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14 March 2020 Tablets & Capsules Case study conclusions Success of an insoluble API depends on swift assess- ment of solubility challenges and rapid development of an enabling formulation. Using our solubility enhance- ment expertise, we were able to identify the best solubi- lization technology and the best formulation to scale up to produce clinical materials. Our initial screening studies only used milligram quantities of API to rapidly guide polymer selection. Using solubilization techniques, we were able to formulate poorly soluble API and generate in vivo data that was representative of the final clinical formula- tion. We used this early data for the final GMP formu- lation—spray drying API mixed with Kollidon VA64 and TPGS surfactant, using the THF-ethanol-water mixture as spray drying solvent—and were able to scale up the process and successfully manufacture tab- lets for clinical studies. T&C Ruchit Trivedi, PhD, is director of formulation at BioDuro, a contract research, development, and manufacturing organiza- tion based in San Diego, CA (858 529 6600, www.bioduro. com). He holds a bachelor's degree in pharmacy from North Gujarat University, India, and a doctorate in pharmaceutical sciences from the University of Colorado. Prior to joining Bio- Duro, he held positions at Array Biopharma as a formulation scientist developing amorphous-dispersion-based solid oral formulations and at Banner Life Sciences (formerly Banner Pharmacaps) developing abuse-deterrent formulations. BioDuro's approach for generating solid dosage forms for poorly soluble compounds, called Solution Engine, has led to a 100 percent success rate for solving difficult formulations. We do this by integrating API information from clients, micro-evaporative screening for optimal matrix selection, using our deep experience in amorphous dispersion manufacturing, and in vivo expertise of our in-house DMPK discovery team. All these elements are part of a single workflow—the BioDuro Solution Engine—which both accelerates timelines and rescues programs by developing clinically-acceptable solid oral dosage forms. melting point, which is additional evidence of amor- phous structure. DSC also provides the glass transition temperature, an indication of how stable the amor- phous dispersion is. Pharmacokinetic assessment of formulations in vivo In collaboration with our discovery colleagues, we rapidly generated pharmacokinetic data that correlated well with the non-sink dissolution results. Figure 5 shows the study design comparing the bioavailability of formu- lations using various solubility enhancement techniques: SDD, HME, and micro-evaporation. Organic solvent (PEG) and nano-suspensions were included as controls to show maximum bioavailability, but neither method is suitable for clinical use. The results presented in Table 3 show that the SDD using polymer Kollidon VA64 with TPGS gave simi- lar performance as the organic solvent. HME with the same excipients did not perform as well. However, the micro-evaporation tubes showed similar results to the SDD, underscoring how this screening method can provide an affordable option for early pharmacokinetic studies. Formulation AUC (male) (h*ng/ml) AUC (female) (h*ng/ml) API in PEG 400 (control) 13,704 28,187 API in 80% PEG/20% water 6,318 8,778 Nanosuspension 9,969 10,996 SDD (API-TPGS-Kollidon VA64) 6,975 7,291 HME (API-TPGS-Kollidon VA64) 4,799 4,095 Tubes (API-TPGS-Kollidon VA64) 7,237 7,170 Table 3 Pharmacokinetics data for different solubilized dosage forms Do you have blank tablets or capsules? We have the printer for you. We have the printer for you. e have the printer for you. e have the printer for you. e have the printer for you. e have the printer for you. e have the printer for you.