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Lipospheres for Simultaneous Controlled Release and Improved Pharmacokinetic Profiles of Saxagliptin-Enalapril: Formulation, Optimization, and Comparative In Vitro-In Vivo Evaluation

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Abstract

The current study aims at formulating and optimizing lipospheres (LS) by the Box-Behnken design (BBD) from safe biodegradable carnauba wax (CW) to co-administer saxagliptin (SG) and enalapril (EP) for co-existing chronic hypertensive diabetes in order to overcome inadequacies of conventional modes of drug administration. Optimized liposphere formulation (OLF) was selected by a numerical optimization procedure and a comparative in vivo pharmacokinetic study of OLF and commercial brands was also performed. Discrete, free-flowing, spherical, smooth-surface LS having a size range of 5–10 μm and zeta potential of − 20 to − 30 mV were successfully formulated. Compatibility studies by FTIR and DSC proved the lack of interaction of components while XRD suggested the transformation of crystalline drugs to amorphous form. Outcomes of dependent optimizing variables like percentage yield (30–90%), EP-release (32–92%), and SG-release (28–95%) followed a polynomial quadratic model. Pharmacokinetics studies indicated a significantly lower Cmax of EP (125.22 ± 6.32) and SG (75.63 ± 3.85) and higher mean Tmax values (9.4 h for EP and 10.73 h for SG) from OLF in comparison with reference brands of EP (257.54 ± 8.23 ng/mL) and SG (393.66 ± 2.97 ng/mL). Additionally, a potential rise in half-life and MRT of SG and EP was achieved reaching approximately 2- to 3-fold higher than noted for reference brands. Importantly, the enhanced Tmax and AUC0–24 specified the achievement of enhanced bioavailability of both drugs from LS. Consequently, such an innovative approach could not only control drug release in both in vitro and in vivo analyses but also maintain plasma drug concentration for a longer time without maximizing Cmax leading towards effective management of chronic illnesses.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, 38000, Pakistan

    Safirah Maheen & Akhtar Rasul

  2. College of Pharmacy, University of Sargodha, Sargodha, Pakistan

    Safirah Maheen & Hafeez Ullah Khan

  3. Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan

    Muhammad Hanif

Authors
  1. Safirah Maheen
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  2. Akhtar Rasul
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  4. Hafeez Ullah Khan
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Correspondence to Akhtar Rasul.

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Maheen, S., Rasul, A., Hanif, M. et al. Lipospheres for Simultaneous Controlled Release and Improved Pharmacokinetic Profiles of Saxagliptin-Enalapril: Formulation, Optimization, and Comparative In Vitro-In Vivo Evaluation. AAPS PharmSciTech 21, 188 (2020). https://doi.org/10.1208/s12249-020-01733-w

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