Bioequivalence of two-amlodipine formulation using high-performance liquid chromatography (HPLC)

Abstract

Amlodipine is chemically described as (R.S) 3-ethyl-5-methyl-2-(2 aminoethoxy
methyl) – 4 – (2- chlorophenyl) – 1, 4- dihydro – 6 – methyl – 3,5 pyridine dicarboxylate
benzene sulfonate , its empirical formula C20H25 Cl N2 O5 C6 H6 O3 S. It is one of the most
widely used drugs for the management of essential hypertension. In this study an accurate and
sensitive reversed phase liquid chromatographic method was adopted on deactivated ODS
column using tetrahydrofuran: phosphate buffer pH 6.0 as mobile phase. The injected volume
used was 750 μl to elevate the detection limit up to 5 ng/ml. The bioquivalence trial was carried
out on 20 healthy volunteers aged 25-55 years with a weight range from 60-90 kgm. The time
interval used for collected blood samples from volunteers was from 1- 96 hr.
Subjects were administrated a single 5 mg dose of Samadipin from SDI and reference
product Norvasc (pfizer) according to two period, Two – sequence crossover design, with
wash out period of one week. After oral administration of 5 mg of both formulations,
maximum peak plasma absorption were about 9 hours in both formulations with values of
59.5±4.39 ng/ml for Samadipin and 65.11±3.95 ng/ml for Norvasc (pfizer) respectively. The
peak concentration and area under the curve of plasma concentration were analyzed to obtain
92% confidence intervals. The elimination half-life of boh formula were ranged from 30-45
hours with mean value of 37.86 and 39.026 hours for test and reference drugs respectively.
The calibration curve for peak area verses concentration were linear with regression of
0.998, the detection limit was 5 ng/ml. The standing diastolic pressure was reduced by 4.2
mm Hg six hour after 5 mg amlodipine .There was no significant change in pulse rate .Highly
significant postive correlation were observed between dose and AUC (0-96 hrs). Due to long
half-life and gradual absorpion , amlodipine should be effective in lowering blood pressure
giving once daily , and the incident of side effects due to rapid absorotion should be
minimized.
In conclusion , both test and reference product show no statistically significant
difference), Therefore the two drugs were Bioequivalent.