Transcript Silicone Based Drug Delivery Systems

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
05 March 2009
Pulmonary
DDS
Workshop, KRE COP Bidar
2
Silicone Polymers
1.
2.
3.
4.
5.
6.
Polysiloxane silicones
Dimethyl silicones
Methyl phenyl silicone
Diphenyldimethylpolysilicone co-polymer
Fluorosilicones
Trifluoropropylmethylpolysiloxane
05 March 2009
Workshop, KRE COP Bidar
3
Silicone systems
Adhesives
Emulsifiers
Gels
Resins
Elastomers
05 March 2009
Workshop, KRE COP Bidar
4
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
05 March 2009
Workshop, KRE COP Bidar
5
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.
05 March 2009
Workshop, KRE COP Bidar
6
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.
05 March 2009
Workshop, KRE COP Bidar
7
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.
05 March 2009
Workshop, KRE COP Bidar
8
Silicone Elastomers
Silicone Elastomers
High consistency
Elastomers (rubber)
05 March 2009
Liquid silicone
Rubber or LSR’s
Low consistency
elastomers
Workshop, KRE COP Bidar
Adhesive
9
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.
05 March 2009
Workshop, KRE COP Bidar
10
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.
05 March 2009
Workshop, KRE COP Bidar
11
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
05 March 2009
Workshop, KRE COP Bidar
12
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.
05 March 2009
Workshop, KRE COP Bidar
13
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.
05 March 2009
Workshop, KRE COP Bidar
14
Silicone for Drug Delivery Systems
• Skin adhesiveness
• Topical excipients
• Fluids and emulsions
05 March 2009
Workshop, KRE COP Bidar
15
Adhesives for Transdermal Drug Delivery Systems
• Long-term stability, even under highhumidity conditions
• Optimized skin adhesion
• Easy, comfortable removal, with no
irritating chemical byproducts.
05 March 2009
Workshop, KRE COP Bidar
16
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.
05 March 2009
Workshop, KRE COP Bidar
17
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.
05 March 2009
Workshop, KRE COP Bidar
18
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
05 March 2009
Workshop, KRE COP Bidar
19
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.
05 March 2009
Workshop, KRE COP Bidar
20
Benefits of Silicone Based Drug
Delivery Systems
• Versatility (smart)
• Barrier properties
• Biocompatibility (non-sensitizing and nonirritating)
• Optimizable skin adhesion
• Flexible processing
05 March 2009
Workshop, KRE COP Bidar
21
Transporter/Receptor-Targeted Drug
Delivery
05 March 2009
Workshop, KRE COP Bidar
22
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%)
05 March 2009
Workshop, KRE COP Bidar
23
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
05 March 2009
Workshop, KRE COP Bidar
24
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
05 March 2009
Workshop, KRE COP Bidar
25
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
05 March 2009
Workshop, KRE COP Bidar
26
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
05 March 2009
Workshop, KRE COP Bidar
27
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
05 March 2009
Workshop, KRE COP Bidar
28
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
05 March 2009
Workshop, KRE COP Bidar
29
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
05 March 2009
Workshop, KRE COP Bidar
30
Healthcare Applications
• Silicone oils and crosslinked slogan
systems did not give rise to harmful
consequences when performing
subcutaneous, intracutaneous and
intramuscular administrations.
05 March 2009
Workshop, KRE COP Bidar
31
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.
05 March 2009
Workshop, KRE COP Bidar
32
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.
05 March 2009
Workshop, KRE COP Bidar
33
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.
05 March 2009
Workshop, KRE COP Bidar
34
Enhanced permeability and retention
effect (EPR effect)
05 March 2009
Workshop, KRE COP Bidar
35
Transferrin – mediated targeting
05 March 2009
Workshop, KRE COP Bidar
36
Drug Eluting applications
Antidepressants
Antiviral compounds
Anxiolytics
Opioid analgesic
Vitamins, B6, D & E
Antifungal
05 March 2009
Workshop, KRE COP Bidar
37
Rate enhancing additives
• Fatty acid esters
• Oleic acid
• Isopropyl myristate
• Linoleic acid
• Coproic acid
• Adipic acid
• Lauric acid
• Lanolic acids
05 March 2009
Workshop, KRE COP Bidar
38
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.
05 March 2009
Workshop, KRE COP Bidar
39
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.
05 March 2009
Workshop, KRE COP Bidar
40
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.
05 March 2009
Workshop, KRE COP Bidar
41
05 March 2009
Workshop, KRE COP Bidar
42