Innovations in Design: NIA-West

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MissyLowery,MScHeadofIntegratedMarketingCapsugel,nowaLonza company11/13/2017

Innovations in Design: How Do You Stand Out?

• If all other competitors are the same—be different.

Innovations in design

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Prod

uct

Ran

geDosage form selection can help to answer consumer demand

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Liquid-filled Hard Capsules

Soft Gelatin Capsules SachetHard Capsules

Powder / Multi-particulate Filled Capsules

Osmotic, Matrix, Orally Dissolving Tablets

Key

Se

rvic

es

API Characterization / Pre-formulation Studies

API-in-Capsule / Micro-dosingEvaluations

Commercial Manufacturing

Technology Selection Models / Methodologies

Clinical Trial Material (CTM) Manufacture

CTM Primary / Secondary Packaging & Distribution

Drug Product Intermediate

Specialized Handling (highly potent API, controlled

substances, cold chain, hormones, probiotics, other)

Bioavailability Enhancement Targeted Release Capsule Technologies /

EncapsulationSpecialized Applications

Salt Screening / Selection

Micronization

Spray-Dried Dispersions

Hot-Melt Extrusion

Lipid-Based Formulations

Liquid / Solvent-Based Formulations

Nanotechnologies

• Nano-milling

• Nano-crystals

Enteric / Delayed Release Capsule

Technologies

Multi-particulate Technologies

• Fluid-bed layering

• Extrusion/Spheronization

• Lipid Multiparticulates (LMP)

• Mini-tabs

Fixed Dose Combinations

• Bi/Tri Layer Matrix

• Capsule-in-Capsule

• Multiparticulates

Extended / Controlled Release

• Osmotic / zero order release

• Matrix and MP / 1st order release

Colonic Delivery / Liquid Fill Tech

Gelatin Capsules (Coni-Snap)

Specialty Polymer Capsules

• Vcaps Plus (HPMC)

• PlantCaps and OceanCaps

Enteric Capsules

• DRcaps

• Vcaps Enteric

• enTRinsic DDT

DPI Capsules (inhalation)

Sprinkle Capsules

Encapsulation Technologies

Specialized Clinical Trial Capsules

Taste-Masking Approaches

Pediatric Applications

• MP formulations

• Sprinkle Capsules

Biotherapeutics

• Bio-processing

• Bio-formulations

Inhalation

• SD-based formulations

• DPI capsules

Abuse Deterrent Forms

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Licaps® unique liquid-filled capsule delivery

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• Innovative Liquid Supplement Deliveryü Gelatin, vegetarian and organic capsule options which includes

Non GMO Verified and Clean Label benefitü Filled with liquids, lipids, pastes, and semi-solids

ü Timed release options leveraging polymer choice and combinations

ü Proprietary filling and sealing (fusion) technology

ü Nitrogen bubble helps enhance stability

• Health conscious customersü Combine incompatible ingredients into single doseü Great protection combination depending on

ingredient needs

• Target marketsü Consumer preferring liquid form for faster absorption

ü Unique solution to differentiate performance and consumer identification

DUOCAP® Licaps® Beadlets DUOCAP® with

Beadlets

Liquid Dosage Forms – Gelatin Capsules

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Functionality:1. Lowoxygenpermeability2. Instantsealing(Lowviscosityrequirement)3. Nitrogenbubblehelpsmaintainstability

Benefits:

• EnhancedprotectionforoxygensensitiveproductsExample:Ubiquinol – veryunstablewhenexposedtoair

• EfficientodorandaftertasteprotectionExample:KrillOil– Eliminatesodor

• IncreasecapabilitiesversussoftgelsHighsolidload,lowerviscosity,toleranttoheat

Liquid Solution in a Capsule

• Encapsulation of a pre-solubilized ingredient which is soluble in water or oil

• Designed for improved rate of dissolution for fast release and better bioavailability

• Example uses for this form: üL-Arginine- creation of a free-flowing solution

allows for a higher concentration of active ingredient

üL-Carnitine- liquid form can contain pure L-Carnitine rather than the less soluble salts

L-Arginineinsuspension

L-Argininesolubilized

Micronized Liquid Suspension in a Capsule

• Encapsulation of an insoluble ingredient that has been micronized to a particle size less than 10 microns üSuspended in a lipid or solvent fillüParticles flow freely and are barely

detectable

• Also designed for improved rate of dissolution and better bioavailability

Beadlets in a liquid-filled capsule

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Beadlets in a Liquid-filled Capsule

• Multi component, multi-sized beadlets are suspended in a liquid-fillüLiquid can also contain active ingredients

• Designed to offer flexibility in multiple release rates (immediate, delayed)

• Good for combining incompatible actives or allowing an active to by-pass gastric acids

– Beads allow for targeting and varying levels of controlled release– Can combine fast acting liquid with slow release ingredients

Powder-filled Inner Capsule in a Liquid-filled Outer Capsule

• Size 3 or 4 HPMC capsule filled with a moisture sensitive compound and suspended in a liquid filled HPMC capsule

• Benefits of the MDS/Capsule-in-a-Capsule:ü Designed for a delayed release: inner capsule will

rupture 1-2 hours after ingestionü Protects moisture sensitive compounds

– Water activity in the liquid fill is lower than that of the inner capsule contents, drawing moisture away from the active

– HPMC capsule creates a protective barrier from the outside environment

• Ideal for moisture sensitive compounds such as probiotics and enzymes

§ Studyconfirmedstabilityofprobiotics inDUOCAP®capsule§ CapsugelrecommendationtouseGlycerolasliquidfillinoutsidecapsule

for Probiotics –DUOCAP capsule Stability Study Results

13*recentregistrationchangeSource:CapsugelLabResearch

DUOCAP® Dissolution Case Study

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• Capsule design eliminates the need for any coatings

• Slower dissolution of the inner capsule

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PERC

ENTA

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TIME(HOURS)

Outer

Inner

Gelatin

Dissolution testing was performed using an acetaminophen marker in the outer capsule and a caffeine marker in the inner capsule; medium was USP simulated gastric fluid for the first two hours and then changed to USP simulated intestinal fluid

Beadlet-filled Capsule in a Liquid-filled Capsule

• Combines benefits of a capsule in a capsule with the controlled release properties of beadlets for added extended release

• Designed to offer multiple release rates-beadlets in an inner HPMC capsule can release over 6 to 8 hours

• Good uses for this delivery system would be melatonin or caffeine. Immediate release for rest or energy that will keep working over a period of time

• Caffeine• Theacrine

Timed release of ingredients is important to consumer experience during pre-workout, during workout and recovery

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0.0

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%dissolved(LC)

SamplingTime(min)

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CAFFEINECONTROLLED-RELEASECASESTUDY

Providing protection for acid-sensitive ingredients

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• Unlike other consumer health products, enzymes and probiotics are damaged when exposed to harsh stomach conditions and must be maintained as such in order to be efficient.

• A number of sports nutrition ingredients benefit from the delay in release as well

• Humidity

• Temperature

• Acidstomachcondition

DRcaps™ capsules - Proven Targeted Release

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KeyStudyFindings• DRcapscapsulesdisplayeddelayedreleaseproperties

• Disintegrationstartedapproximately45minuteslaterthanatypicalimmediatereleasecapsuleofabout5minutes

• Forthemajorityofsubjects, completereleasetookplaceintheintestine

• Completereleaseoccurred20minutesaftertheonsetofrelease

• DRcapscapsulessignificantly reducedopportunity fornutritionalingredientdegradationcomparedwithstandardimmediatereleasecapsules

DRcaps™CapsuleHumanClinicalStudy

Capsules Sprinkle Capsules

SachetsRTD Powder

Beverage

Lipid Multi-particulate (LMP) dosage form versatility

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LMPs

LMPApplications

Canimprovetheperformanceofnutritionalactivesintwodistinctcategories:

Curcuminü Avoidclumping ofloose ingredientsandlowelectrostatic

attractionü Consistent releaseforupto6hours(no spikes)ü Useforcombination ingredients

Orally DisintegratingTablets (ODTs)Energy Drinks

Case Study: Improving the delayed release of a mood enhancing product

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• Dissolution Study conducted on LMP filled into DRcaps™ capsules• Controls: LMP filled into gelatin capsule; 2 commercial enteric coated tablets• Dissolution was tested in two stage media: 0.1N HCl for two hours followed by pH 6.8

phosphate buffer• USP Apparatus 1, 100 rpm, 37°C

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%Released

Time (Hrs)

LMPinDRCap LMPinHardGelatinCap CommercialProductA CommercialProductB

LMP in DRcaps capsules release about 10% active at 2 hr

BCAA sustained-release LMP

• BCAAs (L-Leucine, L-Isoleucine & L-Valine) comprise 35% of the amino acids that build muscle. L-Leucine is a regulator that activates protein synthesis through the mTOR (mammalian target of rapamycin)

• Some BCAA products are cheap, synthetic versions that are not water soluble

• BCAAs also have been shown to degrade after being subjected to stomach acids

• BCAAs are bitter in taste and have an unpleasant smell

SustainedRelease

TasteMasking

BioavailabilityEnhancement

Min.4hsustained releaseForprotein shakes with (fastand)slowreleaseBCAA

Neutraltasteand smellLess sugar and flavor needed

Improved stability instomach acids

Less dosage needed

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