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DRcaps did not exhibit any significant delay at the pH 6.8 JP2 stage. The study also showed that the capsules' acid resistance is not affected by the presence of as much as 40 percent alcohol (ethanol) in the dissolution media, which may help prevent alcohol dose dumping in delayed- release products [2]. The results of an earlier study showed that a single DRcaps capsule offered similar pro- tection in the presence of as much as 40 percent alcohol in JP2 protocol dissolution studies with caffeine. That same study also showed that "stacked" DRcaps extended acid protection of the formu- lation [3]. The combined results confirm that DRcaps capsules can be considered for use in extended delayed-release formulations. A human in vivo study of DRcaps that used gamma scintigraphy also documented their ability to delay deliv- ery of acid-sensitive ingredients. The capsules protected the ingredients from early activation by stomach acid, and then released them completely in the intestines. The cap- sules began to release in a mean time of 52 minutes after ingestion (45 minutes later than an immediate-release cap- sule), and completely released the ingredients in a mean time of 72 minutes after ingestion. For the majority of subjects, complete release took place in the intestine [4,5]. Another study—the results of which appeared in med- ical journals—described how investigators at Massachusetts General Hospital used DRcaps for an unusual treatment of a serious medical problem. They used prescreened frozen fecal material from healthy donors to treat recurrent diarrhea caused by a Clostridium difficile infection, a major cause of morbidity and mortal- ity. The capsules obviated the need for invasive proce- dures and thereby eliminated procedure-related complica- tions and reduced the cost of treatment. Among the 20 patients treated, 14 had clinical resolution of diarrhea after the first administration and remained symptom-free at 8 weeks. The six non-responders were re-treated and five of them had resolution of diarrhea. The overall rate of clini- cal resolution of diarrhea was 90 percent [6]. Capsules with full enteric protection In 2015, Capsugel introduced its enTRinsic drug deliv- ery technology. These capsules provide full enteric pro- tection and targeted release of acid- and heat-sensitive ingredients in the upper GI tract without using functional coatings. Examples include nucleotides, peptides, vac- cines, and live biotherapeutic products. The intrinsically enteric capsules, which use approved pharmaceutical polymers, have been shown to rapidly release at pH 5.5, allowing optimal absorption in the upper GI tract. The technology also enables formulators to accelerate product development of acid-labile or gastric-irritating com- pounds because the capsules eliminate the preparation, application, scaleup, and process validation steps associ- ated with functional coatings. 20 March 2017 Tablets & Capsules liquid fills, as well as filled capsules. A capsule-in-capsule technology we offer uses specialized liquid-filling tech- niques and equipment to place a prefilled smaller capsule into a larger, liquid-filled capsule. The smaller inner capsule can contain a liquid, solid, or semi-solid formulation. Based on the formulation or product requirements, either or both capsules can be made of gelatin or HPMC and coated, if desired, to achieve enteric protection or provide colonic drug delivery. These and other fixed-dose combination products can improve both the therapeu- tic effect and patient com- pliance. Products with a dual-release profile, such as pulsatile- or combination-release functionality, enable formulators to target more than one area of the GI tract. Acid-resistant capsules Launched in 2011 and intended for the nutraceutical market, Capsugel's DRcaps are delayed-release capsules geared toward delivering acid-sensitive ingredients. These capsules protect the ingredients from fully releas- ing and disintegrating in the stomach, then allow com- plete dissolution in the intestine. They also mask unpleas- ant tastes and odors without using shellac or artificial coatings. With a moisture content of 4 to 6 percent at 50 percent relative humidity, the capsules enhance the sta- bility of moisture-sensitive probiotics. They are also suit- able for liquid fills (photo). A number of studies have been conducted with DRcaps, including one that evaluated acid resistance in a capsule-in-capsule format. In this study, pure aceta- minophen was filled into different sizes of capsules, which were then filled into other capsules. Next, the double cap- sules were subjected to in vitro dissolution and disintegra- tion tests. The results showed that the capsule-in-capsule format using DRcaps significantly increased acid resis- tance (pH 1.2) and delayed dissolution in a pH 6.8 JP2 buffer. Under disintegration test conditions, the double DRcaps capsules protect ingredients from fully releasing and disintegrating in the stomach, then allow complete dissolution in the intestine. They accept powder and liquid fills. Acid-resistant capsules protect ingredients from early activation by stomach acid and then release them completely in the intestines.