Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches

The purpose of this study was to apply the Quality by Design (QbD) approach to the electrospinning of fibres loaded with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin (INDO) and diclofenac sodium (DICLO). A Quality Target Product Profile (QTPP) was made, and risk assessments (preliminary hazard analysis) were conducted to identify the impact of material attributes and process parameters on the critical quality attributes (CQAs) of the fibres. A full factorial design of experiments (DoE) of 20 runs was built, which was used to carry out experiments. The following factors were assessed: Drugs, voltage, flow rate, and the distance between the processing needle and collector. Release studies exhibited INDO fibres had greater total release of active drug compared to DICLO fibres. Voltage and distance were found to be the most significant factors of the experiment. Multivariate statistical analytical software helped to build six feasible design spaces and two flexible, universal design spaces for both drugs, at distances of 5 cm and 12.5 cm, along with a flexible control strategy. The current findings and their analysis confirm that QbD is a viable and invaluable tool to enhance product and process understanding of electrospinning for the assurance of high-quality fibres.

[1]  R. Linhardt,et al.  Electrospinning: A novel nano-encapsulation approach for bioactive compounds , 2017 .

[2]  T. Hemamalini,et al.  Comprehensive review on electrospinning of starch polymer for biomedical applications. , 2018, International journal of biological macromolecules.

[3]  P. Supaphol,et al.  Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs , 2006 .

[4]  Sundararajan V Madihally,et al.  Recent advances in multiaxial electrospinning for drug delivery. , 2017, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[5]  M. Edirisinghe,et al.  Engineering a material for biomedical applications with electric field assisted processing , 2009 .

[6]  Andrew Franklin,et al.  Implementation of QbD for the development of a vaccine candidate. , 2014, Vaccine.

[7]  Ju-Hyun Lee,et al.  Granulation development in batch-to-batch and continuous processes from a quality by design perspective , 2018, Journal of Drug Delivery Science and Technology.

[8]  R. Cselkó,et al.  Alternating current electrospinning for preparation of fibrous drug delivery systems. , 2015, International journal of pharmaceutics.

[9]  Z. Ahmad,et al.  Fibrous polymeric buccal film formulation, engineering and bio-interface assessment , 2017 .

[10]  Anurag S Rathore,et al.  Quality by Design (QbD)-Based Process Development for Purification of a Biotherapeutic. , 2016, Trends in biotechnology.

[11]  Darrell H. Reneker,et al.  Electrospinning jets and polymer nanofibers , 2008 .

[12]  Z. Ahmad,et al.  Development and characterisation of cellulose based electrospun mats for buccal delivery of non‐steroidal anti‐inflammatory drug (NSAID) , 2017, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[13]  Ron Taticek,et al.  QbD implementation and Post Approval Lifecycle Management (PALM). , 2016, Biologicals : journal of the International Association of Biological Standardization.

[14]  Benjamin Chu,et al.  Functional electrospun nanofibrous scaffolds for biomedical applications. , 2007, Advanced drug delivery reviews.

[15]  M. Edirisinghe,et al.  Electrospinning Optimization of Eudragit E PO with and without Chlorpheniramine Maleate Using a Design of Experiment Approach , 2019, Molecular pharmaceutics.

[16]  Z. Ahmad,et al.  Facile Preparation of Drug-Loaded Tristearin Encapsulated Superparamagnetic Iron Oxide Nanoparticles Using Coaxial Electrospray Processing. , 2017, Molecular pharmaceutics.

[17]  Jingwei Xie,et al.  Electrospinning: An enabling nanotechnology platform for drug delivery and regenerative medicine☆ , 2018, Advanced drug delivery reviews.

[18]  Lixin Yang,et al.  Biodegradable electrospun fibers for drug delivery. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[19]  Zhigang Xie,et al.  Electrospinning of polymeric nanofibers for drug delivery applications. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[20]  Z. Ahmad,et al.  Broad Scale and Structure Fabrication of Healthcare Materials for Drug and Emerging Therapies via Electrohydrodynamic Techniques , 2018, Advanced Therapeutics.

[21]  Gareth R. Williams,et al.  A thermosensitive drug delivery system prepared by blend electrospinning. , 2017, Colloids and surfaces. B, Biointerfaces.

[22]  T. Sui,et al.  Operando observation of the Taylor cone during electrospinning by multiple synchrotron X-ray techniques , 2016 .

[23]  He Lian,et al.  Melt electrospinning vs. solution electrospinning: A comparative study of drug-loaded poly (ε-caprolactone) fibres. , 2017, Materials science & engineering. C, Materials for biological applications.

[24]  Seeram Ramakrishna,et al.  Electrospun Nanofibers: Solving Global Issues , 2006 .