Solid dispersion approach for overcoming bioavailability problems due to polymorphism of nabilone, a cannabinoid derivative
Thakkar, A.L.; Hirsch, C.A.; Page, J.G.
Journal of Pharmacy and Pharmacology 29(12): 783-784
1977
ISSN/ISBN: 0022-3573 PMID: 22636 Document Number: 121929
Nabilone is a potential anti-anxiety agent. Nabilone can occur in at least 4 distinct polymorphic forms depending upon the crystallization conditions and solvent. All the forms appeared to be equally hydrophobic and insoluble. All the bioavailable forms tend to convert upon heating, grinding or prolonged storage to the nonbioavailable Form A, which is evidently the thermodynamically-stable form. An effective way to prevent this conversion is to keep nabilone dispersed in the H2O-soluble matrix of polyvinylpyrrolidone (PVP). The PVP dispersion of nabilone appears to be noncrystalline, as seen from a diffuse X-ray diffraction pattern. Whereas nabilone itself is extremely hydrophobic, the PVP dispersion is hydrophilic. When the preparation is added to H2O, the PVP dissolves readily and nabilone is exposed in the form of a fine milky suspension. When capsules containing nabilone dispersed in PVP were administered to dogs at 1 mg kg-1, the onset of pharmacological response was within 1.5 h after dosing, with maximum intensity at 3-5 h. In normal volunteers, this preparation produces relaxant and sedative effects at a dose as low as 1 mg of nabilone.