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Processability and Oral Bioavailability Improvement of Itraconazole by Particle Engineering Technique

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Abstract

The current study aimed to improve the processability and oral bioavailability of itraconazole (ITZ) via spherical agglomeration. ITZ-spherical agglomerates (ITZ-SA) and ITZ-poloxamer 407-spherical agglomerates (ITZ-PLX-SA) were optimized using Box-Behnken design. Here, the drug release was affected by polymer concentration and stirring speed, whereas particle size was altered by stirring speed, polymer concentration, and amount of bridging liquid. Heckel and Kawakita studies showed a reduction in mean yield pressure and remarkably lowered 1/b value than ITZ, indicating better compactibility and flowability of ITZ-PLX-SA. Physicochemical interactions were not observed during the process, as indicated by ATR-FTIR, DSC, and XRPD. The significant improvement in % drug release of ITZ-PLX-SA was attributed to better wettability and the presence of polymer than ITZ-SA and ITZ. The pharmacokinetic study in rats indicated fivefold enhanced Cmax and twofold improved AUC for ITZ-PLX-SA than plain drug. Thus, spherical agglomeration could improve overall processability and pharmacokinetic profile of ITZ.

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Data will be made available on request.

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Acknowledgements

The authors are thankful to Metrochem API Pvt Ltd, Hyderabad, India, for providing a gift sample of itraconazole.

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Authors and Affiliations

  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L.Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Hiral Kapalatiya, Dhrumi Patel, Alok D. Singh & Sarika Wairkar

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  1. Hiral Kapalatiya
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  2. Dhrumi Patel
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  3. Alok D. Singh
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  4. Sarika Wairkar
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Contributions

Hiral Kapalatiya: data collection, investigation, manuscript writing; Dhrumi Patel: data collection, investigation, data analysis, manuscript writing; Alok D. Singh: data collection, manuscript writing; Sarika Wairkar: conceptualization, methodology designing, supervision, manuscript review. and approval.

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Correspondence to Sarika Wairkar.

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Kapalatiya, H., Patel, D., Singh, A.D. et al. Processability and Oral Bioavailability Improvement of Itraconazole by Particle Engineering Technique. AAPS PharmSciTech 24, 27 (2023). https://doi.org/10.1208/s12249-022-02486-4

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