Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

Development and evaluation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and polycaprolactone microparticles of nimodipine.

Polymeric microparticles containing the calcium channel blocker nimodipine were successfully obtained through simple emulsion/ organic solvent evaporating method. The extended release formulations, composed by the polymers poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) and polycaprolactone (PCL), were submitted to characterization through X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared analysis (FT-IR) and determination of the mean particle diameter. All formulations obtained revealed an amorphous characteristic, proven through XRPD and DSC results. Besides, no chemical interaction was observed between drug and polymer in polymeric microparticles. PHBV-NMP formulation showed a higher drug entrapment, a larger particle size, a thermal degradation behavior similar to that observed for nimodipine and a longer drug release time, being selected for in vivo evaluation. The PHBV-NMP polymeric microparticles were able to keep the pharmacological antihypertensive effect for a longer period of time, becoming a good alternative to control nimodipine release in hypertension treatment.