Development of CO2-Based Cryospraying Technologies for Biopharmaceutical Applications
Project Acronym: CRYOPHARM
Project partially funded by ERDF - POR Piemonte 2007-2013 Activity I.1.2 Poli di innovazione.; through the Polo BioPmed.
The project partnership integrated expertise in life science and pharmaceutical R&D sectors. Expertise included physical pharmacy, drug preformulation and formulation development, process technology development, human and animal pharmacology and toxicology, pharmacokinetics, veterinary medicine and bioinformatics.
Cryopharm Project explored the applicability of Variosol®, a novel cryospraying technology based on dense CO2, to the biopharmaceutical sector (link to Variosol page). The technology , originated by by Messer Group, is licensed to SiTec for development and applications in the pharma-biotech areas. Variosol®- based equipment can produce drug-containing microspheres or micronized powders, with improved properties for oral, topical, inhalatory delivery, whereby problems of poor drug bioavailability, high toxicity or patient compliance of drugs are addressed. Such problems are often caused by scarce solubility, instability, or minimal drug permeability (see also www.sitec-pharmabio.com).
After initial drug and formulation screening, Cryopharm Project focused on the design and early development of improved microparticulate systems (Figure 1 - Figure 2) containing Celecoxib, a cyclooxygenase-2 inhibitor anti-inflammatory drug, currently used in treatment of rheumatoid arthritis, and as preventive treatment for precancerous adenomas in colon Celecoxib is a BCS Class II drug (poorly soluble, highly absorbable) and its pharmacokinetics performance is affected by its poor solubility and slow dissolution rate which limits its intestinal absorption. Furthermore, its use is limited by its cardiovascular toxicity. Applying Variosol® technology, we aimed at developing formulated microspheres, whereby celecoxib dissolution profile is modified to improve its oral absorption, and possibly increasing drug bioavailability.
CRYOPHARM project covered several aspects in early drug development path: from the selection of formulation compositions and preparation of micronized systems (Figure 3 - Figure 4) by Variosol® technology, to evaluation of chemical stability and biopharmaceutical properties. A PK/PD investigational study was performed on three prototype microsphere powder formulations, selected on the basis of their in-vitro drug release performance, compared to the commercially available product (Celebrex®).
The results of the CRYOPHARM Feasibility project confirm the technological potential of Variosol® cryospraying process, and its capability to produce micronized systems with improved biopharmaceutical properties.
In-vitro and in-vivo data demonstrated the potential therapeutic relevance of the micronized formulations generated with the technology. The successful conclusion of CRYOPHARM project presented an opportunity for generation of new IP, and sets the bases for the transition from lab to pilot scale operations, compliant with cGMPs.
Furthermore, CRYOPHARM project created opportunities for further collaborations within the partnership, and expanded the partners networks to include other R&D institutions and Companies.