RespireRx Pharmaceuticals Inc, which is developing a dronabinol-based drug to treat obstructive sleep apnea (OSA), has filed a provisional patent application describing novel lipid based formulation technology (LFT) that may be used to improve the solubility and bioavailability of poorly soluble drugs, particularly cannabinoids like dronabinol. The application was filed in association with Jeffrey King, managing attorney at Patent Networks Law Group.
Expansion of dronabinol’s use into OSA and other therapeutic indications will require new, improved formulations, according to RespireRx. As it is commercially sold, dronabinol is formulated as a sesame oil emulsion in a soft gelatin capsule that suffers from poor and highly variable absorption, low blood levels resulting from rapid and extensive (approximately 80%) first pass liver metabolism, as well as a relatively brief half-life (approximately 2 to 3 hours) requiring high doses in order to achieve sustained, therapeutic blood levels for 4 hours or longer.
To circumvent these problems, RespireRx has designated certain important properties around which it has created a number of lipid nanoparticle (LNP) formulations of dronabinol, three of which display appropriate water solubility and dissolution to improve absorption, nano-particle size and resistance to stomach acid conditions in order to reduce first pass liver metabolism and achieve higher and longer blood levels as well as stability and ease of manufacturing to support commercial scale.
Pending additional financing, the company plans to test these formulations in animal and human pharmacokinetic and pharmacodynamic studies. The company states that the development of a novel, proprietary formulation of dronabinol would not require significantly longer time to market entry compared to what would be required if it were to use the currently available soft gel capsule technology.
“We are very enthusiastic about our new [lipid based formulation technology] and its potential use in the development of formulations for a broad range of drugs, particularly our new dronabinol formulations. We believe that they may broaden the dronabinol market to include not only OSA but other indications, as well,” says Arnold Lippa, PhD, chief scientific officer, interim president and interim CEO and executive chairman of the board, in a release. “For example, we believe that while dronabinol is approved for AIDS-related anorexia, its potential use in a broader form of the condition such as anorexia nervosa or avoidant restrictive food intake disorder (ARFID) would benefit from our improved formulations. Since dronabinol already has been approved for AIDS-related anorexia, we believe that a treatment specific formulation of dronabinol could be brought to market rapidly.
“The pharmaceutical use of cannabinoids is beginning to realize commercial expansion and we believe that our new technology can have significant impact.”
ResolutionRx is RespireRx’s business unit focused on pharmaceutical cannabinoids, and it has been developing dronabinol—a synthetic form of ∆9-tetrahydrocannabinol (THC)—that acts upon the nervous system’s endogenous cannabinoid receptors. Dronabinol was approved in 1985 by the FDA as Marinol for the treatment of AIDS-related anorexia and later for the treatment of chemotherapy-induced nausea and vomiting. Using the commercial form of dronabinol, the company has successfully completed two phase 2 clinical trials demonstrating significant reductions in the major symptoms of OSA.
If the company gets the needed financing, then it intends to conduct animal and human pharmacokinetic studies with three new proprietary dronabinol formulations to choose the best one for conducting a phase 3 clinical efficacy study for OSA in 2023.