In vivobrain microdialysis as a formulation-screening tool for a poorly soluble centrally acting drug

Abstract

Hence, brain microdialysis was successfully used to evaluate a dissolution rate enhancing formulation.

Supercritical Carbon Dioxide as a Green Alternative to Achieve Drug Complexation with Cyclodextrins

“…The table is an interesting overview of the wide spectrum of different classes of drugs that were tested over the last years with supercritical fluid techniques. Remarkable drug release improvement was found in most cases and promising in vivo studies were also obtained for pharmaceutical formulations of some drugs, such as carbamazepine [75], dutasteride [71] and simvastatin [69] as well as the achievement of an effective taste masking for the cetirizine/βCD complexes [46]. The main results obtained for each drug are discussed in the following paragraphs.…”

“…This approach is widely used in the great majority of research papers investigated in this work [11,19,21,22,25,27-31,34,39,41-44,46,48-58,60,64,65,67-72,75,76,79-81,84,86-89, 91-94,96,98]. On the other hand, unfortunately not many works report in vivo tests whose details can be found in the specific references [25,49,65,69,71,72,75,80,81]. Other works report different analyses to detect the biological performance of the formulations, such as the evaluation of the antifungal, antibacterial or antioxidant activity [40,67,77,80] as well as in vitro cell culture assays [73] or taste perception tests [46].…”

“…Even though many scCO 2 soluble cyclodextrins are reported in the literature, until now examples of particleformation techniques where scCO 2 acts as a solvent have not been employed to achieve drug/cyclodextrin complexation. On the other hand, examples where scCO 2 is employed either as an antisolvent [11,[46][47][48][49][50][51][54][55][56][68][69][70][71][72][73][74][75][76][78][79][80] or a co-solute [57,77,83] can be found. These techniques match the possibility of achieving drug/cyclodextrin complexation with that of controlling the particle size distribution [49,54,68,73,77,79,83] which may also positively affect the dissolution rate of the obtained products.…”

“…Drug/cyclodextrin systems were processed with the gas antisolvent (GAS) process [56,75,78], the aerosol solvent extraction system (ASES) [11,46,50,68,71,72,76,80], the solution-enhanced dispersion by supercritical fluids (SEDS) [47][48][49]51,54,55,69,70,79] and the atomized rapid injection solvent extraction (ARISE) system [73,74], even though the general acronym SAS is often used to indicate any of the above-cited variations.…”

“…The efficacy of the obtained ternary formulations was evaluated by measuring dopamine responses with in vivo brain microdialysis after oral administration [75]. Compared to the pure drug, the ternary formulations produced elevated levels of dopamine (up to 250% of the baseline) with a stepwise increase and a peak of concentration after 1.5-2 h. According to the authors the presence of nicotinamide does not affect the drug absorption in the gastrointestinal tract after release, since the two components in the co-crystals tend to dissociate after the dissolution [75]. 6.4.6.…”