CONICET | Buscador de Institutos y Recursos Humanos

Introduction Meloxicam (MX) is a non-steroidal anti-inflammatory drug used in the treatment of osteoarthritis and other joint diseases that has low solubility and poor wetting properties. These characteristics make MX a good candidate for the development of solid dispersions (SDs, dispersions of one or more drugs in a solid inert matrix). In order to improve the bioavailability of MX, SDs of the drug with Poloxamer 188 (PX, an amphiphilic copolymer) were prepared by melting. In previous studies, the effects of PX on the MX aqueous solubility and on the in vitro drug dissolution were evaluated. PX was found effective to increase both the apparent solubility and dissolution rate of MX. Furthermore, FT-Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray diffractometry (XRD) and Scanning Electron Microscopy (SEM) allowed postulating that the increase in drug dissolution rate was not due to a MX crystalline-to-amorphous transformation. The results also revealed the lack of homogeneity in physical mixtures (PMs). In this work and for the developed solid products, Hot Stage Microscopy (HSM), Particle Size Distribution (PSD) and Powder Rheology tests were performed in order to clarify the thermal behavior of the samples during heating, the changes in PSDs associated to the production processes and the flow properties, respectively. Materials and methods DSs containing (MX:PX) in proportions between (1:9) and (1:1) were obtained by fusion. For comparative purposes, the homologous PMs were also prepared. Details can be found in Calcagno et al. HSM was carried out in the 30-300 °C range, at a scanning speed of 2 °C/min, with an optic microscope equipped with a hot stage unit and video camera. PSDs were studied through laser scattering by dispersing the powders in glycerin or water. Powder compressibility was evaluated by means of the Carr?s Index (CI). The dynamic angle of repose (α) was determined by the funnel method. Results and discussion HSM was applied to visualize the changes in SDs and PMs during heating. The pictures of the SD (MX: PX): (1:9) confirmed that the MX particles were completely dissolved in the melted PX at 190 °C. In contrast, for the SD (MX: PX): (1:1), some MX crystals were found in the sample at 190 °C. Then, these crystals melted and decomposed at a temperature lower than the true drug melting point (around 265 °C). For all the samples, the melting of PX at 52 °C was first detected. For every (MX:PX) ratio, the behavior of the PMs under heating was analogous to that exhibited by the corresponding SDs. The mean volume particle diameters (dp) for the SDs (85-102 μm) were considerably bigger than those of the homologous PMs (27-34 μm). However, this significant change was not reflected by the variations in the MX dissolution rate, suggesting that the drug crystals size was similar in the SDs and PMs. For both, the SDs and PMS, the dp increased with the PX content. Regarding the powder flow properties, α for the SDs was within the 27-31º range indicating a goodexcellent flow. For the PMs, the values could not be determined due to their bad flow. In addition, the obtained CI showed that the powder flow for the SDs (21-32%) was acceptable-poor, while that of the PMs was very bad8 (above 34%). Conclusions HSM, DSC, FT-IR, XRD and PSDs results confirmed that there were no interactions between PX and MX and/or changes in crystallinity or crystals size of the MX. Therefore, the improvements in the MX dissolution rate could probably be a consequence of the micellar solubilization effect of PX along with its wetting properties. Both, α and CI criteria revealed that the SDs had better flow properties than the PMs, in agreement with the bigger dp found for the SDs with respect to the homologous PMs. Therefore, the addition of a glidant agent could easily enhance the SDs flow to formulate solid dosage forms.

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