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Effect of Lipid Vehicles on Solubility, Stability, and Topical Permeation of Delta-9-Tetrahydrocannabinol

  • Research Article
  • Active and Passive Permeation Enhancement Strategies for Transdermal Delivery of Bioactive Compounds
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A Correction to this article was published on 25 August 2022

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Abstract

Delta-9-tetrahydrocannabinol (THC) is one of the most effective antinociceptive agents used in the treatment of peripheral neuropathy. THC is highly lipophilic and susceptible to thermal and oxidative degradation. Identifying appropriate solvents in which THC is stable as well as adequately solubilized is crucial in developing topical dosage forms. Lipid solvent systems are of utmost utility and relevance for formulating highly lipophilic drugs. Hence, the objective of this project was to screen the solubility of THC in lipidic excipients, monitor THC content in the selected vehicles during stability, and study the influence of these excipients on permeation of THC across skin. The solubility of THC in liquid lipid excipients was in the range of 421 to 500 mg/g. The solubility of THC in solid lipid excipients was in the range of 250 to 750 mg/g. THC in its neat form was poorly stable, but when dissolved in lipid-based excipients, its stability improved significantly. THC in lipid excipients was more stable at 4 ± 3°C compared to samples stored at 25 ± 2°C. The antioxidants (butylated hydroxytoluene and ascorbyl palmitate) used in the excipients further improved the stability of THC. The results demonstrated that the liquid and solid lipid excipients used in the study could solubilize THC freely and mitigate the degradation of THC significantly. The binary combination of lipid excipients enhanced THC skin permeation and retention, demonstrating the potential for topical formulation development of THC.

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Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA

    Vijay Kumar Shankar, Abhishek Shettar & Srinath Rangappa

  2. Gattefosse Corporation, Paramus, New Jersey, 07652, USA

    Inayet Ellis & Masumi Dave

  3. Topical Products Testing LLC, University, Mississippi, 38677, USA

    Reena Murthy & S. Narasimha Murthy

  4. Institute for Drug Delivery and Biomedical Research, Bangalore, India

    S. Narasimha Murthy

Authors
  1. Vijay Kumar Shankar
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  2. Abhishek Shettar
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  3. Srinath Rangappa
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  4. Inayet Ellis
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  5. Masumi Dave
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  6. Reena Murthy
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  7. S. Narasimha Murthy
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Contributions

Vijay Kumar Shankar: conceptualization; methodology; validation; formal analysis; investigation; writing, original draft; data curation; visualization; software. Abhishek Shettar: methodology, validation, investigation, visualization, software, data curation. Srinath Rangappa: methodology, validation, investigation, writing—review and editing. Inayet Ellis: conceptualization; investigation; writing, review and editing; project administration. Masumi Dave: conceptualization, writing—review and editing. Reena Murthy: conceptualization, resources; writing, review and editing; project administration; funding acquisition. S. Narasimha Murthy: conceptualization; resources; data curation; writing, review and editing; supervision; project administration; funding acquisition.

Corresponding author

Correspondence to S. Narasimha Murthy.

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The authors declare no competing interests.

Additional information

Communicated by Jayachandra Babu Ramapuram and Ashana Puri.

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The original article has been updated to change one of the affiliations of author S. Narasimha Murthy. The correction is to remove University of Mississippi affiliation to S. Narasimha Murthy and add Topical Products Testing LLC, University, MS 38677, USA.

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Shankar, V.K., Shettar, A., Rangappa, S. et al. Effect of Lipid Vehicles on Solubility, Stability, and Topical Permeation of Delta-9-Tetrahydrocannabinol. AAPS PharmSciTech 23, 223 (2022). https://doi.org/10.1208/s12249-022-02385-8

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