INTRODUCTION:

Statistical design of experiments is a proven technique that continues to show increasing use in the process industries. As the R & D function comes under increasing pressure to produce fast accurate results, more scientists and engineers are recognizing the assistance that experimental design can provide. Statistical design reduces the lead time and improves their efficiency, particularly when many variables are of potential importance (Shruti Chopra et al., 2007).

Capability to see interactions among experimental variables, leading to more reliable predictions of the response data in areas not directly covered by experimentation it can give more information per experiment than unplanned approaches organized approach toward the collection and analysis of information.

Very often, the conclusions from a statistically designed experiment are evident without extensive statistical analysis (Shruti Chopra et al., 2007)

Oral administration of drugs has been the most common and preferred route for delivery of most therapeutic agents. Advance in technology have resulted in novel modified release dosage from. In contrast to conventional forms, modified release products provide either delayed release or sustained release of drug delivery system. The rationale for development of an extended-release formulation of a drug is to enhance its therapeutic benefits, minimizing its side effects while improving the management of the diseased condition. Besides its clinical advantages, an innovative extended-release formulation provides an opportunity for a pharmaceutical company to manage its product life-cycle (Anirbandeep Bose et al., 2013).

MATERIALS AND METHODS:

Materials

Telmisartan as a gift sample by Aristo pharmaceuticals Pvt. Ltd, Mumbai, All the other chemicals such as NaOH, HCl and KCl of analytical grade and purchased locally.

Methodology

Preparation of 0.2 M HCl (1.2pH)

250 ml of 0.2 M KCl in 1000 ml volumetric flask and add specified volume of 0.2 N HCl (425ml), then fill up with distilled water up to the mark.

Preparation of 6.8 phosphate buffer

250 ml of 0.2M photassiumdihydrogen phosphate and add 112 ml of 0.2 N NaOH, Then make up to 1000 ml with distilled water.

Calibration curve of Telmisartan in 1.2 HCl buffer

Preparation of stock solution

100 mg of Telmisartan was accurately weighed and transferred into a 100ml standard flask and 100 ml 0.1N HCl was added to dissolve the drug.

Standard dilution

Make the 100 µgm/ml solution from over stock solution Then Pipette out 0.2ml, 0.4ml, 0.6ml, 0.8ml and 1ml from above solution transferred in to the 10ml standard flask and diluted to 10ml with 1.2pH HCl.

Preparation of Standard Dilution

0.2 ml → diluted with 0.1 N HCl →10ml → 2µg/ml

0.4 ml → diluted with 0.1N HCl →10ml → 4µg/ml

0.6 ml → diluted with 0.1N HCl →10ml → 6µg/ml

0.8 ml → diluted with 0.1N HCl →10ml → 8µg/ml

1 ml → diluted with 0.1N HCl →10ml → 10µg/ml

Above dilutions are analyzed spectrophotometrically at 296nm in UV for about three times, readings of each dilution using 0.1N HCl. A graph was plotted by taking a concentration of Telmisartan (µg/ml) on X- axis and absorbance on Y-axis.

Calibration curve of Telmisartan in 6.8

Phosphate Buffer Preparation of Stock Solution

100 mg of Telmisartan was accurately weighed and transferred in to a 100ml standard flask and 100 ml of 6.8 phosphate buffer was added to dissolve the drug.

Standard Dilution

100 µgm/ml solution was made from above stock solution. Then was Pipetted out 0.2ml, 0.4ml, 0.6ml, 0.8ml and 1ml from above solution and transferred in to the 10ml standard flask and diluted to 10ml with 6.8 phosphates buffer.

Preparation of Standard Dilution

0.2 ml → diluted with 6.8 buffer →10ml → 2µg/ml

0.4 ml → diluted with 6.8 buffer →10ml → 4µg/ml

0.6 ml → diluted with 6.8 buffer →10ml → 6µg/ml

0.8 ml → diluted with 6.8 buffer →10ml → 8µg/ml

1ml → diluted with 6.8 buffer →10ml → 10µg/ml

Above dilutions are analyzed spectrophotometrically at 296nm in UV for about three times, readings of each dilution using 6.8phosphate buffer A graph was plotted by taking a concentration of Telmisartan (µg/ml) on X- axis and absorbance on Y-axis.

RESULTS AND DISCUSSION:

Table 1: Standard data of Telmisartan in 1.2 HCl buffer at 296nm

S.No	Concentration(µg/ml)	Absorbance (n=3)
0	0	0
1	2	0.239±0.12
2	4	0.422±0.13
3	6	0.622±0.08
4	8	0.842±0.11
5	10	0.976±0.12

Figure 1: Calibration curve of Telmisartan 1.2 HCl buffer

Table 2: Standard data of Telmisartan in 6.8 pH phosphate buffer at 296nm

S.No	Concentration(µg/ml)	Absorbance (n=3)
o	0	0
1	2	0.115±0.09
2	4	0.241±0.06
3	6	0.323±0.05
4	8	0.432±0.08
5	10	0.513±0.05

Figure 2: Calibration curve of Telmisartan in 6.8 pH phosphates buffer

In-Vitro Dissolution studies for the marketed Telmisartan IR tablets

Table 3: 2³factorial designs

S.NO	pH	RPM	TEMPARATURE
F1	1.2	50	37⁰C
F2	1.2	50	40⁰C
F3	1.2	100	37⁰C
F4	1.2	100	40⁰C
F5	6.8	50	37⁰C
F6	6.8	50	40⁰C
F7	6.8	100	37⁰C
F8	6.8	100	40⁰C

Table 4: In-Vitro dissolution drug release F1

S. No	TIME (min)	Absorbance	Conc (µg/ml)	Amount	%Amount release
1	10	0.122	989.7	8.90	44.54
2	20	0.134	1.112	10.02	50.05
3	30	0.146	1.234	11.12	55.56
4	40	0.158	1.346	12.12	60.6
5	50	0.170	1.479	13.31	66.98
6	60	0.196	1.744	15.70	78.8

Table 5: In-Vitro dissolution drug release F2

S. No	TIME (min)	Absor bance	Conc (µg/ml)	Amount	%Amount release
1	10	0.098	744.8	6.70	33.52
2	20	0.140	1.173	10.50	52.8
3	30	0.165	1.428	12.85	69.2
4	40	0.192	1.704	15.33	76.68
5	50	0.207	1.989	17.90	89.5
6	60	0.253	2.326	20.93	104.6

Table 6: In-Vitro dissolution drug release F3

S. No	TIME (min)	Absor bance	Conc (µg/ml)	Amount	%Amount release
1	10	0.132	1.091	9.82	49.13
2	20	0.154	1.306	11.75	58.7
3	30	0.190	1.687	15.15	75.7
4	40	0.210	1.887	16.95	84.9
5	50	0.240	2.193	19.74	98.7
6	60	0.286	2.663	23.96	119.7

Table 7: In-Vitro dissolution drug release F4

S. No	TIME (min)	Absor bance	Conc (µg/ml)	Amount	%Amount release
1	10	0.119	959.1	8.63	43.16
2	20	0.121	1.009	9.25	45
3	30	0.144	1.219	10.92	54.64
4	40	0.168	1.459	13.13	65.60
5	50	0.198	1.765	15.85	79.4
6	60	0.210	1.887	16.9	84.94

Table 8: In-Vitro dissolution drug release F5

S. No	TIME (min)	Absor- bance	Con (µg/ml)	Amount	%Amount release
1	10	0.026	228.7	2.03	10.25
2	20	0.037	421.5	3.78	18.94
3	30	0.058	789.4	7.10	35.52
4	40	0.068	845.2	7.89	38.23
5	50	0.074	982.4	8.84	44.21
6	60	0.099	1.052	9.46	48.9

Table 9: In-Vitro dissolution drug release F6

S. No	TIME (min)	Absor bance	Conc (µg/ml)	Amount	%Amount release
1	10	0.002	75.4	1.57	7.89
2	20	0.036	403.5	3.62	18.94
3	30	0.054	719.2	6.47	32.36
4	40	0.071	1.017	9.15	45.78
5	50	0.098	1.491	13.42	67.10
6	60	0.110	1.701	15.31	76.75

Table 10: In-Vitro dissolution drug release F7

S. No	TIME (min)	Absor bance	Conc (µg/ml)	Amount	%Amount release
1	10	0.03	333.3	3.7	15
2	20	0.042	543.8	4.89	25.5
3	30	0.058	789.4	7.10	35.5
4	40	0.067	947.3	8.52	42.6
5	50	0.078	1.144	10.2	51.3
6	60	0.098	1.491	13.4	67.10

Table 11: In-Vitro dissolution drug release F8

S. No	TIME (min)	Absor bance	Con (µg/ml)	Amount	%Amount release
1	10	0.028	263.5	2.36	11.8
2	20	0.034	368.4	3.31	16.5
3	30	0.048	614.6	5.53	27.6
4	40	0.059	959.6	8.63	43.1
5	50	0.072	1.035	9.31	46.5
6	60	0.096	1.456	13.10	65.5

Table 12: In-Vitro dissolution drug release at 30 minute

Formulation Code	pH	RPM	TEMPARATURE	% Drug release
F1	1.2	50	37⁰C	55.66
F2	1.2	50	40⁰C	69.2
F3	1.2	100	37⁰C	75
F4	1.2	100	40⁰C	59.6
F5	6.8	50	37⁰C	35.6
F6	6.8	50	40⁰C	32.36
F7	6.8	100	37⁰C	50.5
F8	6.8	100	40⁰C	27.8

SUMMARY :

The dissolution of Telmisartan marketed un-coated tablets was performed on different critical process parameters (pH, Temp and RPM), and the % drug release was calculated, which is taken as single variable, that is entered in QbD software and following values were obtained.

Table 13: QbD Values

	COMBINATION		CO-EFFICIENT	SSC RATIO
	b0		50.3388	68
	b1		-33.8386	98.3
	b12		3.0837	0.8164
	b2		-1.2737	0.1393
	b3		2.0563	0.3631
	b13		-1.7163	0.2529
	b23		0.0212	0.01
	b123		-1.1713	0.1178
	Drug release at 30 minutes (y) =50.5388-33.8337x1+3.0837x2-1.2737x12+2.0563x3 1.716x13+0.0212x23-1.1711x123
b1(pH)		Shows more effect (98) and negative co-efficient i.e. on increasing pH, the dissolution rate will be decreased.
b2(rpm)		Shows less effect (0.1393) and negative co-efficient i.e on more increase in rpm results in less decrease in drug release.
b3(temp)		shows significant effect and positive co-efficient i.e on increase in temp shows increase in drug release

Remaining all combinations shows very less effect on drug release.

CONCLUSION :

From the results of the study it is evident that dissolution rate is decreased while pH is enhanced because pH is more effect on the dissolution rate. Change in pH shows more prominent effect than change in rpm. Increasing temperature results in increase in dissolution rate. Increase in rpm increase in dissolution rate.

REFERENCES

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2. Eddy Castellanos Gil, Antonio Iraizoz Colarte. Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride. Int. J of Pharm. 317(2006), 32-39.

3. Mohd Abdul Hadi, Noorana Tehseen, Vinay Rao. Design and characterization of twice daily mini-tablets formulation of Pregabalin. Int. J of Pharmacy and Pharm Sc. 5:1(2013), 168-175.

4. Pao-Chu Wu, Yaw-Bin Huang, Yi-Hung Tsai. Optimization of pH-independent release of Nicardipine hydrochloride extended-release matrix tablets using response surface methodology. Int. J of Pharm. 289(2005), 87-95.

5. Shruti Chopra, K. Motwani. Release modulating hydrophilic matrix systems of Losartan potassium Optimization of formulation using statistical experimental design. Eur. J of Pharm and Biopharmaceutics. 66(2007), 73-82.

Received on 27.08.2016 Modified on 15.10.2016

Res. J. Pharm. Dosage Form. & Tech. 2016; 8(4): 273-276

DOI: 10.5958/0975-4377.2016.00038.0