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Cryogenic Fabrication of Dry Powders to Enhance the Solubility of a Promising Anticancer Drug, SHetA2, for Oral Administration

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Abstract

SHetA2 is a novel anticancer drug with poor aqueous solubility. In formal toxicological studies, Kolliphor HS 15 was used as a solubilizing agent to increase the oral bioavailability of SHetA2. The purpose of this study was to formulate SHetA2 and Kolliphor HS 15 as solid powders to facilitate their filling in hard gelatin capsules for clinical trials. Two manufacturing processes, ultra-rapid freeze-drying (URFD) and spray freeze drying (SFD), were employed to fabricate solid powders of SHetA2-Kolliphor HS 15 and trehalose. The morphology, size, flowability, and compressibility of URFD-SHetA2 and SFD-SHetA2 powders were characterized. The crystallinity and apparent maximum solubility of SHetA2 in both powders were also determined. SFD-SHetA2 powders were spherical in shape, small, and with a wide size distribution while the URFD-SHetA2 powders were irregularly shaped and big but with a narrower distribution. DSC and XRD analyses indicated that SHetA2 was mostly amorphous in both powders. The flow of both powders was categorized as “good” (angle of repose < 35°). The uniformity of drug content in URFD-SHetA2 powders was more variable than that in SFD-SHetA2 powders. The solubility profile of SHetA2 in both powders SGF exhibited a transient supersaturation “spring effect” due to the drug’s amorphousness followed by extended supersaturation “parachute effect” at approximately 6 μg/ml for both powders compared to 0.02 ± 0.01 μg/ml for unprocessed drug. In conclusion, both URFD and SFD formed solid SHetA2 Kolliphor powders that are possible formulation candidates to be filled in hard gelatin capsules for clinical trials.

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Acknowledgments

We appreciate the generous gift of SHetA2 by Dr. Doris Benbrook at the Stephenson Cancer Center and of Kolliphor HS 15 from the BASF Company. We are thankful for Dr. Andrew Madden and Brittany Pritchett for performing the XRD analysis. This work was supported by start-up funds for Dr. Garcia-Contreras provided by the University of Oklahoma, College of Pharmacy. Ms. Ibrahim was partially supported by a Fulbright scholarship from Egypt.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave. Suite 321, Oklahoma City, Oklahoma, 73126-0901, USA

    Mariam Ibrahim, Manolya Kukut Hatipoglu & Lucila Garcia-Contreras

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  1. Mariam Ibrahim
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  2. Manolya Kukut Hatipoglu
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  3. Lucila Garcia-Contreras
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Correspondence to Lucila Garcia-Contreras.

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Ibrahim, M., Hatipoglu, M.K. & Garcia-Contreras, L. Cryogenic Fabrication of Dry Powders to Enhance the Solubility of a Promising Anticancer Drug, SHetA2, for Oral Administration. AAPS PharmSciTech 20, 20 (2019). https://doi.org/10.1208/s12249-018-1204-z

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