Design of Soft Capsule Formulations And Calculation of Softgel Drops

Design of Soft Capsule Formulations and Calculation of Capsule Drops

Pharmaceutical Industry – Li Tongtong, Hou Maojun

Tianjin Central Pharmaceutical Factory No. 2, Tianjin

Abstract

Soft capsules are formulations with gelatin as the shell material. Due to the hydrophilic nature of gelatin, the encapsulated contents must be non-hydrophilic substances. The types of liquid formulations for soft capsules can include oil-oil mixtures. For suspensions containing solid drugs, the formulation can be designed with polyethylene glycol (PEG) as the base or with oil-based systems, but stabilizers must be added. Alternatively, emulsions of oil and PEG can also be formulated.

Keywords:

• Soft capsules

• Oil-oil mixtures

• PEG with solid drugs

• Oil with solid drugs

• PEG-oil with solid drugs

Introduction

In recent years, soft capsule products have gained popularity in the market due to their safety, aesthetic appeal, ease of administration, and high bioavailability. The number of manufacturers and market demand have been steadily increasing. However, the production of soft capsules involves high technical requirements and significant challenges, often leading to difficulties in manufacturing. Issues in formulation design frequently affect product quality, severely limiting production yield and increasing costs. Based on years of practical experience, this article discusses the types and methods of designing liquid formulations for soft capsules.

Since the gelatin shell of soft capsules is hydrophilic, the liquid formulation must meet specific requirements. The moisture content in the formulation must be less than 3% to ensure capsule quality and prevent deformation or leakage caused by moisture absorption.

Soft capsule formulations may consist of oils, oil-oil mixtures, or solid drugs. For solid drugs, they must be processed into suspensions with a suitable base. This article describes methods such as mixing solid drugs with PEG, mixing with oil-based systems, and emulsifying PEG-oil mixtures with solid drugs.

1. Oil-Oil Mixtures

To accommodate the hydrophilic gelatin shell, many soft capsule formulations use oils or oil-oil mixtures as the base. Examples include commercially available evening primrose oil capsules, fish oil capsules, and seal oil capsules.

Formulation Design Steps:

1. Measure the Density of the Oil

• Use a specific gravity balance to determine the density of the oil. For oil-oil mixtures, ensure thorough mixing before measurement.

2. Determine Capsule Fill Weight

• The fill weight is based on customer requirements or pharmacopoeial standards.

3. Calculate Mold Drops

   Calculation:

   Example:
   For a 500 mg evening primrose oil capsule with a density of 0.92 g/mL:

• Volume = 0.5 g / 0.92 g/mL = 0.54 mL

• Drops = 0.54 × 16.23 = 8.67 drops

• A = Capsule fill weight (g) / Filling material density (g/mL) = Volume per capsule (mL)

• B = Volume per capsule (mL) × 16.23 = Drops

• A "drop" is a unit of volume for soft capsule molds, where 1 drop = 1/16.23 mL.

• The number of drops is calculated based on the capsule fill weight and the density of the filling material:

4. Select Capsule Shape

• The shape (e.g., cylindrical, olive-shaped, spherical) should prioritize ease of swallowing. Larger capsules are typically cylindrical, while smaller ones can adopt various shapes.

5. Final Determination of Mold Drops

• Due to machine tolerances, the actual drop count should slightly exceed the theoretical value (e.g., 10 drops for the above example).

This calculation method also applies to the following formulations.

2. Non-Oily Base Suspensions (PEG-Based)

For solid drugs, PEG 400–6000 can serve as a non-oily base to form a homogeneous suspension.

Key Considerations:

• Moisture Absorption: PEG’s hydrophilicity may increase the capsule weight by ~10%, requiring extra volume in the design.

• Drug Solubility: Water-soluble drugs may migrate to the capsule shell.

• Capsule Hardening: PEG absorbs moisture from the shell, necessitating added water/glycerin in the formulation to maintain flexibility.

3. Oily Base Suspensions

Solid drugs can also be suspended in oils with stabilizers.

Key Steps:

1. Particle Size: Solids should pass an 80-mesh sieve for uniformity.

2. Base Adsorption Number: Determines the minimum liquid base required per gram of solid.

• Method: Gradually add oil to 40 g of solid until a smooth, flowable mixture forms (tested at a 45° angle).

• Formula: Adsorption number = Oil weight / Solid weight.

3. Stabilizers: Prevent sedimentation during and after encapsulation.

4. Anhydrous Emulsions

Emulsions (O/P or P/O types) can be formulated using oil and anhydrous phases (e.g., PEG 300–2000 or polyols).

• Note: O/P emulsions exhibit better drug release in physiological environments than P/O types.

Conclusion

Soft capsule formulation design primarily involves the above methods. Practical adjustments based on experience are essential for optimal results. Mastery of these techniques requires long-term practice and refinement.

For the analysis of soft capsule production equipment, please click me.

For the detailed parameters of the softgel encapsulation machine, please click me.