INTRODUCTION:

Teneligliptin Hydrobromide is a Dipeptidyl peptidase-4 inhibitor used for lowering post-prandial blood glucose levels in people with diabetes. The number of people with diabetes is expected to rise from the current estimated of 150 million to 220 million in 2010 and 300 million in 2025¹.

There are two main forms of diabetes, Type 1 diabetes is the most common chronic disease of children and is due to auto-immune-mediated destruction of pancreatic β-cell islets resulting in absolute insulin deficiency².

It can be treated by supplying exogenous insulin. Type 2 diabetes or non-insulin dependent diabetes mellitus which is a multifactorial disease characterized by insulin resistance in peripheral tissues and /or abnormal insulin secretion from the pancreas and increasing blood glucose levels³. Insulin itself inhibits glucose production and increases glucose utilization⁴. Alpha Dipeptidyl peptidase-4 inhibitors are oral anti diabetic drugs used for diabetes which work by preventing digestion of carbohydrates. They are converted into simple sugars by glucosidase enzymes present on the cells lining the intestine. As a Dipeptidyl peptidase-4 inhibitor, the compound exerts its activity within the gastrointestinal tract of humans. The drug hinders glucose absorption and thus, reduces the postprandial blood glucose peaks^5-7. Thus Dipeptidyl peptidase-4 inhibitor reduces the impact of carbohydrates on blood sugar. Teneligliptin Hydrobromide has wide therapeutic and pharmacological belongings, including its admirable inhibitory activity against α-glucosidase and its action in opposition to hyperglycemia. Teneligliptin Hydrobromide, a potent Dipeptidyl peptidase-4 inhibitor used for type 2 diabetes, has anti-obesity and anti diabetic action. Teneligliptin Hydrobromide obtained from organic synthesis processes is similar to structurally related carbohydrates found naturally^8,9. Since most carbohydrates lack chromophore groups, their analysis by liquid chromatography (LC) often requires derivatization procedures¹⁰. Since teneligliptin hydrobromide only absorbs UV in the low wavelength region, it cannot be distinguished with high sensitivity. Hence unique detection methods are required for analysis of teneligliptin hydrobromide. Teneligliptin Hydrobromide shows efficient results for various analytical instruments only in the combination of Taurine and Sodium per iodate¹¹. Drug solution was derivatives using Taurine and Sodium per iodate in water and methanol. Drug exhibited distinct λmax in methanol. Analysis is a significant module in the formulation development of any drug molecule. An appropriate and validated method has to be accessible for the analysis of drug (s) in the bulk, in drug delivery systems, from release dissolution studies and in biological samples. Our main aim is development and validation of UV Spectrophotometric method as per ICH guidelines. Thus the present study was undertaken to develop and validate a simple, sensitive, accurate, precise and reproducible UV method for teneligliptin hydrobromide¹³.

Physico Chemical Properties:

Teneligliptin Hydrobromide is a long-acting, orally bioavailable, pyrolidone-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Teneligliptin Hydrobromide can also scale back plasma triglyceride levels through a sustained increase in GLP-1 levels. Teneligliptin Hydrobromide is eliminated via excretion with a half-life of 24.2 hours in human plasma from the kidney and metabolism involving certain enzymes. The bioavailability of Teneligliptin Hydrobromide is concerning 60-80%¹⁴.

Structure:

Figure 1: Structure of Teneligliptin Hydrobromide

MATERIALS AND METHODS:

Teneligliptin Hydrobromide was procured from Yarrowchem, Pvt. Ltd; Mumbai. Instrument used was UV/Visible double beam Spectrophotometer with matched pair of quartz cell (1.0cm path) was employed for absorption measurements^13-16. Teneligliptin Hydrobromide pure drug was used and analytical grade chemicals and reagents were used for the entire analysis. Teneligliptin Hydrobromide tablets were purchased from local market.

Preparation of Standard Stock Solution:

Standard stock solution of teneligliptin hydrobromide was prepared by dissolving 10mg Teneligliptin Hydrobromide in 100ml of methanol so that the strength is 100μg/ml is derivatized with Taurine and Sodium periodate¹⁵.

Selection of Solvent:

The drug absorbance is at higher value and drug reveal distinct λmax in methanol and hence methanol was chosen as solvent for all analytical performances¹⁶.

Selection of Wavelength:

Scanning of the standard solution was carried out between 200-400nm and found that the peak at 281nm showed maximum absorption as shown in Figure 2.

Preparation of Calibration Curve:

Calibration curve was prepared at λmax 281nm using UV- Visible Spectrophotometer. For this stock solution of 100μg/ml was prepared. A dilution of teneligliptin hydrobromide stock solution was prepared and scanned in the range of 200-400nm. Absorbance was taken at λmax 281nm using methanol as blank¹⁷. The calibration curve was plotted as in Figure 3. The linearity of the response of the drug was verified at 5 to 100μg/ml concentrations, but linearity was found to be between the concentration range of 10 -80μg/ml. The graphs plotted between absorbance versus the concentration data and were treated by linear regression analysis¹⁸. The correlation coefficient (r²) of determination was found to be 0.99.

Preparation of Sample Solution:

The anticipated method was applied to analyte i.e. commercially available teneligliptin hydrobromide tablet. Thirty tablets, each having API of 20mg of teneligliptin hydrobromide was weighed first and average weight was determined¹⁹. Teneligliptin Hydrobromide equivalent to 5mg was weighed, transferred to a 100ml volumetric flask, and made up to volume with methanol and filtered through whatmann filter paper²⁰. From this solution, suitable aliquot was prepared, then these dilutions were derivatized and scanned in UV region and absorbances were recorded at 281 nm²¹.

RESULTS AND DISCUSSION:

Assay of method precision (intraday precision) was evaluated by carrying out six independent assays of test samples of teneligliptin hydrobromide. The intermediate precision (interday precision) of the method was also evaluated using two different analysts, and different days in the same laboratory. The relative standard deviation (RSD) and assay values obtained are shown in Table.1.

A known amount of sample was taken into nine different volumetric flasks and spiked with known quantities of teneligliptin hydrobromide at three different levels in triplicate. The samples were analyzed as per the proposed method. The samples were analyzed as per as the proposed method. The results tabulated in Table shows the accuracy of the method. The precision are tabulated in Table 2 and 3 (Acceptance criteria: Percent accuracy should be in the range of 98-102)

The percentage recovery values specify that there is no hindrance from the recipients used. During the formulation and the newly developed UV analytical method is found to be sensitive, exact, specific and most reproducible This method can be used in Quality control of regular batch analysis for API and formulation of teneligliptin hydrobromide which is shown in Table 4.

Stability in Analytical Solution:

Sample solution was prepared as per the proposed method and absorbance was checked at various time intervals stored at 40^oC the responses are recorded in Table 5. Since percentage difference of response from initial is less than 2.0 hence solution stability is established for up to 12 hours at 40^oC.

Table 1: Compiled data of Method and Intermediate precision

Sample No.	Method precision	Intermediate precision
1	99.3	99.3
2	99.1	100.1
3	99.1	99.1
4	100.0	98.6
5	99.7	99.3
6	100.5	100.4
Mean	99.6	99.4
%RSD	0.56	0.66
Overall % RSD		0.59

Table 2: Accuracy

% Accuracy Level	No.	% Accuracy
50	1	99.9
	2	99.7
	3	100.2
100	1	99.9
	2	99.5
	3	99.3
150	1	99.6
	2	99.8
	3	100.0

Table 3: Precision at Accuracy level

% Accuracy Levels	Mean	% RSD
50	99.9	0.25
100	99.6	0.31
150	99.8	0.20

Table 4: Analysis of Formulation Drug Amount

Name of API	Amount of Drug Claimed	Amount of Drug Actually Found During Analysis	Label Claim Percent
Teneligliptin Hydrobromide	0.2 mg	0.197 mg	98.5

Table 5: Stability in Analytical Solution

Time in Hours	Absorbance	Temperature of the Solution
Initial	0.4785	40.3
2	0.4695	407
4	0.4712	39.8
6	0.4752	40.5
8	0.4605	41.0
10	0.4687	40.3
12	0.4591	40.7

Figure 2: Selection of Wavelength

Figure 3: Calibration Graph of Teneligliptin Hydrobromide 281 nm

CONCLUSION:

The proposed method for estimation of teneligliptin hydrobromide in pharmaceutical formulation was found to be simple, accurate, reasonably inexpensive and quick. The interference of component was neglected by selecting the proper λmax for the component of interest. The results confirm the reproducibility, precision and accuracy of the analytical method on UV. The marketed formulations were analyzed by the proposed method and were found that there was no interference with the recipients included in the tablet formulation as seen from the data. The method depicted can be used for the estimation of tablet formulations due to simplicity in preparation and economical. The results obtained all in close proximity and found to be satisfactory. The method can be implemented for the Qualitative as well as Quantitative analysis of teneligliptin hydrobromide in API as well as for its formulation purposes.

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Received on 19.01.2021 Modified on 10.04.2021

Asian J. Pharm. Ana. 2021; 11(3):195-198.

DOI: 10.52711/2231-5675.2021.00034