Chemical stability of enalapril maleate drug substance and tablets by a stability-indicating liquid chromatographic method

Diego, Marta de; Godoy, G; Mennickent, Sigrid; Godoy, Ricardo

doi:10.1590/s0100-40422011000300016

Cited by 5 publications

References 11 publications

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User-Friendly HPLC Method Development and Validation for Determination of Enalapril Maleate and Its Impurities in Enalapril Tablets

Koppala

Reddy

Anireddy

2017

Journal of Chromatographic Science

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The official method for the determination of Enalapril Maleate and its related substances in European Pharmacopoeia (EP) is a gradient liquid chromatographic method. The method used styrene-divinylbenzene copolymer column, mobile phase buffer pH 6.8 and column oven temperature 70°C. In this method, the separation between main component Enalapril and Ph. Eur. Imp-A was not completed hence the achieving system suitability requirement is a tough task and it requires quite often adjustment in chromatographic parameters. Moreover, column oven temperature 70°C is not user friendly to HPLC instruments and users. In this study, several changes were introduced to the method in order to improve the separation, peak shapes and to overcome the column oven temperature. A new user-friendly stability-indicating RP-HPLC method was developed for Enalapril related substances analysis. The developed method uses a ZORBAX Eclipse XDB-C18 column with column oven temperature at 55°C and mobile phase containing acetonitrile and a phosphate buffer at pH 3.0. The method is capable of separating all the known impurities with resolution more than 3.5, which is much better than that obtained with the existing monograph methods. The optimized method was validated and demonstrated to have acceptable specificity, sensitivity, linearity, accuracy, precision, robustness, solution stability and equivalency to the EP method. The developed method proved to be applicable to a wide number of C18 reversed-phase columns. In addition, the Enalapril assay method also presented with 20 min run time.

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User-Friendly HPLC Method Development and Validation for Determination of Enalapril Maleate and Its Impurities in Enalapril Tablets

Koppala

Reddy

Anireddy

2017

Journal of Chromatographic Science

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Reflection on the Pharmaceutical Formulation Challenges Associated with a Paediatric Investigation Plan for an Off-Patent Drug

Walsh

2016

AAPS PharmSciTech

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In Europe, the development of pediatric medicines for new patent protected products is mandatory and applicants are required to submit a Paediatric Investigation Plan (PIP) to the regulatory authorities. The process is voluntary for off-patent medicines and despite the availability of incentives, there is still a huge unmet need for the development of off-patent pediatric medicines. The aim of the EU grant funded "Labeling of Enalapril from Neonates to Adolescents" (LENA) project is to develop a new pediatric dosage form of the off-patent drug enalapril, for the treatment of heart failure in patients aged from birth to 18 years. This article provides an overview of some of the key formulation challenges that were faced during the product development programme and PIP process, including selection of dosage form and excipients, methodology for administration of the product and evaluation of patient acceptability.

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

Guimarães

Comelli

Tacon³

et al. 2016

AAPS PharmSciTech

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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 10 min. 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 91 days 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.

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Chemical stability of enalapril maleate drug substance and tablets by a stability-indicating liquid chromatographic method

Cited by 5 publications

References 11 publications

User-Friendly HPLC Method Development and Validation for Determination of Enalapril Maleate and Its Impurities in Enalapril Tablets

User-Friendly HPLC Method Development and Validation for Determination of Enalapril Maleate and Its Impurities in Enalapril Tablets

Reflection on the Pharmaceutical Formulation Challenges Associated with a Paediatric Investigation Plan for an Off-Patent Drug

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

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