Lisinopril Dihydrate Research Articles

Biopharmaceutical aspects of the development of transdermal forms of Lisinopril dihydrate

Abstract Prevention and treatment of arterial hypertension is of great importance. Improvement of existing medicines through the use of alternative routes of administration can enhance the pharmacotherapeutic characteristics of active pharmaceutical ingredients (APIs). Transdermal therapeutic systems (TTS) allow for delivery of a drug through intact skin into the systemic circulation, while minimizing side effects. The development of transdermal formulations of antihypertensive drugs, Lisinopril dihydrate in particular, has practical and scientific significance. Optimization of the algorithm for the development of transdermal drugs involves in vitro preformulation studies of the membrane permeability of APIs and the identification of factors that affect this process. The tests were performed by dialysis through a semipermeable hydrophilic membrane using a Valia-Chien diffusion device. The effect of the initial concentration of Lisinopril dihydrate on the flux rate I s was investigated. Different donor concentrations of Lisinopril dihydrate were tested at three levels, 10, 20 and 30 mg/ml, accordingly. It was noted that the permeation process of Lisinopril dihydrate under model conditions corresponds to zero-order kinetics and is characterized by a uniform speed. The correlation coefficient (R 2) for all the kinetic equations was 0.999. A linear dependence of the flux velocity of Lisinopril dihydrate on the initial concentration was indicated. The concentration of Lisinopril dihydrate in the donor solution of 30 mg/ml was found to be optimal for further stages of pharmaceutical development of the transdermal formulation. The studies of Lisinopril dihydrate permeability allow to give a positive assessment of the acceptability of this API for use in the transdermal formulation and the development of TTS.

Development and Validation of Stability Indicating HPTLC Methods for the Estimation of Antihypertensive Drugs (Nebivolol and Hydrochlorothiazide)

The devised method passed the ICH Q2 (R1) validation test, and the findings imply it might be utilised for both the regular monitoring of pharmaceutical formulation and raw material quality. Results for Nebivolol and Hydrochlorothiazide were consistently linear across concentration ranges of 4-24 and 10-60 μg/mL, respectively, according to the linearity study. The proposed approach was determined to be appropriate based on precision data and minimal relative standard deviation (RSD). Our lab confirmed the LOD and LOQ values for cilnidipine and lisinopril dihydrate. The method's accuracy within the given range is demonstrated by the low relative standard deviation (RSD) values. We found that the suggested method was linear, sensitive, accurate, and exact when it came to estimating hydrochlorothiazide and nebivolol in bulk and in pharmaceutical formulations. This conclusion was reached when the validation inquiry was finished and the results were discovered.

Substantiation of creation of transdermal forms of drug delivery with antihypertensive action

The article presents the theoretical justification for the choice of active pharmaceutical ingredients of antihypertensive action for the creation of new forms of delivery - transdermal therapeutic systems.
 Purpose: monitoring of studies on the use of angiotensin-converting enzyme (ACE) inhibitors in the development of transdermal drugs for the treatment of hypertension.
 Materials: open access electronic resources of scientific periodicals from around the world: Google Scholar (https://scholar.google.com/); PubMed (https://pubmed.ncbi.nlm.nih.gov/); Sciencedirect (https://www.sciencedirect.com/); Pubchem (https://pubchem.ncbi.nlm.nih.gov/); National Library of Ukraine named after V. I. Vernadskyi (http://www.nbuv.gov.ua/); Ukrainian Institute of Intellectual Property (Ukrpatent) (https://sis.ukrpatent.org/uk/); Industrial Property (https://base.uipv.org/searchBul/); USPTO. The United States Patent and Trademark Office (https://www.uspto.gov/patents/search); European Patent Office (EPO) (https://www.epo.org/).
 Methods of the research: information search, theoretical analysis and systematization of data from scientific sources, logical analysis.
 Results: a review of scientific sources was carried out, and an analysis of ACE inhibitors as candidates for the creation of transdermal forms for the treatment of arterial hypertension was carried out. The pharmacological and physicochemical aspects of the possibility of their use for introduction through the skin are defined. It has been established that the search and development of the latest means of treatment of arterial hypertension, which would significantly increase the duration and quality of life of patients, are extremely relevant. Transdermal drug delivery systems are one of the pharmaceutical products being developed on the world market, and their use allows overcoming the associated disadvantages of other delivery routes.
 Conclusions: the review of domestic and foreign literature confirmed the relevance of biopharmaceutical research in the field of development of innovative dosage forms - transdermal therapeutic systems for the treatment of hypertension.
 The choice of promising antihypertensive active pharmaceutical ingredients of the ACE group (enalapril maleate, lisinopril dihydrate, and captopril) is substantiated, taking into account their specific physicochemical properties that are suitable for penetration through the skin.
 The market for transdermal drug delivery is increasing, and there is a prospect of higher growth rates in this market in the coming years

Simultaneous determination of amlodipine and lisinopril dihydrate using fourth derivative spectroscopy

A new fast and simple selective method for the simultaneous determination of lisinopril dihydrate and amlodipine in combined drugs was developed using the fourth derivative spectrum method, based on the zero-crossing-point technique for the determination of compounds in drugs. The wavelength values for lisinopril dihydrate and amlodipine in solvent medium were found to be (203, 207, and 231 nm) and (215, 254, and 277 nm), respectively, with the average obeying Beer’s law in the range of lisinopril dihydrate 2.0 to 45.0 µg/mL and amlodipine 2.0 to 35.0 µg/mL. Lisinopril dihydrate has molar absorptivity regions (9227.76-11700.28 L/mol.cm, 203 nm), (15320.74-20795.59 L/mol.cm, 207 nm), and (2207.60-3311.40 L/mol.cm, 231 nm), while amlodipine (5886.72-10914.96 L/mol.cm, 215 nm), (5518.8-6418.16 L/mol.cm, 254 nm) and (1676.08-1921.36 L/mol.cm, 277 nm). The recovery rate of lisinopril dihydrate in the pharmaceutical dosage forms range was 95.13 to 102.60% and amlodipine 95.14 to 102.80%. The results of the relative error showed that the interferences did not affect the method of estimating these compounds. The proposed method has been successfully applied to estimate pharmaceutical dosage forms.

DEVELOPMENT OF SPECTROPHOTOMETRIC METHOD FOR DETERMINATION OF LISINOPRIL IN TABLET DOSAGE FORM

Aim. The research aims at developing a fast, simple, reliable spectrophotometric method according to "green" chemistry principles for the determination of lisinopril in pure substance and in drugs presented on the Ukrainian market.
 Materials and Methods. Chemical reference standard of lisinopril dihydrate (Sigma-Aldrich, ³98%, HPLC), methanol R (Honeywell Riedel-de Haen™, 99.9%), tablets of Lisinopril-Astrapharm 10 mg), Lisinopril-KRKA 10 mg (Slovenia) and Lisinopril-Teva 10 mg (Germany) were used in this study. Double-beam scanning spectrophotometer "Shimadzu UV-1800" (Japan) connected with software package UV-Probe 2.62 were used for measurements. Absorbance of the solutions in the UV region were recorded in 1 cm quartz cells vs. methanol R. Laboratory electronic balance RAD WAG AS 200 / C, ultrasonic bath Sonorex Digitec DT100H and measuring glassware of grade A were used. Statistical processing and determination of validation parameters were performed in accordance with the requirements of State Pharmacopoeia of Ukraine 2.0 and ICH Q2.
 Results and Discussions. The spectrophotometric method for the determination of lisinopril by direct measurement of the absorbance of the tested solutions in the ultraviolet region of the spectrum has been developed (lmax=212 nm). Validation parameters including linearity, range of application, specificity, accuracy, precision, limit of detection and limit of quantification, robustness were calculated for the proposed analytical procedure. The correctness of the analytical method was proved by calculating the complete uncertainty of the latter. The calculated uncertainty of sample preparation (DSP) for the determination of lisinopril in tablets was 2.46%. It was established that the maximum contribution to the uncertainty of sample preparation for operations of the quantification of lisinopril in tablets, make the operations of lisinopril CRS sampling and aliquots pipetting. The total uncertainty of the analytical procedure (DAs) in the analysis of the drug was 2.56%. The predicted complete uncertainty of the analysis results did not exceed critical values (DAs=2.56 % £ maxDAs=3.2 %), the method is correct. The specificity is proved by the absence of interfering influence of excipients due to nonoccurence of absorption at the analytical wavelength in the analysis of methanolic extract of placebo-tested tablets, Beers law was obeyed in the ranges of 20-100 mg / ml. The least squares method was used for statistical processing of the results. Regression analysis yielded the following calibration equation: y=26,791x-0,4398. The limit of detection and the limit of quantification were 2,3 і 6,9 mg/ml. Robustness of the method was estimated by studying of absorbance stability changes of tested solutions over time. Robustness was assessed by studying the absorbance stability of the tested solutions over time. It was found that freshly prepared solutions should be used within 100 min. Developed procedure for lisinopril determination in pure substance and tablet dosage form proved to be an excellent green analysis according to analytical eco-scale.
 Conclusions. Fast, simple, reliable, cost-effective, in accordance with the principles of "green" chemistry spectrophotometric method for determination of lisinopril in pure substance and tablets has been proposed. Validation of the analytical procedure on the parameters of linearity, application range, specificity, accuracy, precision, robustness, limit of detection and limit of quantification was carried out. The complete uncertainty of the analytical procedure at the level of 2.56% was obtained, which proves the possibility of obtaining correct analysis results in other laboratories.

Lisinopril dihydrate loaded nano-spanlastic bio-adhesive gel for intranasal delivery: 23 factorial optimization, fabrication and ex-vivo studies for enhanced mucosal permeation

Lisinopril dihydrate loaded nano-spanlastic bio-adhesive gel for intranasal delivery: 23 factorial optimization, fabrication and ex-vivo studies for enhanced mucosal permeation

Qbd Based RP-HPLC Method Development and Validation for Simultaneous Estimation of Amlodipine Besylate and Lisinopril Dihydrate in Bulk and Pharmaceutical Dosage Form

The objective of this experiment was to develop and validate a simple, robust, and accurate QbD based Reverse-Phase High-Performance Liquid Chromatography method for Simultaneous estimation of Amlodipine besylate and Lisinopril dihydrate in bulk and Pharmaceutical Dosage form. A box-Behnken design was employed for optimizing the mobile phase, flow rate and pH of buffer, the optimized chromatographic conditions were Phosphate buffer: Methanol (25: 75 v/v), pH of buffer: 6.5 and flow rate: 1mL/min.
 Furthermore formulation injected and observed that the additives do not interfere with the peak of Amlodipine besylate and Lisinopril dehydrate. Both drugs are well resolved and Retention times were found to be 2.332 min and 3.584 min respectively.
 Linearity was observed in the concentration range of 10 μg to 50 μg/mL (r2=0.999). The accuracy range was 99.75 to 100.04%. Intra-day and Inter-day precision was found to be less than 2% RSD. The proposed method was useful for the best analysis of Amlodipine besylate and Lisinopril dihydrate in Bulk, pharmaceutical dosage forms and was successfully applied to routine analysis.

Molybdate assisted ninhydrin based sensitive analytical system for the estimation of drugs containing amine group

A sensitive spectrophotometric method for the analysis of isoniazid, lisinopril dihydrate, amoxicillin trihydrate, ampicillin trihydrate, glucosamine sulfate, phenylpropanolamine hydrochloride and gabapentin is described. The analysis is based on the reaction of drug molecules with ninhydrin and sodium molybdate mixture to give Ruhemanns purple product with maximum absorbance λmax) at 570 nm. The statistical analysis of intra-day and inter-day estimation of drugs as well as comparison with reported methods demonstrated high precision and accuracy of the proposed method. The method was successfully applied to the analysis of pharmaceutical preparations. The procedure was suitable for quality control application.

Quantitative determination of Lisinopril Dihydrate in pharmaceutical preparations by direct potentiometriy

A direct potentiometric titration method was applied for determination of Lisinopril Dihydrate. The method was based on the treatment of the primary data with nonlinear regression procedure. An accessible and easy-to-use algorithm for the evaluation (quantification) of a system with acid-base properties has been developed to provide a quick and unambiguous answer for the quantitative content of Lisinopril Dihydrate. The acid-base constants of Lisinopril Dihydrate were determined in aqueous solutions (at constant ionic strength 0.2 mol/l KCl and temperature 25°C). The potentiometric method developed was validated according to ICH and shows very good accuracy and precision. The present approach can be successfully used in routine analysis of the drug in quality control laboratories.

Formulation And In Vitro Evaluation of Transferosomal Patches for Enhanced Drug Delivery of Lisinopril Dihydrate

Formulation And In Vitro Evaluation of Transferosomal Patches for Enhanced Drug Delivery of Lisinopril Dihydrate

Study of the size and shape of lisinopril dihydrate particles and auxiliary substances in order to obtain optimal pharmaceutical-technological properties of tablet mass

Topicality. The particle size of the active substance in medical product significantly affects its solubility, bioavailability, and therapeutic performance that is why the study of the “Particle size” index is compulsory for pharmaceutical development. Aim. Study of the size and shape of lisinopril dihydrate particles and auxiliary substances in order to obtain optimal pharmaceutical – technological properties of tablet mass. Materials and methods. The objects of study are lisinopril dihydrate, excipients, the obtained tablet mass, the samples of experimental series and the reference drug. Studies on the particle size determination of the active substance lisinopril dihydrate and excipients were performed by pharmacopoeial methods, such as optical microscopy (2.9.37), sieve analysis (2.9.12) and laser diffraction (2.9.31). The evaluation of the selected composition was carried out by pharmaceutical-technological tests according to SPhU. Results and discussion. The results of size examination, form of particles as well as fractional composition of lisinopril dihydrate and each of the auxiliary agents were obtained. The technology of tablet mass production was determined and on the basis of experimentally determined pharmaco-technological properties of substances, such as tapped density before and after package, flow property, the optimal composition of the tablet mass with lisinopril dihydrate was developed. Conclusions. In the result of comparative study of the pharmacological properties of the experimental series of tablets with lisinopril dihydrate, 10 mg and medical product Lizinopril-Ratiopharm, 10 mg, we confirmed the practicability of determining and standardizing the index size and shape of particles for active and auxiliary substances in the formation of solids.

Development and Validation of Fast, Simple, Cost-effective and Robust RP-HPLC Method for Simultaneous Determination of Lisinopril and Amlodipine in Tablets

A new Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) method for simultaneous determination of lisinopril dihydrate and amlodipine besylate in tablets was developed and validated. This method operates under moderate chromatographic conditions, avoiding high column temperatures, ion-pair reagents, gradient elution or mobile phases with very low pH value as it is usually recommended by the majority of the existing RP-HPLC methods used for the same purpose. The developed method uses a C18 column, UV-detection and mobile phase consisting of methanol and phosphate buffer with pH 7.3. The method provides chromatograms with excellent peak symmetry and is very simple, selective, accurate, reproducible, robust and cost-effective. The rather moderate experimental conditions make the method favorable with regards to time, chemicals and consumables consumption and consequently very useful for application in the quality control laboratories in pharmaceutical companies. The method performance has been demonstrated using different reversed-phase columns and with different neutral mobile phases showing that it can be adjusted and used in different laboratories for analysis of different combinations of lisinopril with other antihypertensive active ingredients.

‘Temporary Plasticiser’: A novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures

Hypertension and dyslipidaemia are modifiable risk factors associated with cardiovascular diseases (CVDs) and often require a complex therapeutic regimen. The administration of several medicines is commonly associated with poor levels of adherence among patients, to which World Health Organisation (WHO) proposed a fixed-dose combination unit (polypill) as a strategy to improve adherence. In this work, we demonstrate the fabrication of patient-specific polypills for the treatment of CVDs by fused deposition modelling (FDM) 3D printing and introduce a novel solution to meet critical quality attributes. The construction of poly(vinyl alcohol) (PVA)-based polypills containing four model drugs (lisinopril dihydrate, indapamide, rosuvastatin calcium and amlodipine besylate) was revealed for the first time. The impact of tablet architecture was explored using multi-layered and unimatrix structures. The novel approach of using distilled water as a ‘temporary co-plasticiser’ is reported and was found to significantly lower the extruding (90 °C) and 3D printing (150 °C) temperatures from 170 °C and 210 °C respectively, with consequent reduction in thermal stress to the chemicals. XRD indicated that lisinopril dihydrate and amlodipine besylate maintained their crystalline form while indapamide and rosuvastatin calcium were essentially in amorphous form in the PVA tablets. From the multilayer polypills, the release profile of each drug was dependent on its position in the multilayer. In addition to the multilayer architecture offering a higher flexibility in dose titration and a more adaptive solution to meet the expectations of patient-centred therapy, we identify that it also allows orchestrating the release of drugs of different physicochemical characteristics. Adopting such an approach opens up a pathway towards low-cost multidrug delivery systems such as tablets, stents or implants for wider range of globally approved actives.

Development of analytical method and validation for determination of Lisinopril dihydrate in bulk drug and dosage form using HPTLC method

A simple, reproducible and efficient High Performance Thin Layer Chromatography method was developed for Lisinopril dihydrate in bulk drug and dosage form. A constant application rate of 0.1 ml/s with nitrogen aspirator was used, and the space between two bands was 6 mm. The slit dimension was 5 × 0.45 mm, and the scanning speed was 10 mm/s. The mobile phase consisted of n-butanol: methanol: ammonia in the ratio of 3.0: 1.0: 1.0 (v/v/v). The retention time (min) and linearity range (μl) for Lisinopril was (0.20) and (1-5) respectively. The method so developed was validated for its accuracy and precision. The LOD and LOQ were found to be 0.050237 and 0.152233 for Lisinopril respectively. The accuracy was found to be 98.88%. The developed method was found to be accurate, precise and selective for determination of Lisinopril in bulk and dosage form.

Development and validation for determination of lisinopril dihydrate in bulk drug and formulation using RP-HPLC method

A simple, reproducible and efficient reverse phase high performance liquid chromatographic method was developed for Lisinopril in bulk drug and formulation. A column having 150 × 4.6 mm in isocratic mode with mobile phase containing acetonitrile: phosphate buffer (70:30; adjusted to pH 3.0) was used. The flow rate was 0.8 ml/min and effluent was monitored at 216 nm. The retention time (min) and linearity range (μg/ml) for Lisinopril was (1.510) and (10-35). The developed method was found to be accurate, precise and selective for determination of Lisinopril in bulk and formulation.

Spectrofluorometric Determination of Lisinopril dihydrate and Methyl- Dopa in Bulk and Pharmaceutical Formulation by Using Dansyl Chloride

A novel spectrofluorometric method has been developed for quantitative determination of Lisinopril dihydrate and methyldopa either in pure form or in pharmaceutical preparation. The principle of the method based on the reaction of each drug with dansyl chloride [5-(Dimethyl Amino) Naphthalene-1-Sulfonyl chloride] by the aid of sodium hydroxide solution of pH 8.5 resulted in a product of a high fluorescent intensity which was then measured at 511 nm and 516 nm, for lisinopril and methyldopa respectively after excitation at 323 nm. Factors affecting reaction development were studied and optimized. The proposed method was found to be sensitive, selective and reproducible. Calibration curves were linear over the concentration ranges of 3–20 for lisinopril and 7–25 μg/mL for methyldopa. Results obtained from tablets analysis were compared statistically with reported reference methods.

Spectrofluorometric Determination of Lisinopril dihydrate and Methyl- Dopa in Bulk and Pharmaceutical Formulation by Using Dansyl Chloride

A novel spectrofluorometric method has been developed for quantitative determination of Lisinopril dihydrate and methyldopa either in pure form or in pharmaceutical preparation. The principle of the method based on the reaction of each drug with dansyl chloride [5-(Dimethyl Amino) Naphthalene-1-Sulfonyl chloride] by the aid of sodium hydroxide solution of pH 8.5 resulted in a product of a high fluorescent intensity which was then measured at 511 nm and 516 nm, for lisinopril and methyldopa respectively after excitation at 323 nm. Factors affecting reaction development were studied and optimized. The proposed method was found to be sensitive, selective and reproducible. Calibration curves were linear over the concentration ranges of 3–20 for lisinopril and 7–25 μg/mL for methyldopa. Results obtained from tablets analysis were compared statistically with reported reference methods.

FORMULATION DEVELOPMENT AND EVALUATION OF ELEMENTARY OSMOTIC TABLET OF LISINOPRIL DIHYDRATE

Objective: Lisinopril Dihydrate is one of the antihypertensive drug used to control the high blood pressure. Osmotically Controlled release tablet of Lisinopril Dihydrate was performed for reducing dosing frequency and patient compliance.Methods: Elementary osmotic tablets of Lisinopril Dihydrate were developed using Sodium chloride as a key ingredient which gives osmogent property which provides driving force inside the core tablet and which leads to release of the drug. Microcrystalline cellulose used as a release retardant material in the present work. Different formulations were prepared by varying the concentrations using 32 factorial designs. It was applied to see the effect of variables Sodium chloride (X1) and MCC (X2) on the response percentage drug release as a dependent variable. These formulations were evaluated for, Hardness, Flow property, Thickness, Friability, Drug content and In vitro drug release. Tablets were coated with a semipermeable membrane using 5% w/v cellulose acetate(CA) in acetone and PEG 400(1%) used as Plasticizer. Coated Elementary osmotic tablets were drilled for delivery orifice using a standard micro drill of diameter size 0.8 mm.Results: Drug release rate was increased as the increase in the concentration of sodium chloride and release rate decreased on increasing the concentration of MCC. Drug release rate was directly proportional to delivery orifice size. SEM Study carried out for detection of diameter size of the delivery orifice. The FTIR studies demonstrate that there was no interaction between polymer and drug.Conclusion: The optimized formulation was stable for 3 mo of accelerated stability study

Green micellar HPLC analysis of three angiotensin-converting enzyme inhibitors in their mixtures with hydrochlorothiazide and modeling of their retention behavior by fitting to Foley's model.

We present an environmentally friendly method for the analysis of three angiotensin-converting enzyme inhibitors and hydrochlorothiazide simultaneously using a green micellar eluent for the first time. The chromatographic separation of enalapril maleate, lisinopril dihydrate, benazepril hydrochloride, and hydrochlorothiazide was implemented on an octadecyl silica column with a solution containing sodium dodecyl sulfate (0.12M), 1-propyl alcohol (10% v/v), triethylamine (0.3% v/v), and H3 PO4 (0.02M) at pH 3.6 as the mobile phase and UV detection at 210nm. Validity of the method was confirmed and it exhibited good linearity within the ranges of 5.0-50.0μg/mL for hydrochlorothiazide and 10.0-60.0μg/mL for the three angiotensin-converting enzyme inhibitors with a limit of detection of 0.39 to 1.15μg/mL for all the studied drugs. The developed micellar high-performance liquid chromatography method enables the quantification of the targeted angiotensin-converting enzyme inhibitors in combined tablets with hydrochlorothiazide by isocratic elution. There is no need for special precautions to prevent broadening and splitting of their chromatographic peaks. The method fulfills the society rights for safe and green analytical methods. The retention behavior of the four studied drugs was fitted to Foley's model and their association equilibria to the micelles (KAM ) and to the surface-modified stationary phase (KAS ) were calculated.

Development and Optimization of w/o/w Multiple Emulsion of Lisinopril Dihydrate Using Plackett Burman and Box-Behnken Designs

The aim of the present study was to develop water-in-oil-in-water (w/o/w) type Multiple Emulsion of Lisinopril dihydrate for enhancing its oral bioavailability via enhanced permeation. For primary emulsification, corn oil was used as the oil phase, Span 83 as the lipophilic surfactant and Xanthan gum was used as the viscosity enhancer. Primary emulsion was re-emulsified with aqueous phase containing Tween 20 as hydrophilic surfactant. Preliminary screening was performed using a 12-run, 8-factor, 2-level Plackett–Burman design followed by Box Behnken Design for optimization. MEs were characterized and evaluated for macroscopic and microscopic properties, globule size, entrapment efficiency, rheological properties, in vitro and ex vivo drug release and stability studies. In vitro drug diffusion study was done through dialysis bag and ex vivo permeability studies were performed in Franz diffusion cell using rat intestine. The optimized w/o/w ME showed globule size and entrapment efficiency of 15.65 + 1.967 μm and 87.35 + 3.79 % respectively. Drug flux was found to be 119.3 μg/cm2/h for drug loaded w/o/w ME and 105.1μg/cm2/h for plain drug solution. The overall results of the studies showed the potential of the w/o/w ME as promising drug delivery system for Lisinopril dihydrate.