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Strategizing Spray Drying Process Optimization for the Manufacture of Redispersible Indomethacin Nanoparticles Using Quality-by-Design Principles

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Abstract

The present study adopted a Quality by Design (QbD) approach to spray dry indomethacin nanosuspension (IMC-NS) consisting of HPC-SL, poloxamer 407, and lactose monohydrate. The Box-Behnken Design was used to systematically evaluate the effects of inlet temperature, aspiration rate, and feed rate on the critical quality attributes (CQAs) [redispersibility index (RDI; minimize), % yield (maximize), and % release at 15 min (maximize)] of the indomethacin spray dried nanosuspension (IMC-SD-NS). To identify significant main and quadratic effects, two-way interactions, and create a predictive model for the spray drying process, regression analysis and ANOVA were utilized. Following optimization, the IMC-SD-NS was analyzed for its physicochemical properties using X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. Statistical analysis revealed significant independent variables, including inlet temperature, feed rate, and aspiration rate, that critically impacted the solidified end product’s RDI, % yield, and % release at 15 min. The models developed for critical quality attributes (CQAs) were significant at a p-value of 0.05. The crystalline state of IMC was maintained in the solidified product, as confirmed by XRPD, and no interactions were observed between IMC and the excipients as evaluated by FTIR. In vitro dissolution studies showed improved dissolution rate for the IMC-SD-NS (3.82-fold increase in overall drug release), which may be attributed to the readily redispersible nanosized drug particles. The implementation of a well-designed study, utilizing Design of Experiments (DoE) methodology, played a crucial role in the development of a highly effective spray drying process.

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Acknowledgements

The authors are thankful to Division of Pharmaceutical Sciences, Long Island University to provide an opportunity to conduct the above research.

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Authors and Affiliations

  1. Division of Pharmaceutics Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, The Long Island University, Brooklyn, New York, 11201, USA

    Vishal Rathod, Bhavin Gajera, Anusha Pinninti & Rutesh H. Dave

  2. Blueprint Medicines, Cambridge, Massachusetts, 02139, USA

    Vishal Rathod

  3. Alexion AstraZeneca Rare Diseases, Boston, Massachusetts, USA

    Irfan A. Mohammed

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  1. Vishal Rathod
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  2. Bhavin Gajera
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Contributions

Vishal Rathod: methodology, investigation, writing – original draft, experimentation, visualization, validation, investigation, software.

Anusha Pinninti: experimentation, methodology, formal analysis, data curation.

Bhavin Gajera: methodology, supervision, writing - review & editing.

Irfan A. Mohammed: formal analysis, writing - review & editing.

Rutesh Dave: conceptualization, supervision, writing - review & editing.

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Correspondence to Rutesh H. Dave.

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Rathod, V., Gajera, B., Pinninti, A. et al. Strategizing Spray Drying Process Optimization for the Manufacture of Redispersible Indomethacin Nanoparticles Using Quality-by-Design Principles. AAPS PharmSciTech 24, 133 (2023). https://doi.org/10.1208/s12249-023-02589-6

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