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Core in Cup Ethylmorphine Hydrochloride Tablet for Dual Fast and Sustained Pain Relief: Formulation, Characterization, and Pharmacokinetic Study

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Abstract

Ethylmorphine hydrochloride (EtM) is a derivative of morphine used as analgesic to treat severe pain in case of cancer and bone injury. This study aimed to formulate and evaluate core in cup tablets containing 2 doses of EtM, the cup was formulated as lyophilized oro-dispersible tablet (ODT) for immediate release (IR), and the core was formulated as directly compressed tablet for sustained release (SR). Factorial design was adopted for the optimization of tablets prepared via lyophilized form and direct compression techniques: a 41.22 design was used for the former, while a 32 one was used for the latter. All prepared tablets showed acceptable physical properties which were in accordance with pharmacopeial standards. Two lyophilized ODTs (F9 and F10) formulae were selected as the cup for instant release. While one directly compressed tablet formula (S6) was selected based on the in vitro release profile to represent the sustained core, the outcome was 2 core in cup tablets, namely B1 and B2 which were evaluated for their in vivo absorption and showed a maximum plasma concentration (Cpmax) of 354.12 ± 17.55 ng/mL and 350.82 ± 12.15 ng/mL respectively attained after 3.0 h which were twofolds significantly higher in comparison to the market tablet with Cpmax of only 172.05 ± 12.53 ng/mL attained after 2.20 ± 0.24 h.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El Eini St., Cairo, 11562, Egypt

    Aliaa Nabil ElMeshad, Nabaweya A. Abdel Gawad & Mohamed Ahmed El-Nabarawi

  2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza, Egypt

    Khaled M. Abdel-Haleem, Nabaweya A. Abdel Gawad & Nermin M. Sheta

Authors
  1. Aliaa Nabil ElMeshad
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  2. Khaled M. Abdel-Haleem
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  3. Nabaweya A. Abdel Gawad
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  4. Mohamed Ahmed El-Nabarawi
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  5. Nermin M. Sheta
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Correspondence to Aliaa Nabil ElMeshad.

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ElMeshad, A.N., Abdel-Haleem, K.M., Abdel Gawad, N.A. et al. Core in Cup Ethylmorphine Hydrochloride Tablet for Dual Fast and Sustained Pain Relief: Formulation, Characterization, and Pharmacokinetic Study. AAPS PharmSciTech 21, 244 (2020). https://doi.org/10.1208/s12249-020-01759-0

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