(583a) Spray Drying of Ternary Solid Dispersions of Ibuprofen and Indomethacin with Superior Physical Stability

Ibuprofen, indomethacin and similar drugs of low solubility and high permeability (Class II in the Biopharmaceutical Classification System) are more expected to show dissolution-dependent oral bioavailability. Currently, the enhancement of drugs solubility is the most challenging field in pharmaceutical development due to the large number of poorly soluble chemical entities between recently discovered active pharmaceutical ingredients, APIs. So, solid dispersion techniques have been developed to tackle these problems. Spray drying is an effective technology for solid dispersion production as it allows fast solvent evaporation resulting in a fast transformation of an API-carrier solution to solid API-carrier particles. The selection of right polymers (carriers or excipients) is very important in the initial phase of formulation development. Excipient screening would be time-consuming and involves an extra labour with consumption of a large amount of drug.

Therefore, this search was devoted to investigate the interactions of spray drying process parameters with the experimental parameters i.e. polymer and solvent selection, and their effect on the formation, physico-chemical characterization, stability, phase transformation and dissolution of two poorly water-soluble drugs, namely: ibuprofen and indomethacin. Four polymers were selected; two water soluble: soluplus & Kollidon VA 64 and two water insoluble: Kollidon CLF & HPMC-AS. The crosslinked drug-polymer combinations (API/water soluble polymer/water insoluble polymer) of ternary solid dispersions have been prepared by spray drying. A Büchi B-290 instrument was set up in closed mode: two fluid nozzle, aspirator at 100% (equivalent to 35m³/h) and spraying gas N₂. The inlet temperature was maintained at 85°C; the outlet temperature was maintained at 50 to 55°C by adjusting the peristaltic pump rate (%)). All solutions were prepared at 10% total solids in methanol, dichloromethane and 50:50 mixture.

Analytical techniques such as powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), raman spectroscopy and infrared spectroscopic (FT-IR) measurements have employed to examine the miscibility of the drug with the excipient, physical state, phase transformation, possible interactions, proper storage conditions and detect specific polymer-polymer and drug-polymer interactions. Release property of ibuprofen and indomethacin from four different solid dispersions was also investigated. Initial results indicated that both ibuprofen and indomethacin in the solid dispersion are in the amorphous state (XRD scans). From the DSC scans, only one glass transition (Tg) temperature can be detected in all the samples. Tg values shifted to higher temperatures when the HPMC-AS content in the solid dispersions increases up to a concentration of 40% of the total content. Spray-dried formulations are still stable after 3 month storage at 25°C, 60% RH. Enhanced release property was found where the release was compared with pure ibuprofen and indomethacin powder.