Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension

This study employed a Quality by Design (QbD) approach to spray dry amorphous clotrimazole nanosuspension (CLT-NS) consisting of Soluplus^® and microcrystalline cellulose. Using the Box-Behnken Design, a systematic evaluation was conducted to analyze the impact of in let temperature, % aspiration, and feed rate on the critical quality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS).

In this study, regression analysis and ANOVA were employed to detect significant factors and interactions, enabling the development of a predictive model for the spray drying process. Following optimization, the CLT-SD-NS under went analysis using X ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies.

The results showed significant variables, including inlet temperature, feed rate, and aspiration rate, affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significance at a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients.

In vitro dissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-fold increase in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed to rapidly redispersing nanosized amorphous CLT particles. The well-designed study utilizing the Design of Experiments (DoE) methodology.

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Materials

Clotrimazole  (CLT)  was  purchased  from  Letco  Medical. Soluplus® and Microcrystalline cellulose 101 (MCC) were purchased from BASF and FMC biopolymer, respectively. Chemical structure of all the three are presented in Fig. 1 (a).  HPLC-grade ethanol, methanol, DI water and trifluo-roacetic acid (TFA) were  procured  from Fisher Scientific. Aluminum hermetic pans and lids were purchased from TA instruments.

Gajera, B., Shah, H., Parekh, B. et al. Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension. AAPS PharmSciTech 25, 164 (2024). https://doi.org/10.1208/s12249-024-02871-1

Read also our introduction article on Microcrystalline Cellulose here: