Optimization of a Spray Dried Dispersion Powder of Ritonavir with HPMCAS-L Ritonavirin HPMCAS-Lile Püskürterek Kurutulmuş Dispersiyon Tozunun Optimizasyonu

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OKTAY A. N., Polli J. E.

Fabad Journal of Pharmaceutical Sciences, cilt.50, sa.2, ss.293-310, 2025 (Scopus, TRDizin)

Özet

Ritonavir (RTN) is frequently administered as a drug metabolism inhibitor to “boost” other drugs, such as nirmatrelvir to treat COVID-19. However, like many orally administered drugs, RTN has low water solubility. Hence, RTN is formulated as an amorphous solid dispersion (ASD). The objective was to prepare an optimal RTN spray-dried dispersion (SDD) via spray drying. Using the polymer HPMCAS-L, an optimal spray drying condition was identified, where aspirator rate, spray gas flow, and solution feed rate were varied in a 23 (3 repeated) full factorial design. Yield %, moisture %, and Carr index were assessed. Optimal spray drying conditions were an aspirator rate of 38 m3/h, spray gas flow rate of 742 L/h, and solution feed rate of 6mL/min, resulting in the highest yield %, lowest moisture %, and lower Carr index. Next, optimal spray drying conditions were applied to fabricate RTN SDDs using HPMCAS-L, at each 70 and 140 °C inlet temperatures. Particle size, drug content %, DSC, yield %, moisture %, bulk density, tapped density, Hausner ratio, and Carr index of each SDD were assessed or conducted. Solubility, stability, and dissolution studies were also carried out. Both SDD were stable for three months and exhibited improved solubility, compared to unprocessed RTN and physical mixtures. SDD using HPMCAS-L polymer provided rapid RTN release. Overall, an optimal RTN SDD was achieved and employed HPMCAS-L rather than PVP-VA, which is used in several commercial forms of RTN, albeit using hot melt extrusion.