The vacant hypromellose capsules are made from hypromellose and excipients. Hypromellose is 2-hydroxypropyl ether methyl cellulose with a relative molecular weight of 86000. It is derived from cotton linter or wood pulp fiber, which is treated with caustic soda and then etherized with propylene oxide, chlorane and alkali cellulose. Based on the addition of gelling agent, the vacant hypromellose capsules can be divided into two types, one with gelling agent and the other without gelling agent.
Most vacant hypromellose capsule manufacturers add gelling agent (such as carrageenan, gellan gum, sodium alginate, etc.) to hypromellose solution to prepare the vacant capsules, as hypromellose does not have the gelling property. However, the gelling agent is easily affected by pH of the dissolution medium and metal ions. In the simulated dissolution test in vitro, the dissolution rate of capsule shells in different dissolution media slows down, and the dissolution rate of the contents is affected as well.
The vacant hypromellose capsules without gelling agent can be dissolved quickly in different dissolution media to release drugs. Currently only Vcaps®Plus from Capsugel and H-caps®-Pure from Lefancaps® are available in the market.
(1) Low water content without brittleness, even with 1% water content. Less influenced by regional environmental deviation. More suitable for hygroscopic and moisture-sensitive drugs or functional food.
(2) The dissolution rate of the capsules without gelling agent is less affected by temperature and pH of the dissolution medium.
(3) Hypromellose is part of cellulose methyl and polyhydroxypropyl ether with a stable chemical property. No risk of cross-linking and Maillard reactions. No interaction with the contents. Disintegration delay of the vacant hypromellose capsules will not be incurred. The drug release rate is relatively stable. Can be widely used.
(4) The vacant hypromellose capsules have a small or no electrostatic effect, and a small electrostatic adsorption to the contents, which hence works better for drug filling.
(5) Hypromellose is compatible with most polymer materials. Coating material is easily adhered to the capsule shells with a good uniformity. It can be a water-based coating as well as a coating with ethanol and other organic solvents. Especially suitable for the preparation of those capsules with controlled release coatings.
(6) Low occurrence rate of friability. Strong moisture resistance and good stability. The vacant hypromellose capsules are more suitable for dry powder inhalers from security prospective compared with empty gelatin capsules.
(7) The vacant hypromellose capsules have a smaller adhesive force on esophagus than empty gelatin capsules. Less adverse reactions such as foreign body sensation. Improved patient compliance.
(8) Low requirements on storage conditions. Almost non-brittle in low humidity environment, stable in high temperature, and not easily adhered.
(9) Originated from plants. No risk of animal disease. Can meet the needs of people with special religious beliefs and vegetarians.
3. Dissolution test with Lefancaps® capsules
At present Lefancaps® has two types of vacant hypromellose capsules, H-caps® (with gelling agent) and H-caps®-Pure (without gelling agent). With a dissolution test on these two capsules, the results indicate that the dissolution rate of H-caps® is greatly influenced by pH and metal ions, while H-caps®-Pure is not affected by them.
3.1 Test method
0.25g cefradine powder is respectively filled into empty gelatin capsules, H-caps® (type I and II) and H-caps®-Pure (type III). Based on the requirements of Cefradine capsules from Ch.P 2020, Volume II, the dissolution data of above finished drug capsules in purified water, pH 1.2 hydrochloric acid solution, pH 4.5 potassium dihydrogen phosphate solution and pH 6.0 potassium dihydrogen phosphate solution are tested respectively.
3.2 Result analysis
(1) The dissolution curve of the empty gelatin capsules, H-caps® (type I and II) and H-caps®-Pure (type III) in water medium is shown in the figure below.