AAPS PharmSciTech

, Volume 9, Issue 3, pp 982–990 | Cite as

Preformulation Studies of a Prodrug of Δ9-Tetrahydrocannabinol

  • Sridhar Thumma
  • Soumyajit Majumdar
  • Mahmoud A. ElSohly
  • Waseem Gul
  • Michael A. Repka
Research Article


Preformulation studies were performed on a hemiglutarate ester prodrug of Δ9-tetrahydrocannabinol (THC-HG), to facilitate the development of stable formulations by hot-melt methods. The various studies performed included solid-state thermal characterization, pKa, logP, aqueous and pH dependent solubility, pH stability and effect of moisture, temperature and oxygen on solid-state stability. A hot-melt method was utilized to fabricate THC-HG incorporated poly (ethylene oxide) (PEO) matrices and the bioadhesive properties, release profiles and post-processing stability of these matrices were assessed as a function of the polymer molecular weight. The prodrug exhibited a T g close to 0°C, indicating its amorphous nature. Thermogravimetric analysis revealed a rapid weight loss after 170°C. The prodrug exhibited a seven-fold higher aqueous solubility as compared to the parent drug (THC). Also, the solubility of the compound increased with increasing pH, being maximum at pH 8. The prodrug exhibited a v-shaped pH-rate profile, with the degradation rate minimum between pH 3 and 4. The moisture uptake and drug degradation increased with an increase in relative humidity. Solid-state stability indicated that the prodrug was stable at −18°C but demonstrated higher degradation at 4°C, 25°C and 40°C (51.6%, 74.5% and 90.1%, respectively) at the end of 3-months. THC-HG was found to be sensitive to the presence of oxygen. The release of the active from the polymeric matrices decreased, while bioadhesion increased, with an increase in molecular weight of PEO.

Key words

molecular weight PEO preformulation solubility stability THC 



This project was supported by Grant Number P20RR021929 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.


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Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • Sridhar Thumma
    • 1
  • Soumyajit Majumdar
    • 1
    • 2
  • Mahmoud A. ElSohly
    • 1
    • 2
    • 3
  • Waseem Gul
    • 2
    • 3
  • Michael A. Repka
    • 1
    • 2
  1. 1.Department of Pharmaceutics, School of PharmacyThe University of MississippiUniversityUSA
  2. 2.The National Center for Natural Products Research, School of PharmacyThe University of MississippiUniversityUSA
  3. 3.ElSohly Laboratories, Inc.OxfordUSA

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