naphthoquinones and resorcinol

Topics: Aminopyridines; Anthraquinones; Azo Compounds; Coloring Agents; Cresols; Dimethyl Sulfoxide; Dinitrochlorobenzene; Eugenol; Gene Expression; HaCaT Cells; Hair Dyes; Heme Oxygenase-1; Humans; Hydroquinones; In Vitro Techniques; Keratinocytes; Naphthoquinones; NF-E2-Related Factor 2; Phenylenediamines; Proto-Oncogene Proteins c-fos; Pyrogallol; Resorcinols; RNA, Messenger; Sodium Dodecyl Sulfate

The aim of this paper was to compare the in vitro dissolution and in vivo bioavailability of three solubility enhancement technologies for β-lapachone (LPC), a poorly water soluble compound with extremely high crystallization propensity. LPC cocrystal was prepared by co-grinding LPC with resorcinol. LPC crystalline and amorphous solid dispersions (CSD and ASD) were obtained by spray drying with Poloxamer 188 and HPMC-AS, respectively. The cocrystal structure was solved by single crystal x-ray diffraction. All formulations were characterized by WAXRD, DSC, POM and SEM. USP II and intrinsic dissolution studies were used to compare the in vitro dissolution of these formulations, and a crossover dog pharmacokinetic study was used to compare their in vivo bioavailability. An 1:1 LPC-resorcinol cocrystal with higher solubility and faster dissolution rate was obtained, yet it converted to LPC crystal rapidly in solution. LPC/HPMC-AS ASD was confirmed to be amorphous and uniform, while the crystal and crystallite sizes of LPC in CSD were found to be ∼1-3 μm and around 40 nm, respectively. These formulations performed similarly during USP II dissolution, while demonstrated dramatically different oral bioavailability of ∼32%, ∼5%, and ∼1% in dogs, for CSD, co-crystal, and ASD, respectively. CSD showed the fastest intrinsic dissolution rate among the three. The three formulations showed poor IVIVC which could be due to rapid and unpredictable crystallization kinetics. Considering all the reasons, we conclude that for molecules with extremely high crystallization tendency that cannot be inhibited by any pharmaceutical excipients, size-reduction technologies such as CSD could be advantageous for oral bioavailability enhancement in vivo than technologies only generating transient but not sustained supersaturation.

Topics: Administration, Oral; Animals; Biological Availability; Cross-Over Studies; Crystallization; Crystallography, X-Ray; Dogs; Dosage Forms; Drug Compounding; Drug Liberation; Methylcellulose; Naphthoquinones; Particle Size; Poloxamer; Resorcinols; Solubility; Technology, Pharmaceutical

Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone) are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone can reduce the production of melanin. The results also confirmed that resorcinol and lawsone inhibit mushroom and cellular tyrosinase activities in vitro. Resorcinol and lawsone can also downregulate the protein levels of tyrosinase and microphthalmia-associated transcription factor (MITF) in B16-F10 cells. Thus, we suggest that frequent use of hair dyes may have the risk of reducing natural melanin production in hair follicles. Moreover, resorcinol and lawsone may also be used as hypopigmenting agents to food, agricultural and cosmetic industry in the future.

Topics: Ammonium Sulfate; Animals; Cell Line, Tumor; Cell Survival; Coloring Agents; Down-Regulation; Melanins; Melanoma, Experimental; Mice; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Naphthoquinones; Resorcinols; Sodium Compounds; Sulfates

Topics: Chemistry, Pharmaceutical; Cresols; Naphthoquinones; Phenols; Research; Resorcinols; Sodium

Topics: Chemistry Techniques, Analytical; Chemistry, Pharmaceutical; Colorimetry; Naphthoquinones; Pharmacy; Phenols; Research; Resorcinols; Sodium; Sulfonic Acids