The Usefulness of Definitive Screening Design for a Quality by Design Approach as Demonstrated by a Pharmaceutical Study of Orally Disintegrating Tablet

Bioflavonoids from grape seeds feature powerful antioxidant and immunostimulant activities, but they present problems related to solubility and bioavailability. Nanocrystal (NC) incorporated into a mesoporous carrier is a promising strategy to address these issues. However, the preparation of this formulation involves the selection of factors affecting its critical quality attributes. Hence, this study aimed to develop an NC formulation incorporating resveratrol into a soluble mesoporous carrier based on rational screening design using a systematic and continuous development process, the quality-by-design paradigm. A mesoporous soluble carrier was prepared by spray-drying mannitol and ammonium carbonate. The NC was obtained by introducing the evaporated solvent containing a drug/polymer/surfactant and mesoporous carrier to the medium. A 26−2 fractional factorial design (FFD) approach was carried out in the screening process to understand the main effect factors. The type and concentration of polymer and surfactant, resveratrol loading, and solvent were determined on the NC characteristics. The results indicated that drug loading, particle size, and solubility were mainly affected by RSV loading, PEG concentration, and Kolliphor EL concentration. The polymer contributed dominantly to reducing the particle size and enhancing solubility in this screening design. The presence of surfactants in this system made it possible to prolong the supersaturation process. According to the 26−2 FFD, the factors selected to be further developed using a statistical technique according to the quality-by design-approach, Box Behnken Design, were Kolliphor EL, PEG400, and RSV loading.

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Robust Optimization of SWATH-MS workflow for human blood serum proteome analysis using a Quality by Design approach

10.21203/rs.3.rs-347514/v1 ◽

2021 ◽

Author(s):

Edith Serrano-Blesa ◽

Andrew Porter ◽

Dennis William Lendrem ◽

Costantino Pitzalis ◽

Anne Barton ◽

...

Keyword(s):

Validation Study ◽

Quality By Design ◽

Proteome Analysis ◽

Operating Conditions ◽

Design Approach ◽

Screening Design ◽

Study Results ◽

Quality By Design Approach ◽

Operating Window ◽

Structured Approach

Abstract Background: It is not enough to optimize proteomics assays. It is critical those assays are robust to operating conditions. Without robust assays, proteomic biomarkers are unlikely to translate readily into the clinic. This study outlines a structured approach to the identification of a robust operating window for proteomics assays and applies that method to Sequential Window Acquisition of all Theoretical Spectra Mass Spectroscopy (SWATH-MS). Methods: We used a sequential Quality by Design approach exploiting a fractional screening design to first identify critical SWATH-MS parameters, then using response surface methods to identify a robust operating window with good reproducibility, before validating those settings in a separate validation study. Results: The screening experiment identified two critical SWATH-MS parameters. We modelled the number of proteins and reproducibility as a function of those parameters identifying an operating window permitting robust maximization of the number of proteins quantified in human serum. In a separate validation study, these settings were shown to give good proteome-wide coverage and high quantification reproducibility. Conclusions: Using design of experiments permits identification of a robust operating window for SWATH-MS. The method gives a good understanding of proteomics assays and greater data-driven confidence in SWATH-MS performance.

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Robust optimization of SWATH-MS workflow for human blood serum proteome analysis using a quality by design approach

Clinical Proteomics ◽

10.1186/s12014-021-09323-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Edith Serrano-Blesa ◽

Andrew Porter ◽

Dennis W. Lendrem ◽

Costantino Pitzalis ◽

Anne Barton ◽

...

Keyword(s):

Validation Study ◽

Quality By Design ◽

Proteome Analysis ◽

Operating Conditions ◽

Design Approach ◽

Screening Design ◽

Screening Experiment ◽

Quality By Design Approach ◽

Operating Window ◽

Structured Approach

Abstract Background It is not enough to optimize proteomics assays. It is critical those assays are robust to operating conditions. Without robust assays, proteomic biomarkers are unlikely to translate readily into the clinic. This study outlines a structured approach to the identification of a robust operating window for proteomics assays and applies that method to Sequential Window Acquisition of all Theoretical Spectra Mass Spectroscopy (SWATH-MS). Methods We used a sequential quality by design approach exploiting a fractional screening design to first identify critical SWATH-MS parameters, then using response surface methods to identify a robust operating window with good reproducibility, before validating those settings in a separate validation study. Results The screening experiment identified two critical SWATH-MS parameters. We modelled the number of proteins and reproducibility as a function of those parameters identifying an operating window permitting robust maximization of the number of proteins quantified in human serum. In a separate validation study, these settings were shown to give good proteome-wide coverage and high quantification reproducibility. Conclusions Using design of experiments permits identification of a robust operating window for SWATH-MS. The method gives a good understanding of proteomics assays and greater data-driven confidence in SWATH-MS performance.

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Solid State Characterization of Olmesartan medoximil Solid Dispersion and in-silico Formulation Design using Quality by Design Techniques Engendered by Definitive Screening Design

Journal of Young Pharmacists ◽

10.5530/jyp.2021.13.11 ◽

2021 ◽

Vol 13 (1) ◽

pp. 49-53

Author(s):

Shabari Girinath Kala ◽

Santhivardhan Chinni

Keyword(s):

Solid State ◽

Solid Dispersion ◽

In Silico ◽

Quality By Design ◽

Formulation Design ◽

Screening Design ◽

Definitive Screening ◽

Definitive Screening Design ◽

Solid State Characterization

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Process Characterization by Definitive Screening Design Approach on DNA Vaccine Production

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.574809 ◽

2020 ◽

Vol 8 ◽

Author(s):

Lalintip Hocharoen ◽

Sarawuth Noppiboon ◽

Panit Kitsubun

Keyword(s):

Dna Vaccine ◽

Design Approach ◽

Vaccine Production ◽

Screening Design ◽

Process Characterization ◽

Definitive Screening ◽

Definitive Screening Design

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Quality-by-Design Approach and Optimization of Risk Factors by Box-Behnken Design in Formulation Development of Aspirin and Glycine Orally Disintegrating Tablet

Journal of Scientific Research ◽

10.3329/jsr.v13i3.51952 ◽

2021 ◽

Vol 13 (3) ◽

pp. 935-950

Author(s):

R. Kayesh ◽

M. R. H. Bhuiya ◽

M. F. Islam ◽

J. A. Chowdhury

Keyword(s):

Quality By Design ◽

Design Approach ◽

Formulation Development ◽

Disintegration Time ◽

Box Behnken Design ◽

Orally Disintegrating Tablet ◽

Quality Profile ◽

Croscarmellose Sodium ◽

Quality By Design Approach ◽

Fmea Method

Quality-by-design approach (QbD) was applied to develop an orally disintegrating tablet (ODT) formulation of aspirin and glycine. At first, the target quality profile and critical quality attributes (CQAs) of the product were identified. Risk assessment was accomplished by failure mode and effects analysis (FMEA) method to assess the factors having a significant effect on CQAs like disintegration time (DT), friability and assay of aspirin and glycine. Low substituted hydroxypropyl cellulose (L-HPC), croscarmellose sodium (CCS) and punch-diameter were found critical for DT and friability. The box-Behnken design was applied to optimize those 3 factors to reach a target DT of ≤ 30 sec. It was found that a punch-diameter between 8.7 ~ 9.3 mm, CCS in a range of 4 % ~ 5 %, and L-HPC in a range of 2 % ~ 8 % produced the best oral disintegrating property and reduced the risk. In summary, this work represented an excellent example of the application of QbD approach in ODT formulation development.

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