Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design
Abstract:Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental designTo evaluate the influence of different variables on tablet formulations containing enalapril maleate and indapamide as active substances, two separate experimental designs were employed: one for evaluating powder properties and the other for tablet characteristics. Because of the low active pharmaceutical ingredient content, it was … Show more
“…Based on the results of these experiments the optimal run conditions can be statistically determined and the outcome of unperformed experiments predicted with high accuracy (21). Pharmaceutical applications of DoE include the development and optimization of single-component (22,23) and multi-component formulations (24,25), as well as the development and validation of analytical methods (26,27).…”
Offering a systematic and multivariate analysis of the analytical procedure, development and validation of HPLC methods using Quality by Design approach are in the limelight of current research trends. A new, experimental design-aided HPLC method for fampridine was developed and preliminarily validated according to current in-force international guidelines for linearity, accuracy, robustness and precision.The method offers a high throughput sample analysis, with an elution time of 2.9 minutes, and signal detection without excipient interference performed at 262 nm. The method proved to be linear between 1–15 µg mL−1 (R2= 0.9996). The mean recovery was found to be 98.7 ± 1.9 % in the tested range of 2.5–7.5 µg mL−1. Low RSD values (< 1 %) were obtained for both model, intra- and inter-day precision. The limit of detection and limit of quantification were 0.24 and 0.78 µg mL−1, resp. The method proved to be applicable for active substance assay in a pharmaceutical dosage form.
“…Based on the results of these experiments the optimal run conditions can be statistically determined and the outcome of unperformed experiments predicted with high accuracy (21). Pharmaceutical applications of DoE include the development and optimization of single-component (22,23) and multi-component formulations (24,25), as well as the development and validation of analytical methods (26,27).…”
Offering a systematic and multivariate analysis of the analytical procedure, development and validation of HPLC methods using Quality by Design approach are in the limelight of current research trends. A new, experimental design-aided HPLC method for fampridine was developed and preliminarily validated according to current in-force international guidelines for linearity, accuracy, robustness and precision.The method offers a high throughput sample analysis, with an elution time of 2.9 minutes, and signal detection without excipient interference performed at 262 nm. The method proved to be linear between 1–15 µg mL−1 (R2= 0.9996). The mean recovery was found to be 98.7 ± 1.9 % in the tested range of 2.5–7.5 µg mL−1. Low RSD values (< 1 %) were obtained for both model, intra- and inter-day precision. The limit of detection and limit of quantification were 0.24 and 0.78 µg mL−1, resp. The method proved to be applicable for active substance assay in a pharmaceutical dosage form.
“…The up-to-date "quality by design" approach has been successfully used in the pharmaceutical development and characterisation of tablets, optimization of tablet formulations (12,13) and also for the analytical method development and validation of HPLC (14,15) and other analytical methods (16). Design of experiments (DoE) has many advantages in pharmaceutical drug formulations and analytical method development and validation in comparison with techniques like changing one factor at a time (COST).…”
A reverse-phase HPLC (RP-HPLC) method was developed for strontium ranelate using a full factorial, screening experimental design. The analytical procedure was validated according to international guidelines for linearity, selectivity, sensitivity, accuracy and precision. A separate experimental design was used to demonstrate the robustness of the method. Strontium ranelate was eluted at 4.4 minutes and showed no interference with the excipients used in the formulation, at 321 nm. The method is linear in the range of 20-320 μg mL-1 (R2 = 0.99998). Recovery, tested in the range of 40-120 μg mL-1, was found to be 96.1-102.1 %. Intra-day and intermediate precision RSDs ranged from 1.0-1.4 and 1.2-1.4 %, resp. The limit of detection and limit of quantitation were 0.06 and 0.20 μg mL-1, resp. The proposed technique is fast, cost-effective, reliable and reproducible, and is proposed for the routine analysis of strontium ranelate.
“…Compression force, as one should expect, would define tablet hardness and API dissolution from the tablets' matrix, whereas the optimum turret and feeder rotation speed ratio define the mass uniformity. Szabo et al (66) investigated the effect of formulation variables on the manufacturability of tablets containing a combination of enalapril maleate and indapamide. In their study, microcrystalline cellulose, croscarmellose sodium and magnesium stearate had a noticeable impact on manufacturability and in-process control of tablets, while compression force was noted as the most influential process parameter on product performance characteristics.…”
Section: Table I Most Frequently Used Methods In Experimental Designsmentioning
Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through in silico aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.
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