Details
Project title: Experimental development of cryospraying technologies based on supercritical CO2 for biopharmaceutical applications
Acronym: Cryopharm
Coordinator: Hana Danan, SiTec Consulting
TP/LS membership: CMDI/HMNA1
subjects involved: Sitec Consulting, Dirivet, Aethia, University of Turin, University of Eastern Piedmont
Status: Completed
Abstract: The Cryopharm project explored the applicability in the biopharmaceutical sector of an innovative cryospraying technology, Variosol , based on dense CO2. Variosol has been licensed to SiTec for pharma-biotech applications. The technology allows the preparation of active ingredients formulated in micronized powders or microspheres, with optimal absorption characteristics, size and chemical-physical stability.
Micro particles can be further formulated in specific pharmaceutical forms for oral, inhalation or local therapies. Following a first screening of active ingredients, microspheres containing Celecoxib (COX-2 inhibitor, with poor solubility and undesirable effects of cardiovascular toxicity) were developed to improve the dissolution profile of the drug, facilitate oral absorption, and possibly reduce cardiovascular side effects
Contact for further information:
Name: Hana Danan
Organization: Sitec Consulting di Hana Danan
Address: Via Ribes 5 , 10010 Colleretto Giacosa (TO)
Phone: +39 349 3283430
E-mail: h.danan@sitec-consult.com
Web: www.sitec-consult.com
THE ACTIVITIES CARRIED OUT
To achieve the project objectives, the partners completed the following activities:
- Identified the active ingredient and evaluated where the application of cryospraying technology can be of strategic advantage. Celecoxib has been identified as a significant “model drug”.
- Identified, on the basis of literature, the critical aspects of the active substance that limit its therapeutic value.
- Appropriate analytical and bio-analytical methods have been developed for the quantitative determination of Celecoxib in samples from stability, dissolution, in-vivo pharmacokinetics and ex-vivo pharmacodynamics studies.
- Preformulation studies performed to assess the compatibility of Celecoxib with the selected excipients, suitable for cryospraying processes.
- Completed formulation studies and process development using the apparatus Variosol Pharmalab.
- Evaluated the feasibility and adequacy of mathematical models for the definition and control of critical process and/ or formulation parameters.
- Completed preliminary studies of pharmacokinetics/ pharmacodynamics on ex-vivo models and in vivo animal models.
- Analyzed (also statistically) the results of in-vivo and ex-vivo studies and demonstrated the effect of new formulations on AUC levels and plasma levels of the drug, in comparison with the product on the market (Celebrex).
RESULTS ACHIEVED AND EXPLOITATION OF THE RESULTS
The CRYOPHARM project covered several aspects in the “early-stage” development phase: from the selection of compositions and formulation and preparation of micronized systems with Variosol[technology, the assessment of their chemical stability and biopharmaceutical properties. A PK/PD experimental study was carried out on three prototype formulations of powdered microspheres, selected on the basis of their in vitro release profiles, compared to the commercially available product (Celebrex).
The most promising prototype formulations have shown possible advantages over the product currently on the market, e.g. :
- a bioavailability of active ingredient higher than almost 40% to Celebrex – a lower blood peak (about 15-20%): note that high levels of Cmax are often associated with the (cardiovascular) side effects of COX-2 inhibitors
- plasma levels are higher between 3 and 24 hours after administration than Celebrex.
- An anti-inflammatory effect (inhibition of prostaglandins PGE2) at least equal to Celebrex, By keeping the PGE2 at low and constant levels for 24 hours after single administrationProject results allowed the partners to define a path for the exploitation of the results:
- Consolidation of synergies between partners, and creation of further collaborations with other institutions and R&D companies
- Consolidation of technological potential and “awareness” of technology in the pharma-biotech sector
- Completion of a first “preclinical package”, based on innovative technology and a model drug of great therapeutic interest and market value, and with a potential for transfer into clinical development
- Generation of new intellectual property: currently under evaluation compared to Prior art
PROJECT NUMBERS
- Other Private Partners: Aethia Power Computing Srl, DiriVet SaS
- Other Public Partners: University of Turin, University of Eastern Piedmont “A. Avogadro”
- Total number of partners: 5
- Number of dependent researchers (fixed and indefinite time and cocopro) involved: 8
- Duration in months: 12
- Total budget: € 88.500,00
- Funding € 48.370,00
- Number of scientific publications: 3 in preparation, data licensing pending
- Number of presentations at conferences and seminars: 3
- Number of patents filed: 1 patent assessment in progress
- Number of permanent and temporary jobs created: 1
- Number of jobs maintained at the end of the project: 8
- Number of public researchers involved: 5
