Amorphous solid dispersion formation via solvent granulation - A case study with ritonavir and lopinavir.

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Solid State Chemistry

Background:

• Amorphous solid dispersions (ASDs) enhance the solubility and bioavailability of poorly soluble drugs.
• Developing stable ASDs for binary drug systems presents formulation challenges.
• Solvent granulation is a scalable technique for producing pharmaceutical granules.

Purpose of the Study:

• To evaluate solvent granulation for preparing binary drug ASDs containing ritonavir and lopinavir.
• To assess the physical stability and dissolution performance of the prepared ASDs.
• To compare the dissolution profiles of co-granulated versus individually granulated drug systems.

Main Methods:

• Binary drug ASDs of ritonavir and lopinavir were prepared using solvent granulation onto lactose and microcrystalline cellulose.
• Granules were dried, characterized for amorphous content (X-ray amorphous), and subjected to accelerated stability testing (40°C/75% RH).
• Dissolution behavior of compacted granules was assessed and compared to a marketed formulation.

Main Results:

• X-ray amorphous ritonavir and lopinavir were successfully prepared in ASD granules.
• No drug crystallization was observed after 1 month of accelerated stability storage.
• Co-granulation resulted in significantly retarded ritonavir dissolution; individual granulation followed by combination yielded comparable release to the commercial product.

Conclusions:

• Solvent granulation is a viable method for producing stable amorphous solid dispersions of anti-HIV drugs.
• Individual granulation of each drug is crucial for achieving optimal dissolution profiles in binary ASDs.
• This approach shows promise for formulating low-dose drugs with inherently low crystallization tendencies.