The particle Size Wet method is widely used in the Pharma industry to determine the Particle Size distribution (PSD) of a substance. PSD dry method is also another alternate technique.
Particle Size is one of the key physical properties of the substance and is a key technique in the Pharma field. The PSD instrument (Particle Size Analyzer) is used to determine the PSD of a material. Since the Wet PSD technique is critical, a suitable method shall be developed. To cater to the Pharma requirements, an Analytical Method Development procedure is provided as guidance.
Guidance on Particle Size Wet Method Development
Herein useful literature is provided for Particle Size Wet Method Development as guidance. The details are as follows.
Select the medium (Dispersant) that shall be practically insoluble in the test material.
Check the sample dispersion in various solvents & Mineral oils. Better to check it first in light liquid paraffin if the suspension is not good i.e particles are settling down then go for other solvents like n-Hexane, toluene, water, etc.
If particles are sticking to the test tube or dispersion is not good add a suitable surfactant. Whenever suspension is good check the solubility of the sample. By checking obscuration we can confirm the solubility. Approximately the obscuration shall be between 10% to 20%. For finer particles, it shall be between 6% to 10%.
In case of the obscuration decreases it indicates that the sample is dissolving in that medium. If obscuration is stable, means that the sample is not dissolving. In case of the obscuration increases it means particles are breaking.
Go for saturation, if the suspension is good but the sample is slightly dissolving in that medium. (Preparation of saturation: Take 2 to 3 grams of sample dissolved in selected solvent mix well and sonicate for 15 minutes. Then filtrate the solution by using 0.45µm-membrane filter paper and collect the filtrated solution as a saturated solution).
If the suspension is good prepare the sample solution (200mg/20ml of dispersant) and keep the stirring speed at 2000rpm initially and then give the Refractive index (RI) value for the particle (Generally the default value is 1.5) and dispersant (depends upon the dispersant medium) followed by absorption value of the particle.
Dispersant RI is available with System Manual.
Procedure for Analysis of Particle Size Wet Method
Follow the below analytical procedure for the Particle Size Wet Method.
After fixing all the parameters, analyze the sample as per created SOP (method) and check the histogram.
The peak shall be bell shape or Gaussian shape. If any small peaks appear before the main peak, minimize those by changing the stirring speed, Cyclo-mixture time or sonication time, or absorption value.
There shall not be any peak after the main peak (due to agglomeration) if it is not removed change the medium to get a better histogram.
After finalizing the medium check the stirring speed at 1800, 2000, 2200, 2500, and 3000RPM then confirm which stir speed is giving more size, accuracy, and good histogram. At each stir, speed does three replications to check the consistent values.
In the above, all trials keep in mind that the residual shall not be more than 1.0%.
The finalization of the Developed Method will depend on the reproducibility, repeatability, and batch analysis results.
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Particle Size Wet Method Reproducibility
This is a critical parameter in the development of the Particle Size Wet Method. To understand the fitness of the method follow the below procedure.
In reproducibility prepare six different preparations and analyze each once. In repeatability prepare one preparation and analyze it six times using the same solution and check the results at 10%, 50%, and 90% levels.
For the material that has a D (0,5) greater than 10µm
D (0,5) RSD< 10%
D (0,1) and D (0,9) RSD< 15%
For the material that has a D (0,5) less than 10µm, the maximum values are doubled.
If results are within acceptance criteria then this tentative method can be used for regular analysis.
The method validation will decide the confirmation of the tentative method.
Optimize the sonication time by studying at different sonication timings from initial to several minutes. The criteria to be met are, the sample shall not be dissolved, Obscuration shall be as mentioned above and % residuals shall not be more than 1 %.
Method, cross-checking is also to be made against a simple dry powder method. Compare the data against the developed wet method. So as to results shall be comparable or justifiable.
Surfactants used for Particle Size Wet Method Analysis
Types of surfactants available in the market are as follows:
- DOSS [Di Octyl sodium sulfo-succinate]
- SBSS [Sodium bis(2-ethyl hexyl) sulfosuccinate)
- Span 85
- Tween 20
- Tween 80
- Coulter IA
- Nonidet P40
- Triton X100
- Imbentin- AGS/35
- Teepol
- Triton XL 80 N
Chose one of the above surfactants for Particle Size Wet Method Analysis/Technique.
Note:
Use the dry powder method for materials consisting of more than 5 microns
In the dry powder method, particles shall not be fragile nature and fine needles in nature.
Using a microscope, particle size, and shape can be expected, so method selection can be made with respect to the nature of the particle.
Perform the method development activity for sifted, milled, and micronized type materials.
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