当前位置： SCI文献检索 > JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS期刊下所有文献 > Molecular insight into atypical instability behavior of fixed-dose combination containing amlodipine besylate and losartan potassium.

Molecular insight into atypical instability behavior of fixed-dose combination containing amlodipine besylate and losartan potassium.

Abstract：

:Combination therapy with the use of fixed-dose combinations (FDCs) is evincing increasing interest of prescribers, manufacturers and even regulators, evidently due to the primary benefit of improved patient compliance. However, owing to potential of drug-drug interaction, FDCs require closer scrutiny with respect to their physical and chemical stability. Accordingly, the purpose of the present study was to explore stability behavior of a popular antihypertensive combination of amlodipine besylate (AML) and losartan potassium (LST). Physical mixtures of the two drugs and multiple marketed formulations were stored under accelerated conditions of temperature and humidity (40°C/75% RH) in a stability chamber and samples were withdrawn after 1 and 3 months. The physical changes were observed visibly, while chemical changes were monitored by HPLC employing a method that could separate the two drugs and all other components present. The combination revealed strong physical instability and also chemical degradation of AML in the presence of LST. Interestingly, three isomeric interaction products of AML were formed in the combination, which otherwise were reported in the literature to be generated on exposure of AML free base above its melting point. The same unusual products were even formed when multiple marketed FDCs were stored under accelerated conditions outside their storage packs. However, these were absent when AML alone was stored in the same studied conditions. Therefore, reasons for physical and chemical incompatibility and the mechanism of degradation of AML in the presence of LST were duly explored at the molecular level. The outcomes of the study are expected to help in development of stable FDCs of the two drugs.

journal_name

J Pharm Biomed Anal

journal_title

Journal of pharmaceutical and biomedical analysis

authors

Handa T,Jhajra S,Bhagat S,Bharatam PV,Chakraborti AK,Singh S

doi

10.1016/j.jpba.2016.12.035

subject

Has Abstract

pub_date

2017-03-20 00:00:00

pages

66-80

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(16)30622-7

journal_volume

136

pub_type

杂志文章

在线工具

Molecular insight into atypical instability behavior of fixed-dose combination containing amlodipine besylate and losartan potassium.