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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.

The amorphous solid dispersions (ASDs) containing amino methacrylate copolymer and surface-active agents were prepared to improve the nifedipine (NDP) dissolution. The different types of surface-active agent i.e., polysorbates 80, sodium lauryl sulfate (SLS) and polyethylene glycol (PEG) 400 were used. In order to evaluate the ASDs formulation,powder X-ray diffractometry and thermal analysis to characterize NDP crystallinity in ASDs and the dissolution study of NDP have been performed to compare the dissolution profiles. The ASDs were kept for 6 months to investigate the stability. In the X-ray diffraction pattern, no peak was observed in all samples of ASDs. No peak was found in sample of all ASDs from the thermograms. These results suggest that the drug may be molecularly dispersed in matrix of amino methacrylate copolymer. The drug dissolution at 120 min, from ASDs without surface-active agent and NDP powder were 58.31% and 17.95%, respectively. The dissolved NDP from ASDs composed of SLS, polysorbate 80 and PEG400 were 96.25%, 88.86% and 75.32%, respectively. These results may occur due to the reduction of surface tension, the addition of the low amount of high efficiency of surface-active agent e.g., SLS (compared with PEG400 and polysorbate 80) provided the higher NDP dissolution. The content analysis of NDP in selected ASDs was studied at the end of 3 and 6 months, the NDP content remained unchanged after storage.

Polymer solution has been used for increasing viscosity of ophthalmic solution in order to prolong the retention of active drug in the eye. The ophthalmic solution must be sterilized, which may affect the rheology properties of viscosity-inducing polymers. The aim of this study was to investigate the effect of sterilization treatment on viscosity-inducing agents (i.e., poloxamer, polyvinyl alcohol; (PVA), methyl cellulose (MC), polyvinylpyrrolidone (PVP) and carbomer). The effect of membrane filtration and steam sterilization or autoclaving (121 °C, 15 Ib/inch2, 15 min) were determined. A rheometer was used to investigate the viscosity and viscoelastic properties between treated and untreated polymer solutions. The power law model, consistency index (k), and power law index (n) of polymer solution viscosity were compared. For viscoelastic properties, storage modulus and loss modulus were examined. The results demonstrated that, viscosity of carbomer and MC solution (1 and 2 %) were changed after steam sterilization. No difference in viscosity was observed for PVP, PVA and poloxamer solution, between untreated and treated samples. The storage and loss moduli of PVA solution after autoclaving were not different when comparing with the untreated polymer solution. From this study, it could be concluded that the sterilization treatment influenced the viscosity behavior and viscoelastic properties of polymer solution used as viscosity-inducing agent in ophthalmic solution. Therefore, the selection of polymer and sterilization method should be carefully considered.

Recently, monolaurin (ML) has received great interest due to its possible use as an alternative antifungal. However, the limited water solubility of ML is still a major obstacle to its formulation and application. Gel-like microemulsions are one of the promising carriers for low-water-solubility substances due to both the advantages of gels and microemulsions and may be applied for ML. In this study, ML was incorporated into gel-like microemulsions and evaluated for its physicochemical and antifungal properties. The results indicated that the properties of gel-like microemulsion changed after the incorporation of ML, suggesting that ML can induce the transition of internal structure. When simulating the oral cavity environment, changes in the microstructure were observed and depended on the times of dilution. The lamellar structure was formed at 1.5-2 times dilution. However, this structure was disrupted after dilution five times or more. The structural change following dilution was associated with the release profiles. After contacting the formulations with the medium, ML was promptly released, with the majority of ML being released within 2 h. Regarding the antifungal assay, the ML-loaded gel-like microemulsions decreased the survival of Candida albicans within 3 h, although ML was immediately released, suggesting that the ML-loaded in oil droplets required time to permeate through the fungal cell wall. Additionally, the gel-like microemulsions possessed acceptable stability after the temperature cycling test. Therefore, gel-like microemulsions can be a possible carrier for ML loading, and ML-loaded gel-like microemulsions may be applied as an alternative antifungal preparation in the future. Graphical abstract.

Kaempferia parviflora, a medicinal herb, treats hypertension and promotes longevity with good health and well-being. Its bioactive component is poorly soluble in water, resulting in poor ab...

Bacillus subtilis CMs026 is used for plant disease control. However, use of biocontrol for crops is limited by variable performances of control agents. Therefore, this study aimed to develop a ready-to-use, bacteria-based, highly stable, solid dosage formulation for plant disease control. Incubated broths containing B. subtilis CMs026 were centrifuged and sterilized. Supernatants were mixed with silicon dioxides and dried at 80 °C for 48 h. Agar diffusion test using active antifungal substance, surfactin, as a marker revealed the efficacy of dried broth. Subsequently, products were prepared by mixing dried broths with 6% disintegrant, followed by compaction. The compressed tablets were stable after storage for three months. In vivo experiments against Alternaria brassicicola in Chinese kale (Brassica alboglabra) revealed that the products reduced percent crop loss from 88% to 40%.

Ternary solid solutions composed of nifedipine (NDP), amino methacrylate copolymer (AMCP), and polysorbate (PS) 20, 60, or 65 were prepared using a solvent evaporation method. The dissolution profiles of NDP were used to study the effect of the addition of polysorbate based on hydrophilic properties. A solid solution of NDP and AMCP was recently developed, however, the dissolution of NDP was &lt, 70%. In the present study, polysorbate was added to improve the dissolution of the drug by altering its hydrophilicity. The suitable formulation contained NDP and AMCP at a ratio of 1:4 and polysorbate at a concentration of 0.1%, 0.3%, or 0.6%. Differential scanning calorimetry and powder X-ray diffraction were used to examine the solid solutions. No peak representing crystalline NDP was observed in any solid solution samples, suggesting that the drug was molecularly dispersed in AMCP. The NDP dissolution from NDP powder and solid solution without PS were 16.82% and 58.19%, respectively. The highest dissolution of NDP of approximately 95.25% was noted at 120 min for the formulation containing 0.6% PS20. Linear correlations were observed between the surface free energy and percentages of dissolved NDP (R2 = 0.7115–0.9315). Cellular uptake across Caco-2 was selected to determine the drug permeability. The percentages of cellular uptake from the NDP powder, solid solution without and with PS20 were 0.25%, 3.60%, and 7.27%, respectively.

The aim of the present study was to fabricate spontaneous emulsifying powders (SEP) for improving dissolution of poorly water-soluble drugs for oral drug delivery. The effect of drugs with different lipophilicity (logP), that is, nifedipine, felodipine, manidipine, and itraconazole on crystalline properties and dissolution profiles of SEP was also examined. The liquid spontaneous emulsifying formulation (SEF), composing of polyoxyl 35 castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether at a ratio of 1:1:8, was solidified with three different solid carriers, namely, fumed silica, porous silicon dioxide and porous calcium silicate (at 20%–50%). Porous calcium silicate at a concentration of 50% produced an excellent solid SEP formulation with the highest drug dissolution. The SEP formulations were free flowing with similar characteristics as that of liquid SEF. The differential scanning calorimetry and powder X-ray diffraction studies revealed the transformation of crystalline drugs (in pure drugs) to amorphous drugs (in the SEP formulations). This was further confirmed by scanning electron microscopy. Also, SEP containing 50% porous calcium silicate significantly improved the dissolution rate of all drugs tested due to the fast spontaneous emulsion formation and the decreased droplet size. Accordingly, this novel SEP formulation is the versatile and useful formulation that could be used to enhance the oral bioavailability of drugs by improving the dissolution of poorly water-soluble drugs.

The low solubility of poorly water-soluble drug is a major problem of oral drug adsorption. The self-emulsifying system can be applied to eliminate the drug dissolution step and improve the drug absorption. In this research, liquid self-nanoemulsifying drug delivery system (SNEDDS) composing of polyethoxylated castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether was developed. The drugs with similar structure but different lipophilicity (log P), nifedipine (NDP), felodipine (FDP) and manidipine (MDP), were investigated. Size and size distribution of emulsion after dilution in acid medium and in vitro drug dissolution were determined. The results showed that the size of emulsions obtained from dilution of SNEDDS in acidic medium ranged from 100-150 nm. Drug dissolution from SNEDDS was different depending on lipophilicity of drug, i.e., 98.6, 74.3 and 52.5% for NDP (log P 2.50), FDP (log P 4.46) and MDP (log P 5.46), respectively. The results suggested that the difference in lipophilicity may influence the drug dissolution from SNEDDS.

Self-nanoemulsifying drug delivery system (SNEDDS) can be used to improve dissolution of poorly water-soluble drugs. The objective of this study was to prepare SNEDDS by using ternary phase diagram and investigate their spontaneous emulsifying property, dissolution of nifedipine (NDP), as well as the pharmacokinetic profile of selected SNEDDS formulation. The results showed that the composition of the SNEDDS was a great importance for the spontaneous emulsification. Based on ternary phase diagram, the region giving the SNEDDS with emulsion droplet size of less than 300 nm after diluting in aqueous medium was selected for further formulation. The small-angle X-ray scattering curves showed no sharp peak after dilution at different percentages of water, suggesting non-ordered structure. The system was found to be robust in different dilution volumes; the droplet size was in nanometer range. In vitro dissolution study showed remarkable increase in dissolution of NDP from SNEDDS formulations compared with NDP powders. The pharmacokinetic study of selected SNEDDS formulation in male Wistar rats revealed the improved maximum concentration and area under the curve. Our results proposed that the developed SNEDDS formations could be promising to improve the dissolution and oral bioavailability of NDP.

This work has a focus on the self-emulsifying drug delivery system (SEDDS), which can be used in pharmaceutical field for increasing bioavailability of poorly water-soluble drugs. The model drug resveratrol was used because of its poor water-solubility and is of interest because of its wide range of pharmacological effects. It is beneficial to understand the mechanism of SEDDS formation in the human body, therefore, the determination of nanoscale structure was carried out. For this purpose, small angle X-ray scattering (SAXS), photon correlation spectroscopy (PCS), and transmission electron microscopy (TEM) techniques were applied. We have found that the size and size distribution of particles were in nanometers. The inner structure of SEDDS was ordered with the lamellar distances (d-spacing) of < 20 nm. It seems that the prepared SEDDS in water form large oil drops (200-400 nm) in water as well as small micelles with the droplet size of 10-20 nm.

Lipid-based formulations (LBF) including self-emulsifying drug delivery system have been used to improve drug dissolution and bioavailability by avoiding rate-limiting step during dissolution of poorly water-soluble drugs. This study was aimed to investigate the behavior of lipid-based formulations upon dilution in aqueous media by using small angle X-ray scattering (SAXS). LBF is composed of oil (caprylic/capric glyceride), surfactants (polyoxyl 35 castor oil or polyoxyl 40 hydrogenated castor oil), and co-solvent (diethylene glycol monoethyl ether) at a weight ratio of 1:1:8. Nifedipine, a poorly water-soluble drug, was used as a model drug. A 100-fold dilution of the LBF in aqueous media (i.e., simulated gastric fluid USP without pepsin (SGF) and distilled water) resulted in nanosized emulsion (less than 200 nm). The selected formulations were diluted in aqueous media at various ratios (e.g., 0.01, 0.02, 0.04, 0.06, 0.09, 0.11, 0.18, 0.25, 0.67, 1.5, 4, 99, 199 and 300 folds) and then, after equilibrium, monitored by SAXS in order to observe the surfactant rearrangement. The results from SAXS scattering curves (qof 0.027-0.980 Å-1) demonstrated that a lamellar phase or liquid crystalline was not formed upon dilution. The emulsions were formed without the ordered structure.

The ability of self-emulsifying drug delivery system (SEDDS), which is a mixture of oils, surfactants and co-surfactants, to improve dissolution rate of a poorly water-soluble drug, manidipine hydrochloride (MDP), was evaluated in this study. Liquid form of SEDDS containing caprylic/capric glyceride, polyoxyl 35 castor oil, and diethylene glycol monoethyl ether at a weight ratio of 1:1:8 was converted to solid SEDDS by adsorption on to different solid carriers, i.e., Aerosil® 200 and Sylysia® 320. The results demonstrated that the solid carrier of at least 50% (w/w) was required to adsorb liquid SEDDS containing MDP. The results from powder X-ray diffraction, differential scanning colorimetry and scanning electron microscopy showed that MDP in solid SEDDS formulations was in amorphous form while a crystalline form was observed only in MDP raw material and its physical mixture. The in vitro dissolution of MDP from solid SEDDS using Sylysia® 320 was higher than that using Aerosil® 200 as a solid carrier. In summary, the solid SEDDS could be used as a carrier to improve the dissolution of MDP, a poorly water-soluble drug.

Graphical Abstract Unlabelled image, Solid dispersions of nifedipine (NDP), a poorly water-soluble drug, and amino methacrylate copolymer (AMCP) with aid of adsorbent, that is, fumed silica, talcum, calcium carbonate, titanium dioxide, and mesoporous silica from rice husks (SRH), were prepared by solvent method. The physicochemical properties of solid dispersions, compared to their physical mixtures, were determined using powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC). The surface morphology of the prepared solid dispersions was examined by scanning electron microscopy (SEM). The dissolution of NDP from solid dispersions was compared to NDP powders. The effect of adsorbent type on NDP dissolution was also examined. The dissolution of NDP increased with the ratio of NDP:AMCP:adsorbent of 1:4:1 when compared to the other formulations. As indicated from PXRD patterns, DSC thermograms and SEM images, NDP was molecularly dispersed within polymer carrier or in an amorphous form, which confirmed the better dissolution of solid dispersions. Solid dispersions containing SRH provided the highest NDP dissolution, due to a porous nature of SRH, allowing dissolved drug to fill in the pores and consequently dissolve in the medium. The results suggested that solid dispersions containing adsorbents (SRH in particular) demonstrated improved dissolution of poorly water-soluble drug when compared to NDP powder.

The aim of this study was to manufacture the ternary solid dispersions composed of nifedipine, Eudragit® E and adsorbent. Dissolution enhancement of nifedipine was also investigated. The inert solid carriers were added in the mixtures of nifedipine and Eudragit® E at varying ratios. The physicochemical properties of ternary systems, compared to physical mixtures, were analyzed using powder x-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The dissolution of nifedipine from ternary systems was compared to the drug alone. The influence of drug:polymer: adsorbent ratio and type of adsorbent on the dissolution rate of the drug was also evaluated. The PXRD and DSC results of the systems with high amount of polymer showed that the drug was present in an amorphous form. On the other hand, the diffraction patterns and DSC thermograms of the physical mixtures revealed that to some extent the drug was present in a crystalline form. The results from this study demonstrated that an improvement in dissolution rate of nifedipine with Eudragit® E and adsorbents was obtained.

The objective of this study was to prepare spontaneous emulsifying powder (SEP) for improving dissolution and enhancing oral bioavailability of a poorly water-soluble drug, nifedipine (NDP). In order to investigate the effects of solid carrier properties, such as surface area and pore size, and a concurrent food intake on absorption of NDP in rats, different SEP formulations were prepared by adsorbing liquid spontaneous emulsifying formulation (SEF), composing of polyoxyl 35 castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether at a ratio of 1:1:8, onto various solid carriers (i.e., silica (FS), porous calcium silicate (PCS) and porous silicon dioxide). The solid characterization by scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction revealed the absence of crystalline NDP in the formulations. SEP also demonstrated excellent spontaneous emulsification properties similar to SEF. The droplet size of emulsions formed after dilution was less than 200 nm. The solid carriers (particularly PCS) had significant and positive effect in drug dissolution; the mean dissolution time of SEP containing PCS was considerably improved. SEP also provided a good stability after storage in accelerated and long-term conditions for 6 months. The bioavailability study resulted in enhanced values of C max and AUC for SEP formulations, when tested in both fasted and fed rats. Furthermore, comparing the AUC in fasted and fed rats, NDP powder exhibited a significant food effect. The difference in bioavailability of NDP in fed compared to fasted state can be avoided by using SEP.

A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with Imwitor(®) 742 as oil and Tween(®)/Span(®) or Cremophor(®)/Span(®) as mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS containing Tween(®)/Span(®) in aqueous medium was independent of the HLB of a mixed surfactant. The use of the Cremophor(®)/Span(®) blend gave nanosized emulsion at higher HLB. The structure of the surfactant was found to influence the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded liquid SNEDDS comprising Cremophor(®) RH40/Span(®) 80 onto Aerosil(®) 200 or Aerosil(®) R972 as inert solid carrier. Solid SNEDDS formulations using higher amounts (30-50% w/w) of Aerosil(®) 200 exhibited good flow properties with smooth surface and preserved the self-emulsifying properties of liquid SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid SNEDDS revealed the transformation of the crystalline structure of NDP due to its molecular dispersion state. In vitro dissolution study demonstrated higher dissolution of NDP from solid SNEDDS compared with NDP powder.

1, 4, Silpakorn University Science and Technology Journal