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Tablets & Capsules March 2020 13 solubility compared to the API by itself. The SDD showed a 3-fold higher increase in dissolution than the extrusion, while the extrusion still showed 30-fold better dissolution than the API alone. Spray drying resulted in higher solubilit y for about 10 minutes before crystallization in solution. To characterize and confirm the amorphous struc- ture of these API formulations, we used powder X-ray crystallography and DSC. As the X-ray diffraction patterns in Figure 3 show, the API is crystalline, while spray drying with polymers HPMCAS-L or Kollidon VA64 results in amorphous dispersions. As shown in Figure 4, DSC of these formulations showed no clear calorimetry (DSC) with a heat-cool-heat cycle allowed us to determine the heat capacity and miscibility of API-polymer mixtures, using only minimal API. API and polymer were melted and mixed in the DSC pan, then cooled. The API-polymer mixture is then melted again to measure heat capacity. The matrix with the lowest heat capacity has the lowest residual crys- tallinity and the most miscibility, which indicates that the API-polymer will stay as a homogeneous dispersion. Table 2 shows the melt peaks of the API with or without different matrices in this heat-cool-heat DSC analysis. 25:75 API:Kollidon VA64 and 25:10:65 API:TPGS:Kol- lidon VA64 showed the lowest heat capacity and the best miscibility, making them the best candidate amorphous dispersions for HME with this API. We then scaled up select formulations that performed well in our screens and made amorphous dispersions using SDD and HME for in vitro and in vivo assessments. Assessment of formulations in vitro To test for kinetic solubility enhancement of each can- didate formulation, we performed a non-sink dissolution study. We made super-saturated mixtures of API-polymer powder in 1 milliliter of fasted-state simulated intestinal fluid (FaSSIF) and measured how long each formulation could stay in solution. Non-sink dissolution can give you an idea of a formulation's pharmacokinetics because bet- ter kinetic solubility, as measured here, should allow for increased intestinal drug absorption in vivo. As shown in Fig ure 2, the results indicated that 25:10:65 API:TPGS:Kollidon VA64 SDD and 25:10:65 A PI:T PGS:Kollidon VA64 HM E showed improved Figure 4 Differential scanning calorimetry (DSC) thermograms of lead spray dried dispersion 124.19°C Heat flow (W/g) 0.4 0.2 0.0 -0.2 -0.4 Temperature (°C) 0 50 100 150 200 250 300 Rev heat flow (W/g) 0.00 -0.05 -0.10 -0.15 -0.20 -0.25 Nonrev heat flow (W/g) 0.4 0.2 0.0 -0.2 114.41°C 118.11°C(I) Figure 5 Animal study design comparing various solubility enhancement techniques SDD HME PEG solution Micro-evaporation Nano-suspension