Supercritical Precipitation General Case Studies

Case Study #1 – NanoPac® – Micronization Comparison

 

SCP NanoPac was compared to a traditional micronization technique (milling) to show the unique particle characteristics produced during the SCP process.

 

Particle Characteristics

Raw Paclitaxel

Milled Paclitaxel

Supercritical Precipitation NanoPac®

Number Mean
(µm)
1.16 0.89 – 23% 0.82

– 29%

Surface Area
(m2/g)
10.5 15.0 + 42% 39.0

+ 271%

Dissolution
(30 min)
18% 32% + 77% 42%

+ 133%

 


 

NanoPac® – Dissolution

 


 

Residual solvents in NanoPac are virtually eliminated when micronized with CritiTech’s Supercritical Precipitation Technology

Solvent

Raw Paclitaxel (ppm)

Supercritical Precipitation NanoPac® (ppm)

% Solvent Reduction

Methanol Non-Detectable Less than LLQ NA
Acetone* 1,156 84.1

– 93%

Ethyl Acetate Non-Detectable Non-Detectable NA
Heptane 1,799 Non-Detectable

– 100%

*In addition to being present in the raw material, acetone is a process solvent and is still removed to a low level.

 


 

Particle Size Stability

 

Phase I Clinical Trial Material Stability Data

  • 6 month accelerated conditions
  • 24 month long-term conditions
  • No increase in PSD observed

 

Variability is well within the method’s acceptable range.

Case Study #2 – CT-0401 – Particle Size Analysis

 

Where NanoPac was extremely hydrophobic, CT-0401 is extremely hydrophilic and was optimized to immediate release using SCP technology.

Particle Characteristics

Raw
CT-0401

Milled
CT-0401

Supercritical Precipitation CT-0401

Number Mean
(µm)
1.16 0.85

-0.26%

0.20

-82.5%

Surface Area
(m2/g)
5.21 14.7

+182%

60.3

+1,057%

Dissolution
(60 s)
20.1% 26.4%

+31.3%

98.7%

+391%

 

CT-0401 – Dissolution

 

CT-0401 – SEM Micrographs

Raw CT-0401
SCP CT-0401

 

 

Case Study #3 – Insulin Initial Feasibility Study Results

 

Large molecules can be enabled with SCP as well. Initial feasibility study results for insulin are shown below.

Raw Material Insulin

Supercritical Precipitation Insulin

% Change from raw

Number Mean 4.37

0.72

-83%
D-10 0.57

0.52

-9%
D-90 12.15

0.98

-92%
Volume Mean 10.36

4.02

-61%
D-10 1.96

1.52

-23%
D-90 25.12

9.91

-61%

All numbers reported in micrometers

Results based on Initial Feasibility Study. Results do not indicate an attempt to optimize.

 

Case Study #4 – BSA Initial Feasibility Study Results

 

Large molecules can be enabled with SCP as well.  Initial feasibility study results for  bovine serum albumin are shown below.

Raw Material BSA

Supercritical Precipitation BSA

% Change from raw

Number Mean 1.91

0.83

-57%
Volume Mean 13.9

4.23

-70%

All numbers reported in micrometers.

Results based on Initial Feasibility Study.  Results do not indicate an attempt to optimize.

Case Study #5 – Acetaminophen

 

Raw
SPC

 

 

Raw

SCP

% Change

Volume mean (µm) 22.427 6.059 -73 %
D10 (µm) 7.335 3.083 -58 %
D90 (µm) 55.995 10.766 -81 %