Preclinical Formulation Screening
In the drug discovery process, formulation plays a crucial role in assessing the biological characteristics of molecules. Increasing the exposure of the test compound in studies in vivo is one of the main goals of early animal experiments. Choosing a suitable preclinical formulation not only optimizes in vivo PK exposure, but also promotes the optimization, selection, and development evaluation of compounds to provide data support for the design and development of clinical formulations
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Overview
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Assays
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Study Strategies
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Experience
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FAQs
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Related Resources
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Related Services
Overview
For the test compounds in the early screening stage, the unsatisfactory physical and chemical properties, the insufficient compound amount, and the tight time are commonly encountered. To deal with these challenges, the WuXi AppTec DMPK established a team for preclinical formulation screening for PK studies, pharmacodynamic, and toxicological studies. The team has more than ten years of experience and can perform rapid formulation screening and preparation services for large and small animal experiments. They also provide more than nearly 1,000 arms of formulations for preclinical animal experiments every week. They can use limited (milligram) compounds to offer a suitable formulation for preclinical animal experiments within 24 hours.
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Assays
The formulation team provides formulation screening and formulation services for pharmacokinetic studies from the screening stage to the IND application stage. It provides formulation screening services for pharmacodynamic tests and preclinical toxicological experiments. The team can select suitable excipients to dissolve the compound to tackle the solubility issue according to the physical and chemical properties of each specific drug substance (such as dissociation constant pKa, lipophilicity, aqueous solubility). The most suitable formulation for a drug substance is selected by in vitro solubility assessment, homogeneity, and particle size analysis. Further screening is performed from eligible candidates to ensure the formulation with better in vivo bioavailability or good achievement of experimental objectives.
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Study Strategies
The formulation team can select vehicles that meet the requirements of the PK study within one working day. In formulation screening, solubilization technology (such as pH adjustment and cosolvent) is a commonly used technical means. For some poorly soluble compounds, a cosolvent plus surfactant or complexing agent plus pH adjustment are typically used in combination. In addition, the DMPK formulation team can customize the formulation screening strategy according to differentiated project needs
Common methods for preclinical formulation screening
Experience
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12+
Years of experience in preclinical vehicle screening
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1000+
Bottles per week of formulation screening and preparation
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10000+
Vehicle safety database
FAQs
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What is preclinical formulation screening in DMPK studies?
Preclinical formulation screening in DMPK studies focuses on optimizing animal formulations to ensure adequate solubility, stability, and bioavailability during early discovery stage. Key objectives include:
Bioavailability Enhancement: Improve solubility (e.g., pH adjustment, surfactants, lipid carriers) and dissolution rates (micronization,1–10 µm /nano-suspension, 100–500 nm).
Stability Assurance: Prevent degradation in physiological fluids (e.g., simulated gastric/intestinal fluids).
Toxicity Support: Use excipients within species-specific safety limits.
Common strategies involve solubility-enhancing techniques (cosolvents, surfactants, cyclodextrins), particle size reduction, and stability testing. This process reduces development risks by identifying formulation issues early, accelerates timelines, and ensures reliable preclinical data for advancing candidates.
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What methods are used in preclinical formulation screening?
1. Enhancing Compound Solubility in Aqueous Phase
Objective: Improve compound solubility and prevent precipitation through vehicles combinations.
Common Strategies
1.1 pH Adjustment: Utilized for ionizable compounds (acids/bases) to enhance solubility.
1.2 Cosolvents: Incorporation of solvents such as DMSO, PEG 400, ethanol, and propylene glycol, often in combination to mitigate toxicity.
1.3 Surfactants: Use of agents like Tween 80 and Solutol HS15 to form micelles, aiding in solubilization.
1.4 Cyclodextrin Complexation: Utilization of cyclodextrins like HP-β-CD and SBE-β-CD to improve solubility of hydrophobic molecules.
1.5 Oil-Based Carriers: Employment of medium-chain triglycerides (MCT) and soybean oil for compounds with high logP values (logP > 5).
2. Objective: Enhance dissolution rates through physical reduction of particle size.
Common Strategies:
2.1 Micronized Suspensions: Reduction of particle size to a range of 1–10 μm to improve solubility and dissolution.
2.2 Nano Suspensions: Further reduction of particle size to a range of 100–500 nm, significantly boosting bioavailability.
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How can preclinical formulation screening optimize drug development?
Preclinical formulation screening optimizes compound development by enhancing solubility, stability, and biological compatibility while minimizing toxicity risks. Here’s how strategic approaches streamline the process:
1. Combination Strategies for Enhanced Performance
1.1 Optimized Combinations: The synergistic effect of combination strategies surpasses that of individual approaches.
1.2 Advantages:
1.2.1 Reduces excipient toxicity by enabling lower concentrations of individual components.
1.2.2 Broadens applicability across diverse compound classes, including acids, bases, and neutrals.
2. Formulation Assessment
2.1 Solubility: Assessed using HPLC/UV techniques to ensure delivery of the therapeutic dose.
2.2 Precipitation Testing: Conducted in Simulated Gastric Fluid and Simulated Intestinal Fluid to evaluate stability and solubility.
3. Safety & Tolerability Considerations
3.1 Excipient Safety: Compliance with species-specific toxicity thresholds is essential; avoid hemolytic surfactants to ensure safety.
3.2 Dosing Regimen Impact: Includes evaluation of both single-dose and repeat-dose regimens.
Summary:
Preclinical formulation screening optimizes development by delivering bioavailable, stable, and safe formulations through tailored excipient combinations and rigorous testing. This approach shortens timelines, lowers costs, and mitigates risks in translational studies.
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