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Pharmaceutical Technology |
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SEPAREX pharmaceutical technology is committed to transform ideas into reliable and cost-effective technologies for the manufacturing of drug substances and differentiated drug products that show improved clinical performances over existing formulations.
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With an extensive know-how in SCF technology and also in either innovative or established “non-supercritical” pharmaceutical technologies, our team is fully dedicated to the development of scalable API manufacturing and formulation techniques that can be operated in compliance with the Good Manufacturing Practices. |
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We substantially invest in equipment, gradually upgrade our facilities and quality system to pharmaceutical standards and work in close collaboration with the Separex Equipment team so as to secure the development of our Supercritical Technology Platform into state-of-the-art pharmaceutical technologies. |
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Challenges |
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Pharmaceutical product development and manufacturing is in serious need of technical upgrading particularly as regards :
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- Biopharmaceutical challenges: administration of poorly soluble, high-potent and specific APIs, specific-site and/or sustained release delivery, delivery of challenging protein therapeutics…
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- Market challenges: time to market for new drugs, life-cycle management of soon off-patent drug.
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Most of these challenges are related to the engineering of stable drug particles or drug-loaded particles exhibiting a strictly controlled dosage, solid state morphology and particle size distribution. |
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Challenges - API Manufacturing |
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- Particle Engineering of neat Active Pharmaceutical Ingredients |
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Particle engineering is of crucial relevance for the production of oral forms of poorly soluble drugs, as proven by the micronized and more recently nanosized formulations which have been marketed. A fine control of size and polymorphism (crystal engineering) is also required for the development of inhalable drugs, combination therapies and challenging drugs with a narrow therapeutic index. |
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Nevertheless, tailored and differentiated drug particles with low solvent residues are often difficult to produce in a reliable way by currently available techniques such as crystallization or milling, thus hindering the development of new chemical entities and enhanced formulations of off-patent drugs. |
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- Stability of Biopharmaceuticals |
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The development of biotechnology medicines has highlighted issues such as stability during manufacturing operations and long-term storage. These quality and safety issues are basically related to the poor stability of proteins that can be altered by pH, shear stress, surface interactions and temperature leading to potentially immunogenic protein modifications. |
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There is thus a strong need to develop bulk and final product manufacturing techniques that reduce or prevent denaturation, aggregation and other structural changes of biologics so as to quickly get challenging biopharmaceuticals to the market. |
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Challenge - Drug Delivery |
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Conventional drug delivery approaches are often not suitable for emerging drugs such as poorly soluble new chemical entities or fragile macromolecules. Additionaly, differentiated drug delivery systems make it possible to maintain a competitive position for existing drugs for as long as possible through the development of controlled-release formulations or alternative routes of
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administration. |
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Accordingly, the design of formulation technologies and drug delivery systems leading to enhanced efficacy, tolerance and compliance is taking a predominant role in the pharmaceutical industry to improve drug therapy:
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· Long-acting injectable formulations of small drugs and macromolecules. |
· Oral bioavailability enhancement of poorly-soluble drugs. |
· Reduction of pharmacokinetics variability and food interactions. |
· Nasal or pulmonary drug delivery. |
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SCF Technology Platform |
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The development of pharmaceutical products cannot rely on a unique and universal technical approach, our technology offer is thus designed as a multi-process portfolio which make it possible to solve various particle engineering and drug formulation challenges.
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Our proprietary SCF Technology Platform is made up of either established SCF techniques and combination technologies taking advantage of the unique properties of SCF combined with pharmaceutical unit operations routinely used for the manufacturing of drug products and drug substances. |
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API Manufacturing |
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Our Technology Platform can be applied to various drug processing and formulation challenges. Some projects are briefly presented below. |
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- Drying of API from difficult to process organic solutions |
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Using a supercritical anti-solvent process, dry powders of polysaccharides have been produced starting from a solution in a very high boiling point organic solvent (N-methylpyrrolidone). The process has been successfully scaled-up to kg-batches with a particle size distribution and residual solvent amount compliant with our |
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customer's specifications. |
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This approach has also been implemented for one-pot purification and drying of fragile synthesis intermediates which are usually isolated by tedious and multi-step liquid antisolvent techniques. |
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- Nanosized formulation of a poorly soluble API |
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This poorly-soluble API belongs to the class II of the Biopharmaceutic Classification System, and hence its bioavailability can be enhanced by increasing its dissolution rate through particle size reduction. A proprietary process has been carried out to produce highly processable dry powders made of |
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submicronic API particles trapped onto excipient granules. |
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Our customer has easily turned this semi-finished product into enhanced dissolution rate tablets using standard tablet manufacturing unit operations.
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- Crystal engineering |
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This drug can be micronized by milling techniques to the required size, but the milling process results in poorly crystalline particles, with a high content of amorphous phase jeopardizing the drug stability in the final dosage form and leading to erratic bioavailability. A process pertaining to the Separex Technology Platform has made it |
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possible to produce micron-sized and crystalline drug particles. |
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In addition to its ability to tune the solid state morphology of APIs from amorphous to crystalline particles, our SCF Technology Platform has also been has been implemented to produce challenging polymorphs. |
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- Drying and stabilization of fragile proteins
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Protein-loaded solid powder formulations have been produced using peculiar drying technologies pertaining to the Separex SCF Technology Platform which are operated under mild temperature conditions and can process a wide range of stabilizing excipients.
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In-process stability and required shelf-life of the final dosage form have been confirmed |
by our Biotech customers. |
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Drug Delivery Systems |
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Our proprietary Technology Platform allows our customers to solve difficult drug delivery and life cycle management challenges through the development of various innovative formulations, from amorphous solid dispersions or cyclodextrin inclusion complexes for poorly soluble drugs to sustained-release depot polymer or lipid |
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formulations of fragile biopharmaceuticals. |
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R&D |
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| SEPAREX Pharmaceutical Technology owns its entire development tool, including various supercritical units from laboratory to pilot/industrial scale designed for a wide range of processes pertaining to our SCF Technology Platform |
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cGMP Clean Room |
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One of our clean room is dedicated to the development of APIs for use in clinical studies. This clean room is operated under ISO 7 environment (grade C, class 10 000) and includes two laminar flux hoods for critical upstream and downstream operations. |
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Our quality system and equipment are gradually upgraded to operate a broad range of supercritical particle engineering processes in compliance with the Good Manufacturing Practices for Active Substances. |
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