Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. II. Application of reduced pressure treatment for the improvement of dissolution of flufenamic acid.

Abstract

Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) and stored at 60 degrees C at a reduced pressure of about 2.5 mmHg. After storage, when its concentration was not more than 20%, FFA was observed by X-ray diffraction and polarizing microscopy to be amorphous. The dissolution of FFA was thus enhanced in comparison with that of a freshly prepared mixture. Furthermore, the dissolution curves showed a typical supersaturation pattern, and the supersaturation state continued longer, the higher the pH value of the dissolution medium. Flufenamic acid, in a mixture with MAS, became amorphous more rapidly at reduced pressure than at atmospheric pressure, and therefore the effect of improved dissolution appeared earlier at reduced pressure. Infrared spectral studies suggested that FFA, after storage at a reduced pressure with MAS, was dispersed monomolecularly in an ionic form. The technique of treating crystalline medicinals, that have poor solubility in water, with adsorbent at reduced pressure may be useful for improving their dissolution characteristics.

Investigation of Drug–Porous Adsorbent Interactions in Drug Mixtures with Selected Porous Adsorbents

“…In recent years, porous adsorbents have captured the attention of some scientists, leading them to investigate their possible applications in drug delivery. The main investigational application of these porous adsorbents was their role in enhancing the solubility of poorly water soluble drugs 1–10. Poor aqueous solubility is one of the main reasons many drug candidates cannot reach the market in spite of exhibiting potential pharmacodynamic activity 11.…”

Quantitative measurement of indomethacin crystallinity in indomethacin-silica gel binary system using differential scanning calorimetry and X-ray powder diffractometry

“…Other analytical methods should be considered in such a situation. There have been increased interests in using porous adsorbents to improve the dissolution rate of poorly water-soluble drugs either by simple mixing or solid dispersion, [20][21][22] and DSC has been routinely used as a qualitative method to study such phase transformation in crystalline drugs/porous adsorbents mixtures. [23][24][25] Here, we report the development of quantitative methods using both DSC and XRPD to measure the crystallinity of indomethacin (IMC) in mixtures with the adsorbent, silica gel (SG).…”

Amorphous Solid Dispersions

“…The extent of drug loading and degree of amorphization is influenced by various factors like time and intensity of mixing, reduced pressure, humidity, and silanol content. In most of the earlier studies, the extent of amorphization is found to be proportional to time and intensity of mixing (Konno and Kinuno 1989;Konno et al 1986). However, contradictory observations were made with a study conducted by Pan et al (2008) where the amorphization of indomethacin was found to be independent of both parameters, which is explained by the low glass transition temperature (T g ) of the drug.…”