Enalapril Maleate Research Articles

LC-MS/MS assay for quantitation of enalapril and enalaprilat in plasma for bioequivalence study in Indian subjects.

Background:Enalapril (EPL) is an angiotensin-converting enzyme inhibitor for the treatment of hypertension and chronic heart failure. Enalaprilat (EPLT) is an active metabolite that contributes to the overall activity of EPL.Aim:To quantitate EPL along with its metabolite EPLT using LC–MS/MS, a bioanalytical method was developed and validated with tolbutamide in human plasma using a protein precipitation technique.Results:The sensitive and selective method has an LLOQ of 1 ng/ml with a linearity range of 1–500 ng/ml for both EPL and EPLT using 300 µl of plasma without any matrix effect.Conclusion:Linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples after oral administration of 20 mg of EPL maleate in healthy volunteers demonstrate applicability to bioavailability/bioequivalence studies.

Rapid analysis of drug dissolution by paper spray ionization mass spectrometry

With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs − enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90min to 6min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests.

Effects and mechanisms of Shenkang injection promoting extracellular matrix degradation via regulating ERK1/2/MMPs signaling pathway in renal failure rats

This study aimed to clarify preliminarily the effects and mechanisms of Shenkang injection (SKI) promoting extracellular matrix(ECM)degradation via regulating extracellular-signal regulated protein kinase(ERK)1/2/matrix metalloproteinases(MMPs)signaling pathway in renal failure rats. Twenty rats were randomly divided into 4 groups：the Sham group,the Model group,the SKI group and the Enalapril maleate(EM)group. The model rats with renal failure were induced by intragastric administration of adenine and unilateral ureteral obstruction(UUO). After modeling, the rats in SKI group and EM group were intervened by intraperitoneal injection of SKI or intragastric administration of the EM suspension,while the rats in Sham group and Model group were administrated with distilled water respectively for 3 weeks. The 24 h urinary protein excretion(Upro)and urinary N-acety1-β-D-glucosaminidase(UNAG)in all rats were tested after drug administration. All rats were sacrificed after drug administration for 3 weeks,blood and kidney were collected,renal morphological characteristics were observed. Furthermore,serum biochemical indices and the protein expressions of collagen type IV(CIV),MMP-2,MMP-9,tissue inhibitors of metalloproteinase(TIMP)-1,ERK1/2 and phosphorylated-ERK1/2(p-ERK1/2)in the kidney were evaluated respectively. The results indicated that,after the intervention of SKI,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),albumin(Alb),Upro,UNAG and renal morphological change in model rats were improved at different levels,respectively. Moreover,these actions were similar to EM. In addition to these,SKI adjusted the protein expressions of MMP-2,MMP-9 and TIMP-1,and down-regulated the protein expressions of p-ERK1/2 in the kidney. Moreover,these actions were different from EM. In conclusion,SKI promotes ECM degradation and delays the progression of renal failure possibly through regulating ERK1/2 signaling pathway activation in the kidney and intervening MMPs/TIMP-1 expressions in vivo.

Development and validation of multivariate calibration methods for simultaneous estimation of Paracetamol, Enalapril maleate and hydrochlorothiazide in pharmaceutical dosage form

Three multivariate calibration spectrophotometric methods were developed for simultaneous estimation of Paracetamol (PARA), Enalapril maleate (ENM) and Hydrochlorothiazide (HCTZ) in tablet dosage form; namely multi-linear regression calibration (MLRC), trilinear regression calibration method (TLRC) and classical least square (CLS) method. The selectivity of the proposed methods were studied by analyzing the laboratory prepared ternary mixture and successfully applied in their combined dosage form. The proposed methods were validated as per ICH guidelines and good accuracy; precision and specificity were confirmed within the concentration range of 5–35μgmL−1, 5–40μgmL−1 and 5–40μgmL−1of PARA, HCTZ and ENM, respectively. The results were statistically compared with reported HPLC method. Thus, the proposed methods can be effectively useful for the routine quality control analysis of these drugs in commercial tablet dosage form.

Fluidized Bed Hot Melt Granulation with Hydrophilic Materials Improves Enalapril Maleate Stability.

This work aimed at developing enalapril maleate granules in order to improve its stability in solid dosage form. Granules were prepared by hot melt granulation using a fluidized bed apparatus. Gelucire 50/13®, polyethylene glycol 6000 e Poloxamer 407® were studied and compared as binders in 2 × 2 factorial designs where the proportions of enalapril maleate, binders and spray dried lactose were varied. The granulation process resulted in high yields and granule sizes that indicated the prevalence of particles coating. Furthermore, the granules obtained showed adequate flowability and a fast dissolution rate of enalapril maleate with almost 100% of the drug released in 10min. The stability of enalapril maleate in hard gelatin capsules showed that the drug stability was greatly increased in granules, since for raw drug, the remaining content of enalapril maleate after 91days was 68.4% and, for granules, the content was always above 93%. This result was confirmed by the quantification of the degradation products, enalaprilat and diketopiperazine, which were found in very low content in granules samples. The results demonstrate that fluidized bed hot melt granulation with hydrophilic binders is a suitable alternative for improving the chemical stability of enalapril maleate.

Effect of aqueous extract of the Vigna angularis in rats subjected to an experimental model of moderate chronic kidney disease.

To evaluate the effect of the aqueous extract of the Vigna angularis, popularly known as "Azuki beans", in rats subjected to an experimental model of moderate chronic kidney disease. Thirty rats underwent two surgeries - Ormrod and Miller (1980) - to obtain Moderate Chronic Kidney Disease (CKD-M). The animals were randomized into 3 groups. Group 1 (Control): distilled water. Group 2 (Azuki): Vigna angularis 5% aqueous extract. Group 3 (Treatment): 10mg/kg of enalapril maleate. The rats received their respective treatments for 14 days. The treatment with azuki beans produced an increase in urine output from the second day until the end of the experiment compared to the Control groups (p<0.01) and Treatment (p<0.05). The treatment with azuki also produced significant reductions in the levels of glucose, triglycerides, VLDL, uric acid, Alanine aminotransferase (p<0.05), urea and serum creatinine (p<0.01), besides having produced a significant increase in the levels of HDL when compared to the Control group. Treatment with Azuki beans produced improvements in the parameters of renal function and significantly reduced glucose levels, triglycerides, VLDL, alanine aminostransferase, uric acid and creatinine, besides having produced a significant increase in the levels of HDL in rats submitted to a model of moderate chronic kidney disease.

Theoretical repeatability assessment without repetitive measurements in gradient high-performance liquid chromatography

This paper puts forward a time and material-saving method for evaluating the repeatability of area measurements in gradient HPLC with UV detection (HPLC-UV), based on the function of mutual information (FUMI) theory which can theoretically provide the measurement standard deviation (SD) and detection limits through the stochastic properties of baseline noise with no recourse to repetitive measurements of real samples. The chromatographic determination of terbinafine hydrochloride and enalapril maleate is taken as an example. The best choice of the number of noise data points, inevitable for the theoretical evaluation, is shown to be 512 data points (10.24s at 50 point/s sampling rate of an A/D converter). Coupled with the relative SD (RSD) of sample injection variability in the instrument used, the theoretical evaluation is proved to give identical values of area measurement RSDs to those estimated by the usual repetitive method (n=6) over a wide concentration range of the analytes within the 95% confidence intervals of the latter RSD. The FUMI theory is not a statistical one, but the “statistical” reliability of its SD estimates (n=1) is observed to be as high as that attained by thirty-one measurements of the same samples (n=31).

Buccal Transmucosal Delivery System of Enalapril for Improved Cardiac Drug Delivery: Preparation and Characterization

Purpose: To prepare and characterize buccal transmucosal delivery system of enalapril maleate for overcoming its low bioavailability, and hence provide improved therapeutic efficacy and patient compliance.Methods: Transmucosal drug delivery systems of enalapril maleate were formulated as buccal films by solvent casting technique using polyvinylpyrrolidone K90, hydroxypropyl methylcellulose, sodium carboxymethylcellulose (high viscosity). The films were evaluated for film weight, thickness, folding endurance, drug content uniformity, surface pH, in vitro residence time, in vitro drug release and ex-vivo permeation.Results: All the formulations showed high drug content (96.45 to 98.49 %). Those with good swelling showed good residence time. In vitro drug release was highest for films prepared with high viscosity grade sodium carboxymethylcellulose (SCMC- HV,F2), releasing 92.24 % of drug in 1.5 h) followed by F4 (containing polyvinyl pyrrolidone K-90 1 % w/v and SCMC (HV) 1 % w/v). Ex-vivo drug permeation at the end of 10 h was 82.24 and 89.9 % for F2 and F4, respectively.Conclusion: Prompt drug release was obtained from the formulation (F2) containing SCMC 2 % w/v with 10 mg enalapril. However, on the basis of the highest swelling and residence time, and controlled drug release, formulation F4 (containing PVP K-90 and SCMC HV) would be suitable for the development of buccal film for effective therapy of cardiac diseases.Keywords: Cardiac disease, Transmucosal, Buccal films, Enalapril maleate, Drug release, Ex-vivo permeation

Designing of Fast Disintegrating Tablets for Antihypertensive Agent Using Superdisintegrants

The aim of present study was to formulate and evaluate Fast dissolving tablet (FDT) of Enalapril maleate. FDT of this drug improved efficacy by minimizing the disintegration time and by providing fast release. FDT of Enalapril maleate, using different superdisintegrants like sodium starch glycolate, cross carmellose sodium and other excipients like mannitol, microcrystalline cellulose, magnesium sterate and talc by direct compression technique. All the optimized formulations were characterized on the basis of post-compression parameters, such as determination of disintegration time, in-vitro dispersion time, drug content, in-vitro dissolution study, wetting time, water absorption time,. Formulation F6 containing crospovidone (20%) with appropriate amount of other excipients was considered to be the optimized formulation with desired drug content 99.48%, wetting time 11.68±1.21 second, water absorption time 86.28±0.62 second, in-vitro disintegration time 13.68±1.68. FDT rapidly dissolve in oral cavity within 13.68 second without need of drinking water, had a pleasant mouth feel with improved patient compliance, particularly for those who have difficulty in swallowing like paediatric and geriatric patients. In-vitro drug release showed fast behaviour of F6 formulation. All the physical and chemical parameters were found to be in acceptable range and fulfil the entire requirement for FDT.

Comparative effects of antihypertensive therapy modes on the wall rigidity of various blood vessels

Objective. The purpose of the study was the comparative analysis of the vasoprotective effects of a fixed combination of perindopril and indapamide (Noliprel A‑Bi-Forte, Servier) and the combination of enalapril and hydrochlorothiazide (Co-Renitec, MSD) on various sites of the arterial bed in hypertensive patients. Design and methods. Depending on the mode of antihypertensive therapy (AHT) the patients were randomized into 2 groups: patients of the 1st group (41 persons) received a fixed combination of perindopril A (10,0 mg) and indapamide (2,5 mg), and those from the 2nd group (34 persons) received a fixed combination of enalapril maleate (20,0) mg and hydrochlorothiazide (12,5 mg). The aorta and major arteries were assessed with the use of the device VaSera‑1000 («Fukuda Denshi», Japan), and the following parameters were evaluated: velocity of propagation of pulse wave in the aorta, cardio-ankle vascular index and biological age of the arteries. The peripheral arteries were estimated using the device Pulse Trace PCA, and stiffness index, reflection index and vascular age were measured. All assessments were performed at baseline and at 1-, 3‑and 6‑months and at 1‑year follow-up. Results. Both combinations resulted in a significant decrease of vascular wall stiffness of the aorta and major arteries, but in the 1st group of patients the changes were observed earlier (after 3 to 6 months), and were more expressed. At the same time vasoprotective effects in peripheral arteries were observed only in 1st group of patients who received perindopril and indapamide. Conclusions. Leading to a significant reduction of the vascular wall rigidity both in aorta, major and peripheral arteries, a combination of perindopril and indapamide provides the most effective vasoprotection.

Development of Validated Specific Stability Indicating HPTLC Method for Simultaneous Estimation of Enalapril Maleate and Losartan Potassium in its Combined Dosage Form

Development of Validated Specific Stability Indicating HPTLC Method for Simultaneous Estimation of Enalapril Maleate and Losartan Potassium in its Combined Dosage Form

SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril)-Induced Cough: a Pharmacogenetic Study.

Clinical observations suggest that incidence of cough in Chinese taking angiotensin converting enzyme inhibitors is much higher than other racial groups. Cough is the most common adverse reaction of enalapril. We investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of inter-individual variability in enalapril pharmacokinetics, are associated with the enalapril-induced cough. A cohort of 450 patients with essential hypertension taking 10 mg enalapril maleate were genotyped for the functional SLCO1B1 variants, 388A > G (Asn130Asp, rs2306283) and 521T > C (Val174Ala, rs4149056). The primary endpoint was cough, which was recorded when participants were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. SLCO1B1 521C allele conferred a 2-fold relative risk of enalapril-induced cough (95% confidence interval [CI] = 1.34–3.04, P = 6.2 × 10−4), and haplotype analysis suggested the relative risk of cough was 6.94-fold (95% CI = 1.30–37.07, P = 0.020) in SLCO1B1*15/*15 carriers. Furthermore, there was strong evidence for a gene-dose effect (percent with cough in those with 0, 1, or 2 copy of the 521C allele: 28.2%, 42.5%, and 71.4%, trend P = 6.6 × 10−4). Our study highlights, for the first time, SLCO1B1 variants are strongly associated with an increased risk of enalapril-induced cough. The findings will be useful to provide pharmacogenetic markers for enalapril treatment.

Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva.

Drugs that are effectively used to treat hypertension in adults (e.g., enalapril) have not been sufficiently investigated in children. Studies required for pediatric approval require special consideration regarding ethics, study design, and conduct and are also associated with special demands for the bioanalytic method. Pediatric-appropriate assays can overcome these burdens and enable systematic investigations of pharmacokinetics and pharmacodynamic in all pediatric age groups. Tailored assays were developed for pharmacokinetic investigation of a drug in 100 μL of serum, saliva, and urine. All assays were applied in a proof-of-concept study to 22 healthy volunteers who had been given 300 mg aliskiren hemifumarate or 20 mg enalapril maleate and allowed for dense sampling. Changes in humoral parameters of the renin-angiotensin-aldosterone system were also evaluated with 6 parameters in 2.1 mL blood per time point. The pharmacokinetic results of aliskiren and enalapril obtained by low-volume assays in serum and urine were comparable to that noted in the literature. The dense sampling enabled very detailed concentration-time profiles that showed high intersubject variability and biphasic absorption behavior of aliskiren. The replacement of invasive sampling by saliva collection appears inappropriate for both drugs because the correlations of drug concentrations in both fluids were low. A low-volume assay was also used to determine values for in the renin-angiotensin-aldosterone system and to compare those results with the published literature. These results support both the use of low-volume assays in pediatric research and the systematic investigation of their use in neonates and infants. Use of this assay methodology will increase information about drug pharmacokinetics and pharmacodynamics in this vulnerable population and might contribute to safe and effective use of pharmacotherapy.

Recovery of extracellular matrix components by enalapril maleate during the repair process of ultraviolet B-induced wrinkles in mouse skin

The renin–angiotensin system is known to be involved in skin remodeling and inflammation. Previously, we reported that ultraviolet B (UVB) irradiation enhanced angiotensin-converting enzyme (ACE) expression and angiotensin II levels in hairless mouse skin, and an ACE inhibitor, enalapril maleate (EM), accelerated repair of UVB-induced wrinkles. In this study, we analyzed gene expression profiles by DNA microarray and protein distribution patterns using an immunofluorescence method to clarify the process of EM-accelerated wrinkle repair in UVB-irradiated hairless mouse skin. In the microarray analysis, we detected EM-induced up-regulation of various extracellular matrix (ECM)-related genes in the UVB-irradiated skin. In the immunofluorescence, we confirmed that type I collagen α1 chain, fibrillin 1, elastin and dystroglycan 1 in the skin decreased after repeated UVB irradiation but staining for these proteins was improved by EM treatment. In addition, ADAMTS2 and MMP-14 also increased in the EM-treated skin. Although the relationship between these molecules and wrinkle formation is not clear yet, our present data suggest that the molecules are involved in the repair of UVB-induced wrinkles.

FEATURES MANAGING PATIENTS WITH DIABETIC NEPHROPATHY WITH SECONDARYHYPERTENSION IN THE PRACTICE DOCTOR OF GENERAL PRACTITIONERS AND FAMILY MEDICINE

The aim of our research was to prove the feasibility of early diagnosis of diabetic nephropathy (DN), to optimize the treatment policy in the management ofpatients in I - II stage of chronic renal failure with hypertension.&#x0D; Materials and methods. We examined 43 patients with DN and chronic renal failure in I - II stages. Age fluctuations were in the range of 31 - 67 years. The ratio of male to female is, respectively, 1: 3. The disease duration of type 2 diabetes ranges from 2 to 15 years. Patients were evaluated after 1, 3 and 6 months. They were divided into two groups: the control group - 20patients treated: ACE inhibitor enalapril (active ingredient enalapril maleate, a daily dose of10 mg twice daily), if necessary, by combining with a blocker of slow calcium channels dihydropyridine amlodipine (active substance S - amlodipine 5 mg) and a diuretic (hydrochlorothiazide - 12.5 mg daily in the morning) or an aldosterone antagonist (spironolactone - 25 mg daily in the morning); main group - 23patients received an angiotensin IIreceptor antagonist type AT1 valsartan 80 mg or 160 mg or combined preparation - 80mg, 160 mg of valsartan hydrochlorothiazide - 12.5 mg, if needed and / or early treatment combining amlodipine. Mandatory was to determine the level of daily proteinuria, serum creatinine and GFR calculation of sample Rehberg.&#x0D; The results of research. Source circadian AH type «dipper» is fixed in 62,8%, «non - dipper» - 27,9%, «over - dipper» - 7,0%, and «night - peaker» - 2,3% ofpatients. In 6 months were fixed an increasing number ofpatients with hypertension daily profile «dipper» up to 76.7%, the lack ofpatients with «night - peaker» and a decrease in the number ofpatients with «over - dipper» to 2.1%, and «non - dipper» - up to 21, 0% in the study group. In the control group these indicators were less pronounced. Statistically, there were no changes in the level of proteinuria as well as a decrease in the index of left ventricular mass in the control and in the main groups.&#x0D; Conclusions. In the absence of significant differences between the comparison groups of antihypertensive effect nephroprotective action, reducing the index of left ventricular mass, tolerability of treatment in the study group was significantly better than the control. Patients of the main group is significantly less needed for supplemental amlodipine. The use of valsartan hydrochlorothiazide had its preferences: BP control during the day and a single dose of the drug daily. It is known that patients category «non - dipper» have a worse prognosis than the category «dipper»; valsartan eliminates this effect in 76.7% ofpatients of the category «non - dipper», making them comparable to those forecasts in patients category «dipper».&#x0D; All of the above gives grounds to recommend these drugs to general practitioners (family medicine) as the drug of choice for the management ofpatients with chronic renal failure in I - II stages and hypertension with DN proves the need for comprehensive early diagnosis (including the identification of not only the common analyzes, microalbuminuria and proteinuria daily, and mandatory definition GFR)

Formulation and evaluation of orodispersible Enalapril maleate tablets: a comparative study on natural super disintegrents and synthetic super disintegrents

The aim of the present investigation is to formulate Enalapril maleate oral disintegrating tablet by using natural and synthetic superdisintegrents..ODTs may also be used to deliver drugs to the oral cavity, for local action or, in some cases, absorption across the oral mucosa, thereby avoiding first-pass hepatic metabolism and potentially increasing the rate and extent of uptake, and reducing undesirable metabolites. The objectives of the research work is to formulate oral disintegrating tablets of Enalapril maleate by using different super disintegrates(Natural, Synthetic) in different ratio by direct compression technique and tablets were evaluated for precompressional and postcompressional Parameters such as angle of repose, bulk density, tapped density, compressibility index, drug content and in-vitro drug release study, hardness, friability, wetting time and invitro dispersion time. To study the physical characteristics of the individual drug and optimized formulations by FTIR spectroscopy. To evaluate various characteristics of the resulting tablets. Formulation CCS3, IH2 were subjected to stability Studies as per ICHguidelines at temperatures and humidity of 255C/605%RH; and 405C/755%RH.Tablets didnt reveal any appreciable changes in respect to hardness, disintegration time, drug content and dissolution profile.

Cardiovascular changes in a dog with a secondary systemic hypertension chronic renal failure: case report

Systemic hypertension in dogs can occur secondary to chronic kidney disease (CKD), because there is activation of the renin angiotensin aldosterone system (RAAS) leading to vasoconstriction and increased blood pressure and afterload, promoting concentric hypertrophy of the ventricular myocardium . The objective of this study is to report the radiographic, electrocardiographic and Doppler echocardiographic a dog carrier hypertension secondary to CKD before and after therapy. We treated a canine patient with CKD presenting unilateral ocular hemorrhagic stroke and presence of mitral murmur grade II / VI. Laboratory tests revealed renal azotemia, with urinalysis showing isosthenuria, proteinuria and granular cylinders. Blood pressure (SBP) showed average values ​​of 250 mmHg. On the chest radiograph Vertebral Heart System (VHS) was 10.7 vertebrae, indicating cardiomegaly and increased left ventricular (LV), as suggested in electrocardiography with increasing duration of QRS Complex. Doppler echocardiography showed hypertrophic cardiomyopathy and decrease in LV internal diâmentro, ventricular septal hypertrophy, dilatation of the aorta and increased fractional shortening (% FEC) LV. Therapy was instituted the basis of enalapril maleate and commercial diet for CKD. After 90 days, there was a reduction in ocular hemorrhagic stroke, with mean SBP maintaining the 130mmHg, reduction in serum biochemical values ​​in VHS (10.6 v) heart in myocardial hypertrophy and LV% FEC. The changes found suggest myocardial remodeling due to hypertension secondary source to CKD, with improvement after therapy instituted.

Development and in vitro evaluation of pulsatile drug delivery system of enalapril maleate

Pulsatile drug delivery of enalapril maleate is one such system that, by delivering drug at the right time, right place and in right amounts, holds good promises of benefit to the patients suffering from hypertension. The basic design involves the preparation of cross linked hard gelatin capsules using formaldehyde. Then the drug diluent mixtures were prepared and loaded which was separated by using hydrogel plug of polymers of different grades such as HPMC 50 cps, HPMC 100 cps, HPMC K4M, HPMC K15M, HPMC K100M, xanthan gum, carbopol 971 and sodium CMC at different amount (100 and 120 mg). Prepared formulations were subjected to evaluation of various physical parameters and in vitro drug release studies. Dissolution tests were performed using the USP type I basket method at 50 rpm in 6.8 phosphate buffer. From the in vitro dissolution studies it was found that by increasing the amount of polymers, release rate was decreased. Here, 100 mg of HPMC K100M showed 80% drug release in 8 hours whereas 120 mg showed 78.87% drug release in 10 hours. Similar decrease in the release rates were found with the increase of other polymers used in this study. The release data was fitted to various mathematical models such as zero order, first order, Higuchi, Korsmeyer Peppas and Hixson Crowell cube root law. The drug release follows mixed order kinetics and mechanism was found to be non-Fickian diffusion.Bangladesh Pharmaceutical Journal 18(1): 66-71, 2015

Application of quantitative NMR for purity determination of standard ACE inhibitors

This study investigated the accuracy of the quantitative NMR method for purity determination of ACE inhibitors reference standards and the discovery of two pairs of new diastereoisomers. Six types of ACE inhibitors, imidapril hydrochloride, benazepril hydrochloride, lisinopril, enalapril maleate, quinapril hydrochloride, and captopril were quantificated and validated for the qNMR method by discussing factors that affect parameters of the qNMR experiment, internal standards, integration, pH-effect, and uncertainty. The results were compared with data obtained by the mass balance method. The study found that maleic acid influenced the quantification of captopril in deuteroxide because of a chemical reaction. The mixtures of the reaction products were isolated by HPLC and structurally elucidated by NMR as two pairs of new diastereoisomers, 1-[(2S,4R)-thio-2-methylpropionyl-5-d-ethanedicarboxylicacid]-l-proline and 1-[(2S,4S)-thio-2-methylpropionyl-5-d-ethanedicarboxylicacid]-l-proline. The results showed that the accuracy and precision of quantitative 1H NMR spectroscopy satisfied the requirements for quantitative analysis of chemical reference standards and provided a simple, rapid, and reliable method for purity determination of ACE inhibitors systematically.

Evaluation of thermal stability of enalapril maleate tablets using thermogravimetry and differential scanning calorimetry

Differential scanning calorimetry (DSC) and thermogravimetry (TG) were used in order to evaluate the thermal stability of an enalapril maleate formulation packaged in two types of packaging, polyvinyl chloride/aluminum blister and aluminum strip. Enalapril and the excipients employed in the formulation were also evaluated by TG and DSC. Tablets were analyzed before and after storage in an acclimatized room at 40 °C and relative humidity of 75 % for 90 days. The DSC and TG results were compared with the results of dosage of enalapril and related compounds obtained by high-performance liquid chromatography. These results indicate an occurrence of chemical interaction between enalapril maleate and the excipients during its storage. After storage, it was observed that the enalapril content reduced and the predominant degradation product was diketopiperazine for both types of packaging. The predominance of diketopiperazine could be related to the absence of sodium bicarbonate in the tablets, alkalinizing agent employed in the thermal stabilization of the drug.