.

3. Sodium Chloride: Included to adjust tonicity and isotonicity. The concentration (0.9%) is typical for
isotonicity adjustment in ophthalmic solutions.

4. Sodium Citrate: Included as a buffering agent. The concentration (0.9%) seems reasonable for
buffering purposes.

5. Disodium EDTA: A chelating agent enhances stability by binding metal ions which catalyze
degradation reactions. The concentration (0.05%) appears appropriate for this purpose.

6. Benzalkonium Chloride: A preservative used to prevent microbial contamination. The concentration

(0.01%) is typical for ophthalmic suspensions.

7. Sterile Water: Used as a vehicle.

 Some suggestions for improvement are:
Mixing Procedure:

1. Consider optimizing the mixing procedure to ensure better content

uniformity throughout the batch. The variation in assay levels (120%,
105%, 85%) suggests uneven dispersion of the steroidal drug within the
suspension.

2. The mixing speed should be of 400-600 RPM for about 10-15

minutes.

3. Ensure that the mixing duration should not exceed 15 minutes, as

doing so may increase the shear rate.
Equipment recommendations:
Exertion of a homogenizer as a mixing equipment initiates many
advantages:

1. Effective homogenization results in a smaller particle size for a

more even distribution of active ingredients.

2. It can also help improve the stability of otherwise unstable active

ingredients., increase efficacy and thus reduce cost as well.

3. Homogenizing should be done in up and down oscillations.

The propellant should be placed in the middle of the vessel. Mixing
equipment
Ultrasonic Homogenizer
Increase the sampling points

1. Sampling should be done from various points of the vessels.

2. Sampling from only three locations (top, middle, bottom) may not
adequately represent the entire batch.

3. To ensure content uniformity, sampling should be done at various

established standard heights
.
 Validation :
• Validation is a critical aspect of ensuring
the safety, efficacy, and quality of
pharmaceutical products.
• This involves demonstrating that an
analytical method used for testing
pharmaceutical products is suitable for its
intended purpose, providing accurate and
reliable results.
• Evaluate the HPLC analysis method used
for assessing content uniformity. Ensure that
the method is sensitive, accurate, and
capable of detecting any potential variations
in drug concentration throughout the batch.
• By implementing these recommendations, we
can enhance the uniformity and consistency
of the sterile ophthalmic suspension
formulation.

THANK YOU