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Ravichandhran. V. Process Optimization of Pantoprazole Sodium Enteric Coated Tablets. Biosci Biotechnol Res Asia 2009;6(2)
Manuscript received on : July 20, 2009
Manuscript accepted on : September 02, 2009
Published online on:  28-12-2009
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Process Optimization of Pantoprazole Sodium Enteric Coated Tablets

V. Ravichandhran

Department of Pharmaceutics,Vels College of Pharmacy, Pallavaram, Chennai India.

Corresponding Author E-mail: sen03mpharm@gmail.com

ABSTRACT: Pantoprazole is proton pump inhibitor, which prevent the production of acid in the stomach. Pantoprazole sodium enteric coated tablets were prepared by direct compression method. During this study the process parameters like granulation process, Compression process and Coating process are optimized by conducting the study with various blending time, blending speed, compression machine speed, pan speed, spray rate, spray gun distance to tablet bed, atomizing air pressure. Based on the evaluation results of various trials the optimum process parameters are selected (bending time-23min,blending speed- 6rpm, compression speed-30rpm, pan speed-9rpm, spray rate- 70ml/gun/min, spray gun distance to tablet bed- 24cm and atomizing air pressure-6kg/cm2). By using this optimized parameters the final batch was prepared it was subjected to evaluation. The results are correlated with the standard specified limits.

KEYWORDS: pantoprazole sodium; process optimization; Granulation process; Compression process

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Introduction                                                                                                              

Optimization is the discipline of adjusting a process so as to optimize some specified set of parameters without violating some constraint. The most common goals are minimizing cost, maximizing output, and/or efficiency. This is one of the major quantitative tools in industrial decision making. It is a useful tools to quantitative a formulation that has been qualitatively determined. The development of formulation or process a series of logical steps are performed changening one variable at a time until a satisfactory and best formulation or process is produced

Objective

The major objective of the present investigation is to optimize the process parameters during preparation of Pantoprozole sodium enteric coated tablets. This work involves two important steps. First step is to study the Granulation, Compression & Coating Processes and parameters. Second step is going to optimize those parameters to be effected by taking different trial batches.

Materials and Methods

Pantoprazole sodium was prepared by direct compression method by using Hypromellose,  Mannitol Crospovidone, Methacrylic acid co polymer type ‘c’ USP, Polyethylene Glycol, Calcium stearate and Titanium dioxide. Optimization of granulation parameters at blending stage (Mixing speed and Mixing time), tablet compression parameters (Compression machine speed), tablet coating parameters (Spray rate, Pan speed, Spray gun distance to tablet bed, Atomizing air pressure )were optimized by conducting various trials(BI,BII,BIII)

Characterization of tablets

 The properties of enteric coated tablet, such as thickness, hardness, friability, weight variation and content uniformity were determined using reported procedure.

In vitro release studies

The in vitro dissolution studies were performed using USP dissolution apparatus (paddle) type at 100 rpm. The dissolution medium consisted of 0.1 N hydrochloric acid for first 2h and subsequent 1h in phosphate buffer pH 6.8

Results and Discussion

The process optimization was determined by different parameters.

Granulation parameters

The optimum blending time was selected by carrying out blending at different duration of time i.e. 18min, 20min, 23min, and 25min, out of that optimum blending time was found to be 23min. During this study, the % drug content in 18min, 20min showed very lesser when compared to 23min and 25 minuts.There is no significant difference in % drug content in 23 and 25 minuts. So optimum blending is time 23min. The optimum blending speed was selected by carrying out blending at different rotation per minute (RPM) namely 4rpm, 6rpm, and 8rpm; out of these the optimum blending Speed was found to be 6rpm. The % drug content was very less with blending speed 4 rpm when compared to 6rpm and 8rpm.In the blending speed of 6rpm and 8rpm there was no significant changes in the % drug content. So optimum blending speed is 6rpm.

Compression parameters

The optimum compression machine speed was selected by running the machine at varying speed from 20 to 35 rpm. It was found that 30 rpm was the optimum speed because above that quality of product is not consistent.

Coating parameters.

The optimum coating pan speed was selected by running the coating pan at varying rpm from 8 to 10 rpm. When it was subjected to 8 rpm, it showed the differences in average weight in all the three batches. Where as in 9 rpm and 10 rpm, the results were correlated with the specification. So optimum coating pan speed is 9 rpm. The optimum atomizing air pressure was selected by continuously changing the air pressure from 5 to 7 kg/cm2, out of these optimum atomization air pressures was found to be 6 kg/cm2. In 5kg/cm2 and 7 kg/cm2 atomizing air pressure, the average weight of tablet showed significant differences. When it was subjected at 6kg/cm2 atomizing air pressure, the results are correlated with the specifications. The optimum spray rate was selected by changing the spray rate from 50 to70 (ml/gun/min), out of these optimum spray rate was found to be 70 ml/gun/min. Since the results (physical parameter evaluation) obtained with 70 ml/gun/min correlated with the specification when compared to the results obtained with 50 (ml/gun/min) and 60 ml/gun/min. By using the above optimized parameters, the Pantoprazole sodium enteric coated tablets were prepared.  Then it was subjected to dissolution study. The dissolution data obtained with all the three batches correlated with the standard specified limits.

Table 1: Optimization of blending time.

Sample % Drug content
BI BII BIII
Blending time Blending time Blending time
18 min 20 min 23 min 25        min 18 min 20 min 23 min 25 min 18 min 20 min 23 min 25 min
1 92.8 95.9 98.3 98.2 92.6 95.4 98.4 98.2 92.7 95.7 98.4 98.6
2 92.9 94.8 98.6 98.8 92.9 95.5 98.4 98.4 92.8 95.3 98.6 98.7
3 92.7 95.2 98.8 98.7 92.6 95.6 98.5 98.6 92.7 95.5 98.5 98.3
Avg. 92.8 95.3 98.6 98.6 92.7 95.5 98.4 98.4 92.7 95.5 98.5 98.5

Table 2: Optimization of blending speed.

Sample % Drug content
BI BII BIII
Blending speed Blending speed Blending speed
4rpm 6 rpm 8 rpm 4 rpm 6 rpm 8 rpm 4 rpm 6 rpm 8 rpm
1 92.3 98.4 98.9 92.5 98.3 98.4 92.1 98.5 98.6
2 92.4 98.4 98.2 92.5 98.8 98.5 92.1 98.4 98.2
3 92.2 98.9 98.6 92.4 98.4 98.6 92.2 98.9 98.9
Avg. 92.3 98.6 98.6 92.5 98.5 98.5 92.1 98.6 98.6

Table no.3 Optimization of compression speed in batch I

Parameter Limit Machine speed (RPM)
20 25 30 35
LHS RHS LHS RHS LHS RHS LHS RHS
Appearance White to off white coloured circular tablets with plain surfaces on both sides Complies Complies Complies Complies Complies Complies Complies Complies
Average Weight 20 tablets(mg) 350mg ± 4%

(336 mg -364 mg)

347 348 349 350 350 351 344 343
Thickness(mm) 3mm±0.2mm

(2.80mm-3.20mm)

2.96 2.95 2.97 2.96 3.12 3.13 3.22 3.23
Hardness(kg/cm2) NLT 2.5 Kg/cm2 4 4 4 4 5 5 3 3
Disintegration time(min) NMT 12min 3’45” 3’50” 3’50” 3’55” 4’05” 4’07” 3’29” 3’31”

Table 4: Optimization of compression speed in batch II.

Parameter Limit Machine speed (RPM)
20 25 30 35
LHS RHS LHS RHS LHS RHS LHS RHS
Appearance White to off white coloured circular tablets with plain surfaces on both sides Complies Complies Complies Complies Complies Complies Complies Complies
Average Weight 20 tablets(mg) 350mg ± 4%

(336 mg -364 mg)

348 348 349 350 351 352 343 343
Thickness(mm) 3mm±0.2mm

(2.80mm-3.20mm)

3.0 2.98 3.02 3.05 3.13 3.13 3.22 3.24
Hardness(kg/cm2) NLT 2.5 Kg/cm2 4 5 5 4 5 5 3 4
Disintegration time(min) NMT 12min 3’43” 3’47” 3’51” 3’54” 4’04” 4’09” 3’30” 3’31”

Table 5: Optimization of compression speed in batch III

Parameter Limit Machine speed (RPM)
20 25 30 35
LHS RHS LHS RHS LHS RHS LHS RHS
Appearance White to off white coloured circular tablets with plain surfaces on both sides Complies Complies Complies Complies Complies Complies Complies Complies
Average Weight 20 tablets(mg) 350mg ± 4%

(336 mg -364 mg)

346 348 349 351 350 351 342 343
Thickness(mm) 3mm±0.2mm

(2.80mm-3.20mm)

2.96 2.94 2.95 2.96 3.10 3.13 3.23 3.23
Hardness(kg/cm2) NLT 2.5 Kg/cm2 5 4 4 4 5 5 3 3
Disintegration time(min) NMT 12min 3’46” 3’48” 3’50” 3’52” 4’03” 4’06” 3’27” 3’29”

Table 6: Optimization of pan speed.

Parameter Limit Pan speed (RPM)
Batch 1 Batch 2 Batch 3
8 9 10 8 9 10 8 9 10
Appearance Off white to yellow Complies Complies Complies Complies Complies Complies Complies Complies Complies
Thickness

(mm)

3.5mm±0.2mm

(3.30mm-3.70mm)

3.31 3.52 3.50 3.2 3.54 3.52 3.39 3.53 3.50
Average Weight 20 tablets(mg) 375mg ± 4%

(360mg – 390mg)

370 375 375 371 377 378 372 375 376

Table 7: Optimization of Atomization air pressure.

Parameter Limit Atomization air pressure (kg/cm2)
Batch 1 Batch 2 Batch 3
5 6 7 5 6 7 5 6 7
Appearance Off white to yellow Complies Complies Complies Complies Complies Complies Complies Complies Complies
Thickness (mm) 3.5mm±0.2mm (3.30mm-3.70mm) 3.5 3.6 3.8 3.3 3.6 3.8 3.4 3.6 3.8
Average Weight 20 tablets (mg) 375mg ± 4%

(360 mg -390 mg)

372 375 380 371 376 381 371 374 380

Table 8: Optimization of of spray rate.

Parameter Limit Spray rate(ml/gun/min)
Batch 1 Batch 2 Batch 3
50 60 70 50 60 70 50 60 70
Appearance Off white to yellow Complies Complies Complies Complies Complies Complies Complies Complies Complies
Thickness (mm) 3.5mm±0.2mm (3.30mm-3.70mm) 3.2 3.3 3.5 3.3 3.3 3.6 3.3 3.4 3.6
Average Weight 20 tablets (mg) 375mg ± 4%

(360 mg -390  mg)

371 373 375 372 374 375 371 374 375

Table 9: Optimization of spray gun distance.

Parameter Limit Spray gun distance(cm)
Batch 1 Batch 2 Batch 3
22 23 24 22 23 24 22 23 24
Appearance Off white to yellow Complies Complies Complies Complies Complies Complies Complies Complies Complies
Thickness (mm) 3.5mm±0.2mm (3.30mm-3.70mm) 3.9 3.9 3.6 4.0 3.9 3.6 3.9 3.8 3.5
Average Weight 20 tablets(mg) 375mg ± 4%

(360 mg -390  mg)

381 380 375 383 381 376 379 379 375

Table 10: Dissolution profile pantoprazole sodium enteric coated tablets BI

 

S.No.

%  Cumulative Drug release
Time interval(min)
  15 20 30 45 60
1 35.1 46.5 63.2 79.3 98.1
2 35.2 46.9 63.2 79.3 98.8
3 35.5 46.5 63.5 79.9 98.6
4 35.3 46.6 63.3 79.5 98.6
5 35.5 46.3 63.4 79.6 98.5
6 35.9 46.4 63.9 79.9 98.3

Table 11: Dissolution profile pantoprazole sodium enteric coated tablets BII

S.No. % Cumulative Drug release
Time interval(min)
15 20 30 45 60
1 37.2 48.1 64.2 80.1 98.3
2 37.4 47.9 64.5 79.8 98.4
3 37.7 47.8 64.4 80.2 98.6
4 37.2 48.2 64.7 80.5 98.2
5 37.6 47.8 64.3 79.9 98.5
6 37.5 48.1 64.4 80.1 98.6

Table 12:  Dissolution profile pantoprazole sodium enteric coated tablets BIII.

S. No. % Cumulative Drug release
Time interval(min)
  15 20 30 45 60
1 36.5 49.1 66.2 78.1 98.2
2 36.7 49.9 66.4 79.2 98.6
3 36.4 49.3 66.7 79.2 98.4
4 36.6 49.4 66.7 79.1 98.6
5 36.2 49.8 66.3 79.9 98.7
6 36.5 49.4 66.4 79.1 98.9

 

Figure 1: Dissolution profile pantoprazole sodium tablets(BI,BII,BIII). Figure 1: Dissolution profile pantoprazole sodium tablets(BI,BII,BIII).
 

Click here to View figure

Conclusion

The process optimization for the preparation of pantoprazole sodium enteric coated tablets was done and the Optimum blending time 23min, Optimum blending speed 6 rpm, Optimum compression speed 30 rpm, Optimum coating pan speed 9 rpm, Optimum coating spray rate 70 ml/gun/min, Optimum coating spray gun distance to tablet bed 24 cm, Optimum coating atomizing air pressure 6 kg/cm2 were selected as optimized parameters for the production of  Pantoprazole sodium enteric coated tablets . The dissolution data obtained with all the three batches correlated with the standard specified limits which were prepared by using the optimized parameters.

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