Design of Experiments in Pharmaceutical Development

Dhoot, Abhishek Sunil; Fernandes, Gasper; Naha, Anup; Rathnanand, Mahalaxmi; Kumar, Lalit

doi:10.1007/s11094-019-02070-4

Cited by 28 publications

(14 citation statements)

References 29 publications

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“…The application of the Design of Experiment (DoE) would be helpful to understand the relationship between independent factors and their responses in drug formulations. The influence of each formulation variable as well as the interaction between different independent factors can be analyzed using DoE in order to assess the most critical variables [ 19 ]. By and large, DoE has three major areas in drug formulations: initially, the screening phase that identifies the most critical factors for a certain process and their appropriate levels [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The influence of each formulation variable as well as the interaction between different independent factors can be analyzed using DoE in order to assess the most critical variables [ 19 ]. By and large, DoE has three major areas in drug formulations: initially, the screening phase that identifies the most critical factors for a certain process and their appropriate levels [ 19 ]. Then, the optimization phase that detects the optimum input variables with their levels to obtain the best possible responses [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

et al. 2021

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The aim of the current study is to establish a comprehensive experimental design for the screening and optimization of Atorvastatin-loaded nanostructured lipid carriers (AT-NLCs). Initially, combined D-optimal screening design was applied to find the most significant factors affecting AT-NLCs properties. The studied variables included mixtures of solid and liquid lipids, the solid/liquid lipid ratio, surfactant type and concentration, homogenization speed as well as sonication time. Then, the variables homogenization speed (A), the ratio of solid lipid/liquid lipid (B), and concentration of the surfactant (C) were optimized using a central composite design. Particle size, polydispersity index, zeta potential, and entrapment efficiency were chosen as dependent responses. The optimized AT-NLCs demonstrated a nanometric size (83.80 ± 1.13 nm), Polydispersity Index (0.38 ± 0.02), surface charge (−29.65 ± 0.65 mV), and high drug incorporation (93.1 ± 0.04%). Fourier Transform Infrared Spectroscopy (FTIR) analysis showed no chemical interaction between Atorvastatin and the lipid mixture. Differential Scanning Calorimetry (DSC) analysis of the AT-NLCs suggested the transformation of Atorvastatin crystal into an amorphous state. Administration of the optimized AT-NLCs led to a significant reduction (p < 0.001) in serum levels of rats’ total cholesterol, triglycerides, and low-density lipoproteins. This change was histologically validated by reducing the relevant steatosis of the liver.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

et al. 2021

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“…To develop a suitable semisolid formulation for topical administration of drugs this property should be characteristic of the system [ 49 ]. Thixotropy is a reversible phenomenon exhibited by non-Newtonian materials, characterized by a reduction in the apparent viscosity when the material is subjected to a constant shear rate (ascendant curve; structure deformation), returning to its original viscosity when the shear forces decreased (descendent curve; structure recovery) [ 8 ]. This study provided qualitative information about the formulation breakdown during a deformation and recovery cycle.…”

Section: Resultsmentioning

confidence: 99%

“…In the pharmaceutical industry, there is a continuous demand for the development of new products and processes, and for the improvement of existing ones, to meet the increasing quality and standards requirements [ 8 ]. Pharmaceutical development aims to design a quality product and its manufacturing process to consistently deliver the intended performance [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

et al. 2021

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Semisolids constitute a significant proportion of topical pharmaceutical dosage forms available on the market, with creams being considered profitable systems for releasing active substances into the skin. This work aimed at the development of a generic Clotrimazole topical cream, based on the assumptions that assist the development of such formulations. First, the critical parameters to obtain a final formulation as similar as possible to the reference product were defined. Then, the percentages of cetyl palmitate and octyldodecanol were identified as critical variables and chosen for optimization in further studies. A “quality by design” approach was then used to identify the effect of process variability on the structural and functional similarity (Q3) of the generic product qualitatively (Q1) and quantitatively (Q2). A two-factor central composite orthogonal design was applied and eleven different formulations were developed and subjected to physicochemical characterization and product performance studies. The results were used to estimate the influence of the two variables in the variation of the responses, and to determine the optimum point of the tested factors, using a design space approach. Finally, an optimized formulation was obtained and analysed in parallel with the reference. The obtained results agreed with the prediction of the chemometric analysis, validating the reliability of the developed multivariate models. The in vitro release and permeation results were similar for the reference and the generic formulations, supporting the importance of interplaying microstructure properties with product performance and stability. Lastly, based on quality targets and response constraints, optimal working conditions were successfully achieved.

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“…In the 1920s, Sir Ronald Fisher, a legendary statistician, laid the foundation for modern statistical research with his contributions to statistics, which have been hailed as "a genius." Research conducted has maintained a proactive stance, which is at the core of the current regulatory system that controls the development of pharmaceutical products [1,2,3]. Walter A. Shewhart, William E. Deming, and Joseph M. Juran extended this work and advocated a process-based culture for incorporating quality into products.…”

Section: Introductionmentioning

confidence: 99%

Design Space by Design of Experiments

Dangat

Patel

Kuchekar

2021

JPRI

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The quality of methods and products are usually influenced by several input factors. Research has recently focused on understanding the effects of multidimensional and interconnected input factors on the results of pharmaceutical products and analytical methods using Design of Experiment (DoE). Furthermore, it examines how DOE may be implemented, both for students and teachers, as well as highlighting historical perspectives on DOE. A good experimental design can help you make the most use of the available resources and make the analysis of the results easier. Collaborations between researchers and practitioners that are pushing the boundaries of experimental design are examined. It provides an overview of the principles and applications of the most common screening and response surface design, as well as creating mixtures designs.

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Design of Experiments in Pharmaceutical Development

Cited by 28 publications

References 29 publications

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

Design Space by Design of Experiments

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