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26 March 2018 Tablets & Capsules dissolution but not so small that the formulation segregates during processing or storage. SDD tablet development must ensure effective in vivo tablet disintegration, which is necessary to expose the SDD for initial wetting and subsequent dissolution in the GI tract. SDDs often contain traditional tablet ingredients, with the balance between disintegrants and fillers optimized using small compaction studies and dissolution testing. After identifying the lead formulation compositions, the next step is to optimize the key process parameters that affect critical product characteristics, such as solid fraction (relative density) during manual slugging, ribbon thickness during roller compaction, and tablet hardness during compression. SDD tablet characterization To characterize an SDD tablet formulation, you must perform standard tests to build a data package, including assay, related substances, and content uniformity. The dissolution test is a critical characterization tool, because the API's release rate is reliant on the disintegration rate of the tablet, the subsequent exposure of the SDD for wetting, and the resultant API dissolution. Using a variety of dissolution media can help to provide a robust understanding of both the initial API release and the subsequent maintenance of the solubilized state at different pH values, mimicking the movement of the drug product through the patient's GI tract. Future outlook The use of SDDs as an enabling technology for poorly soluble APIs is common for early-phase clinical development programs. For example, Quotient has developed more than 250 SDD clinical-stage products in the past decade, with more coming on each year. As products such as these advance through clinical development toward approval, it seems clear that SDDs will become an increasingly common approach for developing new oral tablet drug products. T&C References 1. David J. Hauss, "Oral lipid-based formulations," Advanced Drug Delivery Reviews, Vol. 59, No. 7, pages 667- 676. Nikki Whitfield is vice-president of pharmaceutical sciences at Quotient Sciences, Nottingham, UK (www.quotientsciences. com). She has 23 years of experience in the pharmaceutical industry, including development, transfer, and scale-up of both early-phase and late-phase spray-dried, inhaled, and topical products for both the European and US markets. You can initially manufacture SDD prototypes in batch sizes as small as 500 milligrams to characterize the API-polymer matrix. Techniques such as differential scanning calorimetry (DSC) and x-ray powder diffraction can determine the API-polymer homogeneity and miscibility within the matrix and confirm the amorphous nature of the prototype. Using DSC, you can also determine the formulation's glass transition temperature, which is a key predictor of the SDD's physical stability. This allows you to evaluate the formulation's propensity to crystallize or destabilize during long-term storage. Researchers often use SDDs (routinely administered as a suspension) in early-phase clinical studies. This provides rapid clinical evaluation of the SDD, which is appropriate to determine the API exposure and confirm that the solubilization approach has been successful. However, a conventional tablet format is often the desired drug product form for proof of concept or patient trials. SDD tablet development Successfully developing an SDD into an oral tablet requires that you pay attention to certain considerations during formulation. First, the typical drug load for an SDD is 40 percent, but the acceptable target weight for most tablets is less than 1 gram, which limits the amount of extragranular excipients you can incorporate into the tablet formulation. Second, you must optimize the SDD's particle size to be small enough to ensure rapid Acid Resistant Vegetable Capsules ) ' u n. , u, ' . ' AN EXCELLENT CHOICE FOR DELIVERY OF ACID-SENSITIVE ACTIVE INGREDIENDTS . . . <> . BioCaps Enterprises, Inc. www.biocaps.net • info@biocaps.net US Patent 9452141