A Systematic, Knowledge Space-Based Proposal on Quality by Design-Driven Polymeric Micelle Development

Sipos, Bence; Katona, Gábor; Csóka, Ildikó

doi:10.3390/pharmaceutics13050702

Cited by 14 publications

(10 citation statements)

References 41 publications

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“…The Quality by Design (QbD) concept is a knowledge-, and risk assessment-based quality management approach, used mainly in the pharmaceutical industrial production process [ 6 , 7 ]; however, it also can be extended and applied in the early pharmaceutical research and development (R&D) phase [ 5 , 8 , 9 ]. Nowadays, including the QbD elements during the submissions of the marketing authorisation documents is a regulatory requirement.…”

Section: Introductionmentioning

confidence: 99%

An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

et al. 2021

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Liposomal formulation development is a challenging process. Certain factors have a critical influence on the characteristics of the liposomes, and even the relevant properties can vary based on the predefined interests of the research. In this paper, a Quality by Design-guided and Risk Assessment (RA)-based study was performed to determine the Critical Material Attributes and the Critical Process Parameters of an “intermediate” active pharmaceutical ingredient-free liposome formulation prepared via the thin-film hydration method, collect the Critical Quality Attributes of the future carrier system and show the process of narrowing a general initial RA for a specific case. The theoretical liposome design was proved through experimental models. The investigated critical factors covered the working temperature, the ratio between the wall-forming agents (phosphatidylcholine and cholesterol), the PEGylated phospholipid content (DPPE-PEG2000), the type of the hydration media (saline or phosphate-buffered saline solutions) and the cryoprotectants (glucose, sorbitol or trehalose). The characterisation results (size, surface charge, thermodynamic behaviours, formed structure and bonds) of the prepared liposomes supported the outcomes of the updated RA. The findings can be used as a basis for a particular study with specified circumstances.

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Section: Introductionmentioning

confidence: 99%

An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

et al. 2021

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“…The Quality by Design (QbD) approach [14][15][16][17] and its elements are described in the guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) [18][19][20]. Briefly, the steps of a QbD-guided study are to determine the Quality Target Product Profile (QTPP) that describes the essential parameters of the product from the viewpoint of the patient, the clinics and the industry and that in the ideal case should be achieved.…”

Section: Quality By Design-based Design and Developmentmentioning

confidence: 99%

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives

et al. 2022

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Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 32 fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and −36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations.

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“…The assessment was performed by the LeanQbD ® Software (QbDWorks, LLC, Austin, TX, USA). The final step was to quantify these risks based on probability rating, where the resulting severity scores were plotted as severity scores and the values were further compared [17][18][19].…”

Section: Qbd-based Risk Assessment Processmentioning

confidence: 99%

Characterizing the Drug-Release Enhancement Effect of Surfactants on Megestrol-Acetate-Loaded Granules

et al. 2022

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In this study, the effect of Cremophor® RH 40 (CR 40) classic micelles and Soluplus® (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system containing megestrolacetate (MGA). Using a risk assessment-based approach on the formulation via melt technology resulted in the formation of these granules, presented as the dosage, with proper particle size and flow characteristics. Due to the application of a eutectic carrier base composition, gentle process conditions were reached, retaining the crystalline structure of the carrier system and allowing for the proper distribution of MGA in the granules. The increased water solubility (0.111 mg/mL to 2.154 mg/mL), and the decreased nano particle size (102.27 nm) with uniform distribution (polydispersity index of 0.259) and colloid stability (zeta potential of −12.99 mV) resulted in SP polymeric micelles prevailing over CR 40 micelles in this gastric dissolution study, performed in biorelevant fasted and fed state drug-release media. Mathematical characterization and kinetic model fitting supported the fast drug-release mechanism of polymeric micelles over micelles. The value-added polymeric micelle-containing formulation developed can be successfully administered perorally and the enhanced drug release offers the possibility of greater drug absorption in the gastrointestinal tract.

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A Systematic, Knowledge Space-Based Proposal on Quality by Design-Driven Polymeric Micelle Development

Cited by 14 publications

References 41 publications

An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives

Characterizing the Drug-Release Enhancement Effect of Surfactants on Megestrol-Acetate-Loaded Granules

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