1.Introduction

According to the properties of dissolution and release, the capsules are mainly divided into two types, gastric soluble capsules and enterosoluble capsules.   

Enterosoluble capsules are generally produced by incorporating drugs into the enterosoluble hard capsules, enabling the contents to achieve targeted delivery in the small intestine or big intestine, providing the protection of drugs from gastric enzymes or gastric acid, and avoiding a powerful irritation on the gastric mucosa.

In recent years the pharmaceutical industry have developed rapidly both at home and abroad. In particular, the R&D of new dosage forms and varieties of pharmaceutical preparations plays an important role in improving drug efficacy, reducing drug toxicity and side effects, increasing drug bioavailability and improving patient compliance. The R&D of targeted drug delivery system in the intestines is of significant clinical value. 

2.Process Category

Enterosoluble and delayed release hard capsules are prepared by film-formers and enteric materials under the corresponding process conditions. There are two types of preparation processes, coating process (multiple dip coating) and non-coating process (one-time formation).

At present enterosoluble empty gelatin capsules and enterosoluble vacant hypromellose capsules are available in the market. The former one are usually prepared by crosslinking with formaldehyde, or surface coating with enteric coating materials, such as cellulose acetate phthalate (CAP), hydroxypropylmethyl cellulose phthalate (HPMCP), hydroxypropylmethyl cellulose acetate succinate (HPMCAS), etc. The latter one are prepared by wrapping the capsule shells in a layer of enteric coating, and mainly adopts the process of using the enteric coating materials for secondary coating preparation.

Due to a large number of organic solvents used in coating process (such as ethanol, acetone, etc.) to dissolve enteric materials, there are great potential safety hazards to the operators and production workshops. Moreover, the coating preparation process is very complex at a relatively high cost. Meanwhile, there are a large number of organic solvents volatilized in the production environment, which will bring a great risk on the occupational health of the operators. Hence, the use of enterosoluble capsules with coating is quite restricted, and even banned in European and American countries.

3.Dissolution tests with Lefancaps® capsules

Currently Lefancaps® can offer enterosoluble vacant hypromellose capsules (H-caps®-Enteric) and delayed release vacant hypromellose capsules (H-caps®-DR). These two capsules do not use organic solvents, and are made by a one-time formation process (non-coating) to avoid the risks of fire safety and employee occupational health in the production and storage processes.

1) Dissolution test with H-caps®-Enteric

The dissolution data of finished capsules in gastric fluid and intestinal fluid are tested respectively for the dissolution test. The results indicate that H-caps®-Enteric are insoluble in gastric fluid environment within 2 hours, in compliance with the enteric preparation requirements of Ch.P, USP and EP, can protect acid-sensitive drugs from acidic environment, and avoid a powerful irritation on the gastric mucosa.

2)Dissolution test with H-caps®-DR

0.25g cefradine powder is filled into H-caps®-DR for the dissolution test. Based on the requirements of Cefradine Capsules from Ch.P 2020, Volume II, the dissolution data of finished capsules in gastric fluid is tested. The result indicates that H-caps®-DR are not easily soluable in acidic medium, nor fragile in dry condition. H-caps®-DR are suitable for those substances which will reduce the potency of ingredients by acidity, and have a powerful irritant effect on the gastric mucosa.

4.Applications

Based on the requirements of Enterosoluble Capsules from Ch.P 2020, enterosoluble capsules can protect the contents within 120 minutes in the simulating gastric fluid. H-caps®-Enteric and H-caps®-DR from Lefancaps® not only have the property that protecting acid-sensitive drugs from the acid environment, but also have the advantage of vacant hypromellose capsules with low water content. They are more suitable for Proton Pump Inhibitors (PPIs) drugs that are sensitive to humidity, unstable and degradable under acidic conditions, such as omeprazole, esomeprazole, dexlansoprazole, rabeprazole, pantoprazole and etc.