Wolfe Laboratories - From Concept to Creation with Confidence

>	CASE STUDY 1 Parenteral dosage form development of a highly insoluble molecule
>	CASE STUDY 2 Salt form optimization and lyophilized parenteral formulation development
>	CASE STUDY 3 Oral liquid formulation development
>	CASE STUDY 4 Accelerated stability studies to support a screening IND
>	CASE STUDY 5 Lead Optimization: Solubility and formulation screen for efficacy and PK studies

CASE STUDY 5
Lead Optimization: Solubility and Formulation Screen for Efficacy and PK Studies

Client Profile
A privately-held pharmaceutical company had developed a unique drug discovery technology in target identification and compound screening procedures. The company was applying their technology to reduce the time to market for new drugs in four therapeutic areas.

Business Needs
The company had a series of compounds needing evaluation in efficacy, pharmacokinetic and toxicology studies. In general, the molecules were extremely insoluble in the few vehicles that had been examined. The company sought technical guidance to select vehicles that could be used in intravenous and oral formulations, and required formulation development for approximately 24 compounds per year.

Technical Challenge
The compounds had diverse physicochemical characteristics that necessitated a broad vehicle screen to maximize the solubility characteristics. Very limited quantities (approximately 100 mg) of each compound would be available for solubility screening and formulation testing. The lead compound selection, efficacy and pharmacokinetic testing schedules dictated completion of solubility and formulation screening within two weeks so that the next lead could be screened.

WLI Services
WLI identified a diverse array of vehicles in which each compound’s solubility could be established. Solubilization approaches including pH adjustment, salt formation, cosolvents, surfactants and complexing agents were included in customizing a vehicle screen for this client. Since the vehicles were generally recognized as safe for intravenous and oral dosing, the client appreciated that they would have a significant lead on formulations for early clinical studies. WLI created customized standard procedures to support routine analytical determinations and solubility testing for the series of compounds.

Results
The vehicle solubility screening continues to identify formulations that have been and are being used in ongoing efficacy, pharmacokinetic and bioavailability testing. Upon nomination of a candidate drug, the client has had an existing formulation database from which the toxicology and early human clinical formulations can be selected.

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