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c-Kheurart_10-15_Masters 12/30/13 1:55 PM Page 15 Tablets & Capsules January 2014 15 Figure 1 Conclusion 60 Gelatin LFHCs offer a simple yet effective means of formulating compounds with low aqueous solubility. Even though complete solubilization was not achieved, the in vitro dissolution profile of a low-solubility compound was improved by associating the API with an optimal mixture of solubilizers and bioavailability-enhancers. An excipientmixture approach that takes into consideration the different properties of excipients was used to arrive at this optimal ratio. T&C 40 References In vitro dissolution of selected API-excipient mixtures in 0.1 N HCl 120 100 % dissolved 80 20 0 0 10 20 30 40 Time (min) 50 60 Lot 1 Lot 2 Lot 3 Lot 4 S.E.L.F. 27F 70 S.E.L.F. 27H Figure 2 Lot 1 in vitro dissolution data 120 100 % dissolved 80 60 40 T=0 20 T = 1 month 0 0 10 20 30 40 Time (min) 50 60 70 Figure 3 Lot 3 in vitro dissolution data 1. Lipinski, CA. Reducing the investment made in likely drug development failures. In Transforming the Pharmaceutical Industry: Adapting to Change in Technology and Markets. Cambridge Healthtech Institute, Newton, MA, 2001. 2. Tong, WQ. Developability Assessment Supporting Drug Candidate Selection [Powerpoint]. UT: UoU Integrated Drug Development Process Course; 2006. 3. Wiser L, Gao X, Jasti B, Li X. Solubility of pharmaceutical solids. In: Hu M, Li X, eds. Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications. Hoboken, NJ: John Wiley & Sons, Inc.; 2011. 4. Cowan-Lincoln M. Improve the bioavailability of poorly soluble drugs. PFQ. February/March 2012:12-14. 5. Kommuru TR, Gurley B, Khan MA, Reddy, IK. Selfemulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm. 2001;212(2):233-246. 6. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001;46(1-3):3–26. 7. Keseru GM, Makara GM. Hit discovery and hit-tolead approaches. Drug Discov Today. 2006;11(1516):741-748. 8. Anderson NG. Practical Process Research and Development: A Guide for Organic Chemists. 2nd ed. Oxford, UK: Elsevier, Inc.; 2012:369. 9. Howard JR, Gould PL. Drug release from thermosetting fatty vehicles filled into hard gelatin capsules. Drug Dev. Ind. Pharm. 1987;13(6):1031–1045. 120 100 % dissolved 80 60 40 T=0 20 T = 1 month 0 0 10 20 30 40 Time (min) 50 60 70 Amol Kheur is a technical project leader; Anil Kane is executive director, global head of formulation sciences; Mohammad Aleem is a senior research chemist; and Maureen McLaughlin is a senior manager, analytical development at Patheon Pharmaceutical Development Services, 4721 Emperor Blvd., Suite 200, Durham, NC 27703. Tel. 919 226 3200. Website: www.patheon.com. Kiran Kumar Tumbalam and Shivaprakash Poojary are former employees.