Development and Validation of New Analytical Method for the Determination of Particle Size Distribution in Glimepiride Using Laser Based Particle Size Analyzer

Particle size is a key factor for modern drug quality since it affects the bioavailability and dissolution profile of the drug product. Study for Particle size is helpful to optimize drug product development process and improve the quality of drugs. In Order to determine the particle size of Glimepiride a novel and accurate Particle size determination method has been developed for the determination of particle size distribution of Glimepiride was described in this paper. This method has shown good reproducible results. By using water as dispersant wet method is developed and validated as per International conference on Harmonization guidelines (Q2 (R1)) and found out robust and reproducible with % RSD of d (10), d (50) and d (90) values found within acceptance limit ranges from 6.05% to 21.84% for d(0.1), 3.04% to 9.87% for d(0.5) and 4.69% to 14.32% for d(0.9) in validation. The described method is accurate and validated and successfully applied for the determination of particle size distribution of Glimepiride. Particle size method is discussed in detail to ensure in-depth understanding of particle size distribution and particle size method performance during lifetime of the product.

Relative bioavailability, extended-released along with bioequivalence and immediate released is related to particle size of Glimepiride [9][10][11][12].Literature survey done for Particle size distribution method for Glimepiride and found that particle size determination method is not available.Therefore, study was carried out to develop a method to determine particle size distribution of Glimepiride by Particle size analyzer and further validation of the method, was carried out.

Reagents
Triton x-100, water and Glimepiride was obtained from Indoco Remedies Ltd, Navi Mumbai, India.

Instrumentation
Particle size analyzer system of make Malvern and model is 2000 consists of Dry Scirocco 2000 and wet Hydro2000S accessories.

Analytical method development
The main goal was to develop method to obtain the most stable, reproducible, reliable method.Various dispersant were tried for the Glimepiride on the basis of solubility.Water is found well suitable dispersant to develop method for determination of particle size distribution of Glimepiride.Various trial were taken during method development as mention below, Glimepiride solubility within a suitable solvent system a critical role in particle size wet method development since sample preparation is play vital role.All method parameters were kept as per above only changed in sonication time 50 Sec.and performed the analysis.The obscuration is well within limit it is proved that there is no any effect of sonication time on particle size, Hence, preceded for next trial by changing stirrer speed check the effect on particle size.The obscuration values are well within the limit, from the obtained results there is negligible effect on the particle size by decreased in stirrer speed.

Method validation
The validation work was conducted according to the ICH (International Conference on Harmonization) guidelines Q2R1.The method validation parameters include Precision, Intermediate Precision, Robustness and Batch Analysis.

Method precision
Procedure: Determined the particle size of six precision samples as per above method and recorded the particle size for d(0.1), d(0.5) and d(0.9) in

Intermediate precision
Procedure: Determined the particle size of six Intermediate precision samples as per above method and recorded the particle size for d(0.1), d(0.5) & d(0.9) particles in Table 2 and similarly, calculated cumulative average and cumulative percent relative standard deviation for particle size at d (10)    Acceptance criteria: The % RSD d (10), d(90) particle size values should not be more than 15, d(50) particle size values should not be more than 10.If the particle size is below 10 µm then the % RSD of d (10), d(50), and d(90) will be doubled.

Robustness-2 (change in stirrer speed to 2200 rpm)
Procedure: Determined the particle size of three replicates as per method of analysis, only change the stirrer speed to 2200 rpm and recorded the particle Size for d(0.1), d(0.5) & d(0.9) in Table 4 and similarly, calculated cumulative average and cumulative percent relative standard deviation for particle size at d (10)

Robustness-4 (change in obscuration range to 20-30%)
Procedure: Determined the particle size of three replicates as per method of analysis, only changed the obscuration range to 20 -30 % and recorded the particle size for d(0.1), d(0.5) & d(0.9) in Table 6 and similarly, calculated cumulative average and cumulative percent relative standard deviation for particle size at d (10) Mastersizer, Model Mastersizer 2000, Dispersion Unit Scirocco 2000, Method parameters are kept as Particle Refractive index is 1.520, Absorption is 0.1, Analysis Model General purpose, Obscuration range is 1% to 6%, Dispersive Air pressure is 2.0 bar, Vibration feed rate is 40%, Sensitivity is Normal, Sample measuring time 5 seconds, Background measuring time 5 seconds, sample preparation is Transferred about 1 to 2 g of sample into the sample tray Citation: Gosar A, Jadhav S, Patil V, Folane S, Jadkar A, et al.Development and validation of new analytical method for the determination of particle size distribution in glimepiride using laser based particle size analyzer (2019) Edelweiss Appli Sci Tech 3: 309-312 310 with the help of a cleaned spatula and carried out the analysis The obscuration values are well within the limit and also weighted residual is less than 1%.Hence, proceeded for next trial by changing the feed rate 45% to check the effect on particle size.Various trials were taken by changing instrumental parameters.The obtained results of d(10), d(50) and d(90) values are not reproducible and % RSD is also not well within general criteria of USP, General Chapter <429>.Hence next development was carried out by wet analysis.Method parameters for wet analysis is Equipment Malvern Mastersizer, Model Mastersizer 2000, Sample handling unit is Wet Dispersion Unit, Sample model is Hydro 2000S, Dispersant name is Water, Dispersant refractive index is 1.330, Sample refractive index is 1.520, Sample absorption is 0.1, Sample measurement time is 10 second, Measurement Snaps is 10,000.Background Measurement is 10 second, Background Snaps 10,000, Obscuration range is 10-30%, Stirrer speed is 2000 rpm, No. of measurement cycle 03,sample preparation is Weighed 200.26 mg of sample and transferred in beaker added 1-2 drops of Triton x-100 and few drops of dispersant and make a paste by using glass rod, then added 20 mL of dispersant.Sonicate externally for 40 seconds to form homogeneous solution.Sample solution was added in the dispersion unit when "Add sample under Obscuration" message was shown by the instrument software and performed the analysis.
Acceptance criteria: The % RSD d(10), d(90) particle size values should not be more than 15, d(50) particle size values should not be more than 10.If the particle size is below 10 µm then the % RSD of d(10), d(50), and d(90) will be doubled.
Acceptance criteria: The % RSD d(10), d(90) particle size values should not be more than 15, d(50) particle size values should not be more than 10.If the particle size is below 10 µm then the % RSD of d(10), d(50), and d(90) will be doubled.

Robustness Robustness- 1 (
change in stirrer speed to 1800 rpm) Procedure: Determined the particle size of three replicates as per method of analysis, only change the stirrer speed to 1800 rpm and recorded particle Size for d (0.1), d(0.5) & d(0.9) in Table 3 and similarly, calculated cumulative average and cumulative percent relative standard deviation for particle size at d(10), d(50) & d(90) of nine measurements i.e. six of precision and three of Robustness-1.Citation: Gosar A, Jadhav S, Patil V, Folane S, Jadkar A, et al.Development and validation of new analytical method for the determination of particle size distribution in glimepiride using laser based particle size analyzer (2019) Edelweiss Appli Sci Tech 3: 309-312 311 Acceptance criteria: The % RSD d(10), d(90) particle size values should not be more than 15, d(50) particle size values should not be more than 10.If the particle size is below 10 µm then the % RSD of d(10), d(50), and d(90) will be doubled.Robustness-3 (change in Obscuration range to 10-20%)Procedure: Determined the particle size of three replicates as per method of analysis, only change the obscuration range to 10-20% and recorded the particle size for d(0.1), d(0.5) & d(0.9) in Table5and Similarly, calculated cumulative average and cumulative percent relative standard deviation for particle size at d(10), d(50) & d(90) of nine measurements i.e. six of precision and three of Robustness-3.
Acceptance criteria: The % RSD d(10), d(90) particle size values should not be more than 15, d(50) particle size values should not be more than 10.If the particle size is below 10 µm then the % RSD of d(10), d(50), and d(90) will be doubled.
Acceptance criteria: The % RSD d(10), d(90) particle size values should not be more than 15, d(50) particle size values should not be more than 10.If the particle size is below 10 µm then the % RSD of d(10), d(50), and d(90) will be doubled.Robustness -5 (change in sample measurement time to 9 seconds from 10 seconds)Procedure: Determined the particle size of three replicates as per method of analysis, only changed the sample measurement time to 3 seconds and recorded the particle size for d(0.1), d(0.5) & d(0.9) in Table7and similarly, calculated cumulative average and cumulative percent relative standard deviation for particle size at d(10), d(50) & d(90) of nine measurements i.e. six of precision and three of Robustness-5.

Table 2 :
, d(50) & d(90) of twelve measurements i.e. six of precision and six of Intermediate precision.Intermediate precision.