Hard to Wet Surfaces (Eli Lilly-Hard to Wet Surfaces) - 11.22.16

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
In chemistry, wetting refers to spreading of a liquid over a solid material’s surface, and is a key aspect of the material’s ability to dissolve. The Hard to Wet Surfaces (Eli Lilly-Hard to Wet Surfaces) investigation studies how certain materials used in the pharmaceutical industry dissolve in water while in microgravity. Results from this investigation could help improve the design of tablets that dissolve in the body to deliver drugs, thereby improving drug design for medicines used in space and on Earth.
Science Results for Everyone
Information Pending

The following content was provided by Richard Cope, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Hard to Wet Surfaces

Principal Investigator(s)
Richard Cope, Ph.D., Eli Lilly and Company, Indianapolis, IN, United States

Alison Campbell, Ph.D., Eli Lilly and Company, Indianapolis, IN, United States
Kenneth Savin, Ph.D., Eli Lilly and Company, Indianapolis, IN, United States
Biplob Mitra, Ph.D., Eli Lilly and Company, Indianapolis, IN, United States

ZIN Technologies Incorporated, Cleveland, OH, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Earth Benefits

ISS Expedition Duration
September 2016 - February 2017

Expeditions Assigned

Previous Missions

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Experiment Description

Research Overview

  • The key goal of the Hard to Wet Surfaces (Eli Lily-Hard to Wet Surfaces) investigation is to understand how microgravity effects the dissolution of “hard to wet” solids.
  • There are two factors being studied:
    • Wettability
      • The ability of a liquid to spread over and maintain contact with a solid 
      • The effect of microgravity on wettability is unknown
    • “Float effect” 
      • Solids that are less dense float on top of the liquid, reducing surface area in contact with the liquid 
      • Because density differences are negligible in microgravity, it is hypothesized that solids dissolution will occur more quickly in microgravity 
  • Many APIs (Active Pharmaceutical Ingredients) and excipients (inert substances that serve as a vehicle for drug delivery) commonly used in manufacturing are characterized as “hard to wet” solids.
  • This poor wettability challenges the ultimate pharmaceutical effectiveness and manufacturing and development of the material.
  • Understanding how an API’s inherent wettability might impact the pharmaceutical products in vivo performance is challenging.
  • Understanding the effect of microgravity on dissolution of “hard-to-wet” solids can improve the fundamental understanding of the solid-liquid interface.
  • The solids being studied have been made into tablets since they are more easily visualized and tablet dissolution is a key area of interest for pharmaceutical companies.
  • This effort can potentially lead to better ingredient profiles for future formulation mixtures.


The Hard to Wet Surfaces (Eli Lilly-Hard to Wet Surfaces) investigation is simple, safe, and similar to the standard dissolution experiments run at Eli Lilly. Observing the performance of mini-tablet wetting and dissolution in a controlled situation in a vial helps to establish increased understanding of how a tablet/formulation performs in-vivo.
On earth, the density differences between a hard-to-wet solid/tablet and the solution can result in the solid/tablet floating on top of the solution, thereby exacerbating the dissolution problem. In microgravity, the solid/liquid density differences are negligible, and other factors controlling dissolution rate such as wettability dominate.
Key questions include how the mini-tablet behaves differently in microgravity (float vs. sink, wet out faster or slower, etc.), and will simple mixing have less impact in microgravity (will the tablet/capsule move less?). The mini tablets may also provide some insight into how they dissolve in situ, but are really being used because of the well understood surface and size in the dissolution experiments.
Mini tablets are pre-formed by pressing standard extended-release excipient (hypromellose acetate succinate, HPMCAS) into a standard size tablet. Tablets with two different densities are prepared: one with a density > 1 mg/mL and one with a density < 1mg/mL. A series of 12 vials are preloaded with a magnetic stir bar and single tablet: 6 vials with the less dense tablets, and 6 vials with the more dense tablets. Phosphate buffer is added to each vial via syringe, and the rate of dissolution visually recorded by camera. Intermittent mixing of the vials (once every 30 minutes) by moving the internal mixing magnet up and down within the vial prevents a formation of a concentration gradient, which may complicate results. The rate of dissolution is compared to the ground control samples. Additional analysis of the photographic results is also carried out to analyze the effect of microgravity on dissolution behavior.

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Space Applications
Crew members in space take the same medications as they would on Earth, but microgravity’s effects on these pharmaceuticals are largely unknown. This investigation studies microgravity’s effects on wettability, which is related to a material’s ability to dissolve. Understanding whether microgravity changes the function of common pharmaceutical materials provides new insight on drug performance and may help explain why some drugs seem to be less effective in space.

Earth Applications
Wettability can significantly impact a solid material’s solubility, which refers to a material’s ability to dissolve in liquid. While tablets and pills that don’t dissolve easily might impede a drug’s release into the body, how a product’s wettability affects its performance is not well understood. This investigation provides new understanding of the dissolution process for common pharmaceutical ingredients, which can be used to improve drug delivery for patients on Earth.

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Operational Requirements and Protocols

Two sample modules to be tested.Testing of second module to happen no earlier than one week after first sample. Filling and mixing times are to be recorded by crew. Station video capability is required for the length of the experiment. Images are to be transferred from camera to Space Station Computer (SSC), and then downlinked and processed by Johnson Space Center (JSC) digital imaging lab. Sample Modules are returned to Earth. Filling Syringes can be disposed of.

Once the hardware is on orbit, the crew member removes it from stowage. The crew sets up the camera and module such that the samples can be photographed. The setup uses the Binary Collodial Alloy Test (BCAT) hardware setup, with the HTW module replacing the BCAT module. Setup includes initial photographs to ensure proper imaging is obtained.
As there is no commanding or software, ground support for operations will consist strictly of being on console in the event that the crew member has questions regarding setup. The project will likely request video during setup for the team to monitor the crew member’s progress.
Once the photography setup is complete, the crew member removes the module from the setup to prepare the samples. The crew member injects each of the vials with the appropriate liquid, per the crew procedure. After filling all of the vials, the crew member places the module back into the photography setup and mixes the samples with a magnetic stir bar. The crew then sets and starts the camera capture rate so that the dissolving process can be documented.
The pictures taken during the test are downlinked from the Space Station Computer (SSC) after the crew transfers them from the camera. The pictures are processed by the JSC Digital Imagery Lab and accessible to the investigation team via Digital Imagery Management System (DIMS) exchange. The raw NEF files are sent to the Primary Investigators using the NOMAD Large File Transfer (LFT).

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites

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Filling Syringe components.  This will all be one integrated assembly, design still in process.

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Typical BCAT hardware setup in the JEM.  Hard to Wet Surfaces will use the same setup for testing.

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Hard to Wet Surfaces Sample Module.

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Hard to Wet Surfaces Sample Module Dimensions.

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