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36 May 2017 Tablets & Capsules Conclusion In our case study, we applied DoE using a QbD frame- work in product formulation of and analytical develop- ment for an oil-filled softgel. In product formulation, we determined that both the gelatin type and use level of plasticizer had a significant effect on disintegration time. The lowest values were achieved in formulations that used type B gelatin in com- bination with the highest use level of plasticizer. In analytical development, the dissolution method was not specified in the monograph, so we defined the ana- lytical method using DoE. It was shown that, for an oil- filled softgel formulation, there are some practical and statistical considerations when selecting the analytical conditions for dissolution testing. T&C References 1. Ledward DA (2000) Gelatin. In: Phillips GO, Williams PA (eds) Handbook of hydrocolloids. Woodhead Publishing Limited, Cambridge, UK, 67-86. 2. Reich, G (2004). Formulation and physical proper- ties of soft capsules. In: Podczeck F, Jones BE (eds) Pharmaceutical Capsules, 2nd edn. Pharmaceutical Press, London, UK, 201-212. 3. United States Pharmacopeial Convention. US Pharmacopoeia-National Formulary [USP 39 NF 34]. Rockville, MD, 2016. 4. FDA Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, US Department of Health and Human Services, Centre for Drug Evaluation and Research (CDER), Food and Drug Administration, Rockville, MD, 1997. Claudia Silva, PhD, is new platforms development director, Diego Monterroza is R&D manager, and Jose Acosta is prod- uct development director for Latin America at Procaps, Calle 80, No. 78B-201, Barranquilla, Colombia. Tel. +575 371 9000. Website: www.softigel.com. The company is the largest manufacturer of softgels in Latin America and offers develop- ment, manufacturing, and commercial services. According to the FDA´s Guidance for testing softgels in the flow-through cell, parameters that should be evalu- ated and optimized through DoE are the system flow rate, cell size, sample volume, and mode (open or closed) [4]. A DoE was conducted to determine the analytical con- ditions for the dissolution test of the oil-filled softgels. We selected a fractional factorial design of five variables (surfactant use level, flow rate, cell size, flow type, and system mode). The dependent variable was the dissolu- tion value Q, corresponding to the amount of dissolved API, expressed as a percentage of the labeled content of the product at 60 minutes under each condition. The input variables were the use level of surfactant and the flow rate. We chose a cell 22.6 millimeters in diameter to accommodate the capsule. Figure 4 shows the contour plots for laminar and turbulent flow using that cell. Although the dissolved amount of the API was higher with turbulent flow than laminar flow, the latter was selected due to its highly precise results, which had the lowest RSD. The closed system was selected because it showed lower variability than the open system. After screening to define the analytical method using USP apparatus 4, we decided on a surfactant use level of 6 percent, a flow rate of 16 milliliters per minute, a cell 22.6 millimeters in diameter, laminar flow, and the closed system. Both the use level of the surfactant and flow rate were at the highest levels tested. Figure 4 Contour plots for dissolution of oil-filled softgels using apparatus 4, closed system 90.0 81.7 73.3 65.1 56.3 16 13 10 7 4 16 13 10 7 4 3 3.75 4.5 5.25 6 3 3.75 4.5 5.25 6 96.9 88.6 80.3 71.9 63.6 Note: 5 percent Triton X-100 in water at 37°C Use level Use level Flow rate Flow rate b. Turbulent flow a. Laminar flow