Soft Gel Capsules & Liquid-Filled Hard Shell (LFHS) Manufacturing Solutions
Introducing Soft Gel Capsules
Soft Gel Capsules are beneficial for complex drug manufacturing & development. In addition to the flexible production opportunities, soft gels are beneficial to improve: solubility, stability, bioavailability, permeability, and metabolism inherent to the drug molecule.
SOFT GEL MANUFACTURING CAPACITY FOR YOUR IMMEDIATE NEEDS
Pii is a CDMO leader in soft gel development and manufacturing. With more than 25 years of experience, we have developed over 40 soft gel products, gained approval for multiple soft gel commercial products, and currently have two NDA soft gel products in development. Our highly experienced scientific team has manufactured various batch sizes, from small scale up to 1.5 million units, some of these with potency levels as low as 0.25 micrograms (250 nanograms).
Pii’s Soft Gel Machine Capabilities
- Up to 1.5 Million Capsules Per Batch
- Compounded Bulk up to 700 Liters
- High Potent Compounds, Hormones & Complex Soft Gels
- Manufacturing for Smaller Commercial Batch Requirements (i.e. Orphan Drugs, low-volume products)
- Bottling and Labeling with Serialization
Pii’s Complex Soft Gel Manufacturing Capabilities
Our Soft Gel Capsule Manufacturing team specializes in complex molecules, NCE’s, NDA’s,
with expertise in handling both potent and non-potent programs.
- Orphan Drugs
- High-Potency and Containment Products (Safebridge Category IV & Hormones)
- Low-Dose Programs
- Bioavailability Enhancement Formulations
- Multiple APIs
- DEA-Controlled Substances (Schedule I-V & L1)
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GMP & FDA-Certified CDMO
for Soft Gel Manufacturing
Pii is a GMP-certified CDMO designed to be a one-stop shop for your soft gel capsule development and manufacturing needs. As specialists in complex soft gel formulation and processes, we have designed our services to meet our customers’ needs for on-time delivery of the highest quality products.
Project Management & Personal Relationship
Our analytical, development, manufacturing, quality assurance, and project management teams meet twice a week to review all projects. This leads to better interactive communications and allows us to have streamlined logistics, improving timelines and minimizing delays to bring your product to patients safer and faster.
Facilities Designed to Reduce Supply Chain Risks
Our campus includes four GMP-certified and FDA-certified facilities, housing 70 manufacturing suites with all the necessary analytical and microbiological testing capabilities on-site in Hunt Valley, MD.
All of Pii’s soft gel manufacturing equipment and dedicated production teams are located under one roof. We know how important it is to ensure that proper controls are in place for safe handling of highly potent compounds, hormones or DEA Scheduled drugs, preventing cross-contamination, and ensuring purity of the dosage form. By having our team and production capabilities under one roof, in a dedicated area, we are able to maintain robust processing and safe handling by our experienced team of soft gel experts.
Your Product - Your Patent
Pii does not promote any of its own proprietary technology. With Pii’s technical experience and Scientific Know How, our team designs a formulation and process that allows the product to reach its full potential. This means that all proprietary designs and formulations for your product are yours, with no licensing fees attached.
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Soft Gel Manufacturing
Improve Solubility, Stability, Bioavailability & Permeability with Soft Gel Capsules
Bioavailability enhancement has always been a strong area for Pii, especially within the soft gel area, where many drugs may require a formulation in a lipid, liquid, or suspension state. Understanding the molecule and chemistry is key to designing a formulation that improves bioavailability, provides for better dissolution in the GI tract, and exhibits excellent stability longer term. Based on API solubility, formulations ranging from simple PEG 400 with an acid or base, to triglycerides, lipophilic surfactants, and or hydrophilic surfactants, may be selected for optimal drug absorption.
Pii can design a formulation plan to work with products that may require smaller batch sizes to minimize the use of API during development/clinical phase.
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Soft Gel Capsule Benefits
Soft gels are versatile in size, shape, and color and are easier to swallow, making them ideal for pediatric and geriatric populations. The delivery base is a soft gelatin shell surrounding a liquid or semi-solid center that can mask odors and unpleasant tastes. The outer shell is hermetically sealed, protecting from light and oxygen, making it an ideal, cost-effect delivery method.
Pii’s strong R&D experience and background in soft gel formulations equates to a greater chance of success in a shorter time for your drug development process.
More soft gel capsule benefits include:
- Enhanced solubility
- Enhanced absorption
- Enhanced bioavailability
- Dose uniformity
- Nanosuspension fill
- Quick-acting/dissolution in the stomach
- Helps prevent oxidation for light- and oxygen-sensitive drugs
- Excellent for cytotoxic, potent, and irritating drugs
Bioavailability Challenges? Pii is Here to Help
Soft Gel Capsules are Ideal for LBDDS, SEDDS, & SMEDDS Delivery Systems
Soft gel capsules are ideal for lipid-based drug delivery systems (LBDDS), self-emulsifying drug delivery systems (SEDDS), or self-micro emulsifying drug delivery systems (SMEDDS). LBDDS is specific for formulations containing a dissolved or suspended drug in lipid excipients.
LBDDS can be simple or complex formulations and provide the increased solubilization and absorption needed, resulting in enhanced bioavailability.
Soft Gels with Multiple APIs, High Potency Compounds, & Hormones
Soft gel capsules are a proven drug delivery technology for challenging molecules because of their effectiveness in increasing the solubility and permeability of drugs. An API powder can be contained in a soft gel once it is in a liquid/oil-base state to minimize exposure to employees and prevent cross-contamination. Soft gels are also suitable for cytotoxics, hormones, and other containment products, offering accurate and precise dosing – even at the microgram level.
Key benefits include:
- Delivery of non-aqueous solution/suspensions and solubility enhancement (e.g., SMEDDS, lipid-based systems, nanosuspension)
- Ideal for products with multiple APIs (combination products)
- Delivery of very low doses of API with precision and accuracy
- Protection against oxygen and light for oxygen and photosensitive APIs
- Readily dissolve in vivo, providing faster onset of action
- Manufacturing process minimizes dust generation
- Continuous process leading to seamless scale-up
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Soft Gel Formulation Challenges
Formulation know-how is key!
Critical formulation challenges:
- Compatibility of the shell (gelatin or non-animal based material) and formulation fill material (i.e. certain PEGs, pH, water content)
- Stability (oxygen exposure control, light exposure control, and temperature controls during compounding and filling, as well as drying)
- Long-term stability (leaking, cross-linking, and API degradation)
- Uniformity of drug suspension (API particle size, viscosity, and agitation)
- Fill formulation selection for overall required absorption characteristics
- Cross-linking can be an issue, and controlling cross-linking between fill and gelatin during storage is key
- Requires specialized equipment for production
- Smaller-batch production capabilities available for commercial products that have lower volumes (i.e. orphan drug products)
- Larger batch production (up to 1.5MM units)
Capsules: Soft Gel vs. Hard Shell
A soft gel capsule can be used in place of a hard shell capsule if the fill material is in a liquid, oil-based, suspensions, or semisolids, and if the fill is compatible with the chosen gelatin formulation. Powders, granules, pellets, and other dry materials can be put into hard shell capsules.
Soft Gel Capsules:
- One-piece capsule that is formed from two ribbons of formulated gelatin (gelatin/plasticizers/water) and filled/hermetically sealed in the same process stream
- Typically contain liquids, suspensions, oils, PEGs, lipophilic and hydrophilic surfactants
- Used often for formulations that require bioavailability enhancement to improve absorption (BCS II and IV)
- Easily and rapidly absorbed in stomach
- Come in many shapes, sizes, and colors
- Suited for high drug-load products
- Help prevent oxidation of fill material from light and oxygen exposure
- Excellent for masking bitter taste or unpleasant odor
- Easier to swallow due to the plasticity of the shell
- Can be used for vaginal suppositories or topical applications (twist top)
- Can be used for suspensions and nanodispersions
- Aesthetically, can be custom designed for coloring and imprinting
- Can have enteric properties
Pii’s Liquid-Filled Hard Shell (LFHS) technology includes a more defined development process for compounds that require higher temperature fill (more than 40 degrees.) and cannot be processed via soft gel technology. Pii has a wealth of experience in formulating and testing a variety of complex materials and is ready for your drug development challenges.
Hard Shell Capsules:
- Two-piece gelatin/HPMC capsules that are filled and either lock together or sealed by hydroalcoholic application (liquid-filled hard caps)
- Typically contain powders, granules, pellets, extracts or even liquids that are heated and then, when cooled, congeal
- Can be banded as needed
- Limited shapes, but many sizes and colors
- Can have enteric properties
Gelatin- vs. Vegan-Based Soft Gel Capsules
Gelatin-based (animal) soft gel capsules are more prevalently used than vegetarian-based. Today, most animal-based gelatin products are manufactured and tested to prevent contamination for BSE/TSE. Pii only uses the highest quality vendors and materials to ensure the purity of the material.
Some markets may demand vegan- or vegetarian-based products. These materials tend to be more expensive and require more specialized processing capabilities. In general, the use of animal-based gelatin is more common.
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Soft Gel Glossary of Terms
Bioenhancers: Bioenhancers work to increase a drug's bioavailability and solubility, and help protect a drug from being broken down by stomach acid or digestive enzymes.
Bioenhancers can also improve the rate at which a drug is absorbed into the bloodstream.
Cosolvents: These solvents are added to a drug formulation to improve solubility. Cosolvents reduce the surface tension of the drug, making it easier for the drug to
dissolve.
Encapsulation: Enclosing a drug in a capsule protects the drug from the environment can improve the taste of a drug or make the drug easier to swallow.
Gelatin: This protein is derived from collagen that is then used to make soft gel capsules. Gelatin provides the clear, tasteless, and non-toxic attributes to a soft gel.
Lipid-based formulations: The drug formulations contain lipids, such as oils or fats, and are often used to deliver drugs that are poorly soluble.
Plasticizer: This substance is added to gelatin to make it softer and more pliable. Plasticizers weaken the bonds between the gelatin molecules, making the gelatin more flexible.
Solubility: The solubility of a drug determines how much of the drug will be absorbed into the bloodstream.
Soft gel capsule: A soft gel capsule is a single-piece, sealed dosage form made of gelatin and a plasticizer. Soft gel capsules are often used to deliver liquid/oil-based, suspension, or semisolid formulations.
Suspension: This drug formulation contains solid particles suspended in a liquid. Suspensions are often used to deliver medications that are poorly soluble.
