@article {48825,
	title = {Dabrafenib-panobinostat salt: improving the dissolution rate and inhibition of BRAF melanoma cells},
	journal = {ACS Omega},
	volume = {8},
	year = {2023},
	month = {MAY },
	pages = {18255-18265},
	type = {Article},
	abstract = {<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>
},
	issn = {2470-1343},
	doi = {10.1021/acsomega.3c01881},
	author = {Rai, Sunil K. and Marverti, Gaetano and Gunnam, Anilkumar and Allu, Suryanarayana and Nangia, Ashwini K.}
}
