High Throughput Screening of Excipient - A & C

High Throughput Screening of Excipient

The Tecan-robotic system is one of the latest developments in the pharmaceutical industry, which facilitates the drug formulation of excipients through its advanced technologies to achieve efficiency.

Compounds should be categorized according to toxicology, bioavailability, pharmacokinetics (PK) and pharmacology profiles at the beginning of the drug development stage. The compound should be dissolved in solution at high concentration levels to achieve therapeutic outcome. The main obstacle involved in drug development is low aqueous solubility.

Current methodologies

Chemical modifications, physical modifications and solvent modifications techniques should be used to facilitate solubility levels. These techniques will be determined by the compounds chemicals propertied, the physical state of the formulation and route of administration. Solvent modifications and carrier systems are used frequently during the formation of liquid formulations as they affect the solvation components of the drugs only instead of the solid-state properties.

Excipients should be utilized to increase the solubility of poorly soluble compounds. The variety of excipients depends on several testing trials using several research orientated methodologies to decide on the preferred excipients. This procedure should be taken into consideration, as it is expensive, time consuming and requires large amounts of material.

Developing a high-throughput screening method

The introduction of a highly throughput screening technique should allow pharmaceuticals to address the difficulties in choosing one or more excipients. A methodology would be formed to reduce the amounts of API used, to ensure that it is commercially viable and effective to achieve results. Creating a platform is required to provide information about a compound’s chemical stability for different solvents and excipients to support decision making.

Numerous experiments were conducted to determine the methodology. The screening list is mainly focused on excipients with different solubilisation mechanisms, which consists of water-soluble organic solvents, non-ionic surfactants, water-insoluble lipids, organic liquids/semi-solids, cyclodextrins, and phospholipids.

The drug delivery system will be determined by the type of excipients used. Orally administered compounds will involve various excipients than injectables. The final concentration of the selected excipients is required to ensure that (GRAS) list of recommended concentrations are safe. The identification of the correct excipient in its individual correct maximum concentration is important, especially for parenteral formulations, because doses that are too high can cause pain, hemolysis, or inflammation.

A new methodology

The high-throughput screening platform involves identifying the solubilization capacity of each excipient for a compound. This in turn should reduce shorten the timeframe involved to identify an excipient by allowing multiple tests to be conducted together.

Six commercially available drugs which feature diverse chemical properties were used to develop this method. 30 excipients were dispensed in 96 well-plates via a fully automated robotic system (Tecan) were used to conduct testing. Three plates were scrutinised to determine each compound. The plate was shaken for 48 hours to achieve equilibrium. The results were compared with solubility measurements performed using a manual shake flask method where 15 mg of powder and 2 mL of excipient were added. The samples were again shaken for 48 hours, centrifuged, and then analyzed by high-performance liquid chromatography (HPLC) to determine solubility and detect any degradation. The measurements were performed in triplicates.


Results showed that some excipients offer better solubilization capacity than others. Results confirmed that pH-dependent solubility is a beneficial method for ionisable compounds, especially if it can be combined with another solubilizing excipient. The contribution of solid-state barrier to solubilizing a compound appears to be more pronounced at a cut-off level of solid-state properties. Prior to the cut-off point, the solubilization of the compound was more compound specific, which generates requirements to test on a larger set of excipients.

The high-throughput screening technique results proved that using this method for solubility is not numerically different than the previous achieved when using a manual approach. This method can deliver data on the solubilization capacity of compounds in various excipients, while also offering insight into stability.

The high-throughput screening method addresses the issues referring to the manual approaches by being more cost-effective and economical in the use of materials, while efforts are made to achieve these results in three to five days per for each set of compounds.


The development of the platform has generated new opportunities for reduced drug development timeframe and costs. Also, the information gathered during the screening will be beneficial in the advanced stages of formulation development. Excipients will be chosen according to the API’s unique molecular properties, which provides a aster process. This should transform the way developers assess the solubility of any compound, which helps to increase the probability of successful formulation.
By Amjad Alhalaweh of Pharmaceutical Technology..

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