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Preparation and Characterization of Stable Amorphous Glassy Solution of BCS II and IV Drugs

  • Research Article
  • Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability
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Abstract

The focus of the present investigation was to develop amorphous glassy solutions (AGSs) of BCS Class II and IV drugs using sucrose acetate isobutyrate (SAIB). The drugs studied were rifaximin (RFX), dasatinib (DST), aripiprazole (APZ), dolutegravir (DLT), cyclosporine (CYS), itraconazole (ITZ), tacrolimus (TAC), sirolimus (SRL), aprepitant (APT), and carbamazepine (CBZ). AGSs were prepared by dissolving known quantity of the drug in the SAIB at 120 (TAC and APZ), 140 (CYS) or 150 oC (RFX, DST, DLT, ITZ, SRL, APT, and CBZ). They were characterized visually and by NIR, NIR hyperspectroscopy (NIR-H), and XRPD. Stability were determined by exposing open vials to 40 oC/75% RH for a week. AGSs behave like a glassy solid at room temperature and liquified above 60 oC. The solubility of APT, DLT, SRL, APZ, RFX, CBZ, TAC and CYS in SAIB was 0.4±0.0, 1.7±0.4, 1.9±0.0, 21.6±2.6, 36.4±0.9, 76.5±4.0, 115.1±2.3, and 239.0±12.6 mg/g, respectively. NIR, NIR-H, and XRPD data indicated the amorphous nature of the AGSs. Furthermore, AGSs were stable against devitrification on exposure to high temperature and humidity. In summary, SAIB can be employed to develop stable AGSs of poorly soluble drugs to increase dissolution, and oral bioavailability with the addition of hydrophilic excipients.

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Funding

The research reported in this paper was funded by Eastman Chemical Company, Kingsport, TN.

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Authors and Affiliations

  1. Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, 310 Reynolds Medical Sciences Building, College Station, TX, 77843, USA

    Sathish Dharani, Khaldia Sediri, Mansoor A. Khan & Ziyaur Rahman

  2. Laboratory of Applied Chemistry, ACTR Univ. Ain Temouchent DGRCT, BP 248, 46000, Ain Temouchent, Algeria

    Khaldia Sediri

  3. Eastman Chemical Company, Kingsport, TN, 37662, USA

    Phillip Cook & Rajendran Arunagiri

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  1. Sathish Dharani
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  2. Khaldia Sediri
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Dharani, S., Sediri, K., Cook, P. et al. Preparation and Characterization of Stable Amorphous Glassy Solution of BCS II and IV Drugs. AAPS PharmSciTech 23, 35 (2022). https://doi.org/10.1208/s12249-021-02198-1

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