Issue link: https://www.e-digitaleditions.com/i/1138630
Tablets & Capsules July 2019 19 These next-generation HPMC capsules demonstrate improved performance compared to traditional HPMC capsules due to innovations around the gelling system. Traditional HPMC capsules use a gelling system that includes ionic gel promoters and secondary gelling agents to create the capsule's shell exterior. However, these secondary gelling agents can negatively impact the dissolution profile of the HPMC capsule, causing vari- ability in dissolution rates depending on the pH and ionic strength of the dissolution media. The new class of HPMC capsules was engineered to mitigate these issues around dissolution. Scientists devel- oped a thermo-gelation process that uses only water and HPMC to create the capsule's hard shell, eliminating the need for secondary gelling agents and producing HPMC capsules with a dissolution profile comparable to that of gelatin capsules. Dissolution studies have shown greater performance variability in capsules that include a gelling system in the HPMC matrix, as shown in Figure 1a, and more consistent performance in capsules comprised of only HPMC and water, as shown in Figure 1b [2]. Consistent and predictable dissolution performance of the capsule excipient allows formulators to avoid costly and repetitive stability tests, saving time in the drug development process. number (39 percent) were given fast-track designation, as shown in Table 1 [1]. What do those numbers mean for drug developers? They mean that formulators today are looking at brand new classes of molecules that bring their own sets of challenges to both define and solve, often for a narrower patient population than in the past. And with fast-track and breakthrough designations and priority reviews, drug development groups are having to solve those challenges faster than ever. To keep pace with new chemical entities, formulators require tools to address challenges efficiently and achieve "right-first-time" protocols rather than investing time "going back to the drawing board" to conduct mul- tiple stability and formulation studies. To address both anticipated and unanticipated formulation challenges, many companies have increasingly incorporated capsules made from the excipient polymer hypromellose (hydroxypropyl methylcellulose or HPMC) into their research strategies because of its improved stability and enhanced formulation capabilities. Thermo-gelation advances HPMC hard capsules HPMC was well vetted as a pharmaceutical excipient long before its use as a capsule polymer. To that end, it has attained regulatory approval in all major pharmacope- ias as well as GRAS status by the FDA and food-additive status by the European Commission. Unfortunately, first-generation hard capsules made from HPMC do not dissolve quickly or consistently, potentially rendering the encapsulated compound ineffective and delayed in release. Delays and unreliable release are especially problematic in the formulation of immediate-release drug products. Due to recent advancements, however, a new genera- tion of HPMC capsules is available as an alternative to gelatin capsules for immediate-release formulations. Table 1 Trends in key metrics for new drug approvals Classification Percentage of approvals 2018 2017 2016 2015 Big pharma* 26% 35% 36% 39% Biologicals 36% 45% 55% 39% First in class 43% 35% 41% 41% Orphan drug 56% 39% 36% 41% Fast track 39% 24% 36% 27% Breakthrough therapy 23% 41% 32% 20% Priority review 70% 61% 59% 47% Accelerated approval 8% 12% 27% 12% * "Big pharma" includes: Abbvie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi. Source: FDA Figure 1 Influence of gelling systems on in vitro dissolution of caffeine in HPMC capsules a. HPMC capsules produced with gelling system Caffeine dissolved (%) 100 90 80 70 60 50 40 30 20 10 0 Time (minutes) 0 3 6 9 12 15 18 21 24 27 30 35 40 45 50 55 60 75 pH 1.2 USP pH 6.8 USP pH 6.8 JP2 Simulated milk fluid pH 1.2—2 g KCl/L pH 1.2—9 g KCl/L b. HPMC capsules produced without gelling system (VCaps Plus) Caffeine dissolved (%) 100 90 80 70 60 50 40 30 20 10 0 Time (minutes) pH 1.2 USP pH 6.8 USP pH 6.8 JP2 Simulated milk fluid pH 1.2—2 g KCl/L pH 1.2—9 g KCl/L 0 3 6 9 12 15 18 21 24 27 30 35 40 45 50 55 60 75