Understanding a Compound’s Physical Properties
Averica helps late stage lead development teams understand the physiochemical properties of their lead compound.
The solubility of compounds in vivo is determined by their physical properties. Solubility affects:
- Pharmacokinetic behavior
- Membrane permeability
- Drug distribution in the body
- Drug Development timelines and decision-making
- Data Quality
Averica helps late stage lead development teams understand the physico-chemical properties of their lead compounds. Our assay panel includes several components designed to study compound properties relevant to bioavailability. Our goal is to understand the most soluble and stable environment for your compound.
Averica uses HPLC and multiple detection capabilities as the core technology for these studies. Unlike other analytical protocols, HPLC assays can work with impure and degrading compounds. Using this approach we gain critical information at early stages of development that inform decision-making throughout preclinical study.
Assessing solubility is important because it can correlate with a compound’s absorption and its bioavailability. Drug compounds need to have a certain solubility to enter into the systemic circulation. Low soluble compounds may incur costly formulation expenses or enhancement of the compound solubility. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics.
Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics.
Our approach to thermodynamic solubility method uses an aqueous solvent added to solid compound. Excess solid is present and the solution is shaken for 24 hours. The saturated solution is filtered and the API quantified using HPLC with UV, MS, ELSD, or CAD detection as appropriate.
Kinetic solubility methods are similar to thermodynamic but with several sampling times in the first few hours of mixing, Our kinetic solubility is flexible and the protocol can vary according to your needs, by changing time points, incubation time, and buffers
To understand variables affecting oral absorption of a drug, these methods can be carried out using other aqueous mimicking the gastrointestinal tract and bloodstream, such as PBS, FaSSIF, FeSSIF, and SGF.
Parenteral dosing requires optimum solubility in a water-soluble liquid vehicle to quickly disperse a drug into the bloodstream. To better define an appropriate formulation, Averica screens a panel of common vehicles for parenteral dosing of poorly soluble drugs, using methods similar to those used for aqueous and buffer solubility. Often we can determine an optimal dosing vehicle and volume appropriate for preclinical and early clinical work.
Predictive assays or calculations are established approaches to understanding a drug’s potential bioavailability. A key physical property to understanding this is polar surface area, sometimes discussed as hydrogen bond availability.
Averica was the first contract research lab to offer the EPSA assay, an extension of our deep expertise in SFC technologies and methods.
A unique advantage of using gradient HPLC methods for compound study is the dispersion of the drug peak from impurities and degradants. This allows us to study compounds at earlier development stages, and offers ancillary benefits in cases where the drug degrades in solution under certain conditions. By combining observations from solubility experiments with a standard panel of stress or forced degradation conditions; we can identify key stress conditions, kinetics that affect dosing protocols, and aspects of degradation chemistry.
Lipophilicity is one of the key determinants of the pharmacokinetic action of drugs.
The shake-flask method of measuring log D at any pH is used, partitioning the compound in a buffer octanol mixture. The amount of material is quantitated by HPLC with UV, MS, ELSD, or CAD detection as appropriate. pH-dependent lipophilicity measurements, combined with PSA and pH-dependent solubility, offer a wealth of information about how a compound will behave in vivo.
The Averica Advantage
Averica scientists understand both the requirements of the method and the requirements of the compound. We define and evaluate key method parameters and identify critical quality attributes. Methods we develop are fit for purpose, ranged properly, and can be quickly validated.
- Robust methods for fast method transfer
- Emphasis on definition: making sure that a chromatographic method meets your needs and serves your development effort
- Depth of experience with method development suited to challenging compounds and projects
Custom assay design and physical properties testing
Small scale assay development for when material is limited
- SFC – Analytical
- HPLC – Analytical
- CAD Detection
- Accurate Mass MS
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