Considerations for Generic Product Development · Considerations for Generic Product Development...

Click here to load reader

  • date post

    04-Jun-2018
  • Category

    Documents

  • view

    214
  • download

    0

Embed Size (px)

Transcript of Considerations for Generic Product Development · Considerations for Generic Product Development...

  • 3M Health Care Business Group

    Transdermal Adhesives Considerations for Generic Product Development Tim Peterson

    October 28, 2015

  • 3M Health Care Business Group

    2 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    3Ms Stick to Skin Portfolio

    http://solutions.3m.com/wps/portal/3M/en_US/IP/infectionprevention/solutions/patient-assessment/red-dot-electrodes/red-dot-monitoring-electrodes/http://solutions.3m.com/wps/portal/3M/en_US/IP/infectionprevention/solutions/sterile-field-surface/drapes/

  • 3M Health Care Business Group s

    Transdermal Adhesive Basics

  • 3M Health Care Business Group

    4 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Transdermal System Designs

    Basic Approaches

    Reservoir Multilaminate

    Drug-in-Adhesive

    Backing Drug Membrane Adhesive Liner/Skin

    Three of the most utilized transdermal patch designs.

  • 3M Health Care Business Group

    5 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Key Aspects of Adhesive Performance in Transdermal Systems Secure the

    system to the skin

    Provide a drug and excipient

    reservoir

    Facilitate drug release from the system

    Biocompatible with skin

    Contribute to the stability of

    the system

  • 3M Health Care Business Group

    What is a PSA and how does it work? PSA = Pressure Sensitive Adhesive

    Adheres to a surface using only light pressure

    Removable - no chemical bond between adhesive and substrate

    For good adhesion:

    An adhesive must first wet out the substrate. The degree of wetting depends on the difference in surface energy between the adhesive and substrate

    High energy surface (metal, glass) = greatest wetting

    Low energy surface (polypropylene, teflon, skin)= more difficult wetting

    The adhesive must have the proper rheology to allow the wetting to occur rapidly (~1 sec)

    Mechanisms for adhesion:

    Mechanical adhesion occurs when the adhesive flows into the texture of the substrate.

    Specific adhesive/substrate interactions include electrostatic forces, van der Waals forces and acid-base interactions

    6

  • 3M Health Care Business Group

    7 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Mo

    du

    lus

    Temperature or Time

    Glassy

    Transition

    Rubbery

    Flow

    Dahlquist tack criterion

  • 3M Health Care Business Group

    8 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesives Currently Used in TDD

    Adhesive Polymers:

    Acrylate

    Silicone

    Polyisobutylene

    Synthetic Rubber (e.g. Kraton)

    Product Design Category Adhesive Category

    Transdermal Reservoir

    Systemw/ Adh

    Overlay DIA Multilaminate PIB Acrylate Silicone

    AndrodermR

    (testosterone)

    BuTransR

    (buprenorphine)

    Catapres-TTSR

    (clonidine)

    ClimaraR

    (estradiol)

    Climara ProR

    (estradiol / levonorgestrel)

    CombipatchR

    (estradiol / norethindrone

    DaytranaR

    (methylphenidate)

    DuragesicR

    (fentanyl)

    EmsamR

    (selegiline)

    ExelonR

    (rivastigmine)

    FlectorR

    (diclofenac epolamine)

    LidodermR

    (lidocaine)

    MinitranTM

    (nitroglycerin)

    NeuproR

    (rotigotine)

    Nicoderm CQR

    (nicotine)

    Ortho EvraR

    (ethinyl estradiol / norelgestromin)

    OxytrolR

    (oxybutynin)

    NitroDurR

    (nitroglycerin)

    QutenzaR

    (capsaicin)

    SancusoR

    (granisetron)

    Transderm-NitroR

    (nitroglycerin)

    Transderm ScopR

    (scopolamine)

    Vivelle DotR

    (estradiol)

    Matrix

  • 3M Health Care Business Group

    Polyacrylate PSAs

    Polymers designed to be PSAs

    Workhorse monomers

    acrylic acid acrylamide

    (AA) (ACM)

    OOH ONH2

    -affords tackiness

    -low Tg

    -reinforcing capability

    -polar, interact with substrates

    OO OO

    2-ethyl hexyl butyl n-vinyl pyrrolidone

    (2-EHA) (BA) (NVP)

    NO

    Advantages

    --very diverse chemistry, can adjust

    adhesive properties and solubility

    characteristics

    --excipient/drug tolerant

    --biocompatible

    --Single polymer with no need to tackify

    --good processability

    Disadvantages

    --high solubility

    --can be cross-linked, but not advisable

    with drug present

  • 3M Health Care Business Group

    10 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Advantages

    --low surface energy

    --non-interactive with drug

    --biocompatible

    --MVTR is great

    --low solubility

    SiSiSiSiO O O O

    Silicone

    Polydimethylsiloxane, PDMS

    Dimethicone

    Tackify with silicate resin to make a PSA

    O Si

    CH3

    CH3

    CH3

    silica

    OS

    iC

    H3

    CH

    3

    CH

    3

    OSi

    CH3

    CH3

    CH3

    OSi

    CH3

    CH3

    CH3

    OS

    i

    CH

    3 CH

    3

    CH

    3

    OSiC

    H 3 CH 3

    CH 3

    Disadvantages

    --cost

    --material compatibility

    --low solubility

    Silicone PSAs

  • 3M Health Care Business Group s

    Adhesion to Skin

  • 3M Health Care Business Group

    12 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Factors Affecting Good Skin Adhesion Key Characteristics of Skin

    Human

    Skin

    Breathing, Sensitive Surface

    Cell Renewal

    Cycle

    Elastic Surface

    Low Surface Energy

    Rough Texture

    Stratum corneum - 14 days

    Epidermis - 50 days

    Reversible Stretch up to

    50%

    25 dynes/cm (Skin)

    31 dynes/cm (Polypropylene)

    >700 dynes/cm (Stainless)

    Hair & Growth

    Pores

    Skin Wrinkles

    Dead Skin Cells

    Sweat

    Salt

    Lotions & Powders

    Allergies

    MVTR - Masceration

    Mechanical Trauma

    Contaminated Surface

  • 3M Health Care Business Group

    13 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Epidermal cells on surface of adhesive following removal from skin

    a) Gentle PSA tape, b) Aggressive PSA tape

    Skin / Adhesive Peel Interface

    a) b)

  • 3M Health Care Business Group s

    Design Considerations

  • 3M Health Care Business Group s

    Design Consideration #1: Choose an Adhesive with Optimal Solubility for the API

  • 3M Health Care Business Group

    API solubility is highly

    dependent on adhesive

    selection

    There is no universal

    best choice depends

    on the API

    physicochemical

    properties

    API #1

    API #2

    API #3

    API #4

    API #5

    API #6

    Solubility of API in various TDD Adhesive Materials

  • 3M Health Care Business Group

    17 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Fentanyl solubility in IOA/HEA adhesives

    0

    2

    4

    6

    8

    10

    12

    14

    16

    0 0.1 0.2 0.3 0.4 0.5

    Percent HEA in Soft Segment

    Fen

    tanyl

    Solu

    blit

    y, %

    w/w

    Choice of Acrylate Co-monomer Can Influence Solubility

  • 3M Health Care Business Group

    18 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Assessment of Drug Solubility in Adhesive Matrices Crystal Growth Method

    Growth

    Absorption

  • 3M Health Care Business Group

    19 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Optimal Solubility Choose an adhesive with solubility for the drug and excipients such that:

    Adhesive matrix has adequate solubility to keep drug and excipient in a

    solvated state (unless the design calls for a drug suspension)

    Adhesive matrix has adequate solubility to maintain delivery for the

    desired wear period

    Adhesive matrix does not have excess solubility, otherwise:

    Diffusional driving force is diminished (because the drug has lower

    thermodynamic activity)

    High residual drug may remain in the patch at the end of the wear

    period

    The ability to screen multiple adhesives or modulate drug solubility within the

    adhesive is important.

    Crystallized API in Adhesive Matrix -

    Avoid This!

  • 3M Health Care Business Group s

    Design Consideration #2: Choose an adhesive that has good mechanical properties (adhesion) even when loaded with drug and excipient

  • 3M Health Care Business Group

    Effect of Excipient and Drug Loading

    Excipients (and drugs) alter the physical

    properties of adhesives

    Higher loadings lead to larger effects

    Some adhesive polymers are more

    tolerant of drug/excipient than others

    H-bonding

    polymer

    Add excipient

    Weakened

    polymer to polymer

    interaction

  • 3M Health Care Business Group

    22 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Mo

    du

    lus

    Temperature or Time apply peel

    Add excipients

    Mo

    du

    lus

    Temperature or Time apply peel

    --Excipients are like plasticizers

    --To accept higher excipient levels, the base adhesive may need to be stiff (high modulus)

    Not a PSA. above Dalhquist criterion Excipient loading creates PSA

    Excipients What is Happening to the Rheology?

  • 3M Health Care Business Group s

    Design Consideration #3: Choose an adhesive that is compatible with other components of the system

  • 3M Health Care Business Group

    24 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesive Compatibility with Other System Components

    Adhesive Compatibility

    Compatible with Drug and

    Excipients

    Compatible with Release

    Liner

    Compatible with Backing

    film

  • 3M Health Care Business Group

    25 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesive Compatibility with Other System Components

    Adhesive Compatibility

    Compatible with Drug and

    Excipients

    Compatible with Release

    Liner

    Compatible with Backing

    film

    Ensure low residuals Monomers Initiators Solvents

    Avoid strong intermolecular interactions with drug

  • 3M Health Care Business Group

    26 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesive Compatibility with Other System Components

    Adhesive Compatibility

    Compatible with Drug and

    Excipients

    Compatible with Release

    Liner

    Compatible with Backing

    film

    Ensure release liner peel force remains within an acceptable range throughout the shelf life

    Normal for release liner peel force to build over time

    Acceptable upper limit is ~60 g/cm*

    Wokovich, A. M., Shen, M., Doub, W. H., Machado, S. G. and Buhse, L. F. (2010), Release liner removal method for transdermal drug delivery systems (TDDS). J. Pharm. Sci., 99: 31773187. doi: 10.1002/jps.22067

  • 3M Health Care Business Group

    27 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesive Compatibility with Other System Components

    Adhesive Compatibility

    Compatible with Drug and

    Excipients

    Compatible with Release

    Liner

    Compatible with Backing

    film

    Ensure adequate adhesion to backing to prevent delamination

    Low surface energy substrates )like PE) are more difficult

    May require surface treatment (e.g. corona) to obtain an adequate bond

  • 3M Health Care Business Group s

    Regulatory Considerations

  • 3M Health Care Business Group

    29 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesives for Generic TDD Products

    For generic TDD products (in the U.S.), all components (including adhesive) should have a

    history of use in previously approved products using the same route of administration and

    dosage form.

    Necessitates the use of adhesives that have been used in previously approved TDD products.

    FDAs Inactive Ingredient Database (IID) provides information on which adhesives have been

    used in previously approved products

  • 3M Health Care Business Group

    30 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesives listed in the FDAs Inactive Ingredient Database Ingredient_Name Route Dosage_Form

    CAS_Number

    UNII Potency_A

    mount PotencyUni

    t ACRYLATES COPOLYMER TRANSDERMAL FILM, CONTROLLED RELEASE N/A 382.22 MG

    ACRYLATES COPOLYMER TRANSDERMAL PATCH, CONTROLLED RELEASE N/A 677.68 MG

    ACRYLIC ACID-ISOOCTYL ACRYLATE COPOLYMER TRANSDERMAL FILM, CONTROLLED RELEASE 9017689 Pending 56.4 MG

    ACRYLIC ADHESIVE 788 TRANSDERMAL FILM N/A 10.17 MG

    ACRYLIC ADHESIVE 788 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 20.08 MG

    ACRYLIC ADHESIVE 788 TRANSDERMAL PATCH N/A

    ADHESIVE TAPE TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER TRANSDERMAL FILM, CONTROLLED RELEASE 24938167 905HNO1SIH

    DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER TRANSDERMAL PATCH 24938167 905HNO1SIH

    DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER TRANSDERMAL PATCH, ELECTRICALLY CONTROLLED 24938167 905HNO1SIH 10 MG

    DURO-TAK 280-2516 TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    DURO-TAK 387-2516 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 37.4 MG

    DURO-TAK 80-1196 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 172 MG

    DURO-TAK 87-2070 TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    DURO-TAK 87-2194 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 208.28 MG

    DURO-TAK 87-2287 TRANSDERMAL FILM N/A 537.7 MG

    DURO-TAK 87-2287 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 121.1 MG

    DURO-TAK 87-2296 TRANSDERMAL PATCH, CONTROLLED RELEASE N/A 43 MG

    DURO-TAK 87-2888 TRANSDERMAL PATCH N/A 175.9 MG

    DURO-TAK 87-2888 TRANSDERMAL PATCH, CONTROLLED RELEASE N/A 175.9 MG

    DURO-TAK 87-2979 TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    GELVA 737 TRANSDERMAL FILM, CONTROLLED RELEASE Pending

    POLYISOBUTYLENE TRANSDERMAL FILM 9003274 N/A 16.83 MG

    POLYISOBUTYLENE TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 N/A 119 MG

    POLYISOBUTYLENE TRANSDERMAL PATCH, CONTROLLED RELEASE 9003274 N/A 10.5 MG

    POLYISOBUTYLENE (1100000 MW) TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 FLT10CH37X 69 MG

    POLYISOBUTYLENE (1100000 MW) TRANSDERMAL PATCH 9003274 FLT10CH37X 22.65 MG

    POLYISOBUTYLENE (2300 MW) TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 DSQ2V1DD1K 121.68 MG

    POLYISOBUTYLENE (35000 MW) TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 98553S1MHQ 86 MG

    POLYISOBUTYLENE (55000 MW) TRANSDERMAL FILM 9003274 TQ77WR8A02 238.44 MG

    POLYISOBUTYLENE (55000 MW) TRANSDERMAL PATCH 9003274 TQ77WR8A02 28.32 MG

    POLYISOBUTYLENE (800000 MW) TRANSDERMAL FILM 9003274 Y132ZOQ9H7 159 MG

    POLYISOBUTYLENE LOW MOLECULAR WEIGHT TRANSDERMAL PATCH, CONTROLLED RELEASE 9003274 N/A 8.13 MG

    POLYISOBUTYLENE MEDIUM MOLECULAR WEIGHT TRANSDERMAL PATCH, CONTROLLED RELEASE 9003274 N/A 1.63 MG

    POLYISOBUTYLENE/POLYBUTENE ADHESIVE TRANSDERMAL FILM, CONTROLLED RELEASE N/A 221.25 MG

    SILICONE TRANSDERMAL FILM, CONTROLLED RELEASE 63394025 N/A 353.51 MG

    SILICONE TRANSDERMAL PATCH 63394025 N/A

  • 3M Health Care Business Group

    31 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Adhesives listed in the FDAs Inactive Ingredient Database Ingredient_Name Route Dosage_Form

    CAS_Number

    UNII Potency_A

    mount PotencyUni

    t ACRYLATES COPOLYMER TRANSDERMAL FILM, CONTROLLED RELEASE N/A 382.22 MG

    ACRYLATES COPOLYMER TRANSDERMAL PATCH, CONTROLLED RELEASE N/A 677.68 MG

    ACRYLIC ACID-ISOOCTYL ACRYLATE COPOLYMER TRANSDERMAL FILM, CONTROLLED RELEASE 9017689 Pending 56.4 MG

    ACRYLIC ADHESIVE 788 TRANSDERMAL FILM N/A 10.17 MG

    ACRYLIC ADHESIVE 788 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 20.08 MG

    ACRYLIC ADHESIVE 788 TRANSDERMAL PATCH N/A

    ADHESIVE TAPE TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER TRANSDERMAL FILM, CONTROLLED RELEASE 24938167 905HNO1SIH

    DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER TRANSDERMAL PATCH 24938167 905HNO1SIH

    DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER TRANSDERMAL PATCH, ELECTRICALLY CONTROLLED 24938167 905HNO1SIH 10 MG

    DURO-TAK 280-2516 TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    DURO-TAK 387-2516 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 37.4 MG

    DURO-TAK 80-1196 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 172 MG

    DURO-TAK 87-2070 TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    DURO-TAK 87-2194 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 208.28 MG

    DURO-TAK 87-2287 TRANSDERMAL FILM N/A 537.7 MG

    DURO-TAK 87-2287 TRANSDERMAL FILM, CONTROLLED RELEASE N/A 121.1 MG

    DURO-TAK 87-2296 TRANSDERMAL PATCH, CONTROLLED RELEASE N/A 43 MG

    DURO-TAK 87-2888 TRANSDERMAL PATCH N/A 175.9 MG

    DURO-TAK 87-2888 TRANSDERMAL PATCH, CONTROLLED RELEASE N/A 175.9 MG

    DURO-TAK 87-2979 TRANSDERMAL FILM, CONTROLLED RELEASE N/A

    GELVA 737 TRANSDERMAL FILM, CONTROLLED RELEASE Pending

    POLYISOBUTYLENE TRANSDERMAL FILM 9003274 N/A 16.83 MG

    POLYISOBUTYLENE TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 N/A 119 MG

    POLYISOBUTYLENE TRANSDERMAL PATCH, CONTROLLED RELEASE 9003274 N/A 10.5 MG

    POLYISOBUTYLENE (1100000 MW) TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 FLT10CH37X 69 MG

    POLYISOBUTYLENE (1100000 MW) TRANSDERMAL PATCH 9003274 FLT10CH37X 22.65 MG

    POLYISOBUTYLENE (2300 MW) TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 DSQ2V1DD1K 121.68 MG

    POLYISOBUTYLENE (35000 MW) TRANSDERMAL FILM, CONTROLLED RELEASE 9003274 98553S1MHQ 86 MG

    POLYISOBUTYLENE (55000 MW) TRANSDERMAL FILM 9003274 TQ77WR8A02 238.44 MG

    POLYISOBUTYLENE (55000 MW) TRANSDERMAL PATCH 9003274 TQ77WR8A02 28.32 MG

    POLYISOBUTYLENE (800000 MW) TRANSDERMAL FILM 9003274 Y132ZOQ9H7 159 MG

    POLYISOBUTYLENE LOW MOLECULAR WEIGHT TRANSDERMAL PATCH, CONTROLLED RELEASE 9003274 N/A 8.13 MG

    POLYISOBUTYLENE MEDIUM MOLECULAR WEIGHT TRANSDERMAL PATCH, CONTROLLED RELEASE 9003274 N/A 1.63 MG

    POLYISOBUTYLENE/POLYBUTENE ADHESIVE TRANSDERMAL FILM, CONTROLLED RELEASE N/A 221.25 MG

    SILICONE TRANSDERMAL FILM, CONTROLLED RELEASE 63394025 N/A 353.51 MG

    SILICONE TRANSDERMAL PATCH 63394025 N/A

    From the 8/15/2015 Update of the IID

    37 entries that pertain to adhesives (after filtering on transdermal or topical patches)

    Some entries are duplicative (~20 unique entries)

    Some entries are not very descriptive of the adhesive polymer

  • 3M Health Care Business Group

    32 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Relevant Regulatory Documents and Adhesive Tests USP Topical and Transdermal Drug Products Product Quality Tests

    Peel Adhesion

    Release Liner Peel Test

    Tack - Probe or Rolling Ball (ASTM D3121)

    FDA Guidance on Residual Drug in Transdermal and Related Drug Delivery Systems

    EMA/CHMP/QWP/608924/2014 Guideline on Quality of Transdermal Patches

    Peel Adhesion, Liner Release, Tack, Cold Flow

    Ph. Eur. Monograph 1011 Transdermal Patches

    EMA Guideline on the Pharmacokinetic and clinical evaluation of modified-release dosage

    forms.

    A useful reference:

    Measuring Adhesive Performance in Transdermal Delivery systems, P. Minghetti, F. Cilurzo and A. Casiraghi; Am J Drug Deliv 2

    (3): 193-206, (2004)

  • 3M Health Care Business Group s

    Quality Tests that pertain to Transdermal Adhesives

  • 3M Health Care Business Group

    34 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Quality Testing of PSA Raw Materials

    Adhesive polymers used in TDD products are typically provided in solvent

    Typical Raw Material testing includes:

    ID

    % Solids

    Molecular Weight (or a surrogate such as Inherent Viscosity I.V.)

    Residuals Content

    Initiator

    Monomers

  • 3M Health Care Business Group

    35 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Peel Adhesion

    Measurement of the force

    required to peel an adhesive

    system from a test substrate

    Can be quite sensitive to

    environmental conditions

    Example test substrates are

    stainless steel or HDPE

    Practical experience: There is

    no test substrate that mimics

    skin.

  • 3M Health Care Business Group

    36 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    There is no correlation between adhesion to steel and adhesion to skin

    Adhesion to steel is quite often (but not always!) substantially higher than adhesion to skin

    Increasing the adhesion to steel will not necessarily increase the adhesion to skin (sometimes just the opposite)

    Adhesion to steel is useful as a quality test only

    Useful reference: Fauth C, Wiedersberg S, Neubert RHH, Dittgen M. Adhesive backing

    foil interactions affecting the elasticity, adhesion strength of laminates, and how to interpret these properties of branded transdermal patches. Drug Dev Ind Pharm. 2002;28(10):1251-9.

    Adhesion to Steel vs Adhesion to Skin

    1509 LDPE 1513 PET 9877 PET

    Adhesive Type Acrylate Same as #1509 Synthetic Rubber

    Adhesion to Steel,

    Typical

    1450 g/in 1730 g/in 3400 g/n

    Initial Adhesion to

    Skin, Recorded Range

    30-50 g/in 30-50 g/in 30-50 g/in

  • 3M Health Care Business Group

    37 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Tack

    Measurement of the force required to pull a probe

    (usually stainless steel) away from the adhesive

    Intended to quantify the quick stick of the

    adhesive

    Practical experience probe tack values have no

    correlation with adhesion to skin performance

    Probe Tack

  • 3M Health Care Business Group

    38 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Release from Liner

    Measurement of the force required to peel

    the adhesive system from the release liner

    Peel angle is usually 90 or 180 degrees

    Force is usually quite low (1-60 g/cm)

    This force is very representative of what the

    patient experiences as they remove the liner

    prior to patch application.

  • 3M Health Care Business Group

    39 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Shear Adhesion

    Intended to be a measurement of the

    internal (cohesive) strength of the adhesive

    matrix

    Testing can be either static (hanging weight)

    or dynamic

    Practical experience shear testing is not

    correlated with in vivo adhesion to skin

    performance.

    Static Shear

    Dynamic Shear

  • 3M Health Care Business Group

    40 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Cold Flow

    Measurement of the degree of adhesive

    migration or detachment at the edge of the

    TDD system

    Cold flow (when it occurs) is usually time

    dependent

    A variety of test methods can be used:

    Visual

    Gravimetric

    Microscopic distance measurement

    Assay

  • 3M Health Care Business Group

    41 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Summary

    Adhesive polymers play a crucial role in the performance of

    TDD products

    Selection of an appropriate adhesive for TDD systems

    requires consideration of its impact on many dimensions of

    product performance

    Adhesion to skin is a particular challenge, and in vitro quality

    tests are not predictive of in vivo performance

  • 3M Health Care Business Group

    42 . All Rights Reserved. 28 October 2015 3M 3M Confidential.

    Acknowledgements

    Jim Dizio

    Keith Dahmen

    Kris Godbey

    Steven Schull

  • 3M 2015. All Rights Reserved. 3M Confidential

    Thank you