In May 2020, the formulation team of the Hangzhou Pharmaceutical Research Center took on the urgent task and officially launched the formulation research of Suraxavir Marboxil.
Inside the formulation laboratory, workbenches were piled high with samples. Under the microscope, the processed API particles remained stubborn like "unyielding stone" and proved extremely difficult to optimize.
Ye, the formulation supervisor of the project, frowned as he looked at the mountain of micronized samples in the lab. “We have tried all crystal forms and milling technologies. Even the dissolution curve of nanocrystals remains as flat as an electrocardiogram baseline.”
Lu, head of the Formulation Department, stepped in personally and led the team into countless rounds of trial work in the laboratory to explore new processes. However, the first batch of samples crystallized after just three days in accelerated stability testing, failing dissolution requirements.
Faced with these challenges, Supervisor Ye reviewed relevant literature, his finger tracing a paragraph: “There is insufficient compatibility with the carrier! For drugs with a LogP below 5 and a high melting point, the carrier must effectively inhibit crystal nucleation.”
Based on this judgment, the formulation team screened more than a dozen polymers overnight, including PEG, PVP, HPMCP, HPMCAS and Eudragit. They repeatedly tested hot melt extrusion and spray drying processes, gaining deeper understanding of the raw material characteristics with every attempt. Repeated failures pushed the formulation team to the brink of frustration. At the critical moment, Senior Formulation Expert Lu turned the situation around. The team shifted to an innovative granulation process, which solved the dissolution challenge while also simplifying subsequent formulation procedures and facilitating industrial production.
After multiple formula iterations, they finally achieved ideal results: no impurity growth, controllable residual solvents, reasonable process duration, excellent particle flowability, and ideal dissolution performance that fully passed accelerated stability testing. The drug dissolution problem was finally resolved.
When Phase III clinical trial results were announced, it was like the break of dawn after a long night, illuminating all the hard work of the formulation team.
By reforging technical methods and staying firm in their faith, the once "unyielding stone" was finally refined into a life-saving medicine. As written forcefully on the opening page of the research log: “Some locks cannot be opened simply because we have not yet learned to reforge the key.”