Key Engineering Materials Vol. 914

Abstract: This study aims to formulate and evaluate the meloxicam (MX) transdermal patches using deproteinized natural rubber latex (DNRL) as a polymer matrix due to its good film forming characteristics. Hydrophobic drug, MX was firstly dissolved in hydroalcoholic solution and incorporated into DNRL with various concentrations of the drug (1-5%w/w). These mixtures were then cast on the glass plate prior to drying and thereafter obtaining the MX-loaded transdermal patches. Increasing amounts of the drug provided more opaque films with more precipitation of drug in films. The highest amount of MX was 3%w/w to incorporate with DNRL to obtain the acceptable patch without any visible precipitation. Compatibility of each ingredient in the formulation was confirmed using differential scanning calorimeter and X-ray diffractometer. The in vitro drug release study showed the increment of MX release from 7.88±0.43% to 13.33±0.87% in receptor medium of modified Franz diffusion cell when the drug concentration in the patches was increased from 1 to 3%w/w. The in vitro drug permeation study also found that MX could penetrate from DNRL transdermal patch through the porcine skin. However, these release and permeation amounts of MX were rather low that should be improved with some specific techniques and should be further investigated.

Abstract: Natural rubber latex (NRL) with the deproteinized process was interesting for cosmetic and transdermal drug delivery systems because of its notable characteristics. The purpose of this study was to develop in situ cooling films from deproteinized natural rubber latex (DNRL). Menthol, camphor, and volatile oils were added into DNRL emulsions for cooling effect and pain relief. The pH, rheological properties, particle size, and zeta potential of emulsions were examined. Then, the time of film-formation, morphology, and mechanical properties of the cooling NRL films were evaluated. The resultant emulsions revealed that their pH was about 5.7 - 6.3. The viscosity was in the range of 1000 – 3000 cps and indicated the pseudoplastic flow. The increasing amount of olive oil reduced the particle size and increased the negatively zeta potential of those emulsions. The film formation time of specimens was about 4.5 - 6.5 mins. The cooling films demonstrated smoothness and homogeneity. The presence of olive oil increased the softness of films. The increasing of oil volume increased the elasticity; however, it decreased the ductility of the films. This in situ cooling DNRL film was also effective forward for the development of a transdermal drug delivery system.

Abstract: Supersaturated astaxanthin (AST)-loaded self-microemulsifying delivery system (SMEDS) was developed and formulated with polymeric precipitation inhibitors (PPIs) to improve the dissolution profile of AST. Based on our preliminary in vitro polymer screening test, hydroxypropyl cellulose (HPC-L) and polyvinyl alcohol (PVA8/88) were selected as PPIs and studied further in this work. Microemulsions prepared from AST SMEDS (composed of AST, rice bran oil, Kolliphor^® RH40, and Span^® 20) were mixed with maltodextrin (MD) as a solid carrier and each PPI solution and then solidified using a spray drying technique. Particle size of spray-dried S-MD-HPC powder had larger circular equivalent (CE) diameter (14.69 ± 0.75 μm) than the other formula and showed particle agglomeration in SEM images. Spray-dried S-MD-PVA powder had 8.94 ± 0.37 μm CE diameter, and smooth surface of particles was observed. Amorphous phase transformation and chemical compatibility of both spray-dried powder formulations were detected by FT-IR, PXRD, and DSC. S-MD-HPC had marginally slower dissolution rate and release profile of AST compared to those of S-MD-PVA; however, both HPC and PVA polymers exhibited the ability for AST precipitation prevention and solubilization enhancement. Although AST degradation was caused by high temperature, physicochemical properties of the spray-dried AST SMEDS (S-MD-HPC and S-MD-PVA) powders after reconstitution were not significantly changed upon storage at 30°C/ RH 75%. This study illustrated a novel platform of spray-dried AST SMEDS in combination with HPC or PVA as a polymeric precipitation inhibitor for improvement of AST loading, solubility, and stability.

Abstract: Typically, the emollient effect of the vegetable oil has attributed to its usefulness in skin care preparation. The present study aims to prepare the oil in water emulsion cream containing virgin coconut oil (CO) comprisinghydrophilic and lipophilic surfactants (Tween 80 and Span 80). Stability of creams containing CO upon addition of peppermint oil (PO), co-surfactant (Solutol HS 15, ST), solubilizer (benzyl benzoate, BB) was investigated after the temperature cycling. All prepared creams showed the shear thinning flow behavior. Addition of BB gave the lowest viscosity while that comprising ST exhibited the higher viscosity. The highest viscosity formula was the CO andPO containing cream. The particle size determined using light scattering particle analyzer revealed that the mean particle size of all prepared creamswaslower than 35.56 ± 0.62 µm. The homogenous dispersion of oil globules in emulsion was evident, especially, in formulation II (CO) and IV (COand ST). Although the temperature cycling influenced more or less on the compact structure of gel network of cream, the decrement of viscositywasminimal and not much different for cream containing CO and ST (formulation IV). In addition, the mean particle size wasthe smallest for formulation II (CO) which was followed by formulation IV (CO and ST). There wasthe homogenous dispersion of oil globules in formulation II and IV after temperature cycling. All of the above finding was beneficial for employingCO as the oil phase in producing cream such as the foot massage cream where the addition of ST provided the better stability for the prepared cream containing CO.

Abstract: Several biomaterial presented anticancer activities including volatile oil. Interestingly, the volatile oil from Amomum kravanh has been reported as anticancer activity. Nevertheless, the utilization in native oil might be barrier to apply its as anticancer agent because of the limitation of their water solubility. One of the solutions to this challenge is to use nanoemulsions as a carrier for delivery A.kravanh oil (AMO) into oral cancer cell. In this research, the phase inversion temperature method was used to prepared nanoemulsions containning AMO. The physical and anticancer property of various nanoemulsions were comparatively evaluated. The 8AMO:2Soybean oil (SBO) illustrated spherical and small oil droplet around 80 nm. It also presented good physical stability after temperature cycling test. Regarding anticancer property, the 8AMO:2SBO can considerably arrest oral cancer cells with dose dependent manner at IC₅₀ of 0.76% v/v, and the nuclear fragmentation that was remarkable feature of apoptosis was also found in 8AMO:2SBO group. This discovery demonstrated that the AMO loaded nanoemulsions system can be consider to alternative choices for oral cancer prevention and treatment.

Abstract: Boesenbergia rotunda (B. rotunda) extract-loaded hydrogel patches were fabricated to be an antibacterial dressing. The biological properties such as antioxidant properties, bacterial protection activity, and the effect on normal human fibroblast (NHF) viability were assessed compared with blank hydrogel patches. The antioxidant activity of B. rotunda extract-loaded hydrogel patches was 75.00 ± 0.79 % (at 4-h treatment time), whereas the blank hydrogel patch had low antioxidant activity. The extract-loaded patches exhibited antioxidant activity approximately 16.5 times higher than that of the blank patches. In addition, the qualitative antibacterial activity of the patches was studied by agar disc diffusion. The inhibition zone of the extract-loaded hydrogel discs against Staphylococcus aureus (S. aureus) was 7.33 ± 0.58 mm, whereas the inhibition zone of the discs against Escherichia coli (E. coli) could not be observed. Moreover, the quantitative antibacterial activity showed an inhibition effect of the extract-loaded hydrogels against both types of bacteria. After incubation for 24 h, the extract-loaded hydrogel patches inhibited the growth of S. aureus and E. coli at the percentage of 49.76 ± 3.82 and 20.13 ± 2.75%, respectively. The results from the infiltration test showed that the extract-loaded hydrogel patches could prevent bacteria contamination. In addition, no toxicity to NHF cells had been observed. Therefore, the B. rotunda extract-loaded hydrogel patches could be a candidate material as an antibacterial wound dressing.

Abstract: A floating drug delivery device is one type of gastro-retentive drug delivery system (GRDDS). Carvedilol (CAR) is poorly soluble in alkaline pH (intestinal environment) and has good solubility in the acidic pH (stomach environment). Hence, floating 3D-printed devices (FD) were developed from polylactic acid (PLA) filaments using fused deposition modeling (FDM) and designed to be a tablet shape with an anti-flip-up property as GRDDS of carvedilol tablets. There were two parts of FD, including the cap and the base. The base was designed with different hole diameters (2.5, 3.5, and 4.5 mm) for a controlled drug release. The FD had a smooth texture and white color. All the FD showed the anti-flip-up property. The drug release showed that the FD with 2.5- and 3.5-mm hole diameters had the potential to control the drug release. The CAR tablet-incorporated FD with a 3.5 mm hole diameter showed an optimal sustained-release profile, 99.8 % of drug release in 10 h. Moreover, zero-order kinetic was achieved. Therefore, this device may be promising to provide an extended drug release in the stomach.

Abstract: The objective of this study was to assess feasibility of applying shellac as a biopolymer filament for using in fused deposition modeling (FDM) 3D printing. The shellac matrices were prepared through hot melt process by heating the ground shellac samples at 80°C in a silicone oil bath under continuous stirring for 15 min. Accelerated stability testing (annealing process) was also performed in order to evaluated thermal stability by re-heating shellac matrices at 80 °C for 12 h and 24 h in a hot air oven. The shellac matrices and annealed shellac matrices were then comparatively characterized. In the present study, all shellac matrices were investigated for physical appearance, acid value, insoluble solid, moisture content and also characterized by instrument analysis including Fourier-transform infrared (FTIR) spectroscopy, powder X-ray diffractometry (PXRD) and thermal analysis. The results demonstrated that shellac with initial heat (80°C, 15 min) and annealed at 80°C for 12 h had similar properties except the annealed shellac at 80°C for 24 h which shown the lower acid value and formed insoluble solid. The melting temperature, decomposition temperature and melting enthalpy of shellac were around 63-64°C, over than 200°C and 23 J/g, respectively. Furthermore, the extruded filament based on shellac was achieved by hot melt extrusion (HME) technique. The findings revealed that the shellac properties might be suitable to fabricate FDM filaments.

Abstract: Dissolving microneedles (dis-MNs) are very attractive micro-scale technology and a minimally invasive method to be used as a tool for transdermal delivery, leading to increased bioavailability of drugs bypassing ocular tissue barrier and painless treatment method. This study aims to design and investigate the optimal dis-MNs as a potential device for ocular application using a three-level factorial design. The dis-MNs were fabricated by micromolding technique using chitosan and polyvinyl alcohol (PVA) polymer. The physical appearance of dis-MNs was observed under a digital microscope. The mechanical strength (resistance force and insertion force) was tested with a texture analyzer. The penetration depth and dissolution time at a predetermined time were tested on porcine ocular tissue. The data illustrated that the optimal dis-MNs formulation was 3%chitosan and 20%PVA in 20%PVA in a weight ratio of 1:4. The physical appearance showed pyramidal microneedles with an average 609.01±1.01 µm in height and 200.21+3.57 μm in base width. The optimal dis-MNs showed a resistance force of 40.14±2.10 N. The insertion force into the cornea tissue (1.78 N/225 arrays) was higher than sclera tissue (0.95 N/225 arrays), indicating that the optimal dis-MNs could create micro-channels on both cornea and sclera tissues. The dissolution study showed that the optimal dis-MNs formulation was completely dissolved on cornea tissue (1 min) faster than sclera tissue (3 min). In conclusion, the optimal dis-MNs presented suitable dis-MNs properties with minimally invasive device for ocular tissue, acting as an appropriate dis-MNs model for the ophthalmic drug delivery system.