Utilization and Evaluation of Rice Bran and Rice Bran Wax as a Tablet Lubricant.

The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized full-fatted rice bran (sFFRB), stabilized defatted rice bran (sDFRB), and rice bran wax (RBW) extracted and purified from crude rice bran oil (cRBO) were tested. Two commercial lubricants, including magnesium stearate (MGS) and hydrogenated cottonseed oil (HVO), were employed as the standards in the formulated mixtures, which contained spray-dried rice starch (SDRS) as a diluent. The tableting was carried out for each formulation, and the obtained tablets were physically and mechanically evaluated. Among the parameters investigated were the general appearance, ejection force, weight variation, hardness, friability, and disintegration time. The powder flow was also determined for each formulation. The results showed that the tablet ejection forces for all the lubricated formulations (58-259 N) were significantly lower than that of the non-lubricated control formulation (349 N). The use of sFFRB as a lubricant at 0.5-2.0% w/w could lower the ejection force up to 78%, but the hardness reduced so drastically that the formulations failed the friability test due to the chipping of the tablets' edges. Moreover, sDFRB performed significantly better as the use at 0.5-1.0% w/w in the formulation helped to lower the ejection forces by up to 80% while maintaining the changes in the tablet hardness within 10%. RBW functioned effectively as a tablet lubricant at a concentration of 0.5% w/w, yielding tablets with good strength comparable to standard HVO lubricant while helping to reduce the ejection force by 82%. In formulations with good lubrication, i.e., friability < 1%, the powder flow was improved, and the tablet disintegration times were within the same range as the control and HVO formulations. In conclusion, sDFRB displayed a lubricant property at concentrations between 0.5 and 1.0% w/w, with slightly negative effects on the tablet hardness. RBW from KJ CMU107 rice was an effective tablet lubricant at 0.5% w/w, with no effect on tablet hardness. Both materials can be further developed for use as commercial lubricants in direct compression.

Fabrication and Characterization of Orodispersible Composite Film from Hydroxypropylmethyl Cellulose-Crosslinked Carboxymethyl Rice Starch.

Crosslinked carboxymethyl rice starch (CLCMRS), prepared via dual modifications of native rice starch (NRS) with chloroacetic acid and sodium trimetaphosphate, was employed to facilitate the disintegration of hydroxypropylmethylcellulose (HPMC) orodispersible films (ODFs), with or without the addition of glycerol. Fabricated by using the solvent casting method, the composite films, with the HPMC--LCMRS ratios of 9:1, 7:1, 5:1 and 4:1, were then subjected to physicochemical and mechanical evaluations, including weight, thickness, moisture content and moisture absorption, swelling index, transparency, folding endurance, scanning electron microscopy, Fourier transform infrared spectroscopy, tensile strength, elongation at break, and Young's modulus, as well as the determination of disintegration time by using the Petri dish method (PDM) and slide frame and bead method (SFM). The results showed that HPMC-CLCMRS composite films exhibited good film integrity, uniformity, and transparency with up to 20% CLCMRS incorporation (4:1 ratio). Non-plasticized composite films showed no significant changes in the average weight, thickness, density, folding endurance (96−122), tensile strength (2.01−2.13 MPa) and Young's modulus (10.28−11.59 MPa) compared to HPMC film (135, 2.24 MPa, 10.67 MPa, respectively). On the other hand, the moisture content and moisture absorption were slightly higher, whereas the elongation at break (EAB; 4.31−5.09%) and the transparency (4.73−6.18) were slightly lowered from that of the HPMC film (6.03% and 7.03%, respectively). With the addition of glycerol as a plasticizer, the average weight and film thickness increased, and the density decreased. The folding endurance was improved (to >300), while the transparency remained in the acceptable range. Although the tensile strength of most composite films decreased (0.66−1.75 MPa), they all exhibited improved flexibility (EAB 7.27−11.07%) while retaining structural integrity. The disintegration times of most composite films (PDM 109−331, SFM 70−214 s) were lower than those of HPMC film (PDM 345, SFM 229 s). In conclusion, the incorporation of CLCMRS significantly improved the disintegration time of the composite films whereas it did not affect or only slightly affected the physicochemical and mechanical characteristics of the films. The 5:1 and 4:1 HPMC:CLCMRS composite films, in particular, showed promising potential application as a film base for the manufacturing of orodispersible film dosage forms.

Physicochemical and Functional Properties of Modified KJ CMU-107 Rice Starches as Pharmaceutical Excipients.

Starch extracted from KJ CMU-107 rice, with amylose content of 13.4%, was modified to yield pre-gelatinized starch (PGS), carboxymethyl starch (CMS), crosslinked carboxymethyl starch (CLCMS), crosslinked starch (CLS), and hydroxypropyl starch (HPS). Their physicochemical properties were assessed in comparison with the native starch (NS), and their functional properties were then evaluated for potential use as pharmaceutical excipients. Scanning electron microscopic (SEM) images and X-ray diffraction (XRD) patterns showed that granules of all but one of the modified starches retained the native character and crystalline arrangement. The exception, PGS, exhibited extensive granular rupture, which correlated with the loss of crystallinity suggested by the amorphous halo in XRD. Energy-dispersive X-ray (EDX) data confirmed the modification by the presence of related elements. Carboxymethylation increased solubility in unheated water, while crosslinking improved swelling. All modified starches displayed improved oil absorption capacity by 17-64%, while CMS and CLCMS also exhibited significant moisture sorption at above 75% RH PGS and HPS exhibited lower gelatinization temperature (Tg) and enthalpic change (ΔH), while CLS showed higher Tg and ΔH. CMS, CLCMS, and CLS showed adequate powder flow and compactibility, qualifying as potential tablet excipients. The 5% w/v solutions of CMS, CLMS, and HPS also formed intact films with suitable tensile strength. Overall, modified starches derived from KJ CMU-107 could potentially be developed into new pharmaceutical excipients.

Formulation Study of a Co-Processed, Rice Starch-Based, All-in-One Excipient for Direct Compression Using the SeDeM-ODT Expert System.

A co-processed, rice starch-based excipient (CS), previously developed and shown to exhibit good pharmaceutical properties, is investigated as an all-in-one excipient for direct compression (DC). An SeDeM-ODT expert system is applied to evaluate the formulation containing CS, in comparison with those containing the physical mixture and the commercial DC excipients. The results revealed that CS showed acceptable values in all six incidence factors of the SeDeM-ODT diagram. In addition, the comprehensive indices (IGC and IGCB) were higher than 5.0, which indicated that CS could be compressed with DC technique without additional blending with a disintegrant in tablet formulation. The formulation study suggested that CS can be diluted up to 60% in the formulation to compensate for unsatisfactory properties of paracetamol. At this percentage, CS-containing tablets exhibited narrow weight variation (1.5%), low friability (0.43%), acceptable drug content (98%), and rapid disintegration (10 s). The dissolution profile of CS displayed that more than 80% of the drug content was released within 2 min. The functionality of CS was comparable to that of high functionality excipient composite (HFEC), whereas other excipients were unsuccessful in formulating the tablets. These results indicated that CS was a suitable all-in-one excipient for application in DC of tablets.

Resistant Starch Contents of Starch Isolated from Black Longan Seeds.

A large quantity of longan fruits (Dimocarpus longan Lour.) produced annually are processed into many products, one of which is black longan, from which the dried, dark-brown meat has been used medicinally in traditional medicine, while the starch-containing seeds are discarded. In this study, starch samples (BLGSs) were isolated from seeds of black longan fruits prepared using varied conditions. The in vitro digestibility was determined in comparison with those extracted from fresh (FLGS) and dried (DLGS) seeds. Scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy were employed to evaluate the starch properties. The results showed that the yields of FLGS, DLGS, and BLGSs were 20%, 23%, and 16-22% w/w, respectively. SEM images showed starch granules of mixed shapes, with sizes up to 15 µm in all samples. XRD patterns confirmed an A-type crystallinity for FLGS and DLGS, with strong refraction peaks at 2θ = 15°, 17°, 18°, and 23°, while BLGSs also showed detectable peaks at 2θ = 10° and 21°, which suggested V-type structures. Thermal properties corroborated the changes by showing increases in peak gelatinization temperature (Tp) and enthalpy energy (ΔH) in BLGSs. The paste viscosity of BLGSs (5% w/w) decreased by 20-58% from that of FLGS. The FTIR peak ratio at 1045/1022 and 1022/995 cm-1 also indicated an increase in ordered structure in BLGSs compared to FLGS. The significant increase in the amounts of slowly digestible starch (SDS) and resistant starch (RS) in BLGSs compared to FLGS, especially at a prolonged incubation time of 20 (4.2×) and 30 days (4.1×), was proposed to be due to the heat-induced formation of starch inclusion with other components inside the seed during the black longan production process. Thus, black longan seed could be a new source of starch, with increased RS content, for potential use in the food and related industries.

A Spray-Dried, Co-Processed Rice Starch as a Multifunctional Excipient for Direct Compression.

A new co-processed, rice starch-based excipient (CS) was developed via a spray-drying technique. Native rice starch (RS) was suspended in aqueous solutions of 10%-15% cross-linked carboxymethyl rice starch (CCMS) and 0.5%-6.75% silicon dioxide (in the form of sodium silicate), before spray drying. The resulting CSs were obtained as spherical agglomerates, with improved flowability. The compressibility study revealed an improved plastic deformation profile of RS, leading to better compaction and tensile strength. The presence of CCMS also ensured a rapid disintegration of the compressed tablets. CS-CCMS:SiO2 (10:2.7), prepared with 10% CCMS, 2.7% silicon dioxide, and 40% solid content, was found to exhibit the best characteristics. Compared to the two commercial DC excipients, Prosolv® and Tablettose®, the flow property of CS-CCMS:SiO2 (10:2.7) was not significantly different, while the tensile strength was 23%: lower than that of Prosolv® but 4 times higher than that of Tablettose® at 196 MPa compression force. The disintegration time of CS-CCMS:SiO2 (10:2.7) tablet (28 s) was practically identical to that of Tablettose® tablet (26 s) and far superior to that of Prosolv® tablet (>30 min). These results show that CSs could potentially be employed as a multifunctional excipient for the manufacturing of commercial tablets by DC.

Resistant starch contents of native and heat-moisture treated jackfruit seed starch.

Native jackfruit seed starch (JFS) contains 30% w/w type II resistant starch (RS2) and can potentially be developed as a new commercial source of RS for food and pharmaceutical application. Heat-moisture treatment (HMT) was explored as a mean to increase RS content of native JFS. The effect of the conditions was tested at varied moisture contents (MC), temperatures, and times. Moisture levels of 20-25%, together with temperatures 80-110°C, generally resulted in increases of RS amount. The highest amount of RS (52.2%) was achieved under treatment conditions of 25% MC and 80°C, for 16 h (JF-25-80-16). FT-IR peak ratio at 1047/1022 cm(-1) suggested increases in ordered structure in several HMT-JFS samples with increased RS. SEM showed no significant change in the granule appearance, except at high moisture/temperature treatment. XRD revealed no significant change in peaks intensities, suggesting the crystallinity within the granule was mostly retained. DSC showed increases in T g and, in most cases, ΔT, as the MC was increased in the samples. Slight but significant decreases in ΔH were observed in samples with low RS, indicating that a combination of high moisture and temperature might cause partial gelatinization. HMT-JFS with higher RS exhibited less swelling, while the solubility remained mostly unchanged.

Physicochemical, in vitro digestibility and functional properties of carboxymethyl rice starch cross-linked with epichlorohydrin.

Cross-linked carboxymethyl rice starches (CL-CMRSs) were prepared from reactions between native rice starch and varied concentrations (0.1-15%w/w, M-0.1 to M-15) of epichlorohydrin (ECH) in a simultaneous carboxymethylation-crosslinking reaction setup using methanol as the solvent. The degree of carboxymethyl substitution was between 0.24 and 0.28, while apparent amylose contents were lowered due to modification. SEM images showed minor change on the granule surface, while XRD profiles indicated slight loss of crystallinity. DSC thermograms revealed no transition peak in all treated samples. The water uptake (WU), swelling volume (SV) and free swelling capacity (FSC) of CL-CMRSs increased significantly as a result of the modification, while swelling of CMRSs cross-linked with 2% (M-2) and 3% (M-3) ECH yielded FSC values and WU values that were much greater than those of native starches and were comparable to that of Explotab®. All modified starch samples showed increased amount of rapidly digestible starch (RDS), while cross-linking with 5-7.5% ECH raised the resistant starch (RS) content, compared to native starch. M-2 also showed promising results in tablet disintegration test. ECH-CL-CMRSs could potentially be used as an excipient in pharmaceutical and food/food supplement products.

Preparation of cross-linked carboxymethyl jackfruit starch and evaluation as a tablet disintegrant.

The main purposes of this study are to prepare cross-linked carboxymethyl jackfruit starch (CL-CMJF) and to evaluate its pharmaceutical property as a tablet disintegrant. CL-CMJF was prepared by a dual carboxymethyl-crosslinking reaction in a flask containing jackfruit seed starch (JFS), chloroacetic acid (CAA), sodium hydroxide (NaOH) and sodium trimetaphosphate (STMP). The reaction was carried out using methanol as a solvent for 60 min at 70°C and at JFS:CAA:NaOH:STMP ratio of 1.0:0.29:0.28:0.07. The obtained CL-CMJF, with degree of substitution and degree of crosslinking calculated to be 0.34 and 0.06, respectively, was insoluble but swellable in water. Rheological study revealed a decreased in solution viscosity compared to the non-crosslinked CMJF. The water uptake of CL-CMJF was 23 times higher than that of native starch and was comparable to that of a commercial superdisintegrant, sodium starch glycolate (SSG). The swelling ability of CL-CMRS was similar to that of crosscarmellose sodium (CCS), another commercial superdisintegrant. Disintegration test of aspirin tablets containing 2%w/w of JFS, CL-CMJF, SSG and CCS showed disintegration times in the order of SSG < CCS ~ CL-CMJF <<< JFS. The results suggested that CL-CMJF could be developed as a tablet disintegrant.

Carboxymethyl mungbean starch as a new pharmaceutical gelling agent for topical preparation.

An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1-10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 +/- 105.08 microg/cm(2), which was comparable with 947.66 +/- 133.70 microg/cm(2) obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.

High-performance liquid chromatography and thin-layer chromatography assays for Devil's Club (Oplopanax horridus).

Devil's root, Oplopanax horridus, is a widely used folk medicine in Alaska and British Columbia. The inner bark of the root and stem has been used to treat colds, cough, fever, and diabetes. The present study involves the development of high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC) methods to detect the presence of trans-nerolidol and sterols in the root bark. The HPLC and TLC analytical methods presented are suitable for the characterization and identification of Oplopanax horridus.