Key Engineering Materials Vol. 859

Abstract: The release behavior of doxycycline hyclate (DH) from beta-cyclodextrin (β-CD) in situ gels (ISG) and in situ microparticles (ISM) was investigated using dialysis tube method and direct contact method compared to that from DH solution. From dialysis tube method, DH released completely from solution within 8 h, while it released with more sustainable from ISM and ISG completely at 12 h and 28 h, respectively. The release pattern of them was similar when tested using direct contact method (released completely at 9 days). The DH release from dialysis tube method of all systems was a first order kinetic. DH release from ISM using direct contact method fitted well with a Higuchi’s equation. The dialysis tube method was suitable for determining formula factors affecting the drug release behavior. However, to simulate the pocket condition with contact area is limited, the drug release test with direct contact method was preferred than dialysis tube method.

Abstract: Microneedles (MNs) are attractive micron scale technology, which has been used as a physical force to create transport pathways and enhance the permeability of drugs into the skin. Fluorescein sodium (FS), a hydrophilic drug was loaded in MNs for transportation through skin. The purposes of this study were to develop and evaluate the optimal formulation of FS-loaded polymeric microneedles (MNs) as a device for transdermal drug delivery system. The FS-MNs were fabricated by micro-molding technique and prepared by using Gantrez^® S-97 (G) and hyaluronic acid (HA). The physical appearances were observed under digital microscope. The mechanical properties were determined by a texture analyzer. The insertion study was tested on neonatal porcine skin. The MNs height changing after insertion into the skin at predetermined times was measured to show dissolution ability of MNs. Finally, the drug permeation profile of FS-MNs was investigated by Franz diffusion cell. For the results, all formulations were complete fabrication of conical microneedle array (11 rows x 11 columns in 10 mm² patch area) with average 600 + 20 μm in height, 300 + 5 μm in width, and 600 + 10 μm in interspace. The percent decrease of MNs height in mechanical strength of 30%G+5%HA was significantly less than others at 1.8 to 8.8 N/121 array. The formulation mixing with 30% Gantrez^® S-97 had 100% of penetration into porcine skin. The dissolution ability showed that MNs were completely dissolved within 60 minutes. At 24 h of skin permeation, the FS permeated through the skin from 1%FS solution, 30%G+1%FS MNs, and 30%G+5%HA+1%FS MNs was 1.00%, 4.27% and 7.53%, respectively. The flux values of 1%FS solution, 30%G+1%FS MNs, and 30%G+5%HA+1%FS MNs were 0.006 μg/cm²/min, 0.032 μg/cm²/min, and 0.037 μg/cm²/min, respectively, indicating the highest skin permeability of FS from 30%G+5%HA+1%FS MNs. In conclusion, the 30%G+5%HA+1%FS formulation presented appropriate MNs properties as a device for transdermal drug delivery system.

Abstract: The oral delivery is the most practical route to deliver drugs into the body, however drug-metabolizing enzymes and drug transporters can play important roles in modulating drug absorption. This study intended to find a natural bioenhancer for improving drug bioavailability. Two limonoids, including limonin deepoxy and nomilin, isolated from pomelo pulp were studied and the inhibition effects on human CYP3A4 and P-gp were investigated. Testosterone 6β-hydroxylation was performed in recombinant human CYP3A4 to discover the effects on CYP activity. Daunorubicin transport in Caco-2 and calcein-AM uptake in LLC-PK₁ and LLC-GA5-COL300 were conducted to evaluate the effects on P-gp function. The results show that both limonin deepoxy and nomilin could inhibit CYP3A4 and only nomilin exhibited mechanism-based inhibition. Nomilin was able to inhibit human P-gp in the concentration-dependent manner. Taken together, nomilin demonstrated strong activities on both CYP3A4 and P-gp, indicating that nomilin could possibly be used as a bioavailability enhancer.

Abstract: Quercetin has been used for health promotion for instance anti-bacterial, anti-inflammatory, anti-coagulative, antineoplastic and antioxidant. The poorly water-soluble quercetin has been a significant problem of bioavailability for oral administration. The objective of this study was to improve the quercetin solubility by spontaneous emulsion formulation (SEF). SEF was fabricated by dissolved quercetin in mixture of polyoxyl 35 castor oil, diethylene glycol monoethy ether, caprylic/capric glyceride. The solid-SEF was obtained by incorporation with solid carrier adsorbent (magnesium aluminometasilicate). The photon correlation spectroscopy was used to determine the emulsion size of diluted SEF and solid-SEF. The power X-ray diffraction and differential scanning calorimetry were also employed to elucidate the powder of solid-SEF compared with unmodified quercetin. The dissolution profiled at 120 min of unmodified quercetin, SEF and solid-SEF was about 2%, 77% and 89%, respectively.

Abstract: Mucuna pruriens is a tropical leguminous plant containing L-dopa which is the main active ingredient for Parkinson’s disease therapy. The objective of this study was to investigate the physical, chemical, and microbiological stability of M. pruriens seed extract effervescent powders and suspension. The effervescent powders and suspension were prepared using freeze dried M. pruriens seed extract and were stored at 4 °C, 30 °C, and 45 °C. Physical stability was evaluated by observing appearance and determining rheological behavior. Chemical stability was evaluated by HPLC assay of L-dopa content in the formulation. Bacterial, fungal and mold contaminations were assessed by 3M^TM Petrifilm^TM count plates. Both formulations showed good physical stability. The degradations of L-dopa in effervescent powders and suspension were fitted to pseudo-zero order and second order kinetic models, respectively. M. pruriens seed extract effervescent powders was found to have the longest half-life, about 112 days, when it was stored at 4 °C. The results suggested that M. pruriens seed extract should be formulated in effervescent powders and stored at 4°C to prevent physical and chemical degradation.

Abstract: Other portion of solar spectrum apart from UV, particularly blue light, is currently reported to induce the damaging effects to human skin. This study was aimed to investigate the effect of the combination of tris-biphenyl triazine (TBPT) and inorganic metal oxides as well as the effect of the matrix formulations on UV and blue light protection efficiencies. The protection efficiency of various combinations against UVB, UVA and blue light was determined through sun protection factor (SPF), UVA protection factor (UVA-PF) and porphyrin protection factor (PPF), respectively. The results demonstrated that TBPT combined with nanosize titanium dioxide and blended iron oxides (TT60-IR) achieved the highest SPF and UVA-PF. On the other hand, TBPT combined with submicron-size titanium dioxide and blended iron oxides (TT300-IR) yielded the highest PPF value. The matrix formulation affected the scattering property of the filters (i.e. combined TBPT and inorganic metal oxides). Containing the same amount and types of the filters, the matrix formulation that possessed a high transparency property showed high scattering efficiency against the blue light.

Abstract: This study aimed to develop sunscreen emulsion from natural sunscreening agents, titanium dioxide and Aloe vera gel extract that have good sun protection efficacy. The effects of formulation variables i.e., particle size and amount of titanium dioxide, amount of Aloe vera gel extract (spray dried powder) and combination of sunscreening agents (titanium dioxide and Aloe vera gel extract) on physical properties and sun protection efficacy (e.g., SPF, UVA/UVB ratio, critical wavelength) of sunscreen products were evaluated. The results showed that the smaller particle size of titanium dioxide improved the sun protection efficacy and increased the UVB absorption edge of the products. SPF of the formulations could be ranked as Nanofine TiO₂ (particle size 25–30 nm) > Kingruti T-01 TiO₂ (particle size 200 nm) > Pigment TiO₂ (particle size < 45,000 nm) and UVA/UVB ratio and critical wavelength of the formulations could be arranged in order as follows: Nanofine TiO₂ < Kingruti T-01 TiO₂ < Pigment TiO₂. Increasing amount of titanium dioxide from 5 to 15 %w/w increased significantly viscosity and SPF of formulations. Aloe vera gel extract itself did not significantly affect SPF, however, combination of Aloe vera gel extract and titanium dioxide seemed to have synergistic effect on sun protection efficacy and decreased viscosity of the formulation. According to the results, the good sunscreen formulation consisted of 15 %w/w Nanofine TiO₂, 5 %w/w Aloe vera gel spray dried powder in emulsion base because it was broad spectrum sunscreen and showed high SPF (27.53±1.92), high UVA/UVB ratio with critical wavelength higher than 370 nm.

Abstract: The effect of Perilla frutescens L. leaves extract (PFLE) on melanogenesis regulation in B16F10 cells was investigated. The extract had a significant inhibitory effect on melanogenesis in a dose-dependent manner without cytotoxicity at concentrations between 2.5 and 10 μg/mL. The PFLE was formulated as an underarm serum (PL serum) and evaluated for skin irritation and its skin whitening efficacy on 30 Thai women twice daily for 4 weeks. Changes in skin melanin and erythema index, L* a* values were studied. A gradual decrease in melanin index from 37.94±0.66 to 35.90±0.64 (5.38%), and a significant decrease in erythema index from 11.32±0.79 to 10.21±0.11 (9.80%) could be observed during a 4-week period. Therefore, the efficacy of PL serum in improving skin was demonstrated by a significant decrease in melanin and erythema index compared with initial values and skin tone was improved without skin irritation. Extract from Perilla frutescens L. leaves can be used as a novel whitening cosmeceutical ingredient.

Abstract: This research aims to study the antimicrobial activities of five selected plants, which were cinnamon bark, betel leaves, licorice, ginger, and galangal and select the most effective herbal extracts to be evaluated for their preservative efficacies in aqueous gel formulation. The sequential solvent extraction using hexane and 95% ethanol was used to extract bioactive constituents in the studied plants. After completely evaporated the solvents, the crude extracts were tested for the antimicrobial activities against S.aureus TISTR 1466 (ATCC 6538), P.aeruginosa TISTR 781 (ATCC 9027), E.coli ATCC 7839, C.albicans TISTR 5779 (ATCC 10201) and A.brasiliensis DMST 15538 (ATCC 16404) by agar well diffusion method. The result showed that the cinnamon bark extract macerated in hexane could inhibit the growth of all studied micro-organisms and was more effective than betel leaves, ginger, galangal and licorice extracts, while its 95% ethanolic extracts obviously showed lower antimicrobial activities. The MIC and MBC or MFC of cinnamon bark extract against the testing micro-organisms were in a range of 0.039-0.312 mg/mL and 0.156-1.250 mg/mL/0.078-0.625 mg/mL, respectively. The effective doses of hexane extract of cinnamon bark attempted to be tested as preservative in aqueous gel formulation were 0.3%, 1.25% and 2.5% by weight, which were equal to MIC, 4MIC and 8MIC, respectively. The challenge tests according to ISO 11930 were carried out to determine the preservative efficacy. The results revealed that 1.25% and 2.5% of cinnamon bark extract satisfied the criteria B for bacterial strains and the criteria A for yeast and mold. The LC-MS data confirmed that the two main constituents in hexane extract of cinnamon bark were coumarin and cinnamaldehyde that might play a role in antimicrobial activity.

Abstract: This research aims to develop canine shampoo containing Senna tora seed extract. The crude ethanolic extract was partial purified through column chromatography. The extract and shampoo formulation were identified for four main anthraquinones i.e. aloe-emodin, emodin, chrysophanol and physcion using a RP-HPLC. Formulation development was evaluated for compositions, physical properties, and antifungal activity against Microsporum canis. Our results indicated that sodium lauryl ether sulfate (20%) was an appropriate detergent with cocamidopropyl betain (4-6%) as a foam booster. Polyethylene glycol-120 methylglucose (2-3%) was a thickening agent and propylene glycol (6-7%) was a co-solvent and humectant. This shampoo showed relatively potent antifungal activity against M. canis compared with 2% ketoconazole commercial shampoo (%inhibition 75.27 and 85.85, respectively). The formulation was clear, dark brown liquid with delicate and stable foam, including effective cleaning action. Although this shampoo showed decrease in pH and viscosity after heating and cooling acceleration test, it was still effective as antifungal against M. canis with %inhibition of 69.10. Further long term stability study and some optimizations are still needed.