Some active ingredients tend to absorb moisture from the environment, which can lead to chemical degradation, clumping, or changes in solubility and bioavailability.

Gelatin Capsule Characteristics: Gelatin, being hygroscopic, naturally absorbs moisture. When exposed to high humidity, it can soften or lose its integrity, leading to leakage or the breakdown of the capsule.

Environmental Conditions: Manufacturing or storage environments with uncontrolled humidity levels can accelerate moisture absorption, especially when capsules are not packaged or stored properly.

Insufficient Drying or Curing: If soft gelatin capsules are not adequately dried or cured after filling, they can retain moisture that could compromise the capsule’s integrity over time.

Solutions

1. Moisture-Resistant Capsule Materials

To address moisture sensitivity, manufacturers can consider using capsule materials that are less hygroscopic than gelatin. Hydroxypropyl Methylcellulose (HPMC) capsules are a common alternative, as they have lower moisture absorption compared to gelatin capsules. These capsules are especially beneficial for moisture-sensitive drugs as they help maintain the structural integrity of the capsule and prevent moisture-induced degradation of the API.

2. Use of Moisture-Resistant Coatings

Applying protective coatings to capsules can significantly reduce moisture interaction with both the capsule shell and the API. Enteric coatings or moisture-resistant films can be applied to prevent moisture from reaching the active ingredient. These coatings are especially beneficial for APIs that are moisture-sensitive or require controlled release. Additionally, microencapsulation of the API within a protective shell can provide an extra layer of protection against moisture.

3. Controlled Manufacturing Environment

Maintaining a controlled environment during the manufacturing process is crucial. By managing humidity levels in the production area, manufacturers can prevent excess moisture from being absorbed into the gelatin capsules. This can be achieved by using dehumidifiers and climate-controlled rooms during capsule filling and storage. Additionally, air-conditioning systems and humidity sensors should be employed to monitor and regulate environmental conditions.

4. Proper Drying and Curing Processes

To prevent moisture-related degradation, soft gelatin capsules must undergo an effective drying process. This can be achieved by using tumble dryers or vacuum drying systems that help remove excess moisture from the capsules before packaging. This step is particularly important in preventing the capsule shell from becoming too soft or brittle, which could compromise the drug’s stability. Curing the capsules at appropriate temperatures and humidity levels also ensures they maintain their structural integrity.

5. Packaging with Moisture Barrier Materials

Effective packaging plays a key role in protecting capsules from moisture during storage and transport. Using moisture barrier blister packs or aluminum foil can provide an excellent seal that prevents moisture from affecting the capsules. Additionally, incorporating desiccants (e.g., silica gel) inside the packaging can further help maintain an ideal humidity level and prevent moisture-related issues. Packaging should also be tested for moisture permeability to ensure that it provides adequate protection throughout the product’s shelf-life.

Regulatory Considerations

Regulatory bodies such as the FDA, EMA, and USP provide guidelines regarding the stability and packaging of drug products. The USP <661> Plastic Packaging Systems and USP <671> Containers—Glass standards offer recommendations for packaging materials that help prevent moisture-induced degradation of drugs. Additionally, manufacturers are required to perform stability studies under different environmental conditions to assess the effect of moisture on the product’s stability and integrity. These tests should align with ICH Q1A stability guidelines to ensure compliance with international standards.

Industry Trends

The pharmaceutical industry is increasingly focused on the development of advanced packaging technologies that offer superior moisture protection. Innovations in nanotechnology have led to the creation of advanced moisture-resistant coatings that are more effective and thinner than traditional coatings. Moreover, the development of new bio-based capsule materials that offer better moisture resistance while being more environmentally sustainable is an emerging trend in capsule formulation.

Case Study

Case Study: Moisture Control in Soft Gelatin Capsules for Moisture-Sensitive Drugs

A global pharmaceutical company faced issues with the stability of a hygroscopic API in soft gelatin capsules. The capsules were becoming soft and disintegrating, leading to a reduced shelf-life and inconsistent drug release. The company decided to implement a multi-pronged approach: switching to HPMC capsules, improving the drying and curing process, and enhancing packaging with moisture-resistant blister packs and desiccants. After making these changes, the product’s shelf-life increased by 18 months, and customer complaints related to capsule integrity were virtually eliminated. The company also observed improved stability in the API, which led to fewer product recalls and enhanced customer trust.

FAQs

• How can moisture affect capsule stability?
  Moisture can cause gelatin capsules to soften, leading to leaks or a breakdown of the capsule. For APIs, moisture can also lead to degradation, reduced bioavailability, or a change in the dissolution profile, affecting the drug’s effectiveness.
• What are the best capsule alternatives for moisture-sensitive APIs?
  HPMC capsules are an excellent alternative as they are less hygroscopic than gelatin and provide better moisture protection for sensitive drugs.
• Can moisture-sensitive capsules be stored in high humidity environments?
  Moisture-sensitive capsules should be stored in controlled environments with low humidity. Packaging with moisture barrier properties and using desiccants is also crucial for ensuring stability.