CASE STUDY 7:
Oral Liquid Formulation Development
A West Coast, virtual biotechnology company had recently received $40 M in venture funding. The management did not have plans to assemble a pharmaceutical development team.
The client was optimizing the structure of the lead molecule to fine tune the pharmacokinetics. This would require evaluating the pharmacokinetics in healthy human volunteers. The client had several complex formulation constraints and needed a partner that would work closely through program design and implementation. However, the client did not want to use a formulation facility that would demand intellectual property rights on the formulation.
Though it was too early in the program for a fully validated, stability-indicating HPLC method , the client still wanted an HPLC method developed:
The client needed a minimal amount of drug characterization to support development of parenteral and oral liquid formulations to be used in GLP toxicology studies. They also needed taste-masked oral liquid formulations developed for the clinical trials.
- that could reasonably separate impurities and degradation products
- that would be sufficiently robust to use with all of their structurally related compounds
WLI worked closely with the client to establish the most cost-effective approach for this screening-IND program, recognizing that the client would be investing significant time and money into lead molecules that would not have the desired pharmacokinetic properties. WLI developed and qualified a robust HPLC method that could be used for concentration and purity determination, thus allowing confidence in the data generated. Preformulation tasks were limited to the most relevant physicochemical characterization, including pKa, log P and solubility determination. From these preliminary studies, parenteral and oral liquid formulations were developed for both toxicological and clinical testing. The formulations were evaluated for content uniformity, stability, and compatibility with the dosing componentry.
WLI assisted in transferring the analytical and compounding methodologies to the toxicology houses and to the GMP manufacturing facility. This work was performed on five molecules, the last of which was nominated for full development.
The client was able to develop satisfactory formulations with supporting data to obtain necessary approvals for human pharmacokinetics testing on schedule. The client did not have to give up intellectual property rights for the formulations.
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