Industry Watch

APRIL 2018

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.. **

MARCH 2018

Cell-based flu vaccine 20% more effective than
egg-based vaccine this flu season, says FDA chief

Flucelvax, the only influenza vaccine developed in the U.S. with cell cultures, may have been 20 percent more effective than standard vaccines developed in eggs this flu season, according to comments made by FDA Commissioner Scott Gottlieb, MD, cited by STAT.

Here are five things to know.

  1. Gottlieb first mentioned the 20 percent figure during a March 8 congressional subcommittee hearing on oversights and investigations regarding the severity of this year’s flu season and the estimated poor performance of the seasonal flu vaccine. The FDA chief confirmed the number in an interview with STAT after the hearing.

“The data aren’t final yet, but I’m comfortable saying that I think it’s going to be about 20 percent improved efficacy for the cell-based vaccine relative to the egg-based vaccines,” Dr. Gottlieb told STAT.

  1. The estimate is derived from FDA analysts who have been examining the medical records of 16 million Medicare beneficiaries to determine whether hospitalization rates vary based upon vaccine type and dose.
  2. Though the FDA analysis can’t break down the data by flu virus type, the dominance of the H3N2strain is likely a key reason the cell-culture-based vaccination may have outperformed the egg-based vaccine.
  3. When vaccines are grown in hen’s eggs, they have to adapt, which can sometimes result in mutations. This seems to be especially true with the H3N2 component. Many experts suspect vaccines grown in cell cultures are less likely to acquire mutations, which may contribute to improved efficacy, according to STAT.
  4. Gottlieb told the congressional committee it was too soon to say whether vaccines grown in cell culture are definitely more effective, arguing the vaccine developed in hen’s eggs actually display more protection against flu in some years. Dr. Gottlieb said more research is needed to know for certain, but if studies confirm the cell-culture vaccine performs better against H3N2, the FDA could “make a recommendation that the H3N2 component has to be produced in a cell-based process and the others can be produced in eggs.”
** This article was written by Brian Zimmerman from Beckers Hospital Review. **


Medicine manufacturers ditch batch
methods for continuous production

The widespread trend to move away from batch producing medicine is driving the continuous processing technology market to double in size. Classically, pharma has manufactured medicines in stages, batch by batch ­– which allowed firms to responsively flex output in accordance to demand.

However, recent trends have seen larger pharma firms switch to continuous processing to pick up improvements in productivity. Production steps that are carried out sequentially in a classic batch process are integrated in a continuous process. Active ingredients are produced in compact, closed units, leveraging opportunities for automation and fewer manual interventions.

This method allows manufacturing units to be constantly utilized, so fluctuations in production are reduced and there are opportunities to perform reactions that cannot be run under batch processing.

Continuous manufacturing technology for pharmaceuticals provides superior development speeds and higher process safety when employing hazardous chemistries.

Market growth for this technology  

The continuous manufacturing technology market which was worth US$1.74bn in 2016 is expected to attain a value of US$3.693bn in 2025, according to Transparency Market Research.

The dominant region, Europe, accounted for a 35% share in 2016. This is mainly due to the early availability of advanced technologies and greater number of technology providers across the region.

Biologics driving the market

The key application segment of this technology is biologic medicine, holding around 35% of the market, followed by active pharmaceutical ingredients.

The need for more speed to the market in biomanufacturing is fueling the acceptance and implementation of single use systems in manufacturing lines, despite their complications.

The use of single-use bioprocessing equipment is making product manufacture increasingly efficient and frequently less costly, particularly for early stages of R&D.

Some have fully committed to the shift from stainless steel equipment, with the ambition to have fully disposable manufacturing lines one day.

** This article was written by Chanice Henry from Pharma IQ. **