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Tablets & Capsules March 2020 41 6. Fridrun Podczeck and Brian E. Jones, Pharmaceutical Capsules, 2nd ed., Pharmaceutical Press, London, 2004, pages 96-98. 7. Ewart T. Cole, et al., "In vitro and in vivo pharmacoscintigraphic evaluation of ibuprofen hypromellose and gelatin capsules," Pharmaceutical Research, 2004, Vol. 21, No. 5, pages 793-798. Martin Junginger is chemical engineer, global product management, pharma gelatin, and business development, gel- atin, at Gelita, a global supplier of collagen proteins (www.gelita.com). References 1. US Patent 5698155. 2. Malla Vasavi Chandrika, et al., "Alternatives for gelatin in the prepa- ration of capsules," Advanced Journal of Pharmacie and Life Science Research, 2016, Vol. 4, No. 2, pages 33-42. 3. Shallini Gupta, et al., "Evalu- ation of capsule labeling for its wall contents as gelatin or non-gelatin," International Journal of Basic & Clinical Pharmacology, July 2018, Vol. 7, No. 7, pages 1,387-1,390. 4. Sutapa Majee, et al., "HPMC as capsule shell material: Physicochem- ical, pharmaceutical and biophar- maceutical properties," International Journal of Pharmacy and Pharmaceutical Sciences, August 2017, Vol. 9, No. 10, pages 1-6. 5. Matt Richardson, "Impact of capsule selection on formulation sta- bility in dry powder inhalers (DPIs)," Inhalation, April 2011, Vol. 2, No. 2. Cost HPMC capsules are four to five times more costly to make than gel- atin capsules due to a lower pro- duction yield and conversion ratio compared to the relatively simple and efficient gelatin capsule man- ufacturing process. Also, HPMC capsule production takes more time and more-extensive technology [3], and improving the performance of HPMC capsules on a high-speed fill- ing machine often requires treating the capsules' external surface with a gliding agent [4]. Oxygen permeability G e l a t i n h a r d c a p s u l e s h a v e demonstrated excellent protection against oxygen permeability, which is important for formulations that are sensitive to oxidation [5]. The transmission of oxygen through an HPMC capsule shell is much higher than through a gelatin-based capsule shell. As a result, drug product manu- facturers using HPMC capsules must include an antioxidant in the formu- lation or must package the capsules in a blister package with aluminum foil to protect against oxidation of sensitive active ingredients or excipi- ents [6]. For both gelatin and HPMC hard capsules, the gap between the capsule body and cap requires addi- tional sealing to avoid oxygen seep- ing into the capsules. Performance characteristics Table 1 compares the perfor- mance characteristics of gelatin- based and HPMC-based capsules. Capsule suppliers use gelatin for hard capsules because of its setting properties, gliding characteristics, machinability, dissolution proper- ties, and ability to protect the for- mulation inside the capsule. For some formulations—those that don't require a strong barrier to oxygen or fills with very hygroscopic behav- ior or a high risk of crosslinking— HPMC capsule shells might be the best choice, but for the majority of formulations, the difficulties of pro- ducing HPMC capsules often makes gelatin a better choice. T&C Table 1 Performance characteristics of gelatin versus HPMC hard capsules Gelatin-based hard capsules HPMC-based hard capsules Available in varying sizes, shapes, and colors, including crystal clear +++ +++ Easy to swallow +++ +++ Acceptable taste ++ ++ Provide an oxygen barrier +++ + Support dissolution +++ ++ [7] Transparent +++ +++ Efficient to machine +++ +* Advantageous for highly hygroscopic formulations + +++ Advantageous for formulations that have a very high risk of crosslinking + +++ Prevent microbial growth ++ ++ Acceptable shelf life/stability ++ +++ Permit kosher certification Yes Yes Allow Halal certification Yes Yes Natural +++ - Food or food additive Food Food additive (E464) Vegan/vegetarian - + * Lower manufacturing speed, produces more waste, requires a more-sensitive manufacturing process