Sanofi system

TABLE 28.2 An Example of a Capsule Eormnlation of Naproxen as Generated by the Sanofi System... 

Training aid. All systems have been used to provide training for both novice and experienced formulators. The developers of the SOLTAN system have stated that experienced formulators use their expert systems to expose themselves to new raw material combinations with which they are not familiar. Bateman et al. suggested the documentation used in the development of the Sanofi system be adapted to train novice formulators. 

Head of Metabolism/In vitro Systems Aventis Pharma Deutschland GmbH A company of the Sanofi-Aventis Group Global Metabolism Pharmacokinetics Industriepark Hoechst, Building G876 65926 Frankfurt Germany... 

Personnel at the Sanofi Research Division of Philadelphia recently developed an expert system for the formulation of hard gelatin capsules based on specific preformulation data of the active ingredient. Using Formulogic, the system generates one first-pass clinical capsule formulation with as many subsequent... 

An alternative to the pulmonary route of administration is the nasal route, which is less demanding when it comes to formulation. With regard to, for example, particle size and simpler device development (5,90), examples are Minirin (Ferring), desmopression, and Suprecur (Sanofi-Aventis), buserelin, which are proteins formulated as nasal drops or nasal spray, where bioavailabdities of approximately 3% to 10% can be obtained. The formulations are just protein dissolved in purified water containing preservatives chlorbutanol and benzalkonium chloride (91,92). However, more advanced delivery systems are also used, for example, chitosan formulations where bioavailabihties of 14% to 15% compared to subcutaneous administration can be obtained (90). A recent review by nium (2007) gives more details on nanoparticulate systems used for nasal delivery (93) or consult Costantino et al. (2007) on the physiochemical and therapeutic aspects (5). 

Kahn, Michael, Department of Pathobiology, Box 35 72 38, University of Washington, Seattle, WA 98195, USA Kan, Jean-Paul, Sanofi-Synthelabo Recherche, Departement Systeme Nerveux Central, 371 Rue du Professeur J. Blayac, 34082 Montpellier-Cedex 04, France... 

Recently, further improved yeast systems were reported [395]. These included, among others, CYP71AV1 and an alcohol dehydrogenase and aldehyde dehydrogenase (Adhl and AldHl) from A. annua for the respective conversion of artemisinic alcohol and aldehyde [396]. Titers of artemisinic acid of up to 25 g L were achieved in fermentation experiments and could be further converted to artemisinin by means of classical chemistry or photochemistry [395]. This semisynthetic process is now used at Sanofi for the industrial production of artemisinin. 

Very recently, a further improved yeast system was reported, which induded, among other optimizations and besides CYP71AV1, an alcohol and aldehyde [119] dehydrogenases (ADHl and ALDHl) from A. annua for artemisinic alcohol and aldehyde conversion, respectively (Scheme 5.28). Artemisinic acid titers of up to 25gl i were achieved in fermentation set-up [120]. A process based on the developed artemisinic acid-producing yeast strain is now used for the industrial production of artemisinin at Sanofi (www.rsc.org/chemistryworld/2013/04/sanqfi-launches-malaria-drug-production). 

This topic will be only briefly highlighted here as synthetic biology (SB) is the topic of the previous chapter (Chapter 14) in this edition. Amyris and Sanofi have commercialised a semi-synthetic artemisinic acid process to enable the cost-effective production of artemisinin, a key API for antimalarial combination therapies, by inserting the artemisininic acid pathway into S. cerevisiae For discovery research, SB is starting to provide exciting new pathways into unique and novel secondary metabolites as possible new drugs or lead compounds for semi-synthetics. Walker et al. have demonstrated the ability of two polyketide synthase systems to accept fluoroacetate in place of acetate leading to the production of a number of novel... 

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