Transcript Silicone Based Drug Delivery Systems Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D Associate Professor Department of Pharmaceutics KLE University BELGAUM -590010, Karnataka, INDIA E-mail: [email protected] Cell No: 00919448716277

Silicone Based Drug Delivery Systems
Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D
Associate Professor
Department of Pharmaceutics
KLE University
BELGAUM -590010, Karnataka, INDIA
E-mail: [email protected]
Cell No: 00919448716277
Silicone in Drug Delivery Application
Oral DDS
Nano
Technology
DDS
Parentral DDS
Topical DDS
Buccal DDS
Silicone
Rectal DDS
Nasal DDS
Vaginal DDS
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Pulmonary
DDS
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Silicone Polymers
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Polysiloxane silicones
Dimethyl silicones
Methyl phenyl silicone
Diphenyldimethylpolysilicone co-polymer
Fluorosilicones
Trifluoropropylmethylpolysiloxane
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Silicone systems
Adhesives
Emulsifiers
Gels
Resins
Elastomers
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Silicone Materials
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Silicone Fluids
Silicone gels
Silicone pressure sensitive adhesives
Silicone elastomers
High consistency elastomers
Liquid silicone rubbers or LSR’s
Low consistency
Silicone oil
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Silicone Fluids
• Fluids are non-reactive silicone polymers and
can be formulated with dimethyl, methylphenyl,
diphenyl, trifluoropropylmethyl functionality.
• The viscosity of these materials depends largely
on the polymers molecular weight and steric
hinderance of functional groups on the polymer
chain.
• Fluids are typically used in lubrication and
dampening applications.
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Workshop, KRE COP Bidar
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Silicone Gels
• Silicone Gels are composed of reactive
silicone polymers and reactive silicone
crosslinkers.
• These materials are designed to have a
very soft and compliant feel when cured.
• Typical applications include tissue
simulation and dampening.
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Silicone pressure sensitive adhesives
• Silicone PSA’s are composed of polymers
and resin.
• These materials are designed to perform
in an uncured state.
• PSA’s form a non-permanent bond with
substrates such as metals, plastics, glass
and skin.
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Silicone Elastomers
Silicone Elastomers
High consistency
Elastomers (rubber)
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Liquid silicone
Rubber or LSR’s
Low consistency
elastomers
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Adhesive
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High consistency elastomers
• High consistency elastomers are typically
composed of high viscosity polymers high levels
of reinforcing silica, and some contain
crosslinking polymers.
• These materials are clay like in an uncured
consistency and after good physical properties.
• High consistency materials can be molded into
parts by compression molding or extruded into
tubing configurations.
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Liquid silicone rubbers or LSR’s
• Liquid silicone rubbers or LSR’s are elastomers that
contain medium viscosity polymers and moderate
amounts of silica.
• The cured elastomers have good physical properties.
• They tend to have an uncured consistency like that of
vaseline.
• These materials can be molded into parts and require
the use of liquid injection molding equipment.
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Low consistency elastomers
• Low consistency silicone are pourable systems
that are composed of lower viscosity polymers
and reinforcing fillers such as silica and resin.
• These systems have lower physical properties
than high consistency or LSR formulations but
can easily be processed and molded by hand.
• These materials can be molded into parts by
compression molding or can be used as cured in
place seals or gaskets
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Adhesive
• Adhesive are low consistency elastomers
that contain lower viscosity polymers,
reinforcing silica and adhesion promoters.
• Silicone adhesives are designed to adhere
silicone to various substrate surfaces
including skin, mucousmembrean, metal,
glass and certain plastics.
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Difisivity
• The larger the molecule the less diffusivity and
consequently lower permeation rate.
• When developing silicone based drug delivery
systems, solubility and diffusivity, the two factors
critical to permeability must be understood to
determine if the active agent and silicone can
produce.
• The desired result should developers determine
that the agent-silicone permeability is ideal,
further modifications to the silicone system may
produce optimal release rates.
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Silicone for Drug Delivery Systems
• Skin adhesiveness
• Topical excipients
• Fluids and emulsions
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Adhesives for Transdermal Drug Delivery Systems
• Long-term stability, even under highhumidity conditions
• Optimized skin adhesion
• Easy, comfortable removal, with no
irritating chemical byproducts.
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Excipient and Film-Forming Materials for
Topical Drug Delivery Systems
• Increase formulation compatibility
• Improve formulation aesthetics by
providing a non-greasy, silky feel
• Improve spreading, making topical
products easier to use.
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Emulsions
• Water-in-oil and oil-in-water emulsion can
be formulated with silicone
• Emulsifier is very efficient in stabilizing
water-in-oil emulsion-even in those with a
high water content (up to 80%)
• All silky touch materials can be used in
water-in-oil and oil-in-water emulsion.
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Emulsions
• Silicone Fluid and Silmogen Carrier, which
are very volatile provide a quick
evaporation/breakage of the emulsion on
application.
• Several Silky Touch materials can be
introduce into an emulsion to achieve
synergetic effects
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Gels
• Water-free gels can accept most silky
Touch materials.
• Large amount of silicone (up to 99%) can
be used in such gels.Gels based on
Elastomer exhibit unique aesthetics such
as smooth-silky feel, no tackiness,
superior spreadability, matifying effect and
non-greasiness.
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Benefits of Silicone Based Drug
Delivery Systems
• Versatility (smart)
• Barrier properties
• Biocompatibility (non-sensitizing and nonirritating)
• Optimizable skin adhesion
• Flexible processing
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Transporter/Receptor-Targeted Drug
Delivery
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Aesthetic Benefits of Silicone Excipients
Sensory evaluation (paired comparison) of (a) an ointment containing petrolatum
(70%), ST- Cyclomethicone 5-NF (15%) and ST-Elastomer 10 (15%) versus (b)
petrolatum (100%)
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Aesthetic Benefits of Silicone Excipients
Sensory evaluation (paired comparison) of (a) the hydrogel with Dimethiconol
Blend 20 (5%) and ST-Elastomer 10 (10%) versus (b) the same hydrogel with no
silicone
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Aesthetic Benefits of Silicone Excipients
Sensory evaluation (paired comparison) of (a) water-in-oil based on mineral oil (2%),
petrolatum (5%) and Silky Wax 10 (5%) versus (b) water-in-oil emulsion based on mineral oil
(10%), ST-Cyclomethicone 5-NF (10%) and Dimethiconol Blend 20 (5%). The same silicone
surfactant (2% of Emulsifier 10) has been used in both formulations
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Pharmacokinetic Benefits of Silicone Excipients
Substantivity of silicone gum on skin over the time. Formulation silicone gum
(3%) and hexamethyldisiloxane (97%). Test done on the forearm of 5 panelists.
The silicone remaining on the skin of the panelists is analyzed by ATR-FTIR
spectroscopy
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Pharmacokinetic Benefits of Silicone Excipients
Substantivity of Ketoprofen on skin over time. Formulation (a) Ketoprofen (2.5%),
Hexamethyldisiloxane (94.5%) and silicone gum (3%). Formulation (b) Ketoprofen
(2.5%) and Hexamethyldisiloxane (97.5%). Test done on the forearm of 5 panelist.
Semi-quantitative analysis of Ketoprofen remaining on the skin of the panelists
done by ATR-FTIR spectroscopy
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Pharmacokinetic Benefits of Silicone Excipients
Comparison of the penetration rate of ibuprofen(5%) through hairless rat skin in
static diffusion cells silicone-based formulations (silicone gum in
hexamethyldisiloxane) versus a silicone free hydrogel
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Pharmacokinetic Benefits of Silicone Excipients
Comparison of the penetration rate of econazole nitrate (1%) through hairless rat
skin static diffusion cells silicone-based formulations (silicone gum in
hexamethyldisiloxane) versus a silicone-free emulsion
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Pharmacokinetic Benefits of Silicone Excipients
Comparison of penetration rate of hydrocortisone (5%) through hairless rat skin in
static diffusion cells of silicone-based formulations (silicone gum in
hexamethyldisiloxane) versus a silicone-free emulsion
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Healthcare Applications
• Silicone oils and crosslinked slogan
systems did not give rise to harmful
consequences when performing
subcutaneous, intracutaneous and
intramuscular administrations.
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Evaluation and Fabrication
• The first step in determining general
compatibility of a silicone with an active
agent is determining the solubility of the
agent in silicone
• Silicone oil can be used to determine if an
agent may be soluble in a silicone
elastomer system.
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Evaluation and Fabrication
• Once solubility has been determined, the active
agent can then be tested in the elastomer
system to determine the optimal concentration or
agent configuration for the target release rate
per day and the total number of release days.
• In some devices, the drug is incorporated into a
silicone matrix core or reservoir and the release
rate is controlled by an quitter layer of silicone.
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Evaluation and Fabrication
• A general review suggests that 5% to 50% of the
active agent is optimal for release rates of 10 to
500 micrograms of drug per day.
• These numbers are highly dependent on the
type of drug, silicone, and any rate enhancing
additives.
• The release rate is also cited and has been
characterized as essentially zero order.
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Enhanced permeability and retention
effect (EPR effect)
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Transferrin – mediated targeting
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Drug Eluting applications
Antidepressants
Antiviral compounds
Anxiolytics
Opioid analgesic
Vitamins, B6, D & E
Antifungal
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Rate enhancing additives
• Fatty acid esters
• Oleic acid
• Isopropyl myristate
• Linoleic acid
• Coproic acid
• Adipic acid
• Lauric acid
• Lanolic acids
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Conclusion
• Silicone materials enjoy considerable use
in the health care and drug delivery
industries because of their historic use in
these sensitive applications.
• Drug delivery applications are dependent
on factors like solubility and diffusivity.
• Diffusivity itself relies on crosslink density
to control permeability.
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Conclusion
Cont…
• Drug delivery applications that place very
specific permeation demands on materials
require consistency.
• The lower molecular weight species need to be
removed to produce consistent silicone
products.
• Speculate consistent silicone materials will result
in consistent drug permeability rates.
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Conclusion
Cont…
• Researchers have additional options when it
comes to evaluating different levels of
purification and many find benefit in the fine
tuning the consistency of drug permeation or
adjusting to a specific permeation rate.
• The interaction between drugs, release
enhancing agents, and silicone systems was
characterized by comparing molecule structures
of each.
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