Key Engineering Materials Vol. 859

Abstract: The objective of this study was to investigate the effect of modified hydroxypropyl tapioca starch (HPTS) and % drug loading on physical property of tablet. Paracetamol was used as model drug because of its poor compressibility. The filler ability of modified HPTS such as hydroxyl propyl oxidized tapioca starch (HPOTS), hydroxyl propyl crosslinked tapioca starch (HPCTS) and pregelatinized tapioca starch (PTS) were evaluated and compared with the commercial starch (Starch 1500^®). Tablets were prepared by direct compression method and the percent drug loading were 15, 30, 45, 60, 75%. For modified HPTS, the hardness of the tablets tended to decrease when the concentration of paracetamol increased. At drug concentrations of 15-30%, HPOTS exhibited good performance of tablet as indicated by the high hardness, low friability and acceptable disintegration time. The obtained results were better than HPTS and comparable to Starch 1500^®. Moreover, the results revealed that tablet containing PTS provided the highest hardness and prolonged disintegration time (>30 min) while tablet containing HPCTS showed rapid disintegration time (<2 min). Therefore, modified HPTS disclosed promising properties for application as tablet filler

Abstract: The objective of this study was to apply rice bran protein hydrolysates (RBH) as bioactive additives of gelatin/Eudragit^® NE 30D film and characterize the physicochemical and mechanical properties of its. The RBH was obtained by extraction with 2% sodium chloride (RBH-NaCl) and 0.1 N sodium hydroxide (RBH-NaOH) followed by digestion with Alcalase^®. Then, RBH was incorporated in gelatin/Eudragit^® NE 30D film. Effect of RBHs on film thickness, moisture content, pH, Young's modulus, tensile strength and the elongation at break were investigated. The RBH-NaCl enriched film showed non-homogeneous mixture and reduced moisture content, tensile strength and the elongation at break (1.8 – 2 folds). However, the RBH-NaOH enriched film exhibited a few non-homogeneous mixture and the Young's modulus was slightly decreased. The pH value was increased in the range of 6.77 – 6.88. Our results provide insight for the potential to develop RBH containing films as topical products.

Abstract: The objective of this study was to investigate the effect of polymers and their content level on the taste-masking efficiency of spray-dried microparticles. Diclofenac sodium (DS) was used as a model drug, owing to its bitter taste. Hydroxypropyl methylcellulose F4M (HPMC F4M) and Eudragit^® E PO were involved in the study as a hydrophilic and a pH-responsive polymer, respectively. The taste-masked DS microparticles with the drug:polymer ratios of 1:1, 1:2 and 1:4 were prepared by the spray-drying technique. The collapsed hollow sphere HPMC F4M based-microparticles was observed meanwhile spray-dried Eudragit^® E PO based-microparticles were spherical. Loading capacity of both polymer based-microparticles decreased regarding to the increment of drug:polymer ratio. The Eudragit^® E PO based-microparticle in the ratio of 1:4 provided the highest loading efficiency as 91.97%. According to the simplified dissolution testing, the taste-masking ability of HPMC F4M and Eudragit^® E PO based-microparticles increased upon the increase of drug:polymer ratio. Drug release at the first 5 minutes from dissolution profiles, tested by type II dissolution apparatus, of the Eudragit^® E PO based-microparticles was delayed compared to HPMC F4M based-microparticles. Therefore, it could be assumed that Eudragit^® E PO was a promising taste-masking polymer for DS with a pleasant taste.

Abstract: With regard to the periodontal pocket application of in situ forming systems, the understanding the phase behavior after solidification owing to solvent movement could verify the deformability of specimen and its capacity to reside in the artificial periodontal pocket. The aim of this research was to investigate the phase behavior by determining mechanical properties as hardness and elasticity/plasticity ratio with texture analyzer for matrices obtained from drug-free and doxycycline hyclate (DX)-incorporated bleached shellac (BS) in situ forming gel (isg) and –microparticle (ism) after solvent exchange. The solvents for dissolving BS were 2-pyrrolidone (PYR), N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). The matrix from isg was less rough and bulge than that of isg. The order of mechanical hardness of transformed system prepared with different solvents was presented as PYR > NMP > DMSO, influenced by phase separation rate and porosity. The systems prepared with NMP and DMSO were more likely plastic or able to adapt its geometry to dynamic changes while that prepared with PYR was elastic. DX-incorporated ism matrix was still governed by the oil in external phase; thus, its consequence was reasonably plastic instead. XRD pattern indicated that the solvent type had no effect on the crystallinity of remained BS after solvent movement. SEM topography revealed sponge-like structure of isg prepared with DMSO and NMP whereas that prepared with PYR exhibited only initiated diminutive pores. The size and density of pores increased by time of isg using different solvents as following DMSO > NMP > PYR, whereas ism matrices had less pore density. The level of porosity of each matrix reflected the mechanical strength that a higher porous structure collapsed easily but a dense matrix considerably resisted to a compression.

Abstract: Imatinib mesylate (IM) is a kinase inhibitor with inhibitory effect on colon cancer cell proliferation. However, some adverse effect of imatinib and drug resistance are challenges for maintenance the therapeutic effect with lowering the dose; thus, the combination with other substances was of interest. Gambogic acid (GA), a natural compound from gamboge, was revealed for inhibition of cell proliferation in many types of cancers. This research aimed to investigate the effect of GA on IM response in colorectal cancer cells, HT29 and HCT116. The 50% inhibitory concentration (IC₅₀) of IM and GA was determined. Concentrations which lower than IC₅₀ of each compound were combined and tested for the combination effects on HT29 and HCT116 cells. The results were analyzed using isobologram to assess the types of interaction. The combination index (CI) of the tests was calculated at the 3 different percentages of inhibition (IC₅₀, IC₆₀ and IC₇₀). The finding indicated that IC₅₀ and IC₆₀ of the combination of 5 and 7 μM IM with 0.2-1.2 μM GA showed antagonism while IC₇₀ showed additive effect in HT29 cell line. In HCT116 cell line, IC₅₀ of 10 μM IM with 0.1-0.8 μM GA showed antagonism while IC₆₀ and IC₇₀ expressed additive effect. For the studies with IC₅₀ and IC₆₀ of 12 μM IM with 0.1-0.8 μM GA showed antagonistic result while IC₇₀ showed additive effect. The result indicated that, at the lower IC studied, the CI obtained from the experiments indicated the inhibitory effects, while the higher IC, the results showed the changing trend from antagonistic to additive and synergistic effects of GA on IM.

Abstract: Transdermal patches are attraction and acceptance for the patient due to avoid first-pass metabolism, easy to administer and removal, allows rapid termination of treatment if required etc. Low protein natural rubber latex (LPNRL) is a natural polymer that removed the allergic protein from fresh NRL prepared by treatment with proteolytic enzyme and centrifuging process. LPNRL is used for medical skin applications with the non-allergenic product. The objective of this research aimed to prepare the mefenamic acid – loaded transdermal patches made from LPNRL blended with either hydroxypropyl methylcellulose (HPMC) or polyvinyl alcohol (PVA), glycerin and polyvinylpyrrolidone were used as plasticizer and crystallization inhibitor, respectively. The moisture uptake and swelling ratio showed the increment value after either HPMC or PVA was blended in LPNRL because of the increment of their hydrophilicity. These patches showed the homogeneous films that observed by the researcher. The in vitro release showed a faster release rate after either HPMC or PVA was blended in LPNRL. It was concluded that mefenamic acid – loaded transdermal patches could be prepared by using LPNRL blended with either HPMC or PVA as matrix film former could provide an increased and controlled release of the drug. Moreover, it was safe to apply on the skin as did not cause irritation.

Abstract: The aim of this study was to develop a thermal crosslinkable microneedle (MN) array. Gantrez S-97 was employed as the MN-forming polymer. The MNs were successfully fabricated by micromolding method. The MNs were thermally crosslinked at different times (0.5, 1, 2, 3 h) and temperatures (110, 130, 150°C). The morphology of the MN was observed using a digital microscope. The successful crosslink was confirmed by Fourier transform infrared spectroscopy. The percentages of swelling and MN remaining after being soaked in water were also investigated. Fully formed, sharped MN with desirable morphology was obtained at the Gantrez S-97 concentration of 30 %w/v. The FT-IR spectra confirmed the successful crosslink of the MN. The crosslinked Gantrez MN arrays could absorb massive amount of water, and exhibited excellent swelling capability. Increasing the crosslinking time and temperature resulted in the decrease in the swelling capability but increase in the water insolubilization. The MNs crosslinked at 150°C for 3 h demonstrated almost hundred percent of water insolubilization which desirable for developing hydrogel-forming MN. Therefore, 30% w/v Gantrez S-97 MN could be crosslinked by thermal process, and could provide desirable swelling properties and percentage of water insolubility, and therefore, may be an alternative for fabrication of hydrogel-forming MN for transdermal drug delivery.

Abstract: This study explored the interaction of amphiphilic chitosan derivatives, N-benzyl-N,O-succinyl chitosan (BSCS), N-naphthyl-N,O-succinyl chitosan (NSCS) and N-octyl-N,O-succinyl chitosan (OSCS), with renal organic cation transporter 2 (OCT2). The influence of amphiphilic chitosan derivatives on renal OCT2 transport function was determined by monitoring the transport of a positively charged substrate into human renal proximal tubular epithelial cells (RPTEC/TERT1 cells), and murine kidney. Amphiphilic chitosan derivatives inhibited 3H-MPP (a substrate of OCT2) transport in the renal cells in a concentration-reliance characteristic. OSCS reduced the accumulation of the cationic drug, cisplatin, in RPTEC/TERT1 cells. This effect was more pronounced than that of other chitosan derivatives. In addition, co-administration of cisplatin and OSCS significantly reduced cisplatin accumulation compared with receiving cisplatin alone. This result was accompanied by the decrease in nephrotoxicity induced by cisplatin. In conclusion, OSCS inhibited OCT2 function and reduced cationic drug disposition in human renal proximal tubular cells and murine kidney.

Abstract: Madhuca longifolia (J.Koenig ex L.) Macbr. belongs to the Sapotaceae family. This research work focused on the determination of gallic acid and quercetin in an aqueous leaf extract of M. longilolia. The development and validation of the analytical method using HPLC-DAD have been performed. The validated method was applied to determine both compounds in the leaves of M. longifolia. Optimized HPLC conditions were developed and validated for specificity, linearity, sensitivity, precision and accuracy. The linearity ranges and linear regression value were 3.125 to 100 μg/mL with r²=1 for gallic acid and 0.78 to 50 μg/mL with r²=0.9999 for quercetin, respectively. The LOD and LOQ were 0.24 and 0.73 μg/mL for gallic acid and 0.21 and 0.63 μg/mL for quercetin. Intra and inter-day precision were in the range of 0.18 to 1.76. The recovery percentage were 103.86% to 104.98% for gallic acid and 100.10% to 102.97% for quercetin. The concentration ranges of gallic acid and quercetin in the extracts were 207.95 to 405.79 mg/100 g and 7.31 to 20.56 mg/100 g, respectively. The developed HPLC method was considered to be accurate, precise and reliable for the determination of gallic acid and quercetin in M. longifolia aqueous leaf extract. This may be the first-time report for HPLC-DAD method development for the determination of bioactive phenolic compounds in Madhuca longifolia from Myanmar.