Full System Moisture Management for Drug Preservation SCIENCE OF STABILITY MASHANTUCKET, CT OCTOBER 14, 2015 Public Clariant Healthcare Packaging 14.10.2015
2 Creating value with innovative and sustainable solutions Overview Clariant is an internationally active specialty chemical company contributing to value creation with innovative and sustainable solutions in multiple industries. Clariant s core Key Facts* 17 K employees worldwide to design to produce to market Desired performance in customer products 6.1 Bn CHF sales in 2014 4 Business Areas Headquartered near Basel, Switzerland Listed on the SIX Swiss Exchange *As of Feb 2015
3 Healthcare Packaging falls within the Plastics & Coatings Business Area of Clariant Natural Resources Plastics & Coatings Catalysis & Energy Care Chemicals Oil Services Mining Solutions Refinery Services Functional Minerals Water Treatment Additives Pigments Masterbatches Healthcare Packaging Catalysts Energy Storage Personal Care Industrial Care Home Care Crop Care Industrial Biotechnology Food & Feed
4 Healthcare Packaging s global presence allows us to address your worldwide network Plants Sales offices R&D centers Future plant (2017)
5 Drug degradation induced by uncontrolled moisture Meeting the challenge of stability requires an understanding of the mechanisms leading to a loss in performance of the pharmaceutical. CHEMICAL DEGRADATION LOSS OF POTENCY DEGRADATION PRODUCTS PHYSICAL DEGRADATION API FORM MODIFICATION DISSOLUTION ACCURACY OF DELIVERY MECANICAL PROPERTIES PHYSICAL APPEARANCE
6 The challenge of drug protection STABILITY USAGE
7 Controlled headspace has two primary dimensions An optimized packaging systems calls for combined expertise in Designing the barrier Limiting the ingress of moisture from the outer environment into the packaging s interior Designing the active protection Managing the moisture exchange occurring inside the microenvironment of the packaging
8 Time of protection is not an absolute value Drug protection time is not an absolute value set by packaging design attributes, but will result also from drug properties and conditions of use. Absorption Capacity (mg) Protection time (days) Moisture burden (mg/day)
9 Protective barrier Clariant Healthcare Packaging 14.10.2015
10 Protective barrier Preserves the products contained in the packaging from the environment MVTR quantifies the barrier performance of a package against moisture transmission. Its is the combined result of : Design attributes Usage attributes
Design Attributes Usage Attributes 11 Conclusion (Protective barrier) Passive performance of the packaging is not an absolute value. Moisture transmission rate needs to be expressed in regard with the test conditions Absorption Capacity (mg) Ingress rate (mg/day) = Protection time (days) Passive barrier Size and shape Raw materials Seal quality Usage Climate zone Storage conditions
12 Active Moisture Control Clariant Healthcare Packaging 14.10.2015
13 Active moisture control The role of desiccants is to maintain the atmosphere inside the container below the degradation threshold during the entire shelf-life Desiccant capacity is determined to Compensate for packaging permeability Adsorb the moisture initially introduced inside the packaging
14 Adsorbents Silica gel - amorphous silicon dioxide - water vapor adsorption Molecular Sieve - synthetic zeolite - water vapor and gas adsorption Bentonite - desiccant clay Adsorbents are Hygroscopic substances that physically bind water vapor from the air to fix it on the surface of a solid. They are used to maintain a dry atmosphere in containers. Activated Carbon 2-in-1 ADP - odor adsorption - desiccant + carbon - water vapor and odor adsorption - desiccant polymer - water vapor adsorption and barrier
15 Life cycle of a packaging with desiccant At packaging Moisture enters the headspace In-use by patient Moisture enters through repeated opening/closing cycles 1 4 After packaging Moisture transfers from drug products to the desiccant 2 3 During shelf storage Moisture ingresses by permeation
16 Thinking as a system System oriented mindset is required to Optimize costs of the complete solution Develop customized design for covering the specific drug requirements Reduce stability iterations and save development time Climatic conditions and profile of use Closure Drug product Desiccant Container
Design Attributes Usage Attributes 17 Full system active moisture control requires evaluation of all parameters The actual capacity which is relevant for an application can not be derived from a single data point disclosed by material specification: it has to be considered in regard with the maximum admissible exposure level of the product contained in the packaging. Desiccant Sorption isotherm Dosage Drug product Drug sorption isotherm Chemical stability Physical stability Absorption Capacity (mg) Ingress rate (mg/day) = Protection time (days)
18 Available Desiccant Configurations Clariant Healthcare Packaging 14.10.2015
19 Desiccants within pharmaceutical containers Dropped-in Integrated Integrated Embedded
20 Drop-in desiccants Drop-in desiccants are the most standardized and are fully automatable Canisters & Capsules High speed automatic insertion (300-600 cpm) Continuous run (hopper fed) Printed or labeled Packets Continu-Strip hole punch packets Compatible with all standard insertion equipment on the market
21 Integrated desiccant Desiccant component incorporated into the container or closure Tubes & Stoppers Printed tubes 6-color offset Innovative stopper closure - Desiccant - Tamper evident - Spiral or non-spiral - Hot stamping IDC Built-in desiccant Tamper evident Child resistant (option) Ergonomic Screw or snap cap Precision molding eliminates need for induction seal
22 Embedded ADP Advanced Desiccant Polymer Desiccant embedded directly into plastic, providing humidity protection in limitless configurations Dustless desiccant Conducive to multiple molding processes depending on application Ideal for diagnostic or pharmaceutical applications 1 2 3 1 2 3 Secured cap ADP Insert Exterior HDPE vial
23 Latest developments : EQuilibrium sorbent Clariant Healthcare Packaging 14.10.2015
24 Water activity Introducing a drug product with conventional sorbents inside a container, will change the initial state of the drug product. Typically some moisture from the dosage forms transfers to the desiccant. Standard desiccant dosage will typically maintain low humidity inside the packaging throughout the shelf storage period
25 Impact of relative humidity on hard or soft gel tablets At low humidity, capsules may lose moisture and become brittle. At high humidity, capsules may gain moisture and soften, swell or fuse together Hence, special care for handling and storage is required, and remaining packaging options are often limited.
26 EQ provides moisture regulation within packaging EQ solutions are designed to maintain a specific equilibrium relative humidity Specially engineered to perform simultaneously as an humectant or a desiccant, maintaining a the equilibrium relative humidity (erh) inside a product packaging within a predetermined range. EQ is available via canisters, packets and bags platforms: EQ-Pak and EQ-Can to address : Risks of excessive humidity: Instability, deliquescence; decomposition, microbial growth, Risks of excessive dryness: efflorescence of the coating or API; impairment of drug deposition (inhalation), brittleness (gel caps), electrostatic loading (powder bulks),
Humidity inside packaging 27 EQ provides moisture regulation within packaging Schematic course of %rh overt time inside a packaging Without desiccant Targeted design Space With EQ regulation With conventional Silica gel desiccant Time (in hours)
28 Thank you! Clariant manufactures a full range of protective packaging based on active agents, high-barrier copolymers and market-based functionality. Canisters & Capsules Packets Desiccant Stoppers & Printed Tubes Integrated Desiccant Closure (IDC ) Oxy-Guard Barrier Bottles Advanced Desiccant Polymer (ADP )