Issue link: https://www.e-digitaleditions.com/i/947832
24 March 2018 Tablets & Capsules An API is considered "highly soluble" when the highest clinical dose strength will dissolve in 250 milliliters or less of aqueous media over a pH range of 1 to 7.5 at 37°C. For permeability assessment, an API is considered to be "highly permeable" when the extent of the API absorption (parent drug plus metabolites) in humans is greater than or equal to 90 percent of an administered dose based on a mass balance determination or in comparison to an intravenous reference dose. Trends suggest that the majority of API candidates currently in the development pipeline have a BCS Class II rating [1], meaning that they require a solubilization strategy to promote oral bioavailability and maximize the chance of clinical success. Traditional methods of processing an API for an oral tablet dosage form have used micronization to reduce an API's particle size, which increases its overall surface area and promotes faster dissolution. However, for many Class II APIs, micronization doesn't sufficiently improve API solubility to achieve the desired clinical outcome. While the micronization makes the API particles dissolve faster, the dissolved API may quickly precipitate in vivo before it can be absorbed. This means that today's drug developers must identify more complex techniques for improving and sustaining the solubility of poorly soluble APIs prior to their inclusion in tablets or other solid oral dosage forms. Spray-dried dispersions One well-documented, commercially validated technique for enhancing API solubility is to prepare the poorly soluble API as an amorphous dispersion within a carrier polymer using a spray dryer. The amorphous state of the API means that there are no highly ordered or crystalline interactions between API molecules, which leads to higher solubility in water, relative to a crystalline API. However, an amorphous API tends to be unstable and will recrystallize unless stabilized. A spray-dried Figure 1 Biopharmaceutical classi cation system Class II Low solubility High permeability Class I High solubility High permeability Class IV Low solubility Low permeability Class III High solubility Low permeability Permeability Solubility www.azo.com Raw material feeding for continuous processes AZO Solutions Continuous Processing • control optimization • consistent accuracy • reliable C M Y CM MY CY CMY K AZO10256_BannerAds_ContinuousProcessing_3-3-8inx10in.pdf 1 12/5/17 4:17 PM