Application of quality by design to formulation and processing of protein liposomes

Xu, Xiaoming; Costa, António Pedro; Khan, Mansoor A.; Burgess, Diane J.

doi:10.1016/j.ijpharm.2012.06.002

Cited by 55 publications

(27 citation statements)

References 25 publications

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“…Lipid properties can have a great impact on liposomes' membrane fluidity, permeability, or charge [44]. In this regard, cholesterol increases liposomal stability, reduces membrane fluidity, and, consequently, contributes to an increased EE [45].…”

Section: The Critical Materials Attributes and Critical Process Paramementioning

confidence: 99%

“…Among these, several studies established, through DoE approaches, that lipid molar ratio and lipid-to-drug ratio are the most critical parameters for EE optimization. Using a great amount of lipids for liposome preparation favors the formation of many vesicles with a significant internal volume for drug encapsulation and, consequently, the EE of hydrophilic drugs increases [30,45]. Including cholesterol in liposome formulations increases not only their stability but also the drug content, due to the so-called "pocket" theory, presuming that cholesterol can generate different size pockets inside the lipid bilayer where API can be entrapped [45].…”

Section: Drug Contentmentioning

confidence: 99%

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Pharmaceutical Development of Liposomes Using the QbD Approach

Porfire¹,

Achim²,

Barbălată³

et al. 2019

Liposomes - Advances and Perspectives

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Quality by Design (QbD) is a systematic, risk-based approach to pharmaceutical product and manufacturing development, which uses quality-improving scientific methods upstream in the research, development, and design phases, in order to assure that quality and safety are designed into product at as early stage as possible. This work focuses on the state-of-the-art applications of the QbD principles in the development of liposomes. The QbD approach has recently been proposed as a useful tool to obtain higher-quality liposomal products, as their development is a challenging task, involving intricate formulation and manufacturing processes. Thus, the current strategies to define the relationship between the critical material attributes or process parameters and product critical quality attributes and to establish the design space are overviewed. Additionally, the current characterization methodologies are described, as part of the control strategy required within the QbD paradigm.

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Section: The Critical Materials Attributes and Critical Process Paramementioning

confidence: 99%

Section: Drug Contentmentioning

confidence: 99%

Pharmaceutical Development of Liposomes Using the QbD Approach

Porfire¹,

Achim²,

Barbălată³

et al. 2019

Liposomes - Advances and Perspectives

View full text Add to dashboard Cite

show abstract

“…Quality by design (QbD) and design of experiment (DoE) approaches have been widely used in the development of various pharmaceutical formulations (Gu et al ., 2015; Kumar et al ., 2014; Xu et al ., 2012a). Mathematical models generated from DoE studies can also be used for response prediction and formulation optimization purposes (Xu et al ., 2011, 2012b).…”

Section: Introductionmentioning

confidence: 99%

Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach

Burgess

2015

International Journal of Pharmaceutics

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Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25KDa) and PLGA9010 (113KDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration.

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“…The International Conference on Harmonisation defines QbD as : “ … is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management .” QbD is a new paradigm that emphasizes product and process understanding gained through product development and during the lifecycle of a product. Since the US FDA's Process Analytical Technology (PAT) guideline was released, many studies have been published …”

Section: Introductionmentioning

confidence: 99%

“…Since the US FDA's Process Analytical Technology (PAT) guideline was released, many studies have been published. [3][4][5][6][7][8][9][10][11][12][13] In a QbD study, one major objective is to develop a detailed process and product understanding, which can be reached through well-established design of experiment tools. Conventional experimental approaches have many disadvantages.…”

Section: Introductionmentioning

confidence: 99%