Amlodipine Besilate Research Articles

Targeted and untargeted screening for impurities in losartan tablets marketed in Germany by means of liquid chromatography/high resolution mass spectrometry

Technical advances in the field of quality analysis allow an increasingly deeper look into the impurity profile of drugs. The ability to detect unexpected impurities in addition to known impurities ensures the supply of high-quality drugs and can prevent recalls due to the detection of harmful unexpected impurities, as has happened recently with the N-nitrosamine and azido impurities in losartan (LOS) drug products. In the present study, the LC-MS/HRMS approach described by Backer et al. was applied to an even more complex system, being the investigation of 35 LOS drug products and combination preparations purchased in 2018 and 2022 in German pharmacies. The film-coated tablets were analysed by means of four LC-MS/HRMS method variants. For the separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and for mass spectrometric detection a qTOF mass spectrometer with electrospray ionization in positive and negative mode was used. An information-dependent acquisition method was applied for the acquisition of high-resolution mass spectrometry data. The combination of an untargeted and a targeted screening approach revealed the finding of eight impurities in total. Beside the five LOS related compounds, LOS impurity F, J, K, L, M, and related compound D from amlodipine besilate, LOS azide and an unknown derivative thereof were detected. Identification and structure elucidation, respectively, were successfully performed using in silico fragmentation. Differences in the impurity profiles of drug products from 2018 and 2022 could be observed. This study shows that broad screening approaches like this are applicable to the analysis of drug products and can be an important enhancement of the quality assurance of medicinal products.

Standardized Analytical Procedure for Routine Testing of Amlodipine Besilate and Enalapril Maleate Simultaneously in In-vitro Samples

>This study develops a standardized methodology for routine analysis of in-vitro samples of amlodipine besilate and enalapril maleate concurrently in immediate-release tablet dosage forms. UV-detection was performed at absorption maxima of 237.20 nm and 217.00 nm for amlodipine besilate and enalapril maleate, respectively; 6.8 pH phosphate buffer was used as dissolution media for 30 mintues, on USP II (Paddle) dissolution apparatus, at 50 RPM and 37.0 ± 0.5oC. The fallouts of the analysis were endorsed statistically. Results were satisfactory in the arrays of 1–19 μg mL-1 for amlodipine besilate and 1–9 μg mL-1 for enalapril maleate. The analysis results exhibited that the projected simultaneous method is modest, swift, precise, and accurate and used for the repetitive analysis of dissolution samples of amlodipine besilate and enalapril maleate in combined pharmaceutical dosage forms (tablets).

HPLC Tests in Quality Control under the Market Surveillance Program for Medicinal Products Containing Amlodipine and Valsartan

Background: Quality is one of the three main characteristics of medicinal products. The quality assurance process is multi-stage: during the manufacturing, quality control is the commitment of the manufacturer, but after medicinal products become part of the distribution and pharmacy network, analytical quality control is carried out within the program for Market Surveillance. There are different approaches in conducting quality control of medicinal products under the Market Surveillance Program. Aim: The aim of the study is to compare the results obtained under two approaches: individual testing and testing by groups with the same active substance. Methods: In this study, comparative tests for assay and purity were carried out within two groups of medicinal products from the antihypertensive group containing Amlodipine besilate and Valsartan. Analyses were performed in accordance with the available pharmacopoeial monographs, as well as those from literature sources. Results: The results from the assay tests show a significant difference in the same product tested. Analytical methods for the determination of impurities also show different results when analyzing the same medicinal product. Conclusion: Considering the performed analytical tests, the obtained results can be used to make several conclusions and suggestions concerning the optimisation of the Annual Market Surveillance Program.

EHypertension: A prospective longitudinal multi‐omics essential hypertension cohort

eHypertension: A prospective longitudinal multi‐omics essential hypertension cohort

The Effect of Food Thickeners on the Bitterness and Dissolution of Amlodipine Besilate Powder When Co-Administered with Thickeners to Patients with Dysphagia

Purpose: The present research was performed to evaluate the effect of food thickeners on the bitterness and dissolution of bitter drugs when co-administered to patients with dysphagia. Methods: Amlodipine besilate (AMPB) powder was used as a model drug. Starch- and xanthan gum-based food thickeners were examined, with swallowing-aid jelly as a reference. The line-spread test (LST), texture prolife analysis (TPA) were done firstly. In related to AMPB powder mixed with food thickeners solution, a conventional dissolution test simulating the oral cavity was performed, the amlodipine (AMP) concentration and taste sensor output for dissolved medium versus time profiles were developed. The dissolution test at pH 1.2 and 4.5, representing typical gastric conditions for younger or elderly people, was performed in two kinds of thickener solution and swallowing-aid jelly those were mixed with AMPB powder. Results: LST demonstrated that xanthan gum-based food thickeners fulfilled the requirements for patients with dysphagia but that starch-based food thickeners did not. In TPA, hardness and adhesiveness decreased proportionally as the concentration increased for both kinds of food thickener. Conventional dissolution test simulating oral cavity demonstrated the following bitterness ranking: xanthan gum-based food thickener < starch-based food thickener < swallowing-aid jelly. In dissolution test at pH 1.2 and 4.5, starch-based thickener and swallowing-aid jelly mixed with AMPB powder showed complete AMP dissolution. However, xanthan gum-based food thickeners mixed with AMPB powder showed about only 60% AMP dissolution after 120 minutes. Conclusion: Although xanthan gum-based food thickeners were successful in masking the bitterness of AMP, they may reduce its bioavailability in humans. The 7.1 and 4.7 (w/v) % starch-based thickener show bitterness inhibition under simulated oral cavity conditions and complete dissolution of AMP under simulated gastric conditions.

The Effect of Food Thickeners on the Bitterness and Dissolution of Amlodipine Besilate Loaded Oral Disintegration Tablets: Assessment of Potential Suitability for Patients with Dysphagia

The purpose of this research was to evaluate the effect of starch- and xanthan gum-based food thickeners on the bitterness and dissolution of amlodipine besilate (AMPB) loaded orally disintegrating tablets (ODT) for potential use with patients with dysphagia. A conventional dissolution test simulating the oral cavity was performed and the taste sensor output of the dissolved sample was evaluated over a 60-seconds period. When four types of AMPB loaded ODTs were tested alone, at 60 seconds, branded product (A) was the least bitter, followed by generic product (B)/generic product (C) which were equal, and finally generic product (D) which was the most bitter. Inhibition of bitterness of AMPB loaded ODTs mixed thickeners, 1.0 (w/v) % xanthan gum-based food thickener solution was significantly strong. The 7.1 (w/v) % and 4.7 (w/v) % starch-based food thickeners solution also effective in bitterness inhibition compared to the 2.4 (w/v) % starch-based food thickener solution. The dissolution test under pH 1.2 in related to 7.1 (w/v) % and 4.7 (w/v) % starch-based thickener contained each of AMPB loaded ODTs were associated with an almost complete amlodipine (AMP) dissolution (almost 90% at 10 minutes), whereas the 1.0, 2.0, 3.0 (w/v) % xanthan gum-based food thickener solution containing AMPB loaded ODTs did not show complete AMP dissolution and there were large variations in the initial dissolution stage. This suggests that a mixture of xanthan gum-based thickener and AMPB loaded ODT poses a risk of reduction of bioavailability. In conclusion, a mixture of 4.7 (w/v) % or 7.1 (w/v) % starch-based thickener with ODTs provides complete release of AMP and superior bitterness inhibition, so is the best choice for administration to patients with dysphagia.

ACUTE MYOCARDIAL INFARCTION AND STROKE PREVENTION WITH AMLODIPINE/ ATORVASTATIN SINGLE-PILL THERAPY FOR PATIENTS WITH HYPERTENSION AND DYSLIPIDEMIA

Objective: To evaluate the effect of suppressing the onset of Acute Myocardial Infarction (AMI) and Stroke by using combination tablet of Amlodipine Besilate/ Atorvastatin Calcium Hydrate (Caduet Combination Tablets) or combined use of Amlodipine Besilate and Atorvastatin Calcium Hydrate against patients with Hypertension and Dyslipidemia. Design and method: We build a Markov Model of considering the long-term treatment by using combination tablet of Amlodipine 5 mg/ Atorvastatin 10 mg or combined use of Amlodipine 5 mg and Atorvastatin 10 mg. The target patients were 60 years old with Hypertension (Systolic Blood Pressure 152mmHg) and Dyslipidemia (Total Cholesterol 288 mg/dL). The analyzed cycle was set for one year and we performed the simulation for the lifetime treatment. The medication adherence for the well treated group was 82.4% in the Combination Tablet treatment group and 61.0% in the combined treatment group. Medication adherence for the poor treated group was based on hypothesis as each clinical efficacy index was the same as before treatment. Results: The incidence of AMI and stroke during the lifetime in combination tablet treatment group was estimated to be 21.8% in male and 24.1% in female for patients without diabetes or smoking. For patients without diabetes but smoking, it was 35.8% and 40.6%. For patients with diabetes but no smoking, it was 31.1% and 48.5%. For patients with both diabetes and smoking, it was 47.4% and 68.5%. On the other hand, the incidence of AMI and stroke during the lifetime in combined treatment group was 24.7% in male and 27.5% in female for patients without diabetes or smoking. For patients without diabetes but smoking, it was 39.4% and 44.9%. For patients with diabetes but no smoking, it was 34.5% and 53.1%. For patients with both diabetes and smoking, it was 51.0% and 72.0%. The incidence of AMI and stroke was lower in the combination tablet treatment group compared to the combined treatment group in both men and female. Conclusions: Treatment with combination tablet against patients with hypertension and dyslipidemia improves the medication adherence which resulted in suppressing the onset of AMI and stroke.

Open tubular capillary column immobilized with sulfobutylether-β-cyclodextrin for chiral separation in capillary electrochromatography.

A novel chiral open tubular capillary column was fabricated with sulfobutylether-β-cyclodextrin and glycidyl methacrylate for enantioseparation in capillary electrochromatography. First, the pretreated silica-fused capillary was treated with 3-trimethoxysilyl propyl methacrylate to attach double bond ligand onto the surface. A copolymer layer was formed on the surface of capillary using glycidyl methacrylate and ethylene dimethacrylate by in situ one-pot polymerization. Sulfobutylether-β-cyclodextrin was encapsulated inside the copolymerized layer. The morphology of the developed column was characterized by field emission scanning electron microscopy. The effect of organic percentage and pH value of the mobile phase on electroosmotic flow and resolution was also investigated. The performance of the fabricated column was validated by separation of amlodipine besilate, 2,3-diphenylpropionic acid, tropic acid, and pantoprazole enantiomers with good resolutions of 3.67, 4.82, 3.34, and 2.61, respectively. The repeatabilities of column-to-column and day-to-day through relative standard deviation were found better than 4%, exhibiting satisfactory repeatability of the developed column. The results reveal that open tubular capillary columns modified with β-cyclodextrin show a great prospect for enantioseparation of chiral drugs in capillary electrochromatography.

Improved Hypertension by Investigating Circadian Rhythm of Blood Pressure

Case: The case is 86-year-old male hypertensive patient with anti-hypertensive drug for 5 years. He has been provided Amlodipine besilate 5mg at 0800h and doxazosin mesylate 2mg at 2300h for long. In June 2020, he noticed unstable fluctuation of Blood Pressure (BP) during morning, afternoon and night. Results: Then, he checked the circadian rhythm of BP, which showed higher BP in early morning, decreasing BP 0800-1000h, minimum BP during 1000-1400h, increasing BP during 1400-1800h and stable BP during 1800-2400h. Due to the result, he changed to take amlodipine at 2300h. Consequently, his BP gradually became stable during 24 hours after 2 weeks. Discussion: Some factors may exist for contributing improved BP fluctuation. They include a) pathophysiological characteristics of BP circadian rhythm, b) effective time for anti-hypertensive drug, c) accuracy of the obtained BP data and d) the social and psychological reliability of the patient. Regarding d) he was engaged in research and development work as a senior researcher at a chemical company. He has been also a member of New Elderly Association (NEA), which was established by Shigeaki Hinohara. He lives on the philosophy of Hinohara-ism for long, associated with stable mind and body.

Simple and rapid HPLC-UV methods for gabapentin quantification in human plasma and urine: applicability in pharmacokinetics and drug monitoring

Aim: We aimed to develop methods to determine gabapentin (GAB) in biological samples using high-performance liquid chromatography (HPLC) with application in pharmacokinetics and therapeutic drug monitoring. Methods: Simple, rapid and efficient HPLC-UV methods to quantify GAB in human plasma and urine were developed and validated for clinical analysis of GAB. The 1-fluoro-2,4-dinitrobenzene (FDNB) was used as derivatization agent. For plasma samples, protein precipitation using acetonitrile was performed, before the derivatization reaction. Urine samples were cleaned-up by liquid-liquid extraction with dichloromethane:n-butanol (1:1, v/v) after derivatized. Amlodipine besilate was used as internal standard (IS). Results: Gabapentin and IS were resolved on LiChrospher® C18 RP column and a mixture of 50 mM sodium phosphate buffer (pH 3.9):methanol (27:73, v/v) as mobile phase, at 1.2 mL/min. The methods used small sample volumes, 100 and 50 μL of plasma and urine, respectively. Linearity was obtained in the interval of 0.2-14 μg/mL in plasma and 2-120 μg/mL in urine. Both methods showed to be selective, without carry-over effect, precise, accurate and stable in different conditions. GAB plasma concentration in patients receiving 600 to 3600 mg/day of GAB ranged between 0.40 to 11.94 μg/mL at steady-state. Conclusions: The methods described in this study were simple, rapid and fulfill all validation requirements. They were easily and successfully applied for population pharmacokinetics and therapeutic drug monitoring of GAB in patients with chronic pain.

Simultaneous Assessment of Aliskiren Hemifumarate, Amlodipine Besilate and Hydrochlorothiazide in Tablet Dosage Form by RP-HPLC

Simultaneous Assessment of Aliskiren Hemifumarate, Amlodipine Besilate and Hydrochlorothiazide in Tablet Dosage Form by RP-HPLC

Determination of Amlodipine Besilate and Azilsartan Medoxomil by UHPLC, HPTLC and Spectrophotometric Techniques

Aims: To develop methods with complete validation according to ICH guidelines and to be applied for the determination of both drugs in laboratory prepared mixtures and in synthetic tablets.&#x0D; Study Design: Ultra high performance liquid chromatography (UHPLC), High performance thin layer chromatography (HPTLC) and visible spectrophotometric methods are developed for determination of amlodipine besilate and azilsartan medoxomil in laboratory-prepared mixtures and in synthetic tablets.&#x0D; Methodology: Two techniques have been developed for the simultaneous determination of amlodipine besilate and azilsartan medoxomil in pure form and synthetic tablets. The first was UHPLC in which separation was achieved on a C18 column using 0.1% o-phosphoric acid - acetonitrile - methanol (60:10:30, by volume) as mobile phase with detection at 243nm. The second was HPTLC where separation was performed on silica gel 60 F254 plates using chloroform- tolune-methanol-glacial acetic acid (7: 1.5: 1.5: 0.5 by volume) as a developing system and UV detection at 243nm. In addition, visible- spectrophotometric method was developed for determination of amlodipine besilate in presence of azilsartan medoxomil through formation of yellowish orange colored product after reaction of amlodipine besilate with anisaldehde in acid medium with λmax at 443 nm.&#x0D; Results: UHPLC method was linear over the concentration ranges of 2-20 μg/ mL and 4-40 μg/ mL while HPTLC method was linear over the concentration ranges of 0.2 -4.0 μg/ spot and 0.5-8.0 μg/ spot for amlodipine besilate and azilsartan medoxomil, respectively. The visible spectrophotometric method was found to be valid over the concentration range of 10–80 μg/mL for amlodipine besilate.&#x0D; Conclusion: The proposed three techniques are rapid, accurate and precise, thus can be effectively applied for the routine estimation of both drugs in bulk and in their combined formulations.

Perindopril-induced angioedema of the lips and tongue: a case report

BackgroundAce inhibitor-induced angioedema, characterized by sudden-onset swelling of the mucous membrane, skin, or both, is a rare occurrence in the Kingdom of Saudi Arabia. Because of its safety and efficacy, perindopril is a commonly prescribed angiotensin-converting enzyme inhibitor. Here we describe the clinical manifestations, management, and outcome of perindopril-induced angioedema of the lips and tongue in a 65-year-old Saudi man.Case presentationA 65-year-old Saudi Arab man presented to an emergency department with lip and tongue swelling and dysphagia. There were no systemic symptoms and no past history of a similar event. He had been consuming perindopril 5 mg and amlodipine 5 mg for the last 3 weeks: brand name, Coveram, from the company Servier (Ireland) Industries Ltd.; one tablet of Coveram contains 3.395 mg perindopril corresponding to 5 mg perindopril arginine and 6.935 mg amlodipine besilate corresponding to 5 mg amlodipine. A physical examination revealed considerable swelling of his lips and tongue.Examinations of other systems, including his cardiovascular and respiratory systems, revealed unremarkable findings. All laboratory parameters were also normal. Electrocardiography demonstrated sinus rhythm, a normal P axis, and V-rate of 50–99.A clinical diagnosis of perindopril-induced angioedema was made, and perindopril was discontinued. The angioedema resolved completely after the administration of antihistamines and corticosteroids.ConclusionsAngioedema caused by angiotensin-converting enzyme inhibitors is an uncommon occurrence in Saudi Arabia. The findings from this case are expected to raise awareness about this condition among clinicians in this country.

Investigation of the retention mechanisms of amlodipine besylate, bisoprolol fumarate, and their impurities on three different HILIC columns

Using theoretical models, retention mechanisms of amlodipine besilate and its impurities D, E, and F were tested, as well as bisoprolol fumarate and its impurities A, C, K, and L. Appropriate theoretical retention models for tested compounds were used, which enabled the determination of retention mechanisms responsible for the separation of tested compounds on three different HILIC column: silica, amino, and diol. In order to describe the effect of ratio of aqueous and organic portion of the mobile phase on the retention behavior of tested compounds, as well as the consideration of shares of partition and adsorption processes in HILIC retention mechanism in all three columns, partitioning and adsorption retention theoretical models were calculated. For this purpose, the water content was varied in the range from 4% to 29%, corresponding to the HILIC region of mobile phase composition. During the experiment, values of other factors of mobile phase were maintained at a constant level. Regression coefficients of partition and adsorption retention models and the corresponding determination coefficients were determined (R2). Partitioning models for all tested compounds on amino column had higher R2 values, while adsorption models for all compounds tested on silica and diol column had higher R2 value.

Synthesis and establishment of Amlodipine impurity G reference standard

Dimethyl-4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate which is impurity of amlodipine besilate was synthesized. Hantzsch condensation of methyl acetoacetate with O-chlorobenzadehyde in isopropanol at reflux temperature for about 10 hours yielded the yellow powder. This product was purified by column chromatography and the structure was identified by spectrocospic methods (IR, MS, NMR), that was characterised amlodipine impurity G (dimethyl -4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate). The quality of the impurity was determined by high performance liquid chromatography method validation according to The International Conference on Harmonisation (ICHQ2A) and established impurity reference standard as World Health Organization (WHO technical series 941) and determined homogeneity and assigned value as International Organisation for Standardisation (ISO 13528).

PCV41 - Budget Impact Analysis of Triveram for The Treatment of Hypertension in Italy

The objective of the study was to perform a Budget Impact Analysis (BIA) assessing the introduction of Triveram for the treatment of hypertension into the Italian market. Triveram is a single pill combination of statin (atorvastatin calcium trihydrate), calcium channel blocker (amlodipine besilate) and angiotensin-converting enzyme inhibitor (perindopril arginine) indicated for the treatment of essential hypertension and/or stable coronary artery disease. BIA compared two different scenarios: Scenario 1 without the triple fixed combination therapy vs. Scenario 2 with the introduction of Triveram. Population data were obtained from Local Project Database by Cegedim. The time horizon considered was 3 years from the introduction of Triveram. Total number of patients in each of the 3 years was the same for the two Scenarios, as the model allows only the switch of patients from the dual or triple combinations to the fixed dose treatment with Triveram. The perspective of the Italian National Healthcare Service was considered. The study showed that the introduction of Triveram leads to a reduction in the quantity of pills taken by patients (247.893.255, 270.691.934 and 287.356.690 in Scenario 1 and 224.916.946, 222.121.000 and 214.892.239 in Scenario 2, respectively in year 1, 2 and 3). At a cost of 12,90 €/month, the introduction of Triveram generates savings for the Italian NHS of 10.6, 22.4 and 33.5 million € respectively in year 1, 2 and 3 over the total expenditure of 95, 114.8 and 126.1 million € related to year 1, 2 and 3 in the first scenario. The present study indicates that the introduction of Triveram generates important savings for the Italian NHS and improves the adherence to the therapy, thanks to the reduction in the number of pills taken by patients. Better adherence is also linked to a reduction in the number of hospitalizations and related costs.

Physicochemical qualities and ingestibility of high value-added amlodipine besilate formulations

Objectives The physicochemical qualities and ingestibility of high value-added amlodipine besilate formulations were evaluated using one brand name and four generic orally disintegrating tablets (formulations A, B, C, D, and E) and a generic orally disintegrating film (formulation F). Methods Pushing out from a press-through package, tablet strength, and hydrophilia were examined for the aforementioned formulations A–E, and sensory characteristics according to the disintegration time, taste, and palatability in healthy subjects were evaluated for formulations A–F. Results The strength required for pushing out from a press-through package for formulations A, B, C, D, and E was approximately 20 N, indicating ease of opening for most users. Moreover, hardness and friability of formulations A, B, C, D, and E were more than 0.03 kg/mg and less than 1%, respectively. Thus, all formulations had sufficient tablet strength to endure fall impact in the automatic packing machine and vibration when carrying them from one place to another. The wetting time of formulation E (9 s) was significantly shorter than that of formulations A (27 s), B (34 s), C (28 s), and D (29 s), indicating that with the exception of hydrophilia, the physicochemical qualities of the five aforementioned formulations of orally disintegrating tablets were equivalent. The disintegration time of formulations E (15 s) and F (15 s) in the oral cavity was significantly shorter than that of formulations A (23 s), B (26 s), C (25 s), and D (22 s). Moreover, more than 50% of subjects reported strong or weak bitterness for formulations B, C, D, E, and F. Finally, more than 80% of subjects described formulations A, E, and F as easy to take, indicating good palatability. Conclusions This study provides useful information for selecting high value-added amlodipine besilate formulations for individualized treatments.

Evaluation of herb-drug interaction of a polyherbal Ayurvedic formulation through high throughput cytochrome P450 enzyme inhibition assay

Ethnopharmacological relevanceArishtas are Ayurvedic formulation made with decoction of herbs. Arjunarishta formulation is being used in Ayurveda for cardio-protective activity. Ashwagandharishta formulation possesses antioxidant, anti-atherosclerotic and anti-stress properties. Ridayarishta, a novel empirical formulation was prepared using combination of selected ingredients from these two formulations to support healthy heart functions and to reduce stress. Aim of the StudyAim of the Study was to investigate herb-drug interaction (HDI) of Ridayarishta formulation through human hepatic cytochrome P450 (CYP450) enzyme inhibition assay. Materials and methodsRidayarishta formulation was phyto-chemically standardized against arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A using high performance thin layer chromatography (HPTLC) analysis. The formulation was standardized with respect to ethanol by gas chromatographic (GC) analysis. HDI was evaluated with Ridayarishta formulation and amlodipine besilate, atenolol, atorvastatin, metformin, glipizide glimepiride cocktail using high throughput CYP450 enzyme inhibition assay; against CYP1A2, 2C19, 2D6 and 3A4 isozymes. ResultsContents of arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A in Ridayarishta formulation were found to be 1.76±0.12, 1.51±0.09, 1.85±0.05, 3.2±0.12, 1.21±0.08, and 2.16±0.09ppm, respectively. Quantity of ethanol in Ridayarishta was found to be 7.95±0.023% (V/V). Ridayarishta showed significantly higher (P<0.001) IC50 value against CYP1A2 (IC50–13.80±1.96µg/mL), 2C19 (IC50–14.343±2.28µg/mL), 2D6 (IC50–0.897±0.28µg/mL) and 3A4 (IC50–32.057±2.51µg/mL) compared to positive controls such as furafylline, tranylcypromine, quinidine and ketoconazole respectively. Cocktail of herbal formulation and cardio protective, antihypertensive, anti-diabetic drugs showed significantly (P<0.001and P<0.01) less or negligible HDI. ConclusionRidayarishta formulation alone and cocktail with amlodipine besilate, atenolol, atorvastatin, metformin, glipizide, glimepiride had negligible or insignificant effect on CYP450 inhibition. It may be concluded that consumption of Ridayarishta along with selective cardio protective, antihypertensive and anti-diabetic conventional medicine is safe with negligible or without any significant CYP450 (CYP1A2, 2C19, 2D6 and 3A4) inhibition mediated HDI.

Antihypertensive, Amlodipine Besilate Inhibits Growth and Biofilm of Human Fungal Pathogen Candida.

Candida albicans and Candida glabrata are two important human pathogens associated with high mortality. The anti-Candida potential of an antihypertensive drug, amlodipine besilate (AB), was studied against 10 strains of Candida, including 8 clinical isolates. AB is an inhibitor of voltage-gated Ca2+ channel (VGCC) of mammals. CCH1 expresses in a part of Ca2+ channel of Candida, which is a homologue of α subunit of mammalian VGCC. In plate assays, all strains of Candida showed sensitivity to AB on agar media at 256 μg/mL concentration, AB caused lethality at concentrations of 16 and 64 μg/mL in clinical isolates of C. glabrata and all strains of C. albicans, respectively. Minimum fungicidal concentration (MFC) values of AB varied for different strains. The clinical isolates of C. glabrata turned out to be more susceptible to AB than those of C. albicans. At 16 μg/mL, AB showed reduction of biofilm in the range of 41.51%-79.66% for C. glabrata strains and 32.00%-54.06% for C. albicans strains. AB has shown potential antifungal properties against the laboratory strains and clinical isolates of C. glabrata and C. albicans. In conclusion, AB exhibited potential antifungal properties against planktonic form and biofilm of C. glabrata and C. albicans. It was more effective against C. glabrata than against C. albicans in vitro.

Equilibrium study on enantioselective distribution of amlodipine besilate enantiomers in a biphasic recognition chiral extraction system

The objective of this paper is to present the enantioselective distribution of amlodipine besilate enantiomers (ADB) in a biphasic recognition chiral extraction (BRCE) system. In the BRCE system, hydrophobic tartrate was added in organic phase and hydrophilic β-cyclodextrins in aqueous phase. Tartrate and β-cyclodextrins preferentially recognize (−)-ADB and (+)-ADB, respectively. Impacts of the type and concentration of chiral selectors, the pH value of the aqueous phase solution as well as temperature on the separation efficiency were investigated. Sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and d-isobutyl tartrate (d-IBTA) were found to be the most suitable chiral selectors. By substituting the monophasic recognition chiral extraction (MRCE, with chiral selector in only one phase) system with BRCE system, the distribution ratios of the ADB enantiomers are remarkably increased with a little increase of enantioselectivity. The optimized conditions that are 5 °C of temperature, 7.2 of pH value, 0.05 mol/L of SBE-β-CD as well as 0.1 mol/L of d-IBTA are identified. The experimental results demonstrated that BRCE with strong chiral separation ability possesses good prospect in separation of enantiomers.