Active pharmaceutical ingredients strategies

FIGURE 3.7 The strategy proposed in Sokoliefi et al. [35] for basic active pharmaceutical ingredients. PVA Polyvinylalcohol Injection in step 2a 50 mbar, 5 s. (Reprinted from Sokoliefi, T., KdUer, G. Electrophoresis 2005, 26, 2330-2341. With permission from Wiley VCH.)... 

Due to the brick-and-mortar structure of the stratum corneum, the skin is a difficult layer to permeate across for most active pharmaceutical ingredients. Because of this diffusional barrier, new strategies have been developed to allow compounds to better penetrate the stratum corneum [28], These strategies can be defined as either chemical or physical approaches to disrupting the barrier function of the skin. 

Gavin, RR et al. Quality evaluation strategy for multi-sourced active pharmaceutical ingredient (API) starting materials. J. Pharm. Biomed. 2006, 41, 1251-1259. 

Whilst salts of active pharmaceutical ingredients (APIs) are restricted to (acceptable) counter-ions, the potentially available pharmaceutical space around co-crystals is much broader. Indeed the list of co-formers is long and the API (even if un-ionized) can theoretically be co-crystallized either with acidic, basic or neutral co-formers in multiple combinations thanks to a more adaptive stoichiometry. As one can easily foresee the type of advantageous properties for a solid form that may be accessed in such enlarged space, it is of paramount importance for the pharmaceutical stakeholder to design an efficient strategy for exploring it. 

Figure 9.4 Depiction of strategy used during e.g. lead optimization (API = active pharmaceutical ingredient).

In addition, the definition of a multicomponent domino process would discount any example in which the reaction conditions are altered during the process, the result of which is that some useful reactions have not been discussed. We have decided to briefly detail a recent strategy, involving uninterrupted sequences of one-pot organocatalytic reactions, used to streamline the preparation of active pharmaceutical ingredients, since this approach nicely testifies to the synthetic power of organocatalytic MCRs (Section 42.2.4). 

To take maximum advantage of biocatal)mc ketone reductions for the synthesis of active pharmaceutical ingredients, it is essential to introduce the strategy into the synthetic process design early so that as the product progresses through the clinical pipeline, the enzymatic step will be there from the start. 

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