Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug-Polymer Systems.

In this article we study the effectiveness of three well-known polymers: inulin, Soluplus, and PVP in stabilizing the amorphous form of nimesulide (NMS) drug. The recrystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by broadband dielectric spectroscopy (BDS) and at nonisothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 min. We found that this time can be prolonged to 40 years after adding 20% w/w PVP to NMS. This polymer proved to be the best NMS stabilizer, while the worst stabilization effect was exhibited by inulin. Additionally, our DSC, BDS, and FTIR studies indicate that for suppression of NMS recrystallization in the NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances and the antiplastization effect exerted by the excipient.

The influence of amorphization methods on the apparent solubility and dissolution rate of tadalafil.

This study for the first time investigates the solubility and dissolution rate of amorphous tadalafil (Td)--a poorly water soluble chemical compound which is commonly used for treating the erectile dysfunction. To convert the crystalline form of Td drug to its amorphous counterpart we have employed most of the commercially available amorphization techniques i.e. vitrification, cryogenic grinding, ball milling, spray drying, freeze drying and antisolvent precipitation. Among the mentioned methods only quenched cooling of the molten sample was found to be an inappropriate method of Td amorphization. This is due to the thermal decomposition of Td above 200°C, as proved by the thermogravimetric analysis (TGA). Disordered character of all examined samples was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD). In the case of most amorphous powders, the largest 3-fold increase of apparent solubility was observed after 5 min, indicating their fast recrystallization in water. On the other hand, the partially amorphous precipitate of Td and hypromellose enhanced the solubility of Td approximately 14 times, as compared with a crystalline substance, which remained constant for half an hour. Finally, disk intrinsic dissolution rate (DIDR) of amorphous forms of Td was also examined.

Molecular dynamics, physical stability and solubility advantage from amorphous indapamide drug.

This study for the first time investigates physicochemical properties of amorphous indapamide drug (IND), which is a known diuretic agent commonly used in the treatment of hypertension. The solid-state properties of the vitrified, cryomilled and ball-milled IND samples were analyzed using X-ray powder diffraction (XRD), mass spectrometry, nuclear magnetic resonance (NMR), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). These analytical techniques enabled us (i) to confirm the purity of obtained amorphous samples, (ii) to describe the molecular mobility of IND in the liquid and glassy state, (iii) to determine the parameters describing the liquid-glass transition i.e. Tg and dynamic fragility, (iv) to test the chemical stability of amorphous IND in various temperature conditions and finally (v) to confirm the long-term physical stability of the amorphous samples. These studies were supplemented by density functional theory (DFT) calculations and apparent solubility studies of the amorphous IND in 0.1 M HCl, phosphate buffer (pH=6.8), and water (25 and 37 °C).

Decoupling of conductivity relaxation from structural relaxation in protic ionic liquids and general properties.

The main focus of this work is the study of conductivity relaxation of amorphous lidocaine hemisuccinate near the glass transition at ambient pressure. Measurements have been made using broadband dielectric spectroscopy (BDS) and temperature-modulated differential scanning calorimetry. Our study shows that the ion conductivity relaxation becomes increasingly faster than the structural relaxation as the glass transition temperature Tg is approached. At Tg the structural relaxation time is longer than the conductivity relaxation times by three decades, i.e. the decoupling index Rτ is about 3. Decoupling is accompanied by the ion conductivity relaxation which narrows in its frequency dispersion with decreasing temperature. This abnormal behavior is identical to that found in two other protic ionic liquids (PILs), procaine HCl and procainamide HCl. Considering that the phenomenon has been found before in several inorganic ionic glass-formers and now in three protic ionic liquids, it could be a general property of ionically conducting glass-forming substances, although more cases have to be studied before a definitive conclusion can be made. We show that it can be rationalized within the framework of the Coupling Model.