Nanoemulsions (NMs) are one of the most important colloidal dispersion systems that are primarily used to improve the solubility of poorly water soluble drugs. The main objectives of this study were, first, to prepare an NM loaded with fenofibrate using a high shear homogenization technique and, second, to study the effect of variable using a central composite design. Twenty batches of fenofibrate-loaded NM formulations were prepared. The formed NMs were subjected to droplet size analysis, zeta potential, entrapment efficiency, pH, dilution, polydispersity index, transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry, differential scanning calorimetry (DSC), and in vitro drug release study. Analysis of variance was used for entrapment efficiency data to study the fitness and significance of the design. The NM-7 batch formulation demonstrated maximum entrapment efficiency (81.82%) with lowest droplet size (72.28 nm), and was thus chosen as the optimized batch. TEM analysis revealed that the NM was well dispersed with droplet sizes <100 nm. Incorporation of the drug into the NM was confirmed with DSC studies. In addition, the batch NM-7 also showed the maximum in vitro drug release (87.6%) in a 0.05 M sodium lauryl sulfate solution. The release data revealed that the NM followed first-order kinetics. The outcomes of the study revealed the development of a stable oral NM containing fenofibrate using the high shear homogenization technique. This approach may aid in further enhancing the oral bioavailability of fenofibrate, which requires further in vivo studies.
Conventional melt pelletization and granulation processes produce round and dense, and irregularly shaped but porous agglomerates respectively. This study aimed to design centrifugal air-assisted melt agglomeration technology for manufacture of spherical and yet porous "granulets" for ease of downstream manufacturing and enhancing drug release. A bladeless agglomerator, which utilized shear-free air stream to mass the powder mixture of lactose filler, polyethylene glycol binder and poorly water-soluble tolbutamide drug into "granulets", was developed. The inclination angle and number of vane, air-impermeable surface area of air guide, processing temperature, binder content and molecular weight were investigated with reference to "granulet" size, shape, texture and drug release properties. Unlike fluid-bed melt agglomeration with vertical processing air flow, the air stream in the present technology moved centrifugally to roll the processing mass into spherical but porous "granulets" with a drug release propensity higher than physical powder mixture, unprocessed drug and dense pellets prepared using high shear mixer. The fast-release attribute of "granulets" was ascribed to porous matrix formed with a high level of polyethylene glycol as solubilizer. The agglomeration and drug release outcomes of centrifugal air-assisted technology are unmet by the existing high shear and fluid-bed melt agglomeration techniques.
Natural biopolymers from plant sources contain many impurities (e.g., fat, protein, fiber, natural pigment and endogenous enzymes), therefore, an efficient purification process is recommended to minimize these impurities and consequently improve the functional properties of the biopolymer. The main objective of the present study was to investigate the effect of different purification techniques on the yield, protein content, solubility, water- and oil-holding capacity of a heteropolysaccharide-protein biopolymer obtained from durian seed. Four different purification methods using different chemicals and solvents (i.e., A (isopropanol and ethanol), B (isopropanol and acetone), C (saturated barium hydroxide), and D (Fehling solution)] to liberate the purified biopolymer from its crude form were compared. In most cases, the purification process significantly (p < 0.05) improved the physicochemical properties of heteropolysaccharide-protein biopolymer from durian fruit seed. The present work showed that the precipitation using isopropanol and acetone (Method B) resulted in the highest purification yield among all the tested purification techniques. The precipitation using saturated barium hydroxide (Method C) led to induce the highest solubility and relatively high capacity of water absorption. The current study reveals that the precipitation using Fehling solution (Method D) most efficiently eliminates the protein fraction, thus providing more pure biopolymer suitable for biological applications.
Solubility data of recalcitrant contaminants in cosolvents is essential to determine their potential applications in enhanced soil remediation. The solubilities of phenanthrene, anthracene, fluoranthene and benzo[a]pyrene in ethyl lactate/water and ethanol/water mixtures were measured using equilibrium techniques. The cosolvency powers derived from solubility data were then applied to the model developed from the solvophobic approach to predict the capability of ethyl lactate and ethanol in enhancing the desorption of contaminants from soils. Both ethyl lactate and ethanol cosolvents were shown to be able to enhance the solubilisation of the tested four polycyclic aromatic hydrocarbons by > 4 orders of magnitude above the levels obtained with water alone. However, ethyl lactate demonstrated a greater capacity to enhance PAH solubility than ethanol. The cosolvency powers of ethyl lactate/water system obtained from the end-to-end slope (sigma) and the end-to-half slope (sigma0.5) of the solubilisation curve were 1.0-1.5 and 2.0-2.9 higher than ethanol/water system respectively. In line with this, ethyl lactate/water was demonstrated to enhance the desorption of contaminants from soil by 20%-37% and 18%-61% higher compared to ethanol/water system in low organic content and high organic content soils respectively, with a 2:1 (V/W) ratio of solution:soil and with cosolvent fraction as low as 0.4. With the exception of benzo[a]pyrene, the experimental desorption results agreed fairly with the predicted values, under an applied solution:soil ratio that was enough to hold the capacity of released contaminants.
The effect of heat treatment below the gelatinization temperature on the susceptibility of corn, mung bean, sago, and potato starches towards granular starch hydrolysis (35°C) was investigated. Starches were hydrolyzed in granular state and after heat treatment (50°C for 30 min) by using granular starch hydrolyzing enzyme for 24 h. Hydrolyzed heat-treated starches showed a significant increase in the percentage of dextrose equivalent compared to native starches, respectively, with corn 53% to 56%, mung bean 36% to 47%, sago 15% to 26%, and potato 12% to 15%. Scanning electron microscopy micrographs showed the presence of more porous granules and surface erosion in heat-treated starch compared to native starch. X-ray analysis showed no changes but with sharper peaks for all the starches, suggested that hydrolysis occurred on the amorphous region. The amylose content and swelling power of heat-treated starches was markedly altered after hydrolysis. Evidently, this enzyme was able to hydrolyze granular starches and heat treatment before hydrolysis significantly increased the degree of hydrolysis.
α-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of α-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of α-mangostin's solubility from 0.2 ± 0.2 μg/mL to 2743 ± 11 μg/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between α-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99-127 nm. Powder X-ray diffraction indicated conversion of α-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 ± 4 μg/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of α-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 ± 0.2 μg/mL). Improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of α-mangostin, particularly antitumor efficacy.
Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.
Use of phosphate-solubilizing bacteria (PSB) as inoculants has concurrently increased phosphorous uptake in plants and improved yields in several crop species. The ability of PSB to improve growth of aerobic rice (Oryza sativa L.) through enhanced phosphorus (P) uptake from Christmas island rock phosphate (RP) was studied in glasshouse experiments. Two isolated PSB strains; Bacillus spp. PSB9 and PSB16, were evaluated with RP treatments at 0, 30 and 60 kg ha(-1). Surface sterilized seeds of aerobic rice were planted in plastic pots containing 3 kg soil and the effect of treatments incorporated at planting were observed over 60 days of growth. The isolated PSB strains (PSB9 and PSB16) solubilized significantly high amounts of P (20.05-24.08 mg kg(-1)) compared to non-inoculated (19-23.10 mg kg(-1)) treatments. Significantly higher P solubilization (24.08 mg kg(-1)) and plant P uptake (5.31 mg plant(-1)) was observed with the PSB16 strain at the highest P level of 60 kg ha(-1). The higher amounts of soluble P in the soil solution increased P uptake in plants and resulted in higher plant biomass (21.48 g plant(-1)). PSB strains also increased plant height (80 cm) and improved root morphology in aerobic rice. The results showed that inoculation of aerobic rice with PSB improved phosphate solubilizing activity of incorporated RP.
A split plot 3 by 3 experiment was designed to investigate the relationships among production of primary metabolites (soluble sugar and starch), secondary metabolites (total flavonoids, TF; total phenolics, TP), phenylalanine lyase (PAL) activity (EC 4.3.1.5), protein and antioxidant activity (FRAP) of three progenies of oil palm seedlings, namely Deli AVROS, Deli Yangambi and Deli URT, under three levels of CO₂ enrichment (400, 800 and 1,200 μmol·mol⁻¹) for 15 weeks of exposure. During the study, the treatment effects were solely contributed by CO₂ enrichment levels; no progenies and interaction effects were observed. As CO₂ levels increased from 400 to 1,200 μmol·mol⁻¹, the production of carbohydrate increased steadily, especially for starch more than soluble sugar. The production of total flavonoids and phenolics contents, were the highest under 1,200 and lowest at 400 μmol·mol⁻¹. It was found that PAL activity was peaked under 1,200 μmol·mol⁻¹ followed by 800 μmol·mol⁻¹ and 400 μmol·mol⁻¹. However, soluble protein was highest under 400 μmol·mol⁻¹ and lowest under 1,200 μmol·mol⁻¹. The sucrose/starch ratio, i.e., the indication of sucrose phosphate synthase actvity (EC 2.4.1.14) was found to be lowest as CO₂ concentration increased from 400 > 800 > 1,200 μmol·mol⁻¹. The antioxidant activity, as determined by the ferric reducing/antioxidant potential (FRAP) activity, increased with increasing CO₂ levels, and was significantly lower than vitamin C and α-tocopherol but higher than butylated hydroxytoluene (BHT). Correlation analysis revealed that nitrogen has a significant negative correlation with carbohydrate, secondary metabolites and FRAP activity indicating up-regulation of production of carbohydrate, secondary metabolites and antioxidant activity of oil palm seedling under elevated CO₂ was due to reduction in nitrogen content in oil palm seedling expose to high CO₂ levels.
The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate.
This study focuses on the feasibility of treating aged polycyclic aromatic hydrocarbons (PAHs)-contaminated soils using ethyl lactate (EL)-based Fenton treatment via a combination of parametric and kinetic studies. An optimised operating condition was observed at 66.7 M H2O2 with H2O2/Fe(2+) of 40:1 for low soil organic carbon (SOC) content and mildly acidic soil (pH 6.2), and 10:1 for high SOC and very acidic soil (pH 4.4) with no soil pH adjustment. The desorption kinetic was only mildly shifted from single equilibrium to dual equilibrium of the first-order kinetic model upon ageing. Pretreatment with EL fc = 0.60 greatly reduced the mass transfer coefficient especially for the slow desorbed fraction (kslow) of high molecular weight (HMW) PAHs, largely contributed by the concentration gradient created by EL-enhanced solubility. As the major desorption obstacle was almost fully overcome by the pretreatment, the pseudo-first-order kinetic reaction rate constant of PAHs degradation of aged soils was statistically discernible from that of freshly contaminated soils but slightly reduced in high SOC and high acidity soil. Stabilisation of H2O2 by EL addition in combination with reduced Fe(2+) catalyst were able to slow the decomposition rate of H2O2 even at higher soil pH.
Cellulose carbamate (CCs) was produced from kenaf core pulp (KCP) using microwave reactor-assisted method. The effects of urea concentration and reaction time on the formation of nitrogen content in CCs were investigated. The CCs' solubility in LiOH/urea system was determined and its membranes were characterized. As the urea content and reaction time increased, the nitrogen content form in CCs increased which enhanced the CCs' solubility. The formation of CCs was confirmed by Fourier transform infrared spectroscopy (FT-IR) and nitrogen content analysis. The CCs' morphology was examined using Scanning electron microscopy (SEM). The cellulose II and crystallinity index of the membranes were confirmed by X-ray diffraction (XRD). The pore size of the membrane displayed upward trend with respect to the urea content observed under Field emission scanning electron microscope (FESEM). This investigation provides a simple and efficient procedure of CCs determination which is useful in producing environmental friendly regenerated CCs.
O. stamineus is a medicinal herb with remarkable pharmacological properties. However, poor solubility of the active principles limits its medicinal value. This study sought to prepare nano liposomes of OS ethanolic extract in unpurified soybean phospholipids in order to improve its solubility and permeability. OS liposomes were prepared by the conventional film method, and were characterized for solubility, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), particle size and zeta potential, release, absorption in everted rat intestinal sacs, and DPPH scavenging effect.
With the exponential growth of the global population, the agricultural sector is bound to use ever larger quantities of fertilizers to augment the food supply, which consequently increases food production costs. Urea, when applied to crops is vulnerable to losses from volatilization and leaching. Current methods also reduce nitrogen use efficiency (NUE) by plants which limits crop yields and, moreover, contributes towards environmental pollution in terms of hazardous gaseous emissions and water eutrophication. An approach that offsets this pollution while also enhancing NUE is the use of controlled release urea (CRU) for which several methods and materials have been reported. The physical intromission of urea granules in an appropriate coating material is one such technique that produces controlled release coated urea (CRCU). The development of CRCU is a green technology that not only reduces nitrogen loss caused by volatilization and leaching, but also alters the kinetics of nitrogen release, which, in turn, provides nutrients to plants at a pace that is more compatible with their metabolic needs. This review covers the research quantum regarding the physical coating of original urea granules. Special emphasis is placed on the latest coating methods as well as release experiments and mechanisms with an integrated critical analyses followed by suggestions for future research.
In recent years, the demand for a natural plant-based polymer with potential functions from plant sources has increased considerably. The main objective of the current study was to study the effect of chemical extraction conditions on the rheological and functional properties of the heteropolysaccharide/protein biopolymer from durian (Durio zibethinus) seed. The efficiency of different extraction conditions was determined by assessing the extraction yield, protein content, solubility, rheological properties and viscoelastic behavior of the natural polymer from durian seed. The present study revealed that the soaking process had a more significant (p < 0.05) effect than the decolorizing process on the rheological and functional properties of the natural polymer. The considerable changes in the rheological and functional properties of the natural polymer could be due to the significant (p < 0.05) effect of the chemical extraction variables on the protein fraction present in the molecular structure of the natural polymer from durian seed. The natural polymer from durian seed had a more elastic (or gel like) behavior compared to the viscous (liquid like) behavior at low frequency. The present study revealed that the natural heteropolysaccharide/protein polymer from durian seed had a relatively low solubility ranging from 9.1% to 36.0%. This might be due to the presence of impurities, insoluble matter and large particles present in the chemical structure of the natural polymer from durian seed.
In this study, the preparation of N-pamitoyl chitosan (ChP) anchored oleic acid (OA) liposome was demonstrated. Two different types of water-soluble ChPs with different degrees of acylation (DA) were selected for this study. The presence of ChPs on the surface of OA liposome was confirmed with their micrographs and physicochemical properties. The "peeling off" effect on the surface of the ChP-anchored OA (OAChP) liposomes was observed on the atomic force microscope micrographs and confirmed the presence of the ChPs layer on the liposome surface. The surface tension of the OAChPs liposome solution was found to be higher than that of the OA liposome solution. This result indicated the removal of OA monomer by ChPs from the air-water interface. The increase in the minimum area per headgroup (A(min)) of the OA with the presence of ChPs has further proved the interaction between OA monomer and the hydrophobic moieties of the ChPs. The ChPs anchored onto the OA monolayer increased the curvature of the OAChP liposomes monolayer and reduced the liposome size. The size of the OAChP liposomes was reduced by 30 nm as compared with the unmodified OA liposome. Results revealed that the anchored ChPs can improve the integrity and rigidity of the OA liposome.
Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.
Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion-spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.
Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30-50 mg), ethylcellulose (2-4 mg), microcrystalline cellulose (5-20 mg) and Aerosil® (5-12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated.