Formulation optimization of ritonavir tablets containing spray dried dispersion from HPMCAS-L or PVP-VA and...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Tablets are the preferred oral dosage form due to manufacturing efficiency, cost-effectiveness, stability, and patient compliance.
• Amorphous solid dispersions (ASDs) enhance solubility and bioavailability of poorly soluble drugs, but tablet formulation strategies are underdeveloped.
• Ritonavir, a poorly soluble drug, is often formulated as an ASD to improve its oral absorption.

Purpose of the Study:

• To optimize the formulation and manufacturing process for tablets containing ritonavir-HPMCAS-L ASD.
• To compare the dissolution and permeation performance of ritonavir-HPMCAS-L ASD tablets with those formulated using PVP-VA.
• To investigate the impact of various excipients and processing parameters on ASD tablet performance.

Main Methods:

• Formulation optimization involved screening fillers (microcrystalline cellulose, dibasic calcium phosphate) and disintegrants (croscarmellose sodium, crospovidone, sodium starch glycolate).
• Process optimization included evaluating spray-drying inlet temperatures, direct compression, and dry granulation techniques with varying compaction forces.
• Dissolution and permeation studies were conducted to assess the performance of optimized ASD tablets.

Main Results:

• Optimized ritonavir-HPMCAS-L ASD tablets were achieved using dry granulation with specific parameters: 65.5% ASD, 10% croscarmellose sodium, 24% microcrystalline cellulose, and 0.5% magnesium stearate.
• Tablets formulated with HPMCAS-L exhibited favorable in vitro dissolution, comparable to those with PVP-VA.
• Tablets with PVP-VA showed higher ritonavir permeation than HPMCAS-L tablets, similar to commercial Norvir tablets, suggesting the critical role of the dissolution colloid.

Conclusions:

• Successful optimization of ritonavir-HPMCAS-L ASD tablets was achieved, demonstrating favorable dissolution profiles.
• The choice of polymer (HPMCAS-L vs. PVP-VA) significantly impacts drug permeation, even with similar dissolution rates.
• The characteristics of the dissolution-resulting colloid are critical for overall drug absorption from ASDs, influencing performance beyond simple dissolution.