Silicone Based Drug Delivery Systems

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• 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 bknanjwade_at_yahoo.co.in Ce
ll No 00919448716277
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Silicone in Drug Delivery Application
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Silicone Polymers

• Polysiloxane silicones
• Dimethyl silicones
• Methyl phenyl silicone
• Diphenyldimethylpolysilicone co-polymer
• Fluorosilicones
• Trifluoropropylmethylpolysiloxane

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Silicone systems
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Silicone Materials

• Silicone Fluids
• Silicone gels
• Silicone pressure sensitive adhesives
• Silicone elastomers
• High consistency elastomers
• Liquid silicone rubbers or LSRs
• 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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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 PSAs are composed of polymers and
  resin.
• These materials are designed to perform in an
  uncured state.
• PSAs form a non-permanent bond with substrates
  such as metals, plastics, glass and skin.

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Silicone Elastomers
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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 LSRs

• Liquid silicone rubbers or LSRs 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 high-humidity
  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
  non-irritating)
• 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
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Rate enhancing additives

• Fatty acid esters
• Isopropyl myristate
• Coproic acid
• Lauric acid

• Oleic acid
• Linoleic acid
• Adipic 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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THANKS