A REVIEW ON CHEMISTRY AND PHARMACOLOGICAL ACTIVITY OF METFORMIN HYDROCHLORIDE AND TENELIGLIPTIN HYDROBROMIDE HYDRATE IN COMBINED DOSAGE FORM

 

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ABOUT AUHTOR
Manish Patil*1, Harsha D Jani1, Suleman S Khoja2, Narmin A Pirani3, Shamim S Khoja3
1Department of Quality Assurance,
Shivam Pharmaceutical Studies and Research Centre, Anand
Gujarat, India.

2Resource person in pharmaceutical quality assurance and Audit Compliance, Vapi
3Registered Pharmacist, Gujarat, India

*manishpatil3194@gmail.com

ABSTRACT
This review article presents the pharmacology of combined Metformin hydrochloride and Teneligliptin hydrobromide hydrate is effective on type 2 Diabetes Mellitus. Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Teneligliptin, a third generation Dipeptidyl Peptidase-4 (DPP-4) inhibitor exhibits unique “J shaped” structure with “anchor-lock domain” mechanism which provides potent & long duration of action. The addition of teneligliptin once daily to Metformin was effective and generally well tolerated in Korean patients with type 2 diabetes. The mechanism of Metformin hydrochloride and teneligliptin hydrobromide hydrate is quite different. The main objective of this review article is to provide pharmacological and Analytical information of combination of Metformin hydrochloride and Teneligliptin hydrobromide hydrate to researcher in development of combined dosage form.

REFERENCE ID: PHARMATUTOR-ART-2470

PharmaTutor (ISSN: 2347 - 7881)

Volume 5, Issue 3

Received On: 29/10/2016; Accepted On: 22/11/2016; Published On: 01/03/2017

How to cite this article: Patil M, Jani HD, Khoja SS, Pirani NA, Khoja S;A Review on chemistry and pharmacological activity of metformin hydrochloride and teneligliptin hydrobromide hydrate in combined dosage form; PharmaTutor; 2017; 5(3); 24-30

 

INTRODUCTION:
Type 2 diabetes mellitus:

It a medical condition characterized by an elevation of blood glucose level, this metabolic disorder will taken place as a result of either insulin resistance and/or insulin deficiency. This medical condition consider as one of the most predominant type of diabetes since it represent 90% of diabetic cases.

Moreover, this medical condition required a chronic monitoring and treatment throughout patient life; the treatment will involve several aspects like self-care measures, lifestyle changes (dietary modification) and in some cases medications (metformin and/or insulin). It has been observed during the past 50 years, the rate of incidence of this type of diabetes has markedly increased in parallel with obesity.

This medical problem i.e., high blood sugar when remain for long time this will mainly cause heart disease, strokes, diabetic retinopathy all these will lead to kidney damage.

 

Main Causes for its Incidence of Type 2 Diabetes Mellitus
Many factors play critical role in the incidence of this medical problem, like gender (female), age (increasing age), diet, obesity, lack of sleep, nutritional supplement received by the mother during pregnancy. But the main critical factors that play role are: lifestyle, genetic factors and other medical problems and also avoidance of medical checkup (periodically).

 

Lifestyle
This part will include many factors which are: obesity, stress, poor diet, high waist-hip ratio, high consumption of sweets (drinks and carbohydrate containing mainly glucose food) and lack of motivation and exercises.

Genetic
It has been found that several genes responsible for or related with incidence of type 2 diabetes, even so these genes still not consider as the main critical factor in incidence of this type of diabetes.

Other medical problems
This part include two subdivisions i.e., two factors associated with incidence of type 2 diabetes the first one include the use of some medications like [diuretics (thiazides), antihypertensive treatment (beta-blockers) and antipsychotic treatments. The second division include patients who sufferance from other diseases like gestational diabetes, Cushing’s syndrome, hyperthyroidism

Dipeptidyl Peptidase-4 (DPP-4) inhibitor
Dipeptidyl peptidase IV inhibitors are a class of oral anti hyperglycemic agents for the treatment of type 2 diabetes. The anti glycemic effect of DPP-4 inhibitors is mediated by inhibiting the degradation of the incretin hormone glucagon-like peptide-1 (GLP-1) and stimulating insulin release in response to increased blood glucose levels. Among all DPP-4 inhibitors, vildagliptin, saxagliptin and teneligliptin are peptide mimetic compounds, which have been discovered by replacing segments of peptide-based substrates. Whereas, sitagliptin, alogliptin and linagliptin are non-peptide mimetic compounds, which have been discovered by optimization of the initial lead compounds identified by random screening. Therefore, their chemical structures are diverse, suggesting that each of their binding modes in DPP-4 would be unique.     

Metformin Hydrochloride
Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (Biguanide hypoglycemic agent)(N, N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C4H11N5-HCL and a molecular weight of 165.63 g/mol. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether and chloroform. The pK, of metformin is 12.4.The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown

PHARMACOKINETIC AND PHARMACODYNAMIC PROFILE (7)

Absorption and Bioavailability
The absolute bioavailability of a metformin hydrochloride 500 mg tablet given under fasting conditions is approximately 50-60%. Studies using single oral doses of metformin tablets of 500 mg and 1500 mg, and 850 mg to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. Food decreases the extent of and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak concentration (C,,,) and 25% lower area under the plasma concentration versus time curve (AUC), and a 35 minute prolongation of time to peak plasma concentration (Tmax) following administration of a single 850 mg tablet of metformin with food, compared to the same tablet strength administered fasting. The clinical relevance of these decreases is unknown.

Distribution
The apparent volume of distribution (V/F) of metformin following single oral doses of 850 mg averaged 654 + 358 L. Metformin is negligibly bound to plasma proteins in contrast to sulfonylureas which are more than 90% protein bound, Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of metformin hydrochloride tablets, steady state plasma concentrations of metformin are reached within 24-48 hours and are generally c 1 pg/mL. During controlled clinical trials, maximum metformin plasma levels did not exceed 5 ug/mL, even at maximum doses

Metabolism and Elimination
Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Renal clearance (see Table 1) is approximately 3.5 times greater than creatinine clearance which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

Teneligliptin Hydrobromide Hydrate:                                       
Teneligliptin, is chemically known as a {(2S,4S)-4-[4-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-1-piperazinyl]-2-pyrrolidinyl}(1,3 thiazolidin-3-yl) methanone hemipentahydrobromide hydrate  thiazolidine hemipentahydrobromide hydrate and is peptidomimetic with the molecular formula of C22H30N6OS.2½HBr.xH2O and molecular weight of 628.86 g/mol g/mol for hemipentahydrobromide. The hydrate can be from mono to dihydrate.

Photostability:
Long term: 25oC / 60o RH, 8 month (30 month at RT)
Accelerated Stability Studies 40oC /175o RH

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