This work proposes a methodology for the design, development, optimisation, and evaluation of amorphous rosuvastatin calcium tablets (BCS class II drug). The main goal was to ensure rapid disintegration and high dissolution rate of the active ingredient, thus enhancing its bioavailability. The design started from a careful selection of excipients, which due to their characteristics and proportions within the formulation allowed the use of their properties such as fluidity or granulometric distribution. The formulation was characterised using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) methods. The galenic SeDeM methodology was used to establish the profile of the active ingredient-excipient mixture and guarantee its suitability for producing tablets by the direct compression method. The results demonstrate that the amorphous rosuvastatin calcium tablets formulation developed made it possible to obtain cost-effective tablets by direct compression with optimal pharmacotechnical characteristics that showed a remarkable disintegration and dissolution rate. The manufactured tablets complied with the pharmacopoeia guidelines regarding content uniformity, tablet hardness, thickness, friability, in vitro disintegration time and dissolution profile.

This work proposes a methodology for the design, development, optimisation, and evaluation of amorphous rosuvastatin calcium tablets (BCS class II drug). The main goal was to ensure rapid disintegration and high dissolution rate of the active ingredient, thus enhancing its bioavailability. The design started from a careful selection of excipients, which due to their characteristics and proportions within the formulation allowed the use of their properties such as fluidity or granulometric distribution. The formulation was characterised using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) methods. The galenic SeDeM methodology was used to establish the profile of the active ingredient-excipient mixture and guarantee its suitability for producing tablets by the direct compression method. The results demonstrate that the amorphous rosuvastatin calcium tablets formulation developed made it possible to obtain cost-effective tablets by direct compression with optimal pharmacotechnical characteristics that showed a remarkable disintegration and dissolution rate. The manufactured tablets complied with the pharmacopoeia guidelines regarding uniformity of weight, tablet hardness, thickness, friability, in vitro disintegration time and dissolution profile.

Recebido em 29/1/07; aceito em 11/5/07; publicado na web em 16/10/07 DEVIATIONS FROM LOG-LINEAR SOLUBILITY EQUATION FOR IBUPROFEN AND NAPROXEN IN PROPYLENE GLYCOL-WATER COSOLVENT MIXTURES.The deviations observed in the solubility of ibuprofen (IBP) and naproxen (NAP) in propylene glycol (PG) + water (W) cosolvent mixtures with respect to the logarithmic-linear model proposed by Yalkowsky have been analyzed at 25.00 ± 0.05 °C. Negative deviations were obtained in all cosolvent compositions for both drugs; they were greater for IBP. Another treatment, based on Gibbs free energy relationships, was also employed showing an apparent hydrophobicity chameleonic effect, because at low PG proportions NAP is more hydrophobic, whereas at high PG proportions IBP is more hydrophobic. The results are discussed in terms of solute-solvent and solvent-solvent interactions.Keywords: AINEs; cosolvent mixtures; log-linear solubility equation. INTRODUCCIÓNEl ibuprofén (IBP) y el naproxén (NAP) son fármacos del tipo analgésico-anti-inflamatorios, derivados del ácido propiónico, y clasificados como anti-inflamatorios no esteroidales (AINEs), que son ampliamente utilizados en la terapéutica actual para el tratamiento sintomático de la artritis reumatoidea y en general, para todo proceso agudo o crónico relacionado con dolor e inflamación 1 . En el mercado farmacéutico colombiano, el IBP se dispone comercialmente en forma de tabletas y suspensiones para administración peroral, mientras que el NAP se presenta como tabletas, cápsulas, polvo para suspensión, y además como suspensión preparada, para administración peroral. Así mismo, el IBP no se dispone para administración parenteral, mientras que el NAP si se presenta como inyectable en ampollas de 500 mg/5 mL 2 . De otro lado, es bien sabido que las formulaciones líquidas inyectables se caracterizan por suministrar una alta dosis de fármaco en un pequeño volumen de producto; por lo tanto, algunas propiedades fisicoquímicas tales como la solubilidad y los volúmenes ocupados por los principios activos y los otros componentes en la solución se tornan muy importantes para el diseñador farmacéutico, ya que el conocimiento de estas propiedades, así como el adecuado manejo y de ser posible, la predicción de estos fenómenos, facilita enormemente la labor de este profesional durante su labor en el desarrollo de medicamentos 3 . Por lo anteriormente expuesto, específicamente en lo relacionado con la predicción de propiedades de los sistemas líquidos, en la presente investigación se presenta un estudio fisicoquímico sobre el efecto de la composición cosolvente sobre la solubilidad del IBP y el NAP a 25,00 ± 0,05 °C en mezclas binarias solventes formadas por propilenoglicol (PG) y agua (W). En particular, sobre las desviaciones presentadas por estos dos sistemas respecto al modelo logarítmico-lineal de Yalkowsky y Roseman 4 . El sistema PG-W es de amplio uso en el diseño de formulaciones líquidas de administración parenteral 4,5 y además, ha sido muy bien estudiado desde el punto de vista fisicoquím...

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The solubilities of celecoxib (CLX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water-ethanol and ethanol-ethyl acetate mixtures at several temperatures (288.15-308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures, they showed a single maximum located at 50% ethanol-ethyl acetate (δ1 = 22.50 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs free energy of solution (ΔHS,ΔSS and ΔGShm, respectively). The apparent enthalpies of the solution were a nonlinear function of the ethanol ratio in aqueous mixture. Non-linear enthalpy-entropy compensation analysis was observed indicating different dissolution mechanism with the variation in mixtures composition. The solubility enhancement is entropy driven at water-rich region (0-40% v/v ethanol) and enthalpy controlled at ethanol-rich region (40–100% v/v ethanol), likely due to water-structure loss around nonpolar moieties of the drug and for the ethanol-rich mixtures it is the enthalpy, probably due to the drug better solvation.