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Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole

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Abstract

A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50 kg (0.04 ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32 h−1) and abamectin (0.24 ± 0.08 day−1) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The tmax was delayed for levamisole (2.20 ± 0.45 h) and abamectin (4.20 ± 1.64 days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14 h) and abamectin (8.80 ± 1.39 days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties.

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Acknowledgments

The authors would like to thank Ancare New Zealand Limited for supporting animal studies. The views expressed in this publication are those of the author(s) and not necessarily those of Medsafe, Ministry of Health, New Zealand.

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Authors and Affiliations

  1. Ministry of Health, Wellington, New Zealand

    Peyami Sari

  2. China Pharmaceutical University, Nanjing, People’s Republic of China

    Jianguo Sun

  3. Pharmaceutical Consultant, Auckland, New Zealand

    Majid Razzak

  4. School of Pharmacy, University of Otago, Dunedin, New Zealand

    Ian G. Tucker

Authors
  1. Peyami Sari
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  2. Jianguo Sun
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  3. Majid Razzak
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  4. Ian G. Tucker
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Correspondence to Peyami Sari.

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Peyami Sari is currently employed by Medsafe, Ministry of Health.

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Sari, P., Sun, J., Razzak, M. et al. Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole. AAPS PharmSciTech 18, 1254–1260 (2017). https://doi.org/10.1208/s12249-016-0591-2

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  • DOI: https://doi.org/10.1208/s12249-016-0591-2

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