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Development of Indinavir Submicron Lipid Emulsions Loaded with Lipoamino Acids—In Vivo Pharmacokinetics and Brain-Specific Delivery

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Abstract

The aim of our present work was to develop indinavir O/W submicron lipid emulsions (SLEs) loaded with lipoamino acids for specific delivery to brain. Tetradecyl aspartic acid (A) and decyl glutamic acid (G) loaded stable SLEs of indinavir having a mean size range of 210–220 nm and average zeta potential of −23.54 ± 1.2 mV were developed using homogenization and ultrasonication. The cumulative % drug release from different SLEs varied in between 26% and 85%. The formulations, SLE, SLE-A3, and SLE-G3 were stable to the centrifugal stress, dilution stress, and storage at RT. The total drug content and entrapment efficiency were determined by HPLC method. During pharmacokinetic studies in male Wistar rats there was no significant difference in the serum levels of indinavir for SLE, SLE-A3 and SLE-G3 formulations at all time points. In tissue distribution studies, the therapeutic availability (TA) of indinavir in brain and kidneys for SLE-A3 were 4.27- and 2.66-fold whereas for SLE-G3 were 2.94 and 2.12 times, respectively, higher than that of indinavir solution. But when compared with that of SLE, in brain tissue the levels of indinavir from SLE-G3 and SLE-A3 varied in between 2.5- and 3.38-fold. While in case of the kidney, it was between 1.23- and 1.54-fold only. However, the TA is not significantly different in tissues like the heart, liver, and spleen. Thus, brain-specific delivery of indinavir was improved by including tetradecyl aspartic acid and decyl glutamic acid in submicron lipid emulsions.

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Acknowledgments

We are thankful to Dr. A. Muralidhar Rao and M/s Lipoid, Germany for providing us the gift samples of lipoamino acids and lecithin respectively for the study and Prof. Y. Madhusudan Rao for his kind help for HPLC facility. Mrs. B. Swetha thanks AICTE for the fellowship during her studies. We acknowledge the AICTE, New Delhi for RPS project grant F. No 8023/BOR/RID/RPS-155/2008-09 for doing this work.

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Authors and Affiliations

  1. Nanotechnology Laboratory, Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India, 506009

    Swetha Bollam, Prabhakar Kandadi, Shashank Sridhar Apte & Kishan Veerabrahma

  2. NATCO Research Centre, Sanath Nagar, Hyderabad, India

    Shashank Sridhar Apte

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  1. Swetha Bollam
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  2. Prabhakar Kandadi
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  3. Shashank Sridhar Apte
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  4. Kishan Veerabrahma
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Correspondence to Kishan Veerabrahma.

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Bollam, S., Kandadi, P., Apte, S.S. et al. Development of Indinavir Submicron Lipid Emulsions Loaded with Lipoamino Acids—In Vivo Pharmacokinetics and Brain-Specific Delivery. AAPS PharmSciTech 12, 422–430 (2011). https://doi.org/10.1208/s12249-011-9604-3

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  • DOI: https://doi.org/10.1208/s12249-011-9604-3

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