Issue link: https://www.e-digitaleditions.com/i/626800
Additive manufacturing and other new processes.W i t h a d v a n c e s i n m a n u f a c t u r i n g t e c h n o l o g y c o m e n e w m e t h o d s o f m a n u f a c t u r i n g e x i s t i n g p r o d u c t s a n d t h e a b i l i t y t o c r e a t e p r o d u c t s a n d f o r m u l a t i o n s t h a t w e r e p r e v i o u s l y i m p o s s i b l e . A g o o d e x a m p l e i s a d d i t i v e m a n u f a c t u r i n g , a l s o k n o w n a s 3 D p r i n t i n g , w h i c h h a s i m p r o v e d t h e m a n u f a c t u r a b i l i t y a n d p e r f o r m a n c e o f m a n y i n d u s t r i a l p r o d u c t s . L a s t A u g u s t , i n f a c t , t h e F D A a p p r o v e d S p r i t a m , a 3 D - p r i n t e d o r a l l y d i s i n - t e g r a t i n g t a b l e t , w h i c h i n d i c a t e s t h a t s o m e l i m i t s o r b a r r i e r s t o f o r m u l a t i o n a r e f a l l i n g a w a y [ 1 ] . P e r h a p s t h e n e x t a d v a n c e w i l l e n a b l e f o r m u l a t o r s t o s t r a t e g i c a l l y p l a c e t h e A P I w i t h i n a t a b l e t o r c a p s u l e , o p e n i n g u p m o r e o p p o r t u - n i t y f o r h y b r i d p r o d u c t s t h a t c o m b i n e A P I s i n w a y s n e v e r t h o u g h t p o s s i b l e . M a n y o f t h e s e n e w p r o d u c t c o n f i g u r a - t i o n s c o u l d b e e v a l u a t e d a n d v e r i f i e d u s i n g C T . A d d i t i o n a l l y , C T c o u l d h e l p u s q u i c k l y u n d e r s t a n d t h e l i m i - t a t i o n s a n d v a r i a b i l i t y o f t h e s e n e w p r o c e s s e s a n d a c c e l e r a t e p r o c e s s d e v e l o p m e n t . P r o d u c t s h e l f l i f e . Even under normal environmental conditions, the density of coatings can change over time, and even subtle changes may affect the drug product's per- formance. These changes, at least in some materials, can be detected using high-contrast CT techniques, which can help you establish correlations between coating density, drug product performance, and product expiration dates. Porosity and voids. Some materials, processes, and for- mulations are prone to the development of high porosity or voids. CT can easily detect these anomalies and provide data about their size, absolute volume, and percentage of total product volume (Figure 8). In-motion imaging. Four-dimensional imaging—essen- tially 3D imaging over time—captures true 3D information of an event. Much recent research has focused on CT scan- ning a product while stresses are introduced in order to reveal how the product or its components react and move. Other work involved putting products in contact with differ- ent substances or having substances flow through or around the product. One obvious application of 4D imaging for tablets and capsules is to simulate their behavior in digestive solutions to better understand the dissolution process, from the product's surface to its center. Yet another example: Applying stresses representative of those that the product would undergo during manufacturing or handling processes. By generating multiple, back-to-back CT data sets that cap- ture the product variations under these stresses, you can see how the product's material structure changes over time. From that, you can glean information about how cracks, chips, granular compression, and general surface changes develop and propagate under various stress conditions. At-line application. While there are many applications for doing laboratory work with CT, the size and speed of the equipment makes it well suited for at-line or even in- line use. That would enable you to conduct tests of batch samples at regular intervals and to evaluate how process changes affected the samples. Using automatic reconstruc- tion and analysis algorithms, CT could deliver quick results to help monitor high-volume operations. FDA support. Section 3 of the FDA's "Strategic Plan for Regulatory Science," is titled "Support New Approaches to Improve Product Manufacturing and Quality" [2]. It makes clear that the Agency wants manufacturers to investigate and develop new and improved analytical technologies to support or replace existing methods of evaluating product quality. While the document doesn't name CT, it clearly fits into the FDA's strategy. T&C References 1. FDA approves the first 3D printed drug product. Press release from Aprecia Pharmaceuticals. August 3, 2015. www.aprecia.com/pdf/ 2015_08_03_Spritam_FDA_Approval_Press_Release.pdf. 2. Strategic Plan for Regulatory Science: Advancing Regulatory Science at FDA: A Strategic Plan. August 2011. www.fda.gov/sci- enceresearch/specialtopics/regulatoryscience/ucm268113.htm. Additional reading Riegel's Handbook of Industrial Chemistry. 9th ed. Edited by James A. Kent 2013, New York. Remington: The Science and Practice of Pharmacy. 21st ed. Edited by David B. Troy and Paul Beringer. 2006, Philadelphia. Theory and Practice of Contemporary Pharmaceutics. Edited by Tapash K. Ghosh and Bhaskara R. Jasti. 2004, Boca Raton. On the shelf life of pharmaceutical products. Robert Capen et al. AAPS PharmSciTech. 2012 Sep; 13(3): 911- 918. www.ncbi.nlm.nih.gov/pmc/articles/PMC3429690. Brett Muehlhauser is an R&D technical fellow and Nate DeRoo is a CT applications specialist at North Star Imaging, 19875 S. Dia- mond Lake Road, Rogers, MN 55374. Tel. 763 463 5679. Website: 4nsi.com. Figure 7 CT scans can detect foreign materials. Figure 8 CT can detect anomalies and voids and determine their size, absolute volume, and percentage of total product volume. 18 January 2016 Tablets & Capsules