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Tablets & Capsules March 2017 19 hygroscopic materials and avoids the crosslinking that can occur with gelatin under accelerated storage condi- tions. Its ability to withstand temperature excursions without a change in performance and to meet religious and dietary requirements makes HPMC an important capsule polymer. In 2006, Capsugel offered a new version of its HPMC capsule, Vcaps Plus, that contains no gelling agents, a cause of variable in vitro dissolution. Instead of gelling agents, the capsules are made using a thermo-gelation process at temperatures higher than those of the tradi- tional process. Eliminating the gelling agents gives the capsules pH-independent disintegration, which was shown in a human biostudy involving three APIs to give bioequivalence compared with a gelatin capsule [1]. Figures 1 and 2 compare the in vitro and in vivo perfor- mance of gelatin capsules and Vcaps Plus capsules. The capsules have several advantages over those made from gelatin. In-house studies of Vcaps Plus capsules have shown they undergo no changes in color, transparency, loss on drying, disintegration, dissolution, or filling per- formance at low temperatures. Nor have we observed changes in disintegration, dissolution, or mechanical per- formance at elevated temperatures. Study results also indicate that because the capsules have a lower water content overall (less than 6 percent at ambient condi- tions), they may reduce moisture transfer from the cap- sule to the encapsulated product, which helps maintain product stability. Furthermore, because water is not needed as a plasticizer, the capsules are less likely to break, even in dry conditions, which helps maintain sta- bility. They are also well suited for moisture-sensitive ingredients and can be dried to a lower moisture level— as low as 3 percent—for low-water-activity applications. Fixed-dose combinations Both gelatin and HPMC capsules can over-encapsulate single- and multi-layer tablets, API-layered multiparticulates, Figure 2 In vivo bioequivalence study comparing aceta- minophen encapsulated in gelatin capsules with HPMC capsules made by thermo-gelation Notes: N=24. HPMC capsules are Vcaps Plus, and gelatin capsules are Coni - Snap. 8000 7000 6000 5000 4000 3000 2000 1000 0 0 2 4 6 8 10 12 Q H : ng udi l c n i 0 fi 0 0 , 0 r 9 e v ck o o t s no — s t r a d p n s a r e t l fi o n y so d l a n o e D k a M r e t l fi dge i tr r a C E R H T N H N H A E C CA W s E t r a t p n me me Q e c a l p e d r n s a r e t l fi e . W r o t c le l o e c h r t e t t a o m t n me e c a l p e r r o l f l a t c s r r fi ou s T ers t l fi l e n a P I T F H IG D N I U F O P YO L E H H T D t Q d der y o or w t Call no t the u s o r i e d r ur o o y ur R , o us l . P s e t u n i m e a z i ne the s i m r e t e d e c i v r e t s r e p x , e e v i L t g Q ers t l fi g a B Q b fil g a b d e s t lea P fi k ac p r e t fil ® w e r o C er w o P ers eplacement filt our r y . s ur o 4 h n 2 i th i r w o o e d s an e am m r g o r p p i h y 2 S d a e n i th i d w e u ne o e y l y t d s an u o p y an hel s c t s i l a i c e p s s r e t Q ) e r o m d n , a s n a , f s l o r t n o c , k or w t c du , s e v al v r a ot r , s age c , s r o ot m , e war d ar h ( s t r Pa y r . ts and part