CR formulations provide certain advantages when compared to their IR counterparts. CR formulations can reduce peak to trough fluctuations in the plasma concentration–time profile (compared to multiple-dose administration of an IR product), hence reducing fluctuation-related side effects and/or sub-therapeutic concentrations. CR formulations can increase the exposure over time of drugs with a short elimination half-life, and can be used to target delivery into distal regions
Lapatinib price of the intestine (e.g. colon), or where there is a need for targeted delivery for the treatment of a specific disease, such has Crohn’s disease (Langer, 1990, Rubinstein, 2005 and Thombre, 2005). This can lead to an increased patient compliance. Furthermore, CR formulations can be of use in drug CT99021 development when the standard IR formulation is not an alternative due to unfavourable pharmacokinetic properties of the drug candidate (Langer, 1990, Rubinstein, 2005 and Thombre, 2005). One of the main goals when developing a CR formulation of a marketed drug is
to achieve, at least, the same exposure as the equivalent dose of their IR counterpart. In general however the relative bioavailability of a CR formulation compared to its IR counterpart is expected to be less than 100% (European Medicines Agency, 2013). Several physiological factors can influence the observed Suplatast tosilate differences in systemic exposure between IR and CR. A CR formulation is intended to release its drug content within 12–24 h, in contrast the small intestinal transit time is around 2–5 h (Davis et al., 1986, Fallingborg et al., 1989 and Yu et al., 1996). Therefore a majority of the dose should be released into distal regions of the small intestine and the colon, where the residence time in the colon is about 12–24 h (Coupe et al., 1992, Davis et al., 1986 and Fallingborg et al., 1989). The extended release may limit the absorption potential for a drug formulated as CR as, in
general, the distal regions of the intestine provide a less favourable environment for drug absorption. For instance, the reduced surface area available for absorption in the distal region of the GI tract may limit the absorption for poorly permeable compounds (Tannergren et al., 2009 and Watts and Lllum, 1997), the intestinal pH increases towards the distal portion of the intestine consequently limiting the aqueous solubility of basic compounds (Fallingborg et al., 1989). Finally, the lack of bile salts, less fluid volume in the colon, differences in the regional permeability and possible degradation by colonic microflora can also have a negative impact on the drug absorption of CR formulations (Lennernas, 2014a, Schiller et al., 2005, Sutton, 2009 and Tannergren et al., 2009).