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_address] Cell No: 00919448716277

Silicone in Drug Delivery Application Nano Technology DDS Buccal DDS Rectal DDS Vaginal DDS Pulmonary DDS Nasal DDS Topical DDS Parentral DDS Oral DDS Silicone

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

Polysiloxane silicones

Dimethyl silicones

Methyl phenyl silicone

Diphenyldimethylpolysilicone co-polymer

Fluorosilicones

Trifluoropropylmethylpolysiloxane

Silicone systems Adhesives Elastomers Resins Gels Emulsifiers

Silicone Materials Silicone Fluids Silicone gels Silicone pressure sensitive adhesives Silicone elastomers High consistency elastomers Liquid silicone rubbers or LSR’s Low consistency Silicone oil

Silicone Fluids

Silicone gels

Silicone pressure sensitive adhesives

Silicone elastomers

High consistency elastomers

Liquid silicone rubbers or LSR’s

Low consistency

Silicone oil

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.

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.

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.

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.

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.

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.

Silicone Elastomers Silicone Elastomers High consistency Elastomers (rubber) Liquid silicone Rubber or LSR’s Low consistency elastomers Adhesive

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.

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.

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.

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.

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

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

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.

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.

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.

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.

Silicone for Drug Delivery Systems Skin adhesiveness Topical excipients Fluids and emulsions

Skin adhesiveness

Topical excipients

Fluids and emulsions

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.

Long-term stability, even under high-humidity conditions

Optimized skin adhesion

Easy, comfortable removal, with no irritating chemical byproducts.

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.

Increase formulation compatibility

Improve formulation aesthetics by providing a non-greasy, silky feel

Improve spreading, making topical products easier to use.

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.

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.

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

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

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.

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.

Benefits of Silicone Based Drug Delivery Systems Versatility (smart) Barrier properties Biocompatibility (non-sensitizing and non-irritating) Optimizable skin adhesion Flexible processing

Versatility (smart)

Barrier properties

Biocompatibility (non-sensitizing and non-irritating)

Optimizable skin adhesion

Flexible processing

Transporter/Receptor-Targeted Drug Delivery

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%)

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

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

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

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

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

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

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

Healthcare Applications Silicone oils and crosslinked slogan systems did not give rise to harmful consequences when performing subcutaneous, intracutaneous and intramuscular administrations.

Silicone oils and crosslinked slogan systems did not give rise to harmful consequences when performing subcutaneous, intracutaneous and intramuscular administrations.

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.

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.

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.

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.

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.

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.

Enhanced permeability and retention effect (EPR effect )

Transferrin – mediated targeting

Drug Eluting applications Antidepressants Anxiolytics Vitamins, B6, D & E Antifungal Opioid analgesic Antiviral compounds

Fatty acid esters Isopropyl myristate Coproic acid Lauric acid Oleic acid Linoleic acid Adipic acid Lanolic acids Rate enhancing additives

Fatty acid esters

Isopropyl myristate

Coproic acid

Lauric acid

Oleic acid

Linoleic acid

Adipic acid

Lanolic acids

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.

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.

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.

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.

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.

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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