Sacha.characteristics and Requirements for Large Volume Parenterals
Transcript of Sacha.characteristics and Requirements for Large Volume Parenterals
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Presenter
Characteristics and Requirements for
Large Volume Parenterals (LVPs)USP Workshop on Thresholds andBest Practices for Parenteral and
Ophthalmic Drug Products
Bethesda, MD
February 22 and 23, 2011
Gregory A. Sacha, Ph.D.
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Large Volume Intravenous Solution 2
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A single-dose injection that is intended forintravenous use and is packaged in containerslabeled as containing more than 100 mL.
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Characteristics of LVPs 3
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Packaged in glass bottles or in large volume flexiblecontainers.
May contain greater than 100 ml to greater than 1 or 2 L
Sterile
Pyrogen-Free
Essentially free of particulate matter
No anti-microbial agentsIsotonicity
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Types of Large Volume Intravenous Solutions 4
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Electrolytes
CarbohydratesNutritional Solutions
Proteins
Lipid Emulsions
Peritoneal Dialysis
Irrigating Solutions
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Route of Administration 5
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Intravenous
Direct Injection
Infusion
Subcutaneous
Intramuscular
Intradermal
Intraspinal
Intrathecal
Intra-arterial
Others
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Methods of Delivery for LVPs 6
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Peripheral Vein if solution with low osmolality
Hyper or hypotonicity can irritate the vein - phlebitis
Central Vein Subclavian Vein
A B
A. From http://www.hsc.wvu.edu/mbrcc/bmt/siteImages/centralVenousCatheter.jpg
B. From http://www.nursinghomesabuseblog.com/uploads/image/picc.png
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Methods of Delivery for LVPs 7
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Peritoneal Dialysis
Dialysis membrane assisted hemodialysis
Continuous ambulatory dialysis
Patient warms solution to body temperature
Injects into abdominal cavity
Exchanges solution 4 to 5 times daily
A. From http://www.wirralchesterkidney.nhs.uk/images/principle.jpgA
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Preparation and Hospital Practice 8
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Ready to use solutions stored on nursing units foreasy access. Saline and Dextrose solutions.
Medications can be added to the large volumecontainers in the pharmacy.
Prepared when ordered or in batches every 8 to 12
hours, labeled, and delivered to the nursing unit. Typically expire after 24 hours
Some drugs prepared in LVPs as ready to use
Propofol
Ciprofloxacin
Lidocaine HCl
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Preparation of Parenteral Nutrition Formulations 9
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Custom formulation designed for each patient in US
Use Automix and Micromix compounders to transferquantities of each additive to sterile, empty Viaflexcontainers.
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Materials of Construction 10
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Basic Types of Plastics
Thermoplastics
Polymers that soften upon heating and solidify uponcooling
Most parenteral packaging
Thermosets Chemically reactive polymers in the fluid state
Harden irreversibly by cross-linking
Epoxies, melamine resins, cross-linked polyestersand phenolics
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Most Common Polymers for Sterile Products 11
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Polyethylene (PE)
Polyvinylchloride (PVC)Polypropylene (PP)
Polyamide (Nylon)
Polycarbonate (PC)
Ethylene vinyl acetate (EVA)
Polyolefin (mixtures of low density PE, high densityPE, PP, and EVA)
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Large Volume Flexible Containers 12
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Advantages
Durable and light weight No air interchange. The bag collapses as it empties.
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Large Volume Flexible Containers 13
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Disadvantages
Permeation of vapors and other molecules in eitherdirection through the walls.
Resolved by overwrapping the containers.
Leaching of constituents from the plastic into the product.
Plasticizers and anti-oxidants Sorption of drug molecules or ions on the plastic material.
Proteins, warfarin sodium, diazepam
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Types of Flexible Containers 14
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PVC polyvinylchloride was the first polymer used forcollapsible containers.
Performs best with respect to collapsibility andtransparency
May leach DEHP (di (2-ethyl hexyl) phthalate
Banned by countries such as Germany, Sweden,France, Canada, and others.
Produces dioxin when incinerated
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Types of Flexible Containers 15
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Ethylene vinyl acetate films (EVA)
Developed to improve compatibility and moisture
permeation characteristics However, moisture permeation is poor and film
requires overwrap
Combinations Multilayer films developed to reduce moisture
permeation
Ethylene vinyl alcohol can be used as core film for itshigh gas barrier properties.
Physically bonded between two layers of EVA
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Comparative Properties of Polymers 16
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Sterilization of Flexible Containers 17
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Thermal Sterilization
Many plastics will soften or melt.
Ethylene Oxide (EtO) May be used for the empty container and then aseptically
filled.
Must evaluate possible residues and degradants fromEtO.
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Sterilization of Flexible Containers 18
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Gamma Radiation
May affect the appearance of the plastic and the
stability of the product
PVC can change color from clear to yellow, possiblepH shifts, increases in extractables
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Possible Extractables 19
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Plastics Antioxidants: BHT, thioesters, phosphates
Lubricants: silicones, polyethylene waxes
Plasticizers: phthalates
Glass
Major extractables: silicon and sodium Minor extractables: K, Ca, Ba, Al
Trace extractables: Fe, Mg, Zn
Dependant upon pH, buffer, and other components informulation
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Summary 20
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Contain >100 mL, no antimicrobial agents
Typically simple solutions NaCl, Dextrose, other nutritional solutions
Available in glass and flexible containers
Trend toward multi-chamber bags
Available for infusions, dialysis, irrigation
Plastic films chosen based on flexibility, resistance tomoisture permeation, ability to sterilize