Features of CritiTech's Supercritical Precipitation Technology

  • Near ambient processing temperatures
  • Water and oxygen free processing environment
  • API alone or with excipients
  • Amorphous, crystalline or co-crystalline materials (drug dependent)
  • Non-potent API
  • Non-cytotoxic API
  • Potent API
  • Cytotoxic API (dedicated room, equipment, and handling system)
  • Cytotoxic and non-cytotoxic cGMP materials produced in separate facilities
  • Continuous processing
  • Proof of Concept (POC) through Phase II clinical production
  • Processing in closed system with complete recovery of solvents and CO2

CritiTech’s nanoparticulate drug development and manufacturing process provides the ability to micronize a wide variety of small-molecule and biotechnology drugs using its proprietary Supercritical Precipitation Technology. The technology consistently produces particles with a mean particle size in the range of 500 nanometers to 5 microns and a narrow distribution around that mean.  The technology also includes a method to harvest these particles on a continuous basis.  As a result of working with dozens of drugs, CritiTech’s scientists have deep experience and expertise micronizing drugs. Supercritical Precipitation is an advanced and innovative approach to the production of nanoparticulate pharmaceuticals. The patented processing and compound-harvesting technologies that underpin CritiTech’s drug micronization capabilities are efficient, safe, and friendly to the environment.

Improving the likelihood of Development Success for New Compounds and Novel Agents

Water Solubility Problem

It is estimated that 70% – 90% of all new chemical entities have water-solubility problems that make these compounds unusable as drugs. To address this problem, companies often employ complex strategies to increase water solubility, such as using excipients, co-solvents (alcohol or detergents), prodrug formulations, or combining drugs with a carrier molecule. However, in many cases a reduction in particle size may be the appropriate means. The appeal of improving aqueous solubility via reduction of the size of the drug particle lies in its simplicity. Particle size reduction results in increasing the effective surface area of the compound, thus enhancing its dissolution rate. However, most micronization technologies are unable to reduce particle size to less than 1 micron and include a number of other issues as well. CritiTech’s Supercritical Precipitation Technology overcomes many of the limitations of other drug micronization techniques.

Opportunities to Enhance the Value of Currently Marketed Drugs

A growing number of pharmaceutical companies are now applying the technologies of drug-development/delivery companies to enhance the convenience, safety, and efficacy of currently marketed products. When successful, the approach of adding value to established products can yield substantial commercial success.

Supercritical Precipitation Technology is an Effective Life Cycle Management Strategy for Existing Drugs

There are hundreds of case studies showing that revenues from a drug can decrease by 70% upon patent expiration. Application of CritiTech’s Supercritical Precipitation Technology to existing compounds can potentially create a reformulated and improved 2nd generation drug that would be eligible for an extended period of exclusivity. CritiTech can help enable pharmaceutical companies to cost-effectively introduce a 2nd generation product with improved patient benefits due to the following:

  • Improved pharmacokinetics
    • Increased efficacy
    • Reduced adverse effects
  • Improved dosing regimen
  • New routes of administration

CritiTech’s Supercritical Precipitation Technology should be in your “toolbox” of options to improve pharmacokinetics of challenging drugs that you are working with.

Manufacturing Advantages of CritiTech's Supercritical Precipitation Technology

Benefits of CritiTech’s Supercritical Precipitation Technology

  • Unique particle structures ranging from 250 nanometers to 10 microns
  • Narrow particle distribution range
  • Exponential increase in surface area and dissolution rate
  • Bioavailability enhancement of poorly soluble drugs (BCS II and IV)
  • Improved pharmacokinetics
  • Particles engineered for multiple routes of delivery
  • Can be utilized as a LCM tool for a reformulated and improved 2nd generation product
  • Virtual elimination of residual solvents (no secondary drying required)
  • System ideally suited for oxygen and water sensitive compounds
  • Does not induce electrostatic charges into particles
  • Scalable and reproducible
  • Low moisture content

Environmental Advantages

A final advantage of CritiTech’s Supercritical Precipitation Technology is in the environmentally friendly nature of the processes. Organic solvents traditionally used in the industry may be hazardous to the environment or toxic to humans and animals. Because of the closed loop nature of CritiTech’s micronization process, the release of harmful substances to the atmosphere is substantially reduced, if not totally eliminated.

Case Study Results

CT-0610

Unprocessed

Processed

Number Distribution
(micrometers)
Volume Distribution
(micrometers)
Unprocessed Processed Unprocessed Processed
D10 0.48 0.40 4.94 0.49
Mean 0.83 0.55 8.46 0.74
D90 1.46 0.77 14.41 1.25

CT-0376

Unprocessed

Processed

Number Distribution
(micrometers)
Volume Distribution
(micrometers)
Unprocessed Processed Unprocessed Processed
D10 1.81 0.61 10.44 0.94
Mean 6.10 0.94 15.29 1.99
D90 16.72 1.67 20.37 3.78

Acetaminophen

Unprocessed

Processed

Number Distribution
(micrometers)
Volume Distribution
(micrometers)
Unprocessed Processed Unprocessed Processed
D10 0.74 0.60 8.9 2.2
Mean 5.0 1.7 22.3 4.8
D90 11.2 3.5 42.1 7.5