Department of Pharmaceutics, St. Mariam College of Pharmacy
A simple, rapid, and reliable Fourier Transform Infrared (FTIR) spectrophotometric method was developed and validated for the quantitative estimation of telmisartan and hydrochlorothiazide in combined tablet dosage form using a solid sampling technique. Standard drugs were analyzed by the KBr pellet method, and characteristic absorption peaks were identified for functional group confirmation. Telmisartan exhibited prominent peaks at 1695.45 cm?¹ (C=O), 3387.00 cm?¹ (O–H), and 3637.75 cm?¹ (N–H). Hydrochlorothiazide showed characteristic peaks at 3637.75 cm?¹ (N–H), 1327.03 cm?¹ (SO? asymmetric stretching), and 1165.00 cm?¹ (SO? symmetric stretching). The marketed formulation (Telma H) was successfully analyzed using the developed method. The average recovery was found to be 100% of the labeled claim, and the %RSD values ranged between 0.10–0.97%, indicating excellent precision and accuracy. The method was validated for key parameters and found suitable for routine quality control analysis of telmisartan and hydrochlorothiazide in tablet dosage forms.
TELMISARTAN
Telmisartan is a non-peptide antihypertensive drug belonging to the class of angiotensin II receptor blockers (ARBs). It selectively antagonizes the binding of angiotensin II to the AT1receptor in vascular smooth muscle and the adrenal gland, resulting in vasodilation, reduced aldosterone secretion, decreased sodium and water reabsorption, and a subsequent reduction in arterial blood pressure.
Chemical formula: C33H30N4O2
Molecular weight: 514.6g/mol
IUPAC Name: 2-[4-[[4-methyl-6-(1-methylbenzimidazol-2-yl)-2-propylbenzimidazol-1-yl]methyl]phenyl]benzoicacid.
Structure of telmisartan given in figure1:
HYDROCHLOROTHIAZIDE
Hydrochlorothiazide is a thiazide-type diuretic and antihypertensive medication widely used to manage hypertension (high blood pressure) and edema (fluid retention) associated with conditions such as congestive heart failure, liver disease, and renal disorders. It acts primarily in the distal convoluted tubules of the kidney by inhibiting the sodium-chloride cotransporter, thereby reducing reabsorption of sodium and chloride, increasing urinary excretion of sodium, chloride and water, and ultimately lowering blood volume and blood pressure. Hydrochlorothiazide may be used alone or in combination with other antihypertensive agents to enhance blood pressure control.
Chemical formula: C7H8ClN3O4S2
Molecular weight: 297.7 g/mol
IUPAC Name: 6-chloro-1,1-dioxo-3,4-dihydro-2H-1λ6,2,4-Benzothiadiazine- 7-sulfonamide.
Structure of hydrochlorothiazide given in figure2:
MATERIALS AND METHODS
CHEMICAL AND REAGENTS
Standard samples of telmisartan and hydrochlorothiazide were purchased from dharmtech ltd, navi Mumbai, India. Potassium bromide (IR grade) was obtained from AKCP, viruthu nagar, India.
FTIR INSTRUMENTATION
The FTIR analyses were carried out using shimadzu IR tracer-100 FTIR Spectrophotometer. FTIR spectra were recorded in the wave no range between 4000-400 cm-1averaging 45 scans per sample using an ominal resolution of 8cm-1employing background spectrum of KBr.The IR solution PC software was used for data acquisition, processing & spectral analysis.
Solid sampling technique of FTIR using pressed pellet technique
Steps of KBr with sample pressed pellet formation
Shimadzu IR Tracer-100-FTIR spectrophotometer
PREPARATION OF WORKING STANDARD
Accurately weighed Telmisartan (10mg) was mixed with 990mg of KBr as diluents and further diluted to make a concentration of 1 % w/w of Telmisartan.
SELECTION OF ANALYTICAL WAVENUMBER
Working standard (1% w/w) of pure drug that is Telmisartan was scanned in the IR range of 4000-400 cm-1with resolution of 8 and 45 scans. Wavenumber (intensity) parameter is select for pure drug in such a way that one can select wavenumber in a range. Functional group selected for Telmisartan is carbonyl group, N-H group and O-H group wave number found in range of 1715-1730 cm-1,3500-3700 cm-1& 3300-3400 cm-1IR spectrum of Telmisartan is shown in figure 1
Figure 1: FTIR spectrum of Telmisartan
PREPARATION OF WORKING STANDARD
Accurately weighed hydrochlorothiazide (10 mg) was mixed with 990 mg of KBr as diluent and further diluted to make a concentration of 1 % w/w of hydrochlorothiazide.
SELECTION OF ANALYTICAL WAVENUMBER
Working standard (1% w/w) of pure drug that is hydrochlorothiazide was scanned in the IR range of 4000-400 cm-1with resolution of 8 and45 scans. Wavenumber (intensity) parameter is select for pure drug in such a way that one can select wavenumber in a range. Functional group selected for hydrochlorothiazide is O=S=O (Sulphone), N-H group wavenumber found in range of 1132- 1159 cm-1 & 3500-3700 cm-1 IR spectrum of hydrochlorothiazide is shown in figure 2.
Figure 2: FTIR spectrum of hydrochlorothiazide
METHOD OF VALIDATION
The developed method was validated as per literature available and ICH guidelines by studying the following method validation parameters.
ACCURACY
The accuracy of the developed method evaluated by standard addition method with recovery of pure drug at 3 different quantities (75, 100 and 125 % w/w). To the pre analyzed tablet powder of Telmisartan and hydrochlorothiazide, the known amount of Telmisartan and hydrochlorothiazide studied. Powder corresponds to 75, 100 and 125 % w/w of label claim was added.
Recovery study was performed by 75, 100 and 125 % w/w of working standard to a pre-analyzed sample and the final diluted solutions prepared in such a way that their concentrations should be in linearity range and percentage amount recovered calculated accordingly. The sample was mixed thoroughly and analyzed by making appropriately 1 % w/w dilutions with potassium bromide powder in three replicates. Peak area of this mixture was measured in the range of 1132-1159 cm-1using KBr as blank for background is shown in the table 1.
Table1: Recovery studiesd at a for drugs Telmisartan and hydrochlorothiazide
|
Drug |
Recovery level |
Conc of Sample (microgram/ml) |
Conc of standard added (microgram/ml) |
Conc recovered (microgram/ml) |
% Recovery |
Mean / % RSD |
|
TEL |
75% |
100 |
50 |
150.25 |
100.16 |
100.22/ 0.4626 |
|
100% |
150 |
50 |
199.60 |
99.8 |
||
|
125% |
200 |
50 |
251.80 |
100.72 |
||
|
HCTZ |
75% |
50 |
25 |
75.9 |
100.48 |
100.48/ 0.0507 |
|
100% |
75 |
25 |
100.44 |
100.44 |
||
|
125% |
100 |
25 |
125.68 |
100.54 |
PRECISION
The precision of the method was evaluated by inter-day and intraday variation studies. In intraday studies working dilutions of sample were analyzed triplicate in a day and percentage relative standard deviation (%RSD) was calculated. In the inter-day variation studies, working dilutions of sample were analyzed on three consecutive days and percentage relative standard deviation (% RSD) was calculated shown in table 2.
Table 2 : Intra-day and Inter-day precision
|
Intraday precision |
Conc (micro gram/ ml) |
Mean con (microgram/ ml) ± SD |
% RSD |
Inter day Precision |
Conc (micro gram/ ml) |
Mean conc (microgram/ ml) ±SD |
% RSD |
|
Telmisartan |
4 |
4.0003±0.0100 |
0.2504 |
Telmisartan |
4 |
3.9966±0.0230 |
0.5778 |
|
12 |
1.120337±0.0663 |
0.5512 |
12 |
11.9533±0.0602 |
0.5042 |
||
|
18 |
18.0567±0.0378 |
0.2096 |
18 |
17.9737±0.0553 |
0.3077 |
||
|
HCTZ |
8 |
8.012±0.0081 |
0.1021 |
HCTZ |
8 |
7.9366±0.0503 |
0.6341 |
|
12 |
12.0566±0.0585 |
0.4859 |
12 |
11.8967±0.0602 |
0.5066 |
||
|
16 |
15.99±0.1562 |
0.9768 |
16 |
15.8400±0.0458 |
0.2893 |
ANALYSIS OF MARKETED TABLET FORMULATION
Accurately weighed 20 tablets (i.e, Telma H) and average weight were determined. Powder weight equivalent to 40mg of Telmisartan and 12.5mg of hydrochlorothiazide were taken and mixed with KBr and further diluted to 1% w/w concentration. Peak of these dilutions were measured in the range1132-1159cm-1using KBr as blank is shown in the table 3 and figure3.
Table 3: Analysis data for Telma H using FTIR method
|
Label claim |
Amount (mg) per tablet (label claim) |
Amount found (mg) (mean value) |
Label claim % (mean value) |
Standard deviation (SD) |
% RSD |
|
TEL |
40mg |
39.66 mg |
99.15% |
0.89 |
0.25-0.55% |
|
HCTZ |
12.5mg |
12.49 mg |
99.98% |
0.88 |
0.10-0.97% |
Figure3:FTIR spectrum ofTelma H
RECOVERY STUDIES
To check the accuracy of the developed method and to study the interference of formulation additives, analytical recovery experiments were carried out by standard addition method at 75% 100% and 125% level. From the total carried amount of drug found the % recovery was calculated.
|
Drug |
Level of addition |
% recovery |
|
Telmisartan |
75% 100% 125% |
100.16 99.8 100.72 |
|
Hydrochlorothiazide |
75% 100% 125% |
100.48 100.44 100.54 |
RESULT AND DISCUSSIONS
The new FTIR method was developed for quantization of Telmisartan and hydrochlorothiazide in tablet formulation by using a solid sampling technique. The IR spectra of standard Telmisartan & hydrochlorothiazide obtained by pressed pellet technique using KBr in figure 1 & figure 2. To identification of functional groups in raw materials.
IR spectrum of Telmisartan showed peaks at 1695.45 cm-1,3387.00 cm-1, & 3637.75 cm-1 corresponding to carbonyl group, O-H group, N-H group respectively. Hydrochlorothiazide IR spectrum gave peaks at 3269.34 cm-1, 1327.03 cm-1 & 1165.00 cm-1 corresponding to N-H group, SO2 asymmetric stretching, SO2 symmetric stretching respectively.
The marketed tablet formulation that isTelmaH was analyzed using developed method & the results of analysis are shown in table 3. The average recovery of Telma H was 100% w/w of label claim & the % RSD value was 0.25-0.55% & 0.10-0.97% (< 2%).
CONCLUTION
Traditionally, FTIR spectrophotometer is employed for the qualitative analysis of pharmaceuticals; however, with advent in sampling techniques, FTIR spectrophotometer may serve as useful technique for qualitative and qualitative analysis of solid-state pharmaceuticals. In the present studies, we report the development and validation of eco-friendly stability indicating FTIR method for the quantification of solid-state Telmisartan and hydrochlorothiazide and its successful application to pharmaceuticals. The proposed method was found to be precise, accurate, and suitable for analysis of Telmisartan and hydrochlorothiazide as bulk drug and in pharmaceuticals formulation. Thus, the developed method has the advantage of being solvent free, eco-friendly, cost effective and involving relatively simple sample preparation. The developed validated method, can be useful for the routine quality control analysis of Telmisartan and hydrochlorothiazide in pharmaceuticals industries with desired precise and accuracy.
REFERENCES
Sudha N, Angel J, Ananthi A, Ansar Mohamed Hussain A, Sheik Hussain M, Sornaraj L, Development and Validation of FTIR Method for Telmisartan- Hydrochlorothiazide Tablets, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 3, 2063-2072. https://doi.org/10.5281/zenodo.19104650
10.5281/zenodo.19104650
