Nanocrystal dispersion of DK-I-56-1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: formulation approach toward improved in vivo performance.

Nanocrystal dispersion of DK-I-56-1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: formulation approach toward improved in vivo performance. Eur J Pharm Sci. 2020 Jun 18;:105432 Authors: Mitrović JR, Divović B, Knutson DE, Đoković JB, Vulić PJ, Randjelović DV, Dobričić VD, Čalija BR, Cook JM, Savić MM, Savić SD Abstract DK-I-56-1 (7-methoxy-2-(4-methoxy-d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56-1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56-1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or d-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7-250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56-1 levels after solution (10228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administrat...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research