Downstream processing of amorphous solid dispersions into orodispersible tablets

Developing amorphous solid dispersions into patient-friendly oral dosage forms remains a challenge in pharmaceutical science. Prior research has shown that amorphous solid dispersions (ASDs) can improve drug solubility and bioavailability. However, translating these dispersions into orodispersible tablets (ODTs) has not been fully optimized. Established methods focus on excipient compatibility and mechanical properties of the final product. No prior work had resolved the impact of ASD particle size and co-processed excipient (CPE) choice on ODT performance. This gap motivated the investigation into how ASD particle size and CPE influence disintegration and mechanical strength of ODTs. The study aimed to clarify whether larger or smaller ASD particles would yield better ODT performance. Existing knowledge suggested that excipients like Hisorad® and Ludiflash® are commonly used in ODTs. This paper's contribution lies in systematically evaluating how particle size and excipient selection affect ODT properties.

The aim of this study was to evaluate how ASD particle size and co-processed excipient (CPE) selection influence the disintegration and mechanical strength of orodispersible tablets (ODTs). The researchers focused on two ASDs: one based on ritonavir with PVPVA and another on lopinavir with HPMCAS. They sought to determine whether larger or smaller ASD particles would yield better ODT performance. The motivation stemmed from the need to improve patient compliance through faster disintegration and stronger tablets. The study also aimed to compare the effectiveness of Hisorad® and Ludiflash® as CPEs in ASD-based ODTs. Prior work had not fully explored how these factors interact to affect tablet performance. The authors proposed that ASD particle size and CPE choice are critical variables in ODT development. This investigation sought to provide evidence-based guidance for ASD formulation into ODTs.

The researchers prepared two ASDs using hot melt extrusion (HME): one with ritonavir and PVPVA, and another with lopinavir and HPMCAS. The extrudates were milled and sieved into different particle size ranges. The ASD particles were blended with either Hisorad® or Ludiflash®, two co-processed excipients (CPEs) known for use in orodispersible tablets (ODTs). The blends were then compressed into tablets using a tableting press. Disintegration times were measured for each formulation under controlled conditions. Mechanical strength was assessed through hardness testing. The study compared the effects of varying ASD particle size and CPE type on ODT performance. The researchers used established methods for particle size analysis and tablet evaluation. This approach allowed them to systematically assess how each variable influenced the final product's properties.

The selected ASD particle size significantly affected disintegration time and mechanical strength of the orodispersible tablets (ODTs). For PVPVA-based ASDs, larger particles (>500 µm) enabled rapid disintegration within 30 seconds for ODTs containing 50% ASD. Smaller particles led to longer disintegration times. The choice of co-processed excipient (CPE) was also critical. ODTs with PVPVA-based ASDs performed well only when Hisorad® was used as the CPE. In contrast, HPMCAS-based ASDs showed better compressibility with smaller particle sizes (180-500 µm). ODTs containing up to 75% LPV could be produced with both CPEs while maintaining fast disintegration. The results suggest that particle size and CPE selection are key factors in ASD formulation for ODTs. These findings were consistent across all tested formulations and conditions.

The study's findings suggest that ASD particle size and co-processed excipient (CPE) selection are critical factors in the development of orodispersible tablets (ODTs). Larger ASD particles (>500 µm) enabled faster disintegration for PVPVA-based formulations, while smaller particles improved compressibility for HPMCAS-based ASDs. The performance of PVPVA-based ODTs was highly dependent on the choice of CPE, with Hisorad® yielding better results than Ludiflash®. ODTs containing up to 75% LPV could be produced with both CPEs while maintaining fast disintegration. These results indicate that formulation strategies should consider both particle size and excipient compatibility. The authors propose that these insights can guide future ASD development for ODTs. No generalizations beyond the tested ASDs and CPEs were made in the conclusions.