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Preformulation studies of a prodrug of Delta9-tetrahydrocannabinol.
AAPS PharmSciTech 2008; 9(3):982-90AP

Abstract

Preformulation studies were performed on a hemiglutarate ester prodrug of Delta(9)-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 degrees C, indicating its amorphous nature. Thermogravimetric analysis revealed a rapid weight loss after 170 degrees 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 degrees C but demonstrated higher degradation at 4 degrees C, 25 degrees C and 40 degrees 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.

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18756377

Citation

Thumma, Sridhar, et al. "Preformulation Studies of a Prodrug of Delta9-tetrahydrocannabinol." AAPS PharmSciTech, vol. 9, no. 3, 2008, pp. 982-90.
Thumma S, Majumdar S, Elsohly MA, et al. Preformulation studies of a prodrug of Delta9-tetrahydrocannabinol. AAPS PharmSciTech. 2008;9(3):982-90.
Thumma, S., Majumdar, S., Elsohly, M. A., Gul, W., & Repka, M. A. (2008). Preformulation studies of a prodrug of Delta9-tetrahydrocannabinol. AAPS PharmSciTech, 9(3), pp. 982-90. doi:10.1208/s12249-008-9136-7.
Thumma S, et al. Preformulation Studies of a Prodrug of Delta9-tetrahydrocannabinol. AAPS PharmSciTech. 2008;9(3):982-90. PubMed PMID: 18756377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preformulation studies of a prodrug of Delta9-tetrahydrocannabinol. AU - Thumma,Sridhar, AU - Majumdar,Soumyajit, AU - Elsohly,Mahmoud A, AU - Gul,Waseem, AU - Repka,Michael A, Y1 - 2008/08/28/ PY - 2008/03/17/received PY - 2008/08/13/accepted PY - 2008/8/30/pubmed PY - 2009/5/14/medline PY - 2008/8/30/entrez SP - 982 EP - 90 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 9 IS - 3 N2 - Preformulation studies were performed on a hemiglutarate ester prodrug of Delta(9)-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 degrees C, indicating its amorphous nature. Thermogravimetric analysis revealed a rapid weight loss after 170 degrees 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 degrees C but demonstrated higher degradation at 4 degrees C, 25 degrees C and 40 degrees 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. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/18756377/Preformulation_studies_of_a_prodrug_of_Delta9_tetrahydrocannabinol_ L2 - https://dx.doi.org/10.1208/s12249-008-9136-7 DB - PRIME DP - Unbound Medicine ER -