Vol. 13, Issue 7 (2024)

Introduction: About 40% of newly made active pharmaceutical compounds don't dissolve well in water, which makes them less bioavailable when taken by mouth. Amorphous solid dispersions (ASDs) are widely employed to enhance dissolution and solubility by maintaining the drug in a high-energy amorphous form. This study aimed to develop and assess amorphous solid dispersions (ASDs) of a poorly water-soluble drug employing hot-melt extrusion (HME) and spray drying (SD) techniques.

Materials and Methods: A BCS Class II drug was used that was less than 5 µg/mL soluble in water. Amorphous solid dispersions (ASDs) were made with PVP K30 and HPMCAS at drug-to-polymer ratios of 1:1, 1:2, and 1:3 (w/w). The temperature for HME was between 110 and 130°C, and the screw speed was 50 rpm. The temperature for SD was between 80 and 90°C, and the feed rate was 5 mL/min. DSC, PXRD, FTIR, and SEM were used to do solid-state characterization. Equilibrium solubility and in vitro dissolution (USP II, 900 mL phosphate buffer pH 6.8, 50 rpm) were conducted. For three months, physical stability was tested at 40°C and 75% relative humidity.

Results: The drug's melting peak at 164°C completely vanished in both HME and SD ASDs, as evidenced by DSC thermograms, signifying that amorphization occurred. PXRD patterns did not show any crystalline peaks; instead, they showed halo patterns. The medication went from 4.6 ± 0.2 µg/mL in pure form to 35.4 ± 1.1 µg/mL in HME 1:2 and 42.7 ± 1.4 µg/mL in SD 1:2, which is an 8-fold and a 9.3-fold increase in solubility, respectively. In the same amount of time, dissolving studies indicated that the pure medication only released 18.2% ± 1.6% of its drug content after 60 minutes. This number went up to 78.4% ± 2.3% (HME 1:2) and 86.5% ± 1.7% (SD 1:2). The SEM scans showed that HME was made up of cylindrical extrudates while SD was made up of spherical particles that were between 2 and 5 µm in size. Stability tests showed that neither formulation had recrystallized after three months and that the medication concentration stayed over 97%.

Conclusion: HME and spray drying made the model drug more soluble and easier to dissolve by changing it into a stable amorphous state. Before, it was only slightly water-soluble. Both methods worked well, however spray-dried ASDs had somewhat better solubility and dissolution than HME. HME, on the other hand, was more scalable and could be used without solvents. Results like this support the hypothesis that ASDs could help make drugs with low solubility more available to the body.