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`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 1/26
`
`

`

`
`
`Encyclopedia of
`PHARMACEUTICAL
`
`TECH NO LOGy
`Third Edition
`
`VOLUME 3
`
`edited by
`
`James Swarbrick
`
`PhdrmdCeuTech, Inc.
`Pinehurst, North Caro//nia, USA
`
`i nforma
`healthcare
`
`NewYorkTf'H§“m‘at=e~ria|wasiss-pied
`atthee NLM and ma ‘
`gum-mUW3_W.,i_ A Ewes
`
`Mylan V_ Quancaps,
`QUALICAPS EX. 2019 - 2/26
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 2/26
`
`

`

`Informa Healthcare USA, Inc.
`270 Madison Avenue
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`© 2007 by Informa Healthcare USA, Inc.
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`No claim to original U.S. Government works
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`7* , .
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`Thismateerialwam-vied
`at the NLM and may be
`Sufijggtl_I§S.{:g.py‘fightLa';N‘5
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2019 — 3/26
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 3/26
`
`

`

`XXV
`
`Dosage Regimens and Dose-Response
`
`/ Chyung S. Cook and Azi: Karim .
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`Dressings in Wound Management
`/ Sarah M.E. Cockbill
`Drug Abuse
`/ Richard B. Seymour and David E. Smith .
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`Drug Delivery Systems: Neutron Scattering Studies
`David J. Barlow .
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`/ M. Jayne Lawrence and
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`James C. McElnay and Carmel M. Hughes .
`/
`Drug Delivery: Buccal Route
`Drug Delivery: Controlled Release
`/ Yie W. Chien and Senshang Lin .
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`Drug Delivery: Fast-Dissolve Systems
`/ Vikas Agarwal, Bhavesh H. Kothari,
`Derek V. Moe, and Rajendra K. Kllankari
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`. 1071
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`/ Christel C. Mueller-Goymann .
`Drug Delivery: Liquid Crystals in
`Drug Delivery: Monoclonal Antibodies
`/
`John B. Cannon, Ho—Wah Hui, and
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`Pramod K. Gupta .
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`Drug Delivery: Monoclonal Antibodies in Imaging and Therapy / Ban-An Khaw .
`Drug Delivery: Mucoadhesive Hydrogels
`/ Harts E. Junginger, J. Coos Verhoef, and
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`Maya Thanou .
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`Drug Delivery: Nanoparticles
`/ Elias Fattal and Christine Vauthier .
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`Drug Delivery: Nasal Route
`/ Rene’Bommer .
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`Drug Delivery: Needle-Free Systems
`/ Toby King .
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`Drug Delivery: Ophthalmic Route
`/ Masood Chowhan, Alan L. Weiner, and
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`Haresh Bhagat .
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`Drug Delivery: Oral Colon-Specific
`/ Vincent H.L. Lee and Simian K. Mukherjee .
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`Drug Delivery: Oral Route
`/ Brahma N. Singh and Kwon H. Kinz
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`Drug Delivery: Parenteral Route
`/ Michael J. Akers .
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`Drug Delivery: Pulmonary Delivery / Michael T. New/touse .
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`Drug Delivery: Pulsatile Systems
`/ Till Bussemer and Roland A. Bodmeier .
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`Drug Delivery: Rectal Route /
`J. Howard Rytting and Joseph A. Fix .
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`Drug Delivery: Topical and Transdcrmal Routes
`/ Kenneth A. Walters .
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`Drug Delivery: Tumor-Targeted Systems
`/ Yu Li and Chao—Pin Lee .
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`Drug Delivery: Vaginal Route
`/ Yie W. Chien and Chi H. Lee .
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`Drug Design: Basic Principles and Applications
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`Jacques H. Poupaert .
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`Drug Development Management
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`James E. Tingstad .
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`Drug Information Systems
`/ Linda Lisgarten and Michelle Wake .
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`Drug Interactions
`/ Daniel A. Hussar .
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`Drug Master Files
`/ C. Jeanne Taborsky ana' Brian James Reamer
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`Drug Safety Evaluation / Farrel L. Fort .
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`Dry Powder Aerosols: Emerging Technologies
`/ Hak-Kim Chan and Nora Y.K. Chew .
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`II
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`i
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`'
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`x
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`Index .
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`Volume 3
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`/ Anthony J. Hlinak and Bradley A. Clark .
`Drying and Dryers
`Economic Characteristics of the R&D Intensive Pharmaceutical Industry / Douglas L. Cocks.
`Effervescent Pharmaceuticals
`/ Nils—0lof Lindberg and Henri Hansson .
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`Elastomcric Components for the Pharmaceutical Industry / Edward J. Smith .
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`Electrical Power Systems for Pharmaceutical Equipment
`/
`Joseph Maida .
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`Electroanalytical Methods of Analysis: Polarography and Voltammetry /
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`A. David Woolfson .
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`Electroanalytical Methods of Analysis: Potentiometry / Karel Vytras .
`Electrochemical Detection for Pharmaceutical Analysis
`/ Craig E. Lunte and
`Damon Osbourn .
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`Thismateriialwasmivied
`a“”“”**“'“‘"‘”“”a"“
`in l}jE{T.‘ U33 {:e-pgrrighti Laws
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2019 — 4/26
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`
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`i
`*
`’
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`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 4/26
`
`

`

`Electrostatic Charge in Pharmaceutical Systems
`Hak-Kim Chan .
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`/ Philip Chi Lip Kwok and
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`. 1535
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`. 1566
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`. 1580
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`Emulsions and Microemulsions
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`/ Gillian M. Eccleston .
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`Enzyme Immunoassay and Related Bioanalytical Methods
`Ira Das .
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`John W.A. Findlay and
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`Equipment Cleaning / Destin A. LeBlanc .
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`European Agency for the Evaluation of Medicinal Products (EMEA)
`Evaporation and Evaporators
`/ David P. Kessler .
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`/ David M. Jac()bs
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`/ Patrick J. Crowley and Luigi G. Martini
`Exeipients for Pharmaceutical Dosage Forms
`Excipients: Parenteral Dosage Forms and Their Role
`/ Sandeep Nema,
`Ron J. Brendel, and Richard Washkuhn .
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`. 1593
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`. 1646
`. 1656
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`. 1663
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`/ Hak-Kim Chan and Nora Y.K. Chew .
`Excipients: Powders and Solid Dosage Forms
`Excipients: Safety Testing / Marshall Steinberg and Florence K. Kinoshita .
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`Expert Systems in Pharmaceutical Product Development
`/
`Raymond C. Rowe and Ronald J. Roberts
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`Expiration Dating / Leslie C. Hawley and Mark D. VanArendonk .
`Extractables and Leachables in Drugs and Packaging / Daniel L. Norwood,
`Alice T. Granger, and Diane M. Paskiet
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`Extrusion and Extrudcrs
`/
`J. M. Newton .
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`Film Coating of Oral Solid Dosage Forms
`/ Linda A. Felton .
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`Filters and Filtration’ / Maik W. Jornitz .
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`Flame Photometry / Thomas M. Nowak .
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`Flavors and Flavor Modifiers
`/ Thomas L. Reiland and John M. Lipari .
`Fluid Bed Processes for Forming Functional Particles
`/
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`Yoshinobu Fukumori and Hideki Ichikawa .
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`Food and Drug Administration: Role in Drug Regulation / Roger L. Willianzs
`Fractal Geometry in Pharmaceutical and Biological Applications
`/
`P. Tang,
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`Hak-Kim Chan, and Judy A. Raper .
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`Freeze Drying / Michael J. Pikal
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`Freeze Drying, Scale-Up Considerations
`/ Edward H. Trappler .
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`Gastro-Retentive Systems
`/ Amnon Hoffman and Bashir A. Qadri
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`Gelatin-Containing Formulations: Changes in Dissolution Characteristics
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`Saranjit Singh and Sariputta P. Pakhale .
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`Gels and Jellies
`/ Clyde M. Ofner III and Cathy M. Klech-Gelotte .
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`Generic Drugs and Generic Equivalency / Arthur H. Kibbe .
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`Genetic Aspects of Drug Development
`/ Werner Kalow .
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`Geriatric Dosing and Dosage Forms
`/ Cheryl A. Wiens and Carol A. Borynec .
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`Good Clinical Practices (GCPS): An Overview / Richard A. Guarino .
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`Good Laboratory Practices (GLPS): An Overview / Nigel J. Dent .
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`Good Manufacturing Practices (GMPS): An Overview /
`Ira R. Berry .
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`Handling Hazardous Chemicals and Pharmaceuticals
`/ Antonio Conto .
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`Harmonization of Pharmacopeial Standards
`/ Lee T. Grady and Jerome A. Halperin .
`Headspace Oxygen Analysis in Pharmaceutical Products
`/ Allen C. Templeton and
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`Robert A. Reed .
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`Health Care Systems: Outside the United States
`/ Albert 1. Wertheimer and
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`Sheldon X. Kong .
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`Health Care Systems: Within the United States
`/ Henri R. Manasse, Jr.
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`Homogenization and Homogenizers
`/ Shailesh K. Singh and Venkatesh Naini .
`Hot-Melt Extrusion Technology /
`Jim W. McGinity, Michael A. Repka,
`John J. Koleng, Jr., and Feng Zhang .
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`. 1791
`. 1807
`. 1834
`. 1850
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`. 1875
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`. 1897
`. 1905
`. 1925
`. 1931
`. 1941
`. 1948
`. 1955
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`. 1967
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`. 1977
`. 1985
`. 1996
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`. 2004
`
`Thismaterial*~'asmwiEd
`at the l‘~lLlv1an»:l may be
`p Sm-M US‘Efl.py‘rightLaw‘S
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2019 - 5/26
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 5/26
`
`

`

`xxvii
`
`/ Marta Dolores Blanco, Rosa Maria Olmo, and Jose’Maria Teijo’n .
`Hydrogels
`Hydrolysis of Drugs
`/
`Jason M. LePree and Kenneth A. Connors .
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`Immunoassay / Stephen G. Schulman aria’ G.J.P.J. Beernink .
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`J.-M. Cardot and Erick Beyssac .
`In Vitro—In Vivo Correlation /
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`Inhalation: Dry Powder
`/ Lynn Van Campen and Geraldine Venthoye .
`Inhalation: Liquids
`/ Michael E. Placke, Jeffrey Ding, andAWilliam C. Zimlich, Jr.
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`. 2040
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`. 2048
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`. 2062
`. 2077
`. 2092
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`11
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`Index .
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`Volume 4
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`. 2133
`. 2142
`. 2164
`. 2171
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`. 2192
`. 2202
`. 2216
`. 2231
`. 2237
`. 2243
`. 2257
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`. 2262
`. 2269
`. 2286
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`. 2298
`. 2315
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`. 2328
`. 2339
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`J. Bradley Phipps, Erik R. Scott, J. Richard Gyory, and
`/
`Iontophoresis
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`Rama V. Padmanabhan .
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`Isolators for Pharmaceutical Application / Gordon J. Farquharson .
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`Isomerism / Thomas N. Riley, Jack DeRuiter, William R. Ravis, and C. Randall Clark .
`Laboratory Information Management System (LIMS)
`/ Siri H. Segalstad .
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`Laminar Airflow Equipment: Applications and Operation / Gregory F. Peters .
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`Lead Optimization in Pharmaceutical Development: Molecular and Cellular Approaches
`/
`C. K. Atterwill and M. G. Wing .
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`Lens Care Products
`/ Masood Chowhan and Ralph Stone .
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`Liquid Oral Preparations
`/
`Jagdish Parasrampztria and Stephen William Pitt .
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`Lozenges
`/ Robert W Mendes and Hridaya Bhargava .
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`Materials of Construction for Pharmaceutical Equipment
`/ Michelle M. Gonzalez .
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`Medication! Errors
`/ Diane D. Cousins .
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`Melt Processes for Oral Solid Dosage Forms
`/ Paul WS. Heng and Tin Wui Wong .
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`Metabolite Identification in Drug Discovery / Kathleen A. Cox, Nigel Clarke, and
`Diane Rindgen .
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`Metered Dose Inhalers
`/ Sandy J.M. Munro and Alan L. Cripps .
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`Microbial Control of Pharmaceuticals
`/ Nigel A. Halls .
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`_\/Iicrobiologic Monitoring of Controlled Processes
`/ Gregory F. Peters and
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`Marghi R. McKe0n .
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`Microencapsulation Technology / Kinam Park and Yoon Yeo .
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`.\/licrosphere Technology and Applications
`/ Diane J. Burgess and
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`Anthony J. Hickey .
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`Milling of Active Pharmaceutical Ingredients
`/ Elizabeth S. Fisher .
`Mixing and Segregation in Tumbling Blenders
`/ Troy Shinbrot and
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`Fernando .l. Muzzio .
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`Moisture in Pharmaceutical Products
`/ R. Gary Hollenbeck .
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`Nanoparticle Engineering / Robert 0. Williams III ana' Jason M. Vaughn .
`Neural Computing and Formulation Optimization / Elizabeth Colbourn and
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`Raymond C. Rowe .
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`Non-Prescription Drugs
`/ Sujit S. Sansgiry, Lynn Simpson, Gauri Shringarpure, and
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`Amit Kulkarni
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`Nutraceutical Supplements
`/ G. Brian Lockwood .
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`Optimization Methods
`/ Gareth A. Lewis .
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`Orphan Drugs
`/ Carolyn H. Asbury .
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`Otic Preparations
`/ William H. Slattery III .
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`Outsourcing / Duane B. Lakings .
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`Packaging Materials: Glass
`/ Claudia C. Okeke and Desmond G. Hunt .
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`Packaging Systems: Compendial Requirements
`/ Claudia C. Okeke, Desmond G. Hunt,
`Nicholas Mohr, Thomas Medwick, Eric B. Sheinin, and Roger L. Williams
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`S-u bject LIE Cupyright Laws
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2019 — 6/26
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 6/26
`
`

`

`NATIONAL LIBRARY OF MEDICINE
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`Encyclopedia of
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`PHARMACEUTICAL
`
`TECH N O LOGy
`Third Edition
`
`about the second edition...
`
`"...The depth and breadth of coverage...make it an excellent source for academic and special libraries.
`supporting research programs in the health sciences, pharmacology, and chemical engineering.”
`—American Reference Books Annual
`
`thegen ,
`A
`“
`
`.lo:pedia is in its tremendous breadth....highly recommen.ded...should«bein
`‘ as n_sti:t“t'or involved in pharmaceuticals.”
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`ISBN n—i3.Li=i3—=i3=iLi—=I
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`www.informahealthcarecom
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`NewYork, M10016
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`Abingdon, Oxon OX14 4RN, UK
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`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 7/26
`
`

`

`Film Coating of Oral Solid Dosage Forms
`
`Linda A. Felton
`
`College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, U.$.A.
`
`INTRODUCTION
`
`Polymeric materials have been used to coat pharma-
`ceutical solid dosage forms for decorative, protective,
`and functional purposes. These thin polymeric film
`coatings may improve the esthetic appearance and pro-
`vide easy identification of drug products. Polymer
`coatings may be used to enhance the chemical stability
`of the drug in a dosage form by providing a physical
`barrier to environmental storage conditions.“‘21Appli—
`cation of a polymeric film may also improve the physi-
`cal stability of solid dosage forms by increasing the
`strength and fracture resistance of the solid.[3] Reactive
`components within a single dosage form may be sepa-
`rated using polymeric film coatings. Taste and odor
`masking of drugs may also be accomplished with the
`use of polymeric film coatings.14] One of the most
`common reasons for the application of polymeric coat-
`ings is to alter the release characteristics of drugs.15‘71
`This article discusses formulation development, pro-
`cessing, and testing of polymeric films and film—coated
`products.
`
`FUNDAMENTALS OF FILM FORMATION
`
`industry, polymeric films are
`In the pharmaceutical
`generally applied to solid dosage forms using a spray-
`atomization technique. The polymer is dissolved or
`dispersed in aqueous or organic solvents prior to spraying.
`The solid cores are often preheated in the coating
`equipment prior to initiation of the coating process.
`This prewarming stage is especially important in the
`coating of soft gelatin capsules.[8‘9I The coating solu-
`tion or dispersion is atomized with air into small drop-
`lets, which are then delivered to the surface of the
`
`substrate. Upon contact, the atomized droplets spread
`across the substrate surface. The solvent may penetrate
`into the core, causing surface dissolution and physical
`mixing at the film—tablet interface.“°] As the solvent
`begins to evaporate, the polymer particles densely pack
`on the surface of the solid. A schematic of the film for-
`
`mation process for an aqueous polymeric dispersion is
`shown in Fig. 1. Upon further solvent evaporation, the
`particles flow together due to the cohesive forces
`between the polymer spheres, a process known as
`coalescence. Heat
`is generally added to the coating
`
`equipment to facilitate solvent evaporation and film
`formation.“ '1
`
`Immediately following the completion of the coat-
`ing process, coated solids are generally stored at tem-
`peratures above the glass transition temperature of the
`polymer to further promote coalescence of the filmlél and
`ensure a homogeneous distribution of the plasticizer.“2]
`During this postcoating storage or curing stage,
`the
`microstructure of the polymer is altered,“31 and the
`mechanical, adhesive,“41 and drug release proper-
`ties1'5'”’1 of the film are correspondingly affected. The
`time required to obtain a stable film without further
`aging effects is dependent on a number of factors,
`including the type and concentration of plasticizer,[‘7"81
`the bed temperature used during coating,“(‘] and the
`storage conditions.“” Fig. 2 shows the influence of cur-
`ing on theophylline release from pellets coated with an
`acrylic polymer.“51 Drug release rates slowed during
`storage at elevated temperatures and higher concentra-
`tions of the plasticizer in the coating reduced the time
`necessary for complete film coalescence.
`While the majority of published research has
`shown that curing slows drug release, Bodmeier and
`Paeratakulml
`found that curing could enhance or
`retard drug release, depending on curing conditions,
`plasticizer concentration, and the physicochemical
`properties of the drug. In that study, chlorpheniramine
`maleate was found to have a low affinity for the ethyl
`cellulose polymer and curing slowed drug release. In
`contrast, ibuprofen was found to have a high solubility
`in ethyl cellulose and longer curing times resulted in
`faster drug release. Drug crystals were found on the
`surface of the coated pellets following curing and the
`researchers attributed these findings to diffusion of
`the drug into the film. A subcoat or intermediate seal
`coat was suggested to minimize interaction between
`the drug and the cellulosic polymer.
`
`COATING EQUIPMENT
`
`There are three ‘types of coating equipment used to
`apply polymeric materials: conventional coating pans,
`perforated coating pans, and fluidized beds. More
`detailed discussions of the various coating equipments
`may be
`found elsewhere.“9‘2” The conventional
`coating pan system consists of a round coating pan
`
`Encyclopedia of Pluirmaceutical Teclmology D01: 10.1081 .13-EPT-12 013038 .
`Copyright
`20()7 by lnforma Healthcare USA, Inc. All
`l1‘tE”:5cE%FlPed?’i3““g”"“‘
`a ‘the NLM and may be
`1- *-‘
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`
`Mylan v. Qualicaps, |PR2017—Olg%O3
`9 _
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 8/26
`
`

`

`Film Coating of Oral Solid Dosage Forms
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`Time (hr)
`
`Fig. 2 Change in drug release from theophylline pellets
`coated with Eudragit('” RS 30 D containing 5% Pliarmacoat"'°
`606 and either (A) 20% triethyl citrate or (B) 30% triethyl
`citrate after storage at 40°C/50% relative humidity. For
`(A): ([3) initial; (A) 2hr; (V) 6hr; (I) 24hr; (X) 3 days;
`([1) 7 days; (A) 10 days. For (B): ([1) initial; (A) 3hr; (a)
`6hr; (O) 12 hr. (From Ref.“5].)
`
`move during the coating process. The application zone
`is the area in the pan where the atomized polymer is
`sprayed onto the substrate surface. Tablets must make
`multiple passes through the application zone to form
`the film. Baffles in the perforated coating pans contrib-
`ute to the tumbling action of the tablets and facilitate
`uniform film coverage.
`
`In contrast to the coating pans, small particles such
`as beads, pellets, granules, and powders are generally
`coated using the fluidized bed or air suspension
`method, which utilizes a carrier gas to keep the cores
`in motion. The high air current makes this technique
`more efficient at water removal.[22] The bottom spray
`technique is one of the most common fluidized bed
`application methods and a schematic of this process
`is shown in Fig. 4A. A perforated distribution base
`plate allows sufficient air into the product container
`to force the particles up into a cylindrical or slightly
`conical coating chamber, known as a Wurster insert.
`These inserts have been recently improved to keep
`
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`
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`Water evaporation and
`polymer coalescence
`
`
`
`1730
`
`A
`
`B
`
`°
`
`D
`
`
`
`1 Schematic representation of the film formation pro-
`Fig.
`cess for an aqueous polymeric dispersion: (A) atomization
`of the polymeric dispersion; (B) deposition of the polymeric
`dispersion on the substrate surface; (C) packing of the poly-
`mer spheres with water filling the void spaces; (D) formation
`of continuous polymeric film.
`
`that rotates on an inclined axis. Tablets in the coating
`pan tumble due to pan rotation. Heat is blown across
`the surface of the tumbling tablets and exhaust air is
`withdrawn. The conventional coating pan was orig-
`inally used in the sugar coating process, where syrups
`were ladled onto the substrates. Aqueous polymeric
`film coating, however, requires more rapid solvent
`evaporation and the drying efficiency of conventional
`coating pans was improved by adding perforations.
`These perforations allow air to be forced through the
`tablet bed. A schematic of a perforated coating pan
`is shown in Fig. 3. As with conventional coating sys-
`tems, pan rotation causes the solid cores to continually
`
`This material was Eflpilfiil
`at the N LM a ncl may be
`in iJ_iEs:’tI US {lo-py‘rig.ht Laws
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2019 - 9/26
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 9/26
`
`

`

`
`
`Film Coating of Oral Solid Dosage Forms
`
`1731
`
`
`
`Fig. 3 Schematic of a perforated coating pan apparatus.
`(From Ref.“°].)
`
`the particles away from the spray nozzle until the spray
`pattern is
`fully developedm] The bottom spray
`method provides ideal conditions for complete film
`coa1escence.[3‘” The particle size oftlie pellets, however,
`has been shown to influence fluidization patterns,
`which may ultimately affect the thickness of the film
`coating.[25]
`_
`Two additional spray techniques have been used in
`fluidized bed coating. As shown in Fig. 4B, the top
`spray method, also known as the granulator mode,
`sprays the polymeric material countercurrently into
`the lluidizing particles. Because the coatings produced
`are not uniform in thickness, the top spray technique is
`suitable for taste and odor masking, where drug release
`is not dependent on film thickness.“9] The rotary or
`tangential spray technique, shown in Fig. 4C, uses a
`rotating disk to add a centrifugal force to tluidlzatlon
`
`and gravity. While films produced using this method
`are similar to those created with the Wurster system,m]
`the drying efficiency is improved and higher spray rates
`may be employed. Using the tangential spray system,
`film thickness has been shown to be independent of
`the particle size of the cores.[25] One of the drawbacks
`of this application technique, however,
`is a greater
`potential for adhesion of particles to the upper walls
`of the product chamber.
`Irrespective of the type of coating equipment used,
`polymeric solutions and dispersions are generally
`applied using a spray—atomization technique and two
`types of spray nozzles are employed. With pneumatic
`nozzles, high—pressure air is passed across the fluid
`stream as it exits the nozzle opening.
`In contrast,
`hydraulic nozzles rely on the fluid being pumped at
`relatively high pressures through a small opening.
`One of the advantages of pneumatic nozzles is that
`the atomized droplet size can be controlled indepen-
`dently of the polymer flow rate, whereas changing
`the spray rate of a hydraulic nozzle without adjusting
`the nozzle will result in changes in the atomization
`spray pattern.“9]
`A variety of pumps may be used to deliver the coat-
`ing material to the spray nozzle. The peristaltic pump
`is ideal for delivering latex and pseudolatex polymeric
`dispersions that may coagulate at high pressure. This
`pump is
`the most commonly used and is also the
`easiest to clean. To control the delivery of the liquid
`polymeric material more precisely, a gear pump may
`be employed. Problems with undissolved solids in
`the coating formulation, however, may arise due to
`the tight tolerances between the two gears. The gear
`pump is also more difficult to clean compared to the
`peristaltic system. A piston pump utilizes both air
`and hydraulic systems. One of the advantages of the
`piston pump is that minor clogs in the nozzle may be
`easily cleared due to the pressure reserve. Polymeric
`materials, however, may coagulate due to the high
`
`A
`
`B
`
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`
`
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`<— Filter housing
`
`Particle flow
`pattern
`
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`4_ EXPa"5l°“
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`column
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`t t ‘i-—Spray nozzle
`Air flow
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`
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`Airflow
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`Fig. 4 Schematic of a fluidized bed coating apparatus. (A) bottom spray with Wurster column inseit, (B) top spr 1y tecmique
`(C) tangential spray technique. (From Ref.[25].)
`
`;
`
`
`
`This m.at:=erial was am-pied
`atthe NLlv1an»:l may be
`S-u bject.‘ LIE Ciiti-.p»yright La ws»
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2019 — 10/26
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2019 - 10/26
`
`

`

`
`
`Film Coating of Oral Solid Dosage Forms
`
`associated with side effects may be reduced or eliminated.
`Common sust