02023nas a2200193   4500008004100000022001400041245010300055210006900158260000900227300001600236490000600252520133000258100001901588700002201607700002201629700002401651700002401675856013001699       2023                        eng d  a2470-134300aDabrafenib-panobinostat salt: improving the dissolution rate and inhibition of BRAF melanoma cells0 aDabrafenibpanobinostat salt improving the dissolution rate and i  cMAY   a18255-182650 v83 a<p>
	Cocrystallization of the drug-drug salt-cocrystal of the histone deacetylase inhibitor (HDACi) panobinostat (PAN) and b-rapidly accelerated fibrosarcoma (BRAF) inhibitor dabrafenib (DBF) afforded single crystals of a two-drug salt stabilized by N+-H center dot center dot center dot O and N+-H center dot center dot center dot N- hydrogen bonds between the ionized panobinostat ammonium donor and dabrafenib sulfonamide anion acceptor in a 12-member ring motif. A faster dissolution rate for both drugs was achieved through the salt combination compared to the individual drugs in an aqueous acidic medium. The dissolution rate exhibited a peak concentration (Cmax) of approximately 310 mg cm-2 min-1 for PAN and 240 mg cm-2 min-1 for DBF at a Tmax of less than 20 min under gastric pH 1.2 (0.1 N HCl) compared to the pure drug dissolution values of 10 and 80 mg cm-2 min-1, respectively. The novel and fast-dissolving salt DBF-center dot PAN+ was analyzed in BRAFV600E melanoma cells Sk-Mel28. DBF-center dot PAN+ reduced the dose-response from micromolar to nanomolar concentrations and lowered IC50 (21.9 +/- 7.2 nM) by half compared to PAN alone (45.3 +/- 12.0 nM). The enhanced dissolution and lower survival rate of melanoma cells show the potential of novel DBF-center dot PAN+ salt in clinical evaluation.</p>
1 aRai, Sunil, K.1 aMarverti, Gaetano1 aGunnam, Anilkumar1 aAllu, Suryanarayana1 aNangia, Ashwini, K.  uhttps://library.ncl.res.in/content/dabrafenib-panobinostat-salt-improving-dissolution-rate-and-inhibition-braf-melanoma-cells