(717a) Oral Formulations: Perspectives from Additive Manufacturing

Selection of oral formulation strategy plays a significant role in development of new drug candidates throughout the development and commercial product stages; requirement for oral bioavailability must be balanced against additional complexity in the manufacturing process[1,2]. Formulation strategies may present manufacturing challenges, particularly for poorly water-soluble drugs, resulting from the necessity of particle size reduction and multiple active excipients to achieve bioavailability targets[3]. As an alternative to established manufacturing strategies, much recent work has focused on additive manufacturing, partially due to its capacity for accurate and precise delivery of drug amounts in the micro- to milli-gram range[4]. The technology also exhibits potential as a flexible platform capable of producing doses in a number of formsfrom solvent- and melt-based forumulations[5,6], which may include colloidal particles[7].

The manufacture of multiple capsule-based formulations using non-colloidal particulate suspensions is presented in this study. Particles selected from micronized and non-micronized powder grades are characterized in terms of particle size and bulk powder properties, which, in concert with rheology experiments are used to guide printing fluid formulations. Quantitative measures of product physical properties and respective production rates are presented for four active substances in 1-100 milligram amounts, delivered by hydro-philic/phobic carrier fluid platforms. Based on these results, perspectives are given on the ability of the platforms to complement current formulation selection strategies for BCS Class I and Class II drugs and on the potential for the technology serve at both the personalized medicine and industrial manufacturing scales.

References

1. M. Kuentz, R. Holm, and D. P. Elder, 2016, Methodology of oral formulation selection in the pharmaceutical industry, European Journal of Pharmaceutical Sciences, 87, 136-163.
2. M. Ierapetritou, F. Muzzio, and G. Reklaitis, 2016, Perspectives on the Continuous Manufacturing of Powder-Based Pharmaceutical Processes, AIChE Journal, 62, 1846-1862.
3. H.D. Williams, N.L. Trevaskis, S.A. Charman, R.M. Shanker, W.N. Charman, C.W. Pouton, and C.J.H. Porter, 2013, Strategies to Address Low Drug Solubility in Discovery and Development, Pharmacoligical Reviews, 65, 315-499.
4. R. Daly, T.S. Harrington, G.D. Martin, and I.M. Hutchings, 2015, Inkjet printing for pharmaceutics – A review of research and manufacturing, International Journal of Pharmaceutics, 494, 554-567.
5. L. Hirshfield, A. Giridhar, L.S. Taylor, M.T. Harris, and G.V. Reklaitis, 2014, Dropwise Additive Manufacturing of Pharmaceutical Products for Solvent-Based Dosage Forms, Journal of Pharmaceutical Sciences, 103, 496-506.
6. E. Içten, A. Giridhar, L.S. Taylor, Z.K. Nagy, and G.V. Reklaitis, 2015, Dropwise Additive Manufacturing of Pharmaceutical Products for Melt-Based Dosage Forms, Journal of Pharmaceutical Sciences, 104, 1641-1649.
7. J. Pardeike, D.M. Strohmeier, N. Schrödl, C. Voura, M. Gruber, J.G. Khinast, and A. Zimmer, Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble drugs in personalized medicines, 2011, International Journal of Pharmaceutics, 420, 93-100.