Valentina Martena

Permeation and skin retention of quercetin from microemulsions containing Transcutol® P

A microemulsion for the cutaneous release of quercetin was prepared. An aqueous phase, containing 40% Transcutol® P as solubilizing agent and permeation enhancer, was emulsified with Labrafil® as oil phase and Labrasol®/Capryol™ 90 as Solvent/Co-solvent. Quercetin was dissolved in the microemulsion at the concentration of 1%. Ternary phase diagrams were generated to determine the optimal concentration of each excipient composing the microemulsion. The physicochemical properties of the microemulsion, such as pH, viscosity, refractive index, and particle size distribution were determined. The microemulsion was stable for 12 months at the storing conditions of 25.0 ± 1.0°C. The in vitro quercetin permeability into and through the abdominal hairless pig skin was determined by vertical Franz’s cells. Quercetin showed hardly any permeability through the skin when dissolved in water- and Transcutol® P-free media, whereas a remarkable increase in cutaneous permeability was observed when quercetin was formulated in the microemulsion or when simply dissolved in Transcutol® P. These two last formulations are those showing the lower skin retention.

A new nanospray drying method for the preparation of nicergoline pure nanoparticles

Three different batches of pure nanoparticles (NPs) of nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Büchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.

Influence of pH and method of crystallization on the solid physical form of indomethacin.

The purpose of this study was to investigate the effect of pH and method of crystallization on the solid physical form of indomethacin (IDM). IDM, a non steroidal anti-inflammatory drug poorly soluble in water, underwent two different crystallization methods: crystallization by solvent evaporation under reduced pressure at 50.0°C (method A), and crystallization by cooling of solution from 50.0 to 5.0°C (method B). In both cases, several aqueous ethanolic solutions of IDM of different pHs were prepared. pHs were adjusted by adding acidic solutions (HCl 2M) or alkali (NaOH or NH4OH 2M) to an aqueous ethanolic solution of IDM. Thus, several batches were recovered after crystallization. The chemical stability of IDM was verified through (1)H NMR and mass spectroscopy (FIA-ESI-MS), that revealed that IDM degraded in strong alkali media (pH ≥ 12). Crystals obtained under different crystallization conditions at pHs of 1.0, 4.5, 7.0, 8.0, 10.0 and chemically stable were thus characterized for crystal habit by scanning electron microscopy, for thermal behaviour by differential scanning calorimetry, and thermogravimetry, and for solid state by X-ray powder diffractometry. Under the Method A, IDM always crystallized into pure metastable alpha form when solutions were acidified or alkalized respectively with HCl and NH4OH. On the contrary, in presence of NaOH, IDM crystallized under a mixture of alpha and sodium trihydrate form, because the presence of the sodium counter ion orientates the crystallization towards the formation of the trihydrate salt. Under the method B, at pH of 1.0, IDM crystallized under the alpha form; at pH 4.5, IDM crystallized under the form alpha in presence of some nuclei of gamma form; at pH 7.0, 8.0, and 10.0 for NH4OH, IDM crystallized under the most stable polymorph gamma form, whereas in presence of NaOH, a mix of alpha, and salt forms was formed whatever the pH of the solution.

Physicochemical characterization of nicergoline and cabergoline in its amorphous state

Formulation of poorly water-soluble crystalline drugs into their more soluble amorphous form is a common approach for improving their bioavailability. In this study, the amorphous forms of nicergoline (NIC) and cabergoline (CAB) were obtained by different methods (melting and precipitation under solvent evaporation). The physicochemical characteristics of the samples were determined by HPLC, differential scanning calorimetry (DSC), thermogravimetry, and X-ray powder diffractometry. The physical stability of the amorphous forms was investigated by DSC by considering how the onset temperature and the enthalpy content at the glass transition vary with aging time and temperature. Using the Kohlrausch–Williams–Watts equation on the data obtained from the experiments, the “mean molecular relaxation time constant” (τ) was estimated. This parameter was used to understand the stability of NIC and CAB in their glassy state at different temperatures, and results showed that their stability is adequate to enable the formulation of these drugs into solid dosage forms.