Issues of solubility in 2017 - see links. Yes, they certainly did highlight MPL does not like to be soluble BUT the bigger issue to solve was actually palatability.
27 Jun - https://pharmaust.com/pharmaust-engages-canadian-based-specialists-to-reformulate-monepantel/
20 Sep - https://pharmaust.com/reformulation-project-achieves-first-milestones-and-on-track/
17 Oct - https://pharmaust.com/monepantel-reformulation-project-continues-to-progress/
15 Oct 2018
https://pharmaust.com/pharmaust-progresses-monepantel-tablet-program-for-cancer/
Achieving good palatability and absorption from the new tablet formulation is vital....
the levels of Monepantel in the blood using just one tablet exceeded the levels predicted toachieve anticancer activity.
(extract of document at the link)
The company is investing significant effort in reformulating MPL to improve palatability of MPL and consequently, patient compliance and resolve recruitment challenges. Although a substantial amount of time was lost due to palatability issues during Phase I trials of MPL9, PharmAust has made significant progress with its reformulation. In early 2016, the firm contracted Juniper Pharma Services10 to reformulate the drug into capsules. However, the pill burden remained high (at 1 capsule/kg, 20 capsules for a large dog) and the capsule retained its bitter taste. To overcome these issues, the company contracted BRI Pharmaceutical Research in 2017 with the aims of improving taste and increasing the dosing concentration of MPL adjusted for bioavailability by tenfold relative to the previously tested formulation. In October 2018 the company reported that with BRI Pharmaceutical Research, it has achieved better than expected outcomes through micronization 11, a process that can deliver monepantel in a tablet while also potentially improving palatability. The company reported it reached blood levels
in healthy Beagle dogs, sufficient to give anticancer activity with one tablet 12
11 Micronization refers to a milling technique that grinds MPL into a fine powder that after further processing can then be packaged into capsules and
tablets.
12 Micronization is known to be able to improve the bioavailability of poorly soluble drugs – see Methods Find Exp Clin Pharmacol. 1998 Apr;20(3):211-5.
(IMO) Summary, they worked out the solubility issue sufficiently to enable cancer treatment. Now Covid is a whole new ballgame and this i guess needs a rethink/more solubility than what is needed for cancer. The above tells me they have played in this domain prior and have the information as to what worked and what didn't, what they have tried and what they have not. I reckon they have a very solid starting position to get the problem solved.
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