Pharmaceutical Development and Design of Thermosensitive Liposomes Based on the QbD Approach

Dobó, Dorina Gabriella; Németh, Zsófia; Sipos, Bence; Cseh, Martin; Pallagi, Edina; Berkesi, Dániel; Kozma, Gábor; Csóka, Ildikó

doi:10.3390/molecules27051536

Cited by 5 publications

(5 citation statements)

References 41 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The QbD risk assessment implies an interdependence rating established between the CMAs-CQAs and/or CPPs-CQAs, measuring the impact of each quality attribute on the final product [32,33]. Risk estimation matrix (REM) is a risk rating tool constructed for CMAs and/or CPPs commonly using a three-grade scale (low, medium and high) to describe the criticality in relation to the CQAs [34].…”

Section: Risk Assessmentmentioning

confidence: 99%

“…The QbD approach is mainly applied in the pharmaceutical industry for which the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have issued regulatory guidelines providing directions to integrate the principles of QbD at product development stage. However, lately, the QbD concept is being more and more used in research and development [25,32]. A QbD-assisted approach for the development of liposomes for cancer therapy have been described previously [41].…”

Section: Quality By Design (Qbd) Approachmentioning

confidence: 99%

See 1 more Smart Citation

Quality by Design Approach for the Development of Salinomycin and Gemcitabine Combination Therapy Liposomes for Colorectal Cancer

TEFAS¹

2022

FARMACIA

View full text Add to dashboard Cite

An ideal cancer treatment would eradicate all types of malignant cells, both rapidly replicating and quiescent stem-like cancer cells. Therefore, a combination of drugs capable of targeting all subtypes of cancer cells could offer a better outcome in cancer. Nano-delivery systems for combination therapy represent more secure and efficient platforms for the delivery of anticancer drugs to tumours. Nanocarrier drug development is a complex process which requires careful design and evaluation at various levels to ensure their safety and efficacy. In this sense, the Quality by Design (QbD) approach could help develop a robust, highquality nanocarrier formulation by understanding the properties of the product and the manufacturing process. In this study, the QbD approach was used in the development of liposomes co-loaded with a combination of anticancer drugs, salinomycin (SAL) and gemcitabine (GEM) for colorectal cancer therapy. While GEM is a conventional anticancer drug, SAL has shown selectivity towards cancer stem cells. The implementation of the QbD approach involved the identification of the quality target product profile (QTPP) and critical quality attributes (CQAs) of the liposomes. Based on risk analysis, the Design of Experiments (DoE) methodology was employed to evaluate the impact of critical formulation factors on the liposomes' properties, in a time and cost-effective manner, in order to obtain SAL and GEM co-loaded liposomes with desired characteristics. RezumatTratamentul ideal al cancerului implică eradicarea atât a celulelor maligne care se multiplică rapid, cât și a celulelor stem pasive. De aceea, asocierea de substanțe care țintesc toate subtipurile de celule canceroase ar putea duce la efecte superioare în terapia cancerului. Nanosistemele pentru terapia combinată reprezintă sisteme mai sigure și mai eficiente pentru transportul substanțelor anticanceroase. Dezvoltarea nanosistemelor este un proces complex care necesită atenta formulare și evaluare pentru a conferi acestora siguranță și eficacitate. În acest sens, conceptul de Calitate prin Design (QbD) ar putea ajuta la dezvoltarea unei nanoformulări robuste și calitative prin înțelegerea proprietăților sistemelor de transport și a procesului de fabricație. În acest studiu, abordarea QbD a fost utilizată în dezvoltarea lipozomilor încărcați cu o asociere de substanțe anticanceroase, salinomicină (SAL) și gemcitabină (GEM) pentru terapia cancerului colorectal. În timp ce GEM este un agent anticanceros convențional, SAL a dovedit selectivitate față de celulele stem canceroase. Implementarea conceptului QbD a presupus identificarea profilului de calitate (QTPP) și a atributelor critice de calitate (CQA) ale lipozomilor. Pe baza analizei de risc, a fost utilizată metodologia planurilor experimentale (DoE) pentru a evalua impactul variabilelor critice de formulare asupra proprietăților lipozomilor, într-o manieră eficientă din punctul de vedere al timpului și al costurilor, pentru obținerea lipozomilor cu SAL și GEM care să posede caracteristicile d...

show abstract

Section: Risk Assessmentmentioning

confidence: 99%

Section: Quality By Design (Qbd) Approachmentioning

confidence: 99%

Quality by Design Approach for the Development of Salinomycin and Gemcitabine Combination Therapy Liposomes for Colorectal Cancer

TEFAS¹

2022

FARMACIA

View full text Add to dashboard Cite

show abstract

“…These risks were then denoted as low, medium and high accordingly. Table S4 gave a realistic picture with a correlation of all variables related to process and materials with scrupulous importance to CQAs resulting in precise quantification of threat during the formulation process [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…In other words, it is a graphical representation that divides material/process problems from most common to least common. A typical Pareto chart with respect to CMAs and CPPs is depicted separately in ( Figure 3 a,b) [ 41 ]. It aids in the identification and determination of the root causes of problems during formulation.…”

Section: Resultsmentioning

confidence: 99%

Quality by Design Assisted Optimization and Risk Assessment of Black Cohosh Loaded Ethosomal Gel for Menopause: Investigating Different Formulation and Process Variables

et al. 2023

View full text Add to dashboard Cite

Black cohosh (Cimicifuga racemosa) (CR) is a popular herb and is medically lauded for ameliorating myriad symptoms associated with menopause. However, its pharmaceutical limitations and non-availability of a patient-compliant drug delivery approach have precluded its prevalent use. Henceforth, the current research premise is aimed at developing an ethosomal gel incorporating triterpene enriched fraction (TEF) obtained from CR and evaluating its effectiveness through the transdermal application. TEF-loaded ethosomes were formulated using solvent injection, optimized and characterised. The optimized ethosomes were then dispersed into a polymeric gel base to form ethosomal gel which was further compared with the conventional gel by in-vitro and ex-vivo experiments. Here, the quality by design (QbD) approach was exploited for the optimization and development of ethosomal gel. The elements of QbD comprising initial risk assessment, design of experimentation (DoE), and model validation for the development of formulation have all been described in detail. The optimized ethosomes (F03) showed a nanometric size range, negative zeta potential and good entrapment. The in vitro release profile of gel revealed a burst release pattern following the Korsmeyer Peppas model having Fickian diffusion. The transdermal flux of ethosomal gel was observed to be more than that of conventional gel. Texture analysis and rheological characterization of the gel, revealed good strength showing shear thinning and pseudoplastic behaviour. The confocal microscope investigation revealed the deeper skin permeation of ethosomal gel than conventional gel. This result was further strengthened by DSC, IR and histological assessment of the animal skin (Wistar rat), treated with the optimized formulation. Conclusively, the implementation of QbD in the formulation resulted in a better understanding of the process and the product. It aids in the reduction of product variability and defects, hence improving product development efficiencies. Additionally, the ethosomal gel was found to be a more effective and successful carrier for TEF than the conventional gel through the transdermal route. Moreover, this demands an appropriate animal study, which is underway, for a stronger outcome.

show abstract

“…Thermosensitive liposomes were developed using the QbD approach by Dobo et al [ 4 ] in the next article. Thermosenistive liposomal formulations were produced using different phospholipids and PEGylated lipids and optimized using the QbD approach.…”

mentioning

confidence: 99%

Editorial: Nanomedicine-Based Drug Delivery Systems: Recent Developments and Future Prospects

Shakeel

2023

Molecules

View full text Add to dashboard Cite

show abstract

Pharmaceutical Development and Design of Thermosensitive Liposomes Based on the QbD Approach

Cited by 5 publications

References 41 publications

Quality by Design Approach for the Development of Salinomycin and Gemcitabine Combination Therapy Liposomes for Colorectal Cancer

Quality by Design Approach for the Development of Salinomycin and Gemcitabine Combination Therapy Liposomes for Colorectal Cancer

Quality by Design Assisted Optimization and Risk Assessment of Black Cohosh Loaded Ethosomal Gel for Menopause: Investigating Different Formulation and Process Variables

Editorial: Nanomedicine-Based Drug Delivery Systems: Recent Developments and Future Prospects

Contact Info

Product

Resources

About