Capsule-in-Capsule Technology - Pharmaceutical Technology

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Capsule-in-Capsule Technology
The author outlines how to choose carriers and capsule shells according to dosage requirements and intended use. This article is part of a special Drug Delivery issue.

Pharmaceutical Technology
pp. s26-s29

Capsule-shell choice

The capsule-in-capsule format is independent of hard-capsule source and may be applied to gelatin or hydroxypropyl methylcellulose (HPMC) shells. As a guide, the inner hard capsule should be two sizes smaller than the outer (e.g., a size 2 capsule would fit in a size 0 outer capsule). Size considerations may affected by the introduction of coatings (e.g., enteric or colon-targeted for either or both capsules).


The capsule-in-capsule system has wide potential for commercial exploitation. In particular, it is suited to the delivery, in a single dosage unit, of a selected pharmaceutical active according to a biphasic profile (e.g., a prompt and a slow-release combination suited to oral analgesics). Furthermore, the second-phase delivery of the active ingredient could be targeted by appropriately coating the inner capsule for local delivery to a specific intestinal site (e.g., the colon). In addition to use for single-drug formulations, the system is appropriate for combination products, as described above. In its simplest form, the system could deliver two actives, each of which could be formulated for its specific optimized delivery and stability profiles. Complex combinations may be devised according to compound, delivery, and market needs.

It is important that the system be suited to manufacturing. Manufacturability may be achieved using highly-modified liquid-fill equipment in combination with standard sealing machinery (e.g., S-100 machine, Qualicaps Europe, Madrid). Briefly, the inner capsule is produced on standard filling–sealing equipment. It is further processed on a second dual-station machine in which one of the original liquid-fill stations has been replaced by a unit that feeds the inner capsule into the filled outer-capsule body. Inevitably, this second process is speed-limited to half of that for the original machine and does represent a manufacturing cost. The commercial viability of such an approach will vary according to product and patient convenience. Patents have been granted for this delivery system in Europe and in the US (2, 3). The technical availability of the approach has stimulated the commercialization of a high-end European lipid-based nutraceutical product using HPMC capsules and aimed at travelers. The concept has been well received by various pharmaceutical development groups.


The approach for formulating capsules in a double liquid-filled capsule format is adaptable for various formulation aims and market sectors. It is suitable for pharmaceuticals (e.g., in providing various release profiles, including one or more actives, or for coating and delivery to a specific region of the gastrointestinal tract) and for sports-nutrition products. The system may be used for gelatine and HPMC capsule formats.


The author acknowledges his colleagues Victor Young, development manager at Encap Drug Delivery, and Massoud Bakhshaee, chief scientific officer of Encap Drug Delivery, for their provision of data for this report. The author also acknowledges Stephen Brown, CEO of Encap Drug Delivery, for his helpful suggestions.

W.J. Bowtle is a technical director at Encap Drug Delivery, Units 4, 5 and 6, Oakbank Park, Livingston, United Kingdom EH53 0TH, tel. +44 1506 448080, fax +44 1506 448081,


1. M. Richardson and S. Stegemann, Tablets and Capsules 8 (1), (2007), available at, accessed Aug 15, 2010.

2. M. Bakhshaee, W. Bowtle, and A. Mc Naughton, "Delivery device," European patent 1301178, Jan. 2007.

3. M. Bakhshaee, W. Bowtle, and A. Mc Naughton, "Delivery device, method of using and method of manufacturing," US patent 7,445795, Nov. 2008.


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