How Do Empty Enteric-Coated Capsules Release Their Active Ingredients?

Enteric-coated capsules are widely used in pharmaceutical formulations to protect the active ingredients from the acidic environment of the stomach and ensure their release in the more neutral or alkaline conditions of the small intestine. This targeted release mechanism is crucial for the efficacy of certain drugs, particularly those that are acid-sensitive or intended for local action in the intestines. In this blog post, Wecaps will share with you how hard enteric-coated capsules release active ingredients, focusing on the materials used and the physical and chemical processes involved.

Understanding Enteric Coating

The term "enteric" refers to the small intestine, and enteric coatings are designed to resist dissolution or disintegration in the acidic pH of the stomach (approximately pH 1.5 to 3.5) but to dissolve and release their contents in the more neutral to slightly alkaline pH of the small intestine (pH 5.5 to 7.5). The primary purpose of enteric coatings is to protect the active pharmaceutical ingredient (API) from degradation in the stomach or to prevent the API from irritating the gastric mucosa.

Materials Used in Enteric Coatings

The choice of materials for enteric coatings is critical for ensuring that the capsule performs as intended. Commonly used materials include:

1. Methacrylic Acid Copolymers: These are widely used in enteric coatings due to their well-defined dissolution profiles. For example, Eudragit L100 and S100 are methacrylic acid copolymers that dissolve at pH 6.0 and 7.0, respectively.

2. Cellulose Derivatives: Hydroxypropyl methylcellulose phthalate (HPMCP) and cellulose acetate phthalate (CAP) are popular choices. These materials are insoluble in acidic environments but become soluble as the pH increases.

3. Polyvinyl Acetate Phthalate (PVAP): This material is another common enteric polymer that provides good resistance to gastric fluids and releases its contents in the intestines.

4. Fatty Acids and Waxes: These are often used in combination with other polymers to enhance the protective properties of the coating.

The selection of the coating material is guided by the desired pH threshold for the release, the stability of the API, and the compatibility of the coating with the capsule shell and the API.

Mechanism of Action: How Enteric-Coated Capsules Work

The functionality of enteric-coated capsules hinges on their ability to remain intact in the stomach and then disintegrate or dissolve in the intestines. The process can be broken down into several stages:

1. Stability in the Gastric Environment

When an enteric-coated capsule is ingested, it first enters the stomach. The acidic environment here is designed to mimic the natural pH conditions of the stomach, ensuring that the capsule remains intact. The enteric coating is composed of polymers that are insoluble at low pH, meaning that they do not dissolve or allow the release of the API. This resistance is achieved through the ionization properties of the polymers. For example, methacrylic acid copolymers remain non-ionized in acidic conditions, rendering them insoluble.

2. Transition to the Small Intestine

As the capsule moves from the stomach to the small intestine, it encounters a significant change in pH. The pH gradually increases from around 4 to 5.5 in the duodenum to as high as 7.5 in the ileum. This shift in pH is critical for the activation of the enteric coating.

3. Dissolution in the Intestinal Environment

Once the capsule reaches the small intestine, the enteric coating begins to dissolve. This is due to the ionization of the polymer in the higher pH environment. For instance, methacrylic acid copolymers will ionize at a pH above their specific threshold (e.g., pH 6.0 or 7.0), causing the polymer to dissolve. As the coating dissolves, the capsule shell is exposed to the intestinal fluids, leading to the release of the API.

4. Release of the Active Ingredient

The dissolution of the enteric coating exposes the capsule's contents to the intestinal environment. Depending on the formulation, the API may be released rapidly or in a controlled manner. If the capsule contains a powder, granules, or pellets, these will disperse in the intestinal fluids, allowing for the dissolution of the API and subsequent absorption through the intestinal wall.

In some formulations, the release of the API is further controlled by additional layers or coatings inside the capsule, ensuring that the drug is released over an extended period or at a specific site within the intestines. Enteric-coated capsules represent a sophisticated drug delivery system that protects sensitive APIs from the harsh acidic environment of the stomach and ensures their release in the small intestine.