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Tablets & Capsules July 2019 21 approach that can reduce or even eliminate the potential for repetitive formulation and stability studies. T&C References 1 . w w w . f o r b e s . c o m / s i t e s / b e r n a r d m u n o s / 2019/01/14/2018-new-drugs-approvals-an-all-time-record- and-a-watershed/#749eb840332d. 2. s3.amazonaws.com/cpsl-web/kc/library/WP- VcapsPlus_30270_FIN_10-8-12.pdf. 3. s3.amazonaws.com/cpsl-web/kc/Capsugel%C2%AE- Vcaps%C2%AE-Plus-In-Vivo-whitepaper.pdf. 4. Ewart T. Cole, Robert A. Scott, Dominique Cade, Alyson L. Connor, and Ian R. Wilding. "In Vitro and in Vivo Pharmacoscintigraphic Evaluation of Ibuprofen Hypromellose and Gelatin Capsules." Pharmaceutical Research. Vol. 21, No. 5, pages 793-798. 5. Daniel Ouellet, Kenneth F. Grossman, Giselle Limentani, Noelia Nebot, Kevin Lan, Lara Knowles, Michael S. Gordon, Sunil Sharma, Jeffrey R. Infante, Patricia M. Lorusso, Girish Pande, Elizabeth C. Krachey, Samuel C. Blackman, Stanley W. Carson. "Effects of par- ticle size, food, and capsule shell composition on the oral bioavailability of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors." Journal of Pharmaceutical Sciences. Vol. 102, No. 9, pages 3,100-3,109. Matt Richardson, PhD, and Nicolas Madit, PhD, are busi- ness development managers for Capsule Delivery Solutions at Lonza Pharma & Biotech (201 316 9200, www. lonza.com). Similarly, the amount of moisture content in the cap- sule shell can impact hygroscopic formulations. Hygroscopic compounds can often pull water from the environment and have been shown to pull moisture from the capsule shell as well. For gelatin, loss of moisture typ- ically impacts the capsule's mechanical resistance if the resultant water content drops below the recommended 13 to 16 percent described previously. Desiccants in packaging materials often produce the same result. Unlike gelatin capsules, HPMC capsules do not rely on water for plasticity, so they can tolerate a lower average water content and can sustain mechanical stability at a lower relative humidity range than gelatin capsules can, as shown in Figure 3. An important differentiator of HPMC capsules from gelatin capsules is their ability to increase bioavailability for some high-energy formulation types (such as amor- phous dispersions and salts) and molecules with low solu- bility. These formulation types are likely to become supersaturated and precipitate in the stomach's acidic environment. Several publications list the ability of HPMC to affect crystallization, and some report an increase in API bioavailability via this method by reduc- ing the potential for crystallization, which leads to a supersaturated state of the drug molecule(s) in vivo [5]. This benefit helps formulators select the appropriate dos- age form for drug molecules with low aqueous solubility. Conclusion With the resurgence of pharmaceutical approvals, notably those of first-in-class molecules and those with shortened approval pathways, strategies to handle a broad array of drug molecules are critical. Next- generation HPMC capsules without gelling systems con- tinue to gain traction for their ability to simplify the drug development timeline via a "right-first-time" development Figure 3 Relation between storage conditions (% RH) and capsule water content (% LOD) a. HPMC capsules (Vcaps Plus) Capsule water content (% LOD) 14 12 10 8 6 4 2 Storage conditions (% RH) 10 20 30 40 50 60 70 80 90 <2% moisture in shell leads to capsule breakage ≥10% moisture in shell leads to capsule softening 2-9% moisture content is ideal b. Gelatin capsules Capsule water content (% LOD) 30 25 20 15 10 5 Storage conditions (% RH) 10 20 30 40 50 60 70 80 90 <10% moisture in shell leads to capsule breakage ≥18% moisture in shell leads to capsule softening 12-16% moisture content is ideal