Transcript Drug Delivery Systems

Transparent UV Protective Backings containing Nanosized Titanium Dioxide for Transdermal Drug Delivery Applications
Chad R. Wold
3 Drug Delivery Systems, St. Paul, MN, USA 55144
Introduction
Results
Fig 1 – UV Absorbance range of several inorganic and organic materials
suitable for dermal applications.
Zinc Oxide (micronized)
Depending on the type and content of the UV protective components, a systematic
reduction in drug degradation was observed. The addition of 0.5 % w/w of nanosized
TiO2 in the transdermal backing substantially decreased the amount of drug
degradation versus the control study that was not irradiated by UV-Visible exposure.
Fig 2 – UV Absorbance ability of TiO2 as a function of concentration
in backing film.
4.5
0% TiO2
4
Fig 4 – Pros and Cons of Inorganic versus Organic Absorbers.
0.5 % TiO2
1.0% TiO2
3.5
Absorbance
Various active drugs used in transdermal drug delivery systems are widely known to exhibit
photochemical degradation upon light exposure. During storage, these products are well
protected from light by the packaging foil. However, during wear, exposure to sunlight may
result in undesired degradation of the active drug.
Historically, transdermal drug delivery systems with ultraviolet (UV) sensitive components
often utilized an opaque backing material to reduce photo-degradation. These backings,
which are usually pigmented or contain a metallic foil layer, are limited by their aesthetic
appearance. The purpose of this work was to develop a backing film that provides UV
protection by utilizing nanosized TiO2 while maintaining transparency of the backing film.
Results, Cont.
2.0% TiO2
• Micronized Inorganic Blockers
5.0% TiO2
3
– Pros
2.5
•
•
•
•
2
1.5
– Cons
1
Titanium Dioxide
(micronized)
• High concentrations reduces opacity
• Dispersion
0.5
• Ultraviolet Organic Absorbers
0
Oxybenzone
Low content
Low irritation
Inert
Transparent at low concentrations
200
300
400
500
600
700
800
Wavelength (nm)
Dioxybenzone
– Pros
• Many FDA approved compounds
– Used in sunscreens/cosmetics
– Cons
Cinoxate
Avobenzone
UV-C
220
240
UV-B
260
280
UV-A
300
320
340
•
•
•
•
•
Fig 3 – Effect of TiO2 concentration on the loss of drug content
upon UV exposure at ICH conditions.
360
380
400
Drug content after UV exposure
Wavelength (nm)
Estradiol
Example No. % TiO2 Conc.
Methods
Novel transparent olefin backings with exceptional UV protective properties were
developed in this study. The backings were developed by first compounding nanosized
TiO2 into the polymer matrix. These compounded polymers were then extruded as thin
films for analysis. The resulting thin films were then used as the backing component in a
drug-in-adhesive patch construction containing two UV-sensitive labile drugs. The
transdermal patches were then tested by irradiating the patches under ICH guidelines of
not less than 1.2 million lux hours of visible exposure and not less than 200 watt hours/m 2
of UV exposure.
Content
Shelf life
Compatibility with polymer matrix
Potential interaction with drug, excipient, adhesive
Migration
Estrogenic?
Levonorgestrel
% Degradation
Content
% Degradation
Conclusions
In Film
[mg/g]
[mg/g]
A
0
18.75
8.3
4.34
34.1
B
0.5
19.42
5.0
5.38
18.4
C
1.0
19.77
3.3
5.92
10.1
D
2.0
20.19
1.3
6.38
3.2
The addition of nanosized TiO2 into the transdermal backing substantially enhanced
the UV-protective properties while maintaining transparency. The results demonstrate
that incorporation of nanosized TiO2 into the transdermal backing significantly
decreased photochemical degradation of the active drug.
3 Drug Delivery Systems