Investigation of the degradation-retarding effect caused by the low swelling capacity of a novel hyaluronic Acid filler developed by solid-phase crosslinking technology.

BACKGROUND: A variety of hyaluronic acid (HA) fillers demonstrate unique physical characteristics, which affect the quality of the HA filler products. The critical factors that affect the degradation of HA gels have not yet been determined. OBJECTIVE: Our objective was to determine the characteristics of HA gels that affect their resistance to the degradation caused by radicals and enzymes. METHODS: Three types of HA fillers for repairing deep wrinkles, Juvederm Ultra Plus (J-U), Restylane Perlane (Perlane), and Cleviel, were tested in this study. The resistance of these HA fillers to enzymatic degradation was measured by carbazole and displacement assays using hyaluronidase as the enzyme. The resistance of these fillers to radical degradation was measured by the displacement assay using H2O2. RESULTS: Different tests for evaluating the degradation resistance of HA gels can yield different results. The filler most susceptible to enzymatic degradation was J-U, followed by Perlane and Cleviel. The HA filler showing the highest degree of degradation caused by H2O2 treatment was Perlane, followed by J-U, and then Cleviel. Cleviel showed higher enzymatic and radical resistances than J-U and Perlane did. Furthermore, it exhibited the highest resistance to heat and the lowest swelling ratio among all the fillers that were examined. CONCLUSION: The main factor determining the degradation of HA particles is the gel swelling ratio, which is related to the particle structure of the gel. Our in vitro assays suggest that the decrease in the swelling ratio will lead to a retarding effect on the degradation of HA fillers.

Titanium dioxide inclusion in backing reduce the photoallergenicity of ketoprofen transdermal patch.

Ketoprofen (KP) is a widely used transdermal non-steroidal anti-inflammatory drug. However, increasing number of adverse effect case reports suggests that KP transdermal formulation can cause photoallergic reaction. The photoallergic potential of KP is attributable to the instability of KP under UV/visible light and subsequent formation of reactive degradation products. In this study, we investigated whether the inclusion of titanium dioxide (TiO(2)), a well-known mineral sunscreen agent, in the KP transdermal patch can prevent the photodegradation of KP and ultimately, can reduce photoallergic reaction. TiO(2) inclusion in fabric backing effectively decreased the UV transmission through fabric patch throughout all UVA region from 320 to 380 nm and consistently, KP patch with TiO(2) exhibited significantly increased photostability of KP. This enhanced photostability of KP resulted in reduced generation of photodegradation product as determined by HPLC-UV analysis. In a good accordance with these in vitro results, photosensitization test in guinea pig in vivo demonstrated low photoallergic reactions of KP patch with TiO(2) compared to KP patch without TiO(2), indeed. This study demonstrated that KP transdermal patch with TiO(2)-included backing can provide with improved photostability and photosafety over conventional fabric KP patch.

A novel transdermal patch incorporating meloxicam: in vitro and in vivo characterization.

A monolithic drug-in-adhesive (MDIA) type patch containing meloxicam (MX) was designed with an acrylic adhesive, a solubility modulator increasing MX solubility, and enhancers. MDIA patches having one adhesive layer between the backing and the release liner give high productivity and improve patient compliance. The biggest problem to prepare MDIA patch including MX was poor solubility of MX. In this research, solubility modulators to increase solubility of MX and acrylic adhesives and skin permeation enhancers were investigated through solubility tests, in vitro skin permeation tests, and stability tests. Consequently, the composition of sodium methoxide (SM), an acrylic adhesive containing poly(vinyl pyrrolidone) blocks (MAS683), polyoxyethylene cetylether (BC-2), and diisopropanolamine (DIPA) made it possible for MX to be contained in an adhesive layer at a concentration of as much as 15 wt% without MX crystal and with high skin permeation over 400 microG/cm(2). Finally, the patch formulation containing MX (MX-patch) selected through our in vitro study was characterized by in vivo using an animal study to acquire pharmacokinetic (PK) parameters and to confirm the anti-inflammatory efficacy of MX-patch. In the animal study, MX-patch was compared with a commercially available piroxicam patch (PX-patch). The amount of MX delivered from MX-patch to the skin surface was believed to be higher than the amount of MX diffused from the skin tissue to circulatory system because the plasma concentration of MX continuously increased up to 32 h, the end time of PK study, although the patch samples were detached at 24 h. PX-patch produced a C(max) at 8 h. MX-patch showed better significant efficacy than PX-patch in adjuvant arthritis model.