Liquid-Filled Hard-Capsule Technology

Over the last twenty years, we have built an unrivaled level of experience and track record in designing and developing LFHC formulations, as well as the liquid filling of hard shell capsules. Capsugel has manufacturing sites in the U.S., Europe and Asia producing billions of soft gelatin and liquid-filled hard capsule (LFHC) units annually for the pharmaceutical and health & nutrition market segments. More than 25 commercial biopharmaceutical liquid-filled hard capsule products are produced annually as well as hundreds of health and nutrition products.

• Five LFHC commercial manufacturing sites in the US, Europe and Japan serving biopharmaceutical and consumer health & nutritional customers
• Co-located product development, pilot and commercial scale manufacturing
• Feasibility, stability and clinical batch supply
• Non-GMP and GMP facilities with separate clean room suites
• FDA/MHRA inspected and accredited sites
• Specialized manufacturing for cytotoxics, antibiotics, peptides and high potency compounds
• High containment capability to OEB 4-5
• Capsule coating as an additional lever for modified release and colonic delivery
• Banding or proprietary Licaps® Fusion technology for optimized LFHC sealing efficiency
• Primary and secondary packaging

Our LFHC Center of Excellence for the biopharmaceutical market is located in Edinburgh, Scotland (UK) and serves the global market with integrated product design, development and manufacturing of drug products. Formerly Encap Drug Delivery, this facility is the largest in the world dedicated to pharmaceutical liquid and semi-solid production using LFHC technology. Capsugel Edinburgh has an extensive track record in designing optimized lipid / semi-solid / liquid formulations, and advancing compounds from feasibility through clinic to commercialization. 
 
The Edinburgh site is US FDA and MHRA accredited, and has controlled substance licenses as well as dedicated high containment / isolation capability. 

Additional integrated LFHC design, development and manufacturing sites include Greenwood, South Carolina; Ploermel / Colmar, France; and Sagamihara, Japan.
 
Our product development teams share best practices in identifying optimal technologies and approaches for formulation challenges. A full range of pre-formulation and feasibility studies, including solubility screening for new chemical entities, is conducted for client compounds. For formulations being developed used LFHC technology, dedicated development suites are used for small-scale lab encapsulation for feasibility assessments, stability data and final formulation selection. 

• Lipid / solvent / co-solvent formulations 
• Liquid / semi-solid products 
• Colonic delivery using LFHC and specialized coatings 
• Dual delivery with specialized capsule-in-capsule technology 
• Abuse-deterrent formulations 

• Poorly soluble compounds 
• Potent and highly potent compounds 
• Cytotoxics, antibiotics, peptides 

• Integrated product development and commercial manufacturing at one site
• Specialized isolation capabilities for potent and highly potent compounds 
• Multiple production lines with capacity >100MM LFHC units per annum 
• Pilot and commercial manufacturing 
  – Non-GMP and GMP capabilities
  – Feasibility, stability and clinical batches 
• In-line printing capabilities 
• Primary and secondary packaging

Capsugel’s focus on science & engineering has led to the development of proprietary equipment and processing techniques, to provide optimal efficiency, reliability and productivity for our LFHC clients.

• Optimized capsule design to increase mechanical strength
• High precision liquid dosing pump can handle free-flowing to highly viscous suspensions
• Proprietary fusion sealing technology allows high efficiency capsule handling and sealing; optional capsule banding
• New automated on-line systems for 100% inspection

Specialized liquid filling and sealing equipment has also been engineered for lab and pilot scale manufacturing of liquid-filled hard capsule dosage forms. Banding capability is also in place as a capsule sealing option.

Two sealing technology options are available to pharmaceutical and biotech companies developing liquid-filled hard capsule products. Capsule banding, where a visible band of gelatin or HPMC is applied around the joint between the capsule – thus sealing the caps to the body of the capsule – is one approach often favored for client branding (band coloring), dose identification, or tamper-evidence considerations. The second option is Capsugel’s proprietary LEMS® (Liquid Encapsulation Micro Spray) or “Fusion” technology, which utilizes the application of a fine micro-spray of sealing solution around the joint between the body and the cap of the capsule so that the contacting surfaces of the cap and the body are effectively fused together. 
 
Capsugel’s engineering advancements in capsule filling and sealing of liquid hard shell capsules – spanning more than 25 years – helps ensure consistent product quality and a robust, leak-proof seal using either of these sealing technologies.