Propofol is an injectable, potent, short-acting, non-barbiturate sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Propofol is currently marketed as an oil-water emulsion (1% or 10 mg/mL propofol) under the US tradename Diprivan®, or as a generic formulation of Diprivan® by several companies.
The NanoMedex drug product, Macrofol™ represents an improved formulation with the same concentration of propofol as the marketed products, in a novel and proprietary oil-in-water emulsion suitable for intravenous administration. This formulation has several clinically and commercially attractive features over the initial and currently marketed formulations of propofol.
• Macrofol™ does not contain egg lecithin or soybean oil and therefore, it would not be contraindicated in patients with allergies to eggs, egg products, soybeans or soy products, or patients opposed to use of animal products.
• Macrofol™ avoids use of Cremophor EL that was associated with anaphylaxis in earlier marketed formulations of propofol.
• Uniquely, the proprietary Macrofol™ formulation includes primary and secondary oils that may serve to minimize the concentration of “free” propofol and result in less injection-site pain, inflammation, and irritation than conventional propofol emulsion formulations.
• Macrofol™ does not contain EDTA, which is of concern in patients with renal impairment. Nor does Macrofol™ contain sulfites. Additionally, this formulation has inherent properties that may reduce the risk for microbial contamination.
The components of the Reference Listed Drug(RLD) Diprivan® and the available generics macroemulsions are compared in the table below to NanoMedex’s Macrofol™ formulation.
|Currently Marketed Propofol Formulations vs Macrofol™|
|Anti-microbial||EDTA||Benzyl alcohol||Metabisulfite||Benzyl alcohol|
Several pre-clinical studies have been completed and Macrofol™ has demonstrated excellent results. In in vivo pre-clinical models, the live-phase and histopathology data demonstrated no adverse effects for Macrofol™ versus Diprivan®, including phlebitis. In addition, PK/PD data collected to date suggest bioequivalence to support use of the FDA 505(b)(2) NDA regulatory pathway for US registration.
Macrofol™ is manufactured using conventional emulsion manufacturing technology and stability data to date suggest long term stability and product shelf life similar to Diprivan®. Oil droplet size has remained consistent over the stability test period and is similar to Diprivan®.
Macrofol™ is covered under U.S. Patent Application with a priority date of February 5, 2015.
The NanoMedex proprietary emulsion technology may have broad applicability for use with other lipophilic drugs such as cancer chemotherapeutics, antifungals and immunotherapeutics.
Data generated to date support continued development of Macrofol™. NanoMedex, LLC welcomes inquiries regarding partnering interest in Macrofol™ by prospective partners that have a clear commitment to the anesthesia space and the appropriate expertise to rapidly advance this program. In addition, NanoMedex welcomes inquiries regarding interest in its proprietary emulsion formulation for use with other active pharmaceutical drug products. For further information, please contact the company via the link below: