betadex and avobenzone

Lipid microparticles loaded with the complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) and the sunscreen agent, butyl methoxydibenzoylmethane (BMDBM) were evaluated for their effect on the UV filter percutaneous penetration. The microparticles were prepared by the melt emulsification technique using tristearin as lipidic material and hydrogenate phosphatidylcholine as the surfactant. Human skin penetration was investigated in vivo by the tape stripping technique, a minimal invasive procedure based on the progressive removal of the upper cutaneous layers (stratum corneum) with adhesive tape strips. The amount of sunscreen fixed to each strip was determined by HPLC after solvent extraction. The recovery of the UV filter from spiked adhesive tapes was >94.4% and the precision of the method was better than 7.6% relative standard deviation. Non-encapsulated BMDBM, its complex with HP-β-CD, the lipid microparticles loaded with the sunscreen alone or the BMDBM/HP-β-CD complex were introduced into oil-in-water emulsions and applied to human volunteers. Compared to the cream with the non-encapsulated sunscreen agent (percentage of the applied dose penetrated, 9.7%±2.5), the amount of BMDBM diffusing into the stratum corneum was increased by the formulations containing the BMDBM/HP-β-CD complex (17.1%±3.2 of the applied dose) or the microparticles loaded with BMDBM only (15.1%±2.7 of the applied dose). On the contrary, a significant decrease in the level of UV filter penetrated into the stratum corneum was achieved by the cream containing the microencapsulated BMDBM/HP-β-CD complex (percentage of the applied dose penetrated, 6.0%±1.5). The reduced BMDBM percutaneous penetration attained by the latter system should enhance the UV filter efficacy and limit potential toxicological risks.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Adult; Alkanes; beta-Cyclodextrins; Chalcones; Cyclodextrins; Drug Compounding; Emulsions; Filtration; Humans; Hydrogenation; Lipids; Microscopy, Electron, Scanning; Microspheres; Middle Aged; Molecular Structure; Particle Size; Phosphatidylcholines; Propiophenones; Skin; Skin Absorption; Sunscreening Agents; Surface-Active Agents; Triglycerides; Ultraviolet Rays

The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the transdermal penetration and photostability of a model ultraviolet A (UVA) absorber, butyl methoxydibenzoylmethane (avobenzone), and to determine the influence of complexation on in vivo photoprotection. Avobenzone-HPCD complexation was demonstrated by differential scanning calorimetry. Formulations containing 0.12 mg/ml avobenzone and up to 30% (w/w) HPCD were prepared. Transdermal penetration was conducted using a modified Franz diffusion cell apparatus. As the concentration of HPCD was increased from 0% to 20%, transdermal permeation increased. Maximum flux occurred at 20% HPCD, where sufficient cyclodextrin was present to completely solubilize all avobenzone. When the concentration of HPCD was increased to 30%, transdermal penetration decreased, suggesting the formation of an avobenzone reservoir on the skin surface. Photostability of avobenzone was investigated under 100, 250, and 500 kJ/m2 UVA irradiation. The 30% HPCD formulation was the most photostable, followed by 20%, 10%, and 0% formulations. In vivo, the 30% HPCD formulation afforded the best photoprotection, as evidenced by the lowest extent of sunburn cell formation and edema induction. This work indicates that inclusion of HPCD in sunscreen formulations may enhance photoprotection by reducing both skin penetration and photodecomposition of UV absorbers.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Cutaneous; Algorithms; Animals; beta-Cyclodextrins; Chalcones; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Stability; Female; In Vitro Techniques; Mice; Mice, Hairless; Photochemistry; Propiophenones; Radiation-Protective Agents; Skin Absorption; Ultraviolet Rays

The aim of this study was to investigate the incorporation into lipospheres of the complex between hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and the sunscreen agent, butyl methoxydibenzoylmethane (BMDBM) and to examine the influence of this system on the sunscreen photostability. The formation of the inclusion complex was confirmed by thermal analysis and powder X-ray diffraction. Lipid microparticles loaded with free BMDBM or its complex with HP-beta-CD were prepared using tristearin as the lipid material and hydrogenated phosphatidylcholine as the emulsifier. The obtained lipospheres were characterized by scanning electron microscopy and differential scanning calorimetry. The microparticle size (15-40 microm) was not affected by the presence of the complex. Release of BMDBM from the lipospheres was lower when it was incorporated as inclusion complex rather than as free molecule. Unencapsulated BMDBM, its complex with HP-beta-CD, the sunscreen-loaded lipospheres or the lipoparticles containing the BMDBM/HP-beta-CD complex, were introduced into a model cream (oil-in-water emulsion) and irradiated with a solar simulator. The photodegradation studies showed that all the examined systems achieved a significant reduction of the light-induced decomposition of the free sunscreen agent (the BMDBM loss decreased from 28.9 to 17.3-15.2%). However, photolysis experiments performed during 3 months storage of the formulations, demonstrated that the photoprotective properties of the HP-beta-CD complex and of BMDBM alone-loaded lipospheres decreased over time, whereas the microencapsulated HP-beta-CD/BMDBM complex retained its photostabilization efficacy. Therefore, incorporation in lipid microparticles of BMDBM in the cyclodextrin complex form is more effective in enhancing the sunscreen photostability than the complex alone or the liposphere-entrapped free BMDBM.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Alkanes; beta-Cyclodextrins; Chalcones; Drug Compounding; Drug Stability; Emulsions; Excipients; Liposomes; Particle Size; Phosphatidylcholines; Photolysis; Propiophenones; Solubility; Sunscreening Agents; Time Factors; Triglycerides; Ultraviolet Rays

The aim of the study was to investigate the effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the photo-induced production of free radicals by the sunscreen agent, butyl-methoxydibenzoylmethane (BMDBM). Spin-trapping/electron paramagnetic resonance spectroscopy was used to evaluate the formation of radicals and the extent of BMDBM photodegradation was measured by high-performance liquid chromatography. The stable 2,2,6,6-tetramethylpiperidine-1-oxyl, nitroxide radical (TEMPO) was used as spin-trap. Any free radicals generated during irradiation of the sunscreen agent will couple with the TEMPO radicals giving diamagnetic species and thus a decrease of the signal intensity in the electron paramagnetic resonance spectrum. Following 2-h illumination with simulated sunlight, the solution containing free BMDBM exhibited a 93.9% decrease of the intensity of the TEMPO signal. Under the same irradiation conditions, only a 12.2% reduction of the TEMPO concentration was measured in the sample containing BMDBM complexed with HP-beta-CD. Moreover, the decrease of the spin-trap level observed for the HP-beta-CD/BMDBM complex was not significantly different from that produced when solutions containing TEMPO only or TEMPO in the presence of HP-beta-CD alone were subjected to irradiation. In addition, the photodegradation of the sunscreen agent was reduced by complexation with HP-beta-CD (the extent of degradation was 27.6% for the complex compared with 63.1% for free BMDBM). The results obtained indicate that the free radicals generated by BMDBM when exposed to simulated sunlight are effectively scavenged by inclusion complexation of the sunscreen agent with HP-beta-CD.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Alkanes; Benzoates; beta-Cyclodextrins; Chalcones; Chromatography, High Pressure Liquid; Cyclodextrins; Differential Thermal Analysis; Drug Stability; Electron Spin Resonance Spectroscopy; Free Radicals; Propiophenones; Spectrophotometry, Ultraviolet; Sunscreening Agents; Time Factors; Ultraviolet Rays; X-Ray Diffraction