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Objective: This study aimed to prepare fluconazole (FZ)-loaded solid lipid nanoparticles (SLNs) using a simplex centroid design and fatty acids to optimize the SLNs to get small-sized nanoparticles with a narrow distribution. Methods: Hot emulsification was used to prepare the FZ-loaded SLNs. Stearic acid (Sa) (X1), palmitic acid (Pa) (X2), and myristic acid (Ma) (X3) were the solid lipids. The effect of various types and amounts of fatty acids on the particle size, polydispersity index, zeta potential, and pH of the SLNs was studied using the simplex centroid design. Results: The particle size of all formulations ranged between 16.49 nm and 56.65 nm, and the polydispersity index (PDI) ranged between 0.258 and 0.676, indicating a relatively narrow size distribution. The zeta potential ranged from–7.47 to–12.2 mV. The pH was around 4.63–4.77, indicating that the SLN system was a weak acid. Design-Expert® software was used to design the responses of all model formulations and to select the optimized formulation. The optimal formulation comprised 0.190 g Sa, 0.048 g Pa, and 0.002 g Ma. The experimental values of the particle size and PDI of the optimal formulation did not differ significantly from the predicted values and lay within a 95% confidence interval (CI). Conclusion: Therefore, the simplex centroid design using fatty acids could efficiently formulate and optimize FZ-loaded SLNs.

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.

In this study, 3D-printed tablets with a constant surface area were designed and fabricated using polylactic acid (PLA) in the outer compartment and polyvinyl alcohol and felodipine (FDP) in the inner compartment. The influences of different surface geometries of the inner compartment, namely, round, hexagon, square, and triangle, on drug release from 3D-printed tablets were also studied. The morphology and porosity of the inner compartment were determined using scanning electron microscopy and synchrotron radiation X-ray tomographic microscopy, respectively. Additionally, drug content and drug release were also evaluated. The results revealed that the round-shaped geometry seemed to have the greatest total surface area of the inner compartment, followed by square-shaped, hexagon-shaped, and triangle-shaped geometries. FDP-loaded 3D-printed tablets with triangle and hexagon surface geometries had the slowest drug release (about 80% within 24 h). In the round-shaped and square-shaped 3D-printed tablets, complete drug release was observed within 12 h. Furthermore, the drug release from triangle-shaped 3D-printed tablets with double the volume of the inner compartment was faster than that of a smaller volume. This was due to the fact that a larger tablet volume increased the surface area contacting the medium, resulting in a faster drug release. The findings indicated that the surface geometry of 3D-printed tablets with a constant surface area affected drug release. This study suggests that 3D printing technology may be used to develop oral solid dosage forms suitable for customized therapeutic treatments.

The goal of this study was to develop a 3D-printed bento box model (3D-printed BB) with one or two chambers containing propranolol hydrochloride (PNL) as powder and matrix tablet for controlled drug release at varying times using United States Pharmacopeia (USP) dissolution guidelines. The 3D-printed BBs were made with commercial polyvinyl alcohol filament and a fused deposition modeling (FDM) 3D printer, with varying infill percentages and wall thicknesses. The physicochemical properties of the 3D-printed BBs, including appearance, thickness, size, weight, hardness, swelling, and erosion properties were investigated. The surface and cross-section morphologies of the 3D-printed BBs were characterized using a FESEM. According to FESEM images, the different infill percentages had a significant effect on the internal structure of the 3D-printed BBs' caps, but a minor effect on the internal structure of their walls. PNL release from the 3D-printed BB began in a pH 1.2 medium, followed by drug release in a pH 6.8 medium. Some formulations of 3D-printed BB could achieve a drug release percentage within all the ranges specified by USP dissolution guidelines. 3D-printed BBs, therefore, have the potential to revolutionize the future of the pharmaceutical industry by facilitating control of the amount of drugs released at predetermined intervals.

The objective of this study was to stabilize the enteric property of bleached shellac by composite formation with ethyl cellulose. The composite film at the ratio of 9:1, 8:2, 7:3, 6:4, and 5:5 was prepared by the film casting method. The physicochemical properties were acid value, insoluble solid, water permeability coefficient, % polarity, mechanical property, FTIR, PXRD, DSC, % solubility in aqueous, and various pH (1.2 and 7.4). All the films were able to protect against the low pH and water. The total solubility at pH 7.4 was reported for the low ratio of ethyl cellulose (9:1 and 8:2). The stability of all films was then investigated for 180 days. The results demonstrated that the ethyl cellulose could stabilize the bleached shellac indicated by the low changes in acid value and insoluble solid. The higher ratio of ethyl cellulose contributed to the lower polymerization during storage. The results were due to the protection of the bleached shellac's active sites. The entanglement of ethyl cellulose caused interaction difficulties between active groups leading to stabilized bleached shellac. The proper ratio was 7:3 because of high solubility, and low polymerization. The findings demonstrated that the composite film could improve the enteric property of bleached shellac for a long period.

Quercetin (QCT), a natural flavonoid, is of research interest owing to its pharmacological properties. However, its pharmacokinetic limitations could hinder its widespread therapeutic use. Nanocarriers, especially solid lipid nanoparticles (SLNs), might overcome this constraint. This study aimed to investigate QCT-loaded SLNs prepared via a new approach using a volatile oil. The phase-inversion temperature method was used to incorporate rosemary oil (RMO) into SLNs prepared using solid lipids possessing different chemical structures. Among the solid lipids used in the formulations, trilaurin (TLR) exhibited the smallest particle size and good stability after a temperature cycling test. SLNs prepared with a ratio of RMO to TLR of 1:3 could load QCT with an entrapment efficiency of >60% and drug loading of ~2% w/w. The smallest particle size was achieved using the polyoxyethylene-hydrogenated castor oil RH40, and the particle size depended on the concentration. The drug-release profile of QCT_TLR exhibited prolonged biphasic release for >24 h. QCT_TLR was a safe formulation, as indicated by a cell viability percentage of >75% at

The major bioactive components of Kaempferia parviflora (KP) rhizomes, 3,5,7,3′,4′-pentamethoxyflavone (PMF), 5,7-dimethoxyflavone (DMF), and 5,7,4′-trimethoxyflavone (TMF), were chosen as the quantitative and qualitative markers for this plant material. In order to extract bioactive components (total methoxyflavones) from KP rhizomes, ultrasound-assisted extraction (UAE) was proposed as part of this study. Plackett–Burman design (PBD) and Box–Behnken design (BBD) were utilized to optimize the effects of UAE on extraction yields and total methoxyflavone contents in KP rhizomes. First, PBD was utilized to determine the effect of five independent variables on total yields and total methoxyflavone contents. The results indicated that the concentration of the extracting solvent (ethanol), the extraction time, and the ratio of solvent to solid were significant independent terms. Subsequently, BBD with three-level factorial experiments was used to optimize the crucial variables. It was discovered that the concentration of ethanol was the most influential variable on yields and total methoxyflavone contents. Optimum conditions for extraction yield were ethanol concentration (54.24% v/v), extraction time (25.25 min), and solvent-to-solid ratio (49.63 mL/g), while optimum conditions for total methoxyflavone content were ethanol concentration (95.00% v/v), extraction time (15.99 min), and solvent-to-solid ratio (50.00 mL/g). The relationship between the experimental and theoretical values was perfect, which proved that the regression models used were correct and that PBD and BBD were used to optimize the conditions in the UAE to obtain the highest yield and total methoxyflavone content in the KP rhizomes.

The purpose of this study was to prepare solid dispersions of triamterene (TRT) with ascorbic acid (AA) or ascorbic acid 2 glucoside (AA2G) and to evaluate their physical properties. Solid dispersions were prepared by dissolving each sample in an organic solvent and evaporation (EVP). Powder X-ray diffraction (PXRD) revealed a halo pattern for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT = 1/1). In differential scanning calorimetry (DSC), endothermic peaks due to the melting of TRT and AA disappeared for EVP1 (AA/TRT = 1/1), and the melting peaks of TRT and AA2G disappeared for EVP2 (AA2G/TRT = 1/1). Fourier transform infrared (FT-IR) spectroscopy revealed broadened peaks for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT = 1/1) due to the hydroxyl groups (-OH) of AA and the amino groups (-NH2) of TRT and also revealed a peak shift due to the pteridine skeleton (C = N) of TRT. In near-infrared absorption (NIR) spectroscopy, peaks due to the hydroxyl groups (-OH) of AA and AA2G were found for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT = 1/1), respectively. A peak due to the amino groups (-NH2) was evident. This suggested the formation of an evaporation, in which TRT interacted with AA or AA2G. In the dissolution test, the dissolved fraction of TRT alone after 3 min was 30%, whereas the fractions were enhanced to approximately 90% for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT= 1/1). Results confirmed that dissolution properties were improved as a result of complex formation. The above findings indicated improvement the dissolution properties of TRT.

Recently, essential oil from Amomum kravanh (AMO) was reported to exert anti-oral cancer effects. Although it was more effective after being loaded into nanoemulsions, AMO without an Ostwald ripening inhibitor was unable to form stable nanoemulsions because of the Ostwald ripening phenomenon. In this study, we examined the influence of Ostwald ripening inhibitors, such as fixed oils and polyethylene glycol 4000 (PEG 4000), on nanoemulsion properties prepared by a phase inversion temperature method. Several fixed oils, including virgin coconut oil (VCO), palm oil (PMO), olive oil (OLO), and PEG 4000, were evaluated, and their Ostwald ripening inhibitory effects were compared. The results suggest that the type and ratio of AMO:fixed oils influence the formation and characteristics of nanoemulsions. PEG 4000 was unable to produce nanoemulsions; however, stable nanoemulsions with small droplet sizes were observed in preparations containing OLO and VCO at an AMO:fixed oil ratio of 80:20, which may be the result of specific molecular interactions among the components. Using an MTT assay, we demonstrated that the AMO:OLO (80:20) nanoemulsion produced the most significant cytotoxic effect on oral cancer cells with a percentage of 99.68 ± 0.56%. Furthermore, the AMO:OLO 80:20 nanoemulsion inhibits metastasis and induces oral cancer cell death through the intrinsic apoptosis pathway. In conclusion, AMO nanoemulsion with anti-oral cancer activity was successfully produced by varying the amount and type of fixed oils. In the future, this discovery may lead to the development of stable nanoemulsions employing additional volatile oils.

Graphical Abstract The shellac nanofibers loaded with monolaurin were prepared by electrospinning technique based on a full factorial design. The obtained nanofibers exhibited antimicrobial activities against Staphylococcus aureus and Candida albicans over a period of time. Image, graphical abstract, The aim of this study was to elucidate the optimized fabrication factors influencing the formation and properties of shellac (SHL) nanofibers loaded with an antimicrobial monolaurin (ML). The main and interaction effects of formulation and process parameters including SHL content (35%–40% w/w), ML content (1%–3% w/w), applied voltage (9–27 kV) and flow rate (0.4–1.2 ml/h) on the characteristic of nanofibers were investigated through a total of 19 experiments based on a full factorial design with three replicated center points. As a result, the SHL content was the major parameter affecting fiber diameter. Another response result revealed that the SHL content would be also the most significant negative impact on amount of beads. An increase in the concentration of SHL leaded to a reduction in the amount of beads. From the results of characterization study, it was proved that ML might be entrapped between the chains of SHL during the electrospinning process exhibiting an excellent encapsulation. According to the response surface area, small (~488 nm) and beadless (~0.48) fibers were obtained with the SHL and ML contents of 37.5% and 1.1% w/w respectively, at the applied voltage of 18 kV and the flow rate of 0.8 ml/h. In addition, the results of the kill-kinetic studies showed that SHL nanofibers loaded with ML exhibited an excellent antibacterial activity against Staphylococcus aureus, while Escherichia coli was less affected due to the hydrophilic structure of the its outer membrane. ML also exerted an antifungal activity by reducing the number of Candida albicans colonies. Based on their structural and antimicrobial properties, SHL nanofibers containing ML could be potentially used as a medicated dressing for wound treatment.

In this study, we developed a polymeric nanofiber patch (PNP) for topical disease treatment using electrohydrodynamic atomization (EHDA). The nanofibers were prepared using various concentrations of polyvinyl alcohol (PVA) and tamarind seed gum and loaded with clindamycin HCl as a model drug. The precursor polymer solutions were sprayed using the EHDA technique; the EHDA processing parameters were optimized to obtain blank and drug-loaded PNPs. The skin adherence, translucence, and ventilation properties of the prepared PNPs indicated that they are appropriate for topical application. The conductivity of the polymer solution increased with increasing PVA and clindamycin concentrations, and increasing the PVA concentration enhanced the solution viscosity. Based on scanning electron microscopy analysis, the PVA concentration had a pronounced effect on the morphology of the sprayed product. Nanofibers were fabricated successfully when the solution PVA concentration was 10%, 13%, or 15% (w/v). The applied voltage significantly affected the diameters of the prepared nanofibers, and the minimum nanofiber diameter was 163.86 nm. Differential scanning calorimetry and X-ray diffraction analyses indicated that the model drug was dispersed in PVA in an amorphous form. The PNP prepared with a PVA:gum ratio of 9:1 absorbed water better than the PVA-only PNP and the PNP with a PVA:gum ratio of 9.5:0.5. Moreover, the PNPs loaded with clindamycin at concentrations of 1%–3% prohibited the growth of Staphylococcus aureus more effectively than clindamycin gel, a commercially available product., Graphical abstract Image, graphical abstract

The biological activity of coconut (Cocos nucifera L.) extracts from its kernels and various parts was reported by many previous studies, it is therefore believable that the extracts of its kernels might show some activities in topical formulations. Among several kernel extracts, the TC06 extract prepared by soaking the steamed coconut kernels in hot water showed the highest total phenolic content (6.98 ± 0.30 mg GAE/g extract) and the strongest antioxidant activity as determined using FRAP and DPPH methods with a reducing power value of 4.12 ± 0.16 mg AAE/g of extract and an SC50 value of 2.38 ± 0.14 mg/ml, respectively. In addition, this extract did not display any cytotoxic effects in the concentration range of 50–3200 µg/ml. Meanwhile, it revealed cytoprotective effects against t-BHP-induced cytotoxicity in HaCaT cells at concentrations higher than 400 µg/ml. The results of phytochemical investigations including a chemical color test, TLC, 1H NMR and FTIR suggested that the TC06 extract was mainly composed of flavonoids and terpenoids. Furthermore, the concentrations of heavy metals including As, Cd, Hg, and Pb in the TC06 extract were below permissible limits. According to the solubility, the TC06 extract was incorporated into gels using Carbopol Ultrez 21 as a gelling agent. The formulated gel containing 3% (w/w) TC06 extract was stable at 4 °C and 25 °C with 75% RH throughout the storage period. It was found that the Carbopol Ultrez 21-based hydroalcoholic gel containing an aqueous extract of coconut kernels exhibited antioxidant activities in the two assays and showed a sufficient consistency, a pleasing color, and a non-oily perception during the period of observation., Graphical abstract Image, graphical abstractEthanolic and aqueous extracts of coconut kernels were composed of phenolic compounds exhibiting antioxidant activities as determined using DPPH and FRAP methods. An aqueous extract (TC06) was selected for the topical preparation of a hydroalcoholic gel due to its nontoxicity, water solubility, and chemical constituents. The hydroalcoholic gel composed of TC06 extract, Carbopol Ultrez 21, ethanol, and triethanolamine appeared to be a suitable formulation due to its physicochemical characteristics and stability.

Graphical Abstract Unlabelled image, The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10–30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

The effects of salt forming agents for chitosan on the potential for nanoparticle formation was investigated. The salt forms were prepared from the amino acid group, including glutamic and aspartic acids, and the alpha hydroxyl acid group, including lactic and glycolic acids. All types of chitosan salt could be used to prepare bovine serum albumin (BSA) loaded nanoparticles. The chitosan salts prepared from the amino acid group showed a higher salt formation ability as demonstrated using FTIR, hence a higher %encapsulation efficiency (%EE) and a reduction in zeta potential were obtained. The difference was due to the different organic acids used giving different polymer conformations and pH values in solution. Chitosan glutamate gave the highest salt formation ability and hence the highest %EE was obtained. The release of protein from all types of chitosan was similar and chitosan glutamate exhibited the highest release. Chitosan salt is therefore a material of choice for protein-loaded nanoparticles and the characteristics of nanoparticles can be readily modulated by different types of salt form.

The aim of this study was to prepare inclusion complexes of hinokitiol (HT)/α-cyclodextrin (α-CD) and HT/β-cyclodextrin (β-CD) by cogrinding and to evaluate the differences in their formation. The physical properties of the preparation were evaluated by Job’s plot, phase solubility studies, differential scanning calorimetry, powder X-ray diffraction, solid fluorescence spectra, and infrared absorption spectra. Intermolecular interaction in the solid state was confirmed to be in the ratios HT/α-CD = 1/2 and HT/β-CD = 1/1. Results indicated that the dissolution property of HT was improved by inclusion in the complexes HT/α-CD and HT/β-CD compared with HT crystals. The 1H-1H ROESY NMR spectrum of HT/α-CD showed that part of the seven-membered ring of HT and the isopropyl group of HT was linked to the wider edges of the two α-CDs. In HT/β-CD, the seven-membered ring of HT interacted with the narrower edge of β-CD and the isopropyl group of HT interacted with the wider edges. This structure of inclusion complexes was attributed to the difference in the cavity diameter of the CD and was thought to influence the dissolution properties.

Spearmint oil (SMO) has been revealed to inhibit oral cancer cells. Its activity increases when it is incorporated into nanoemulsions. However, SMO alone cannot be prepared into stable nanoemulsions without an Ostwald ripening inhibitor. This study aimed to evaluate the effect of an Ostwald ripening inhibitor, i.e., fixed oil, on the formation and characteristic of anticancer nanoemulsions. Various fixed oils, namely, virgin coconut oil (VCO; C12), palm oil (PMO; C16), olive oil (OLO; C18:1), soybean oil (SBO; C18:2), and perilla oil (PRO; C18:3), were selected, and their abilities to stabilize nanoemulsions were compared. Results indicated that the formation and characteristic of nanoemulsions were dependent on the type of fixed oils and the ratio of SMO to fixed oils. Nevertheless, the stable nanoemulsions with nearly the same droplet size could be prepared at a ratio of 80:20 regardless of the type of fixed oils. The stable nanoemulsions might be a result of specific molecular interactions among surfactants, SMO, and fixed oils. Among the nanoemulsions with fixed oils, 80:20 SMO:PRO nanoemulsion showed the most potent cytotoxic effect against oral cancer cells and therefore was selected for further study. The influence of excipients on the properties, including droplet size, carvone content, and cytotoxic activity, of the formulated nanoemulsions were comparatively evaluated after storage at 40 °C for 6 months. Both nanoemulsions had excellent stability. An apoptotic property assay was employed to probe the cell death mechanism. 80:20 SMO:PRO nanoemulsion could induce cancer cell death via the intrinsic apoptosis pathway, which was the desirable pathway for candidate anticancer agents. In conclusion, nanoemulsions containing SMO with cytotoxic effects against oral cancer cells were successfully prepared by selecting specific amounts and types of surfactants and fixed oils. This research might serve as a basis for fabricating stable nanoemulsions containing other volatile oils.

Manidipine (MDP) is generally used clinically as an antihypertensive agent; however, the bioavailability of orally administered MDP is limited due to their very low water solubility.The objectives of this research were, therefore, to increase the solubility of MDP by the formation of ternary solid dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to improve their stability.Solid ternary phase diagram was constructed to find homogeneous solid dispersion region after melting and solidifying at low temperature with different quenching substances. The pulverized powder of solid dispersions was then determined, for their physicochemical properties, by differential scanning calorimetry, powder X-ray diffractometry, Fourier transform infrared (FTIR) spectroscopy and hot stage microscopy. The solubility and dissolution of MDP from the tSD were investigated. The physical stability of tSD was also determined under accelerated condition at 40 °C/75% relative humidity (RH) for 6 months.The results showed that MDP was molecularly dispersed in PEG4000 and copovidone when the tSD was created from homogeneous region of solid ternary phase diagram. FTIR results confirmed that strong hydrogen bonding was presented between MDP and copovidone, leading to a significant increase in the solubility and dissolution of MDP. After storage at accelerated condition (40 °C/75%RH) for 6 months, the tSD still showed a good appearance and high solubility.The results of this study suggest that tSD prepared by melting has promising potential for oral administration and may be an efficacious approach for improving the therapeutic potential of MDP.

The present study aims to develop floating drug delivery system by sublimation of ammonium carbonate (AMC). The core tablets contain a model drug, hydrochlorothiazide, and various levels (i.e., 0-50% w/w) of AMC. The tablets were then coated with different amounts of the polyacrylate polymers (i.e., Eudragit® RL100, Eudragit® RS100, and the mixture of Eudragit® RL100 and Eudragit® RS100 at 1:1 ratio). The coated tablets were kept at ambient temperature (25°C) or cured at 70°C for 12 h before further investigation. The floating and drug release behaviors of the tablets were performed in simulated gastric fluid USP without pepsin at 37°C. The results showed that high amount of AMC induced the floating of the tablets. The coated tablets containing 40 and 50% AMC floated longer than 8 h with a time-to-float of about 3 min. The sublimation of AMC from the core tablets decreased the density of system, causing floating of the tablets. The tablets coated with Eudragit® RL100 floated at a faster rate than those of Eudragit® RS100. Even the coating level of polymer did not influence the time-to-float and floating time of coated tablets containing the same amount of AMC, the drug release from the tablets coated with higher coating level of polymer showed slower drug release. The results suggested that the sublimation technique using AMC is promising for the development of floating drug delivery system.

To enhance the dissolution of poorly soluble mefenamic acid, self-emulsifying formulation (SEF), composing of oil, surfactant and co-surfactant, was formulated. Among the oils and surfactants studied, Imwitor ® 742, Tween ® 60, Cremophore ® EL and Transcutol ® HP were selected as they showed maximal solubility to mefenamic acid. The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading. The droplet size after dispersion and drug dissolution of selected formulations were investigated. The results showed that the formulation containing Imwitor ® 742, Tween ® 60 and Transcutol ® HP (10:30:60) can encapsulate high amount of mefenamic acid. The dissolution study demonstrated that, in the medium containing surfactant, nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min. In phosphate buffer (without surfactant), 80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min, from the commercial product. The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.

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.

Context: Low bioavailability of oral manidipine (MDP) is due to its low water solubility. Objective: The objective of this study was to increase the solubility and bioavailability of MDP by fabricating ternary solid dispersion (tSD) with d-α-tocopherol polyethyleneglycol-1000-succinate and copovidone. Methods: In this study, solid ternary phase diagram was applied in order to check the homogeneity of tSD prepared by melting and solidifying with dry ice. The physicochemical properties of different formulations were determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and hot stage microscopy. Their solubility, dissolution, stability and bioavailability were also investigated. Results and discussion: The results demonstrated that tSD obtained from ternary phase diagram divided into homogeneous and non-homogeneous regions. In the homogenous region, the transparent characteristics of tSD was observed and considered as a glass solution, which have a higher MDP solubility than that in non-homogenous region. The hot stage microscopy, DSC and PXRD confirmed that solid dispersion was formed in which MDP was molecularly dispersed in the carriers, especially in the homogenous region of phase diagram. FTIR analysis demonstrated strong hydrogen bonding between amine groups of MDP and carbonyl groups of copovidone, which supported a higher solubility and dissolution of tSD. The pharmacokinetic study in Wistar rats showed that the tSD had the greatest effect on oral bioavailability. Immediate hypotensive effect of tSD was also observed in vivo. Conclusions: The improvement of stability, dissolution and oral bioavailability of MDP could be achieved by using tSD technique.

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 potential of using two natural polymers (chitosan and shellac) for the formation of nanoparticles by the process of ionic cross-linking to encapsulate bovine serum albumin, a model protein was investigated. Depending on the concentrations of chitosan, shellac and bovine serum albumin, three physical states - nanoparticle, aggregation, and solution could be observed as a result of the electrostatic force. The formation of nanoparticles was due to the balance between the repulsion force and attractive force while the imbalance between both forces resulted in the formation of aggregation and solution. The Fourier transform infrared spectroscopy and differential scanning calorimetry were applied to prove the nanoparticle formation. The particle size was characterized by the light scattering technique and was found in the range between 100 and 300 nm. The morphology of the particles, detected by transmission electron microscopy was spherical shape. The result showed that the zeta potential of the nanoparticles possessed positive charges. The concentrations of chitosan, shellac and bovine serum albumin had an influence on the physicochemical properties of the nanoparticles such as the particle size, the zeta potential, the encapsulation, the loading efficiencies and the cumulative release. Therefore, chitosan and shellac could be used to form nanoparticles for protein delivery by the ionic cross-linking method.

Purpose: To prepare and evaluate poly(methacrylic acid (MAA)-co-ethylene glycol dimethacrylate (EGD)) as a tablet disintegrant. Methods: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms at cross-linker (EGD) levels of 0.25 -16 % were synthesized and subjected to Fourier transform infrared spectroscopy. Swelling capacity, disintegration efficiency and cytotoxicity to Caco-2 cells were determined using standard procedures. Results: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms were successfully prepared. In contact with water, the polymers in Na form swelled more than those in H form. The swelling capacities of polymers in H and Na forms decreased with increasing amounts of cross-linker. Incorporation of the polymers accelerated the disintegration of microcrystalline cellulose tablets (placebo), and the disintegration efficiency depended on the salt form and amount of cross-linker. The Na salt form of the polymer crosslinked at 16 % EGD was the best candidate disintegrant. When used at 2.5 and 10 %, the selected polymer effectively promoted the disintegration and drug release of propranolol hydrochloride tablets. Moreover, cytotoxicity tests showed that it was non-toxic to Caco-2 cells. Conclusion: The developed poly(MAA-co-EGD) possesses good disintegration and dissolution functionalities. Thus, it may be adopted as a new super-disintegrant for fast-release tablets. Keywords: Tablet disintegrant, Methacrylic acid, Ethylene glycol dimethacrylate, Propranolol hydrochloride

Stability enhancement of protein-loaded chitosan microparticles under storage was investigated. Chitosan glutamate at 35 kDa and bovine serum albumin as model protein drug were used in this study. The chitosan microparticles were prepared by ionotropic gelation, and polyethylene glycol 200 (PEG 200) was applied after the formation of the particles. All chitosan microparticles were kept at 25°C for 28 days. A comparison was made between those preparations with PEG 200 and without PEG 200. The changes in the physicochemical properties of the microparticles such as size, zeta potential, pH, and percent loading capacity were investigated after 0, 3, 7, 14, and 28 days of storage. It was found that the stability decreased upon storage and the aggregation of microparticles could be observed for both preparations. The reduction in the zeta potential and the increase in the pH, size, and loading capacity were observed when they were kept at a longer period. The significant change of those preparations without PEG 200 was evident after 7 days of storage whereas those with PEG 200 underwent smaller changes with enhanced stability after 28 days of storage. Therefore, this investigation gave valuable information on the stability enhancement of the microparticles. Hence, enhanced stability of chitosan glutamate microparticles for the delivery of protein could be achieved by the application of PEG 200.

The objective of this study was to prepare and evaluate the pectin-based dosage form for buccal adhesion. Carbenoxolone sodium, which is used for the treatment of aphthous ulcers in oral cavity, was used as a model drug. The pectin buccal discs were prepared by direct compression. The water uptake and erosion of pectin disc increased progressively with the swelling time. The bioadhesion of dried pectin discs decreased when either the discs were hydrated or the buccal tissue was wet with a small volume of medium. The influencing factors such as pectin type, pectin to lactose ratio, and sweetener type on the formulations were investigated. The results demonstrated that buccal discs prepared from pectin with a high degree of esterification (DE) showed a weaker and more friable characteristic than that with low DE. Decreasing pectin to lactose ratio resulted in the high dissolution rate with low bioadhesive properties. Addition of sweetener in the formulations also affected the hardness, friability, and bioadhesive properties of the discs. The pectin discs containing sweetening agent showed a higher drug release than those without sweetener. The results suggested that pectin-based bioadhesive discs could be used to deliver carbenoxolone sodium in oral cavity.

Spray-dried chitosan acetate (CSA) and ethylcellulose (EC) were used as new compression coats for 5-aminosalicylic acid tablets. Constrained axial or radial swelling of pure CSA and EC/CSA tablets in 0.1 N HCl (stage I), Tris-HCl, pH 6.8 (stage II), and acetate buffer, pH 5.0 (stage III), was investigated. Factors affecting in vitro drug release, i.e., % weight ratios of coating polymers, dip speeds of dissolution apparatus or pH of medium or colonic enzyme (beta-glucosidase) in stage III, and use of a super disintegrant in core tablets, were evaluated. Swollen CSA gel dissolved at lower pH and became less soluble at higher pH. The mechanism of swelling was Fickian diffusion fitting well into both Higuchi's and Korsmeyer-Peppas models. EC:CSA, at 87.5:12.5% weight ratio, provided lag time rendering the tablets to reach stage III (simulated colonic fluid of patients), and the drug was released over 90% within 12 h. The system was a dual time- and pH-control due to the insolubility of EC suppressing water diffusion and the swelling of CSA in the stages I and II. The erosion of CSA gel in the stage III induced the disintegration of the coat resulting in rapid drug release. The lower dip speed and higher pH medium delayed the drug release, while a super disintegrant in the cores enhanced the drug release and no enzyme effect was observed.

The objective of this study was to improve the properties of shellac by composite salts formation. The shellac samples were prepared in various salt forms by dissolving them with 2-amino-2-methyl-1-propanol (AMP) and ammonium hydroxide (AMN) at various ratios of AMP:AMN. The results demonstrated that aqueous solubility of the shellac salts was improved as the ratio of AMP:AMN increased. The absorbance ratio of the FTIR peaks assigned to CO stretching of carboxylate and carboxylic acid (ABS1556/ABS1716) was increased with the increase of the AMP fraction, suggesting that the solubility enhancement was due to more ionization of AMP salts. Moisture adsorption studies indicated that shellac salts were more hygroscopic as AMP content increased. After storage at 40 degrees C, 75% RH, the acid value and insoluble solid of AMP salts were relatively constant even after storage of up to 180 days, suggesting that AMP should protect polymerization. The ABS1556/ABS1716 values of the shellac salts were rapidly decreased after storage, especially for those consisting of a high percentage of AMN. Thus, AMP should bind much tighter at the carboxylate binding site as compared with AMN, resulting in more solubility and stability. In conclusion, optimized shellac properties could be easily accomplished by composite salts formation.

The objective of this study was to investigate the potential of chitosan salts as a carrier in the preparation of protein-loaded nanoparticles. Glutamic and aspartic acids were used to prepare chitosan salts of 35, 100, and 800 KDa. Nanoparticles of chitosan base, chitosan glutamate, and chitosan aspartate were produced by ionotropic gelation with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model protein at loading concentrations ranging from 0.2 to 2 mg/mL. The size of the nanoparticles, as measured by photon correlation spectroscopy, was in the range of 195 to 3450 nm, depending on type and molecular weight of chitosan. Nanoparticles prepared with higher molecular weight chitosan showed larger sizes. The encapsulation was controlled by the competition of BSA in forming ionic cross-linking with chitosan and by the entrapment of BSA during the gelation process. Higher BSA encapsulation efficiency (EE) was obtained for nanoparticles prepared with chitosan salts compared to those prepared with the base. The higher EE was a result of a higher degree of ionization, causing more active sites to interact with BSA. In addition, a higher and faster release of BSA from the nanoparticles into pH 7.4 buffer medium was observed for nanoparticles of the chitosan salts than was observed for nanoparticles of the chitosan base. The higher and faster release was attributed to higher EE and lower entrapment of BSA within the matrix of the nanoparticle during the gelation process. The influence of molecular weight on the property of nanoparticles exhibited different effects. The difference was a result of different organic acids used to prepare nanoparticles leading to the difference in polymer conformation and viscosity of organic acid solution. Therefore, this study showed that the characteristics of chitosan nanoparticles loaded with a protein drug could be readily modulated by changing the salt form or the molecular weight of the chitosan carrier.

The objective of this study was to investigate the effect of alkali treatment on properties of shellac. The native shellac was treated with sodium hydroxide for 15, 30, and 60 min to obtain hydrolyzed shellac. All types of shellac, namely native and hydrolyzed shellac at various times of treatment, were then prepared in films as free acid and ammonium salt forms by using ethanol and ammonium hydroxide solution, respectively. The results showed that alkali treatment caused an increase in acid value and a decrease in ester value. This is due to higher free carboxylic and hydroxyl groups caused by ester bond breaking. The longer the alkali treatment the higher impact of bond breaking, therefore, causing an increase in acid value, solubility at pH 7, strain, a decrease in ester value, water vapor permeability coefficient, and stress. The films were then kept at 40 degrees C, 75% RH for a period of three months. The aging effect led to an esterification of free carboxylic and hydroxyl groups, resulting in the significant change of acid value, ester value, and insoluble solid for both native and hydrolyzed shellac films in acid form. On the other hand, all types of shellac films in ammonium salt form exhibited a reasonable stability in physicochemical and mechanical properties as all films were protected from the esterification due to the formation of ammonium salt at the carboxylic binding site. It could be concluded that alkali treatment could produce hydrolyzed shellac with higher solubility in the intestine, the stability was yet in dilemma unless the shellac was in an ammonium salt form. The result obtained could, thus, provide a guideline in the use of shellac.

The shellac was modified by partial hydrolysis with 2.0% (w/w) NaOH for different times. The hydrolysed shellac was then evaluated for physicochemical and film properties in comparison with native shellac. The tablets coated with native and hydrolysed shellac were also evaluated. The results demonstrated that acid value (AV) of shellac increased with prolongation of hydrolysis time. The solubility of shellac in buffer solution (pH < or = 7) gradually increased with increasing hydrolysis time. The films prepared from hydrolysed shellac were more flexible and soft than those prepared from native shellac. The increasing of flexibility was correlated with the increasing of soft resin in shellac. The water vapor permeability of hydrolysed shellac film was lower than that of native shellac film. The higher acid permeability of the tablet coated with hydrolysed shellac was observed. In ethanol-based film coating, shellac had lower solubility and thus lower drug dissolution from coated tablets was observed. In ammonia-based film coating, the solubility of shellac was improved higher nearby pH 7.0 by an ammonium neutralisation method because of forming well-soluble salts, thereby higher drug dissolution was obtained. Partial hydrolysis provided modified shellac, which is more effective for ammonium salt formation, thus very higher drug dissolution was achieved in the ammonia-based coated tablets.

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.

The production of pharmaceutical nanoparticles by the spinning disk processing (SDP) technique has advantages in terms of its scalability and its capacity to produce readily tunable nanoparticles of narrow size distribution. In this study, we successfully developed a novel multiple stepwise SDP technique to develop aggregates of uniformly sized poly(methyl acrylates)-coated chitosan–diclofenac sodium nanocores (CS–PMA NPs) for colonic drug delivery. The processing conditions were optimized using the Box–Behnken design. SEM and TEM micrographs showed the optimized system to consist of 10 μm-sized agglomerates of CS–PMA NPs, the latter measuring 10 nm in diameter. High drug entrapment of 88% was attained. Potential colon-targeted drug release from the CS–PMA NPs was demonstrated, with retardation of drug release in simulated gastrointestinal fluids and over 90% of the drug load released into simulated colonic fluid within 8 h. Drug uptake from CS–PMA NPs into Caco-2 cells was threefold higher than that from a control drug solution, with no apparent cytotoxicity observed at the NP doses administered. The collective data suggest that the SDP is a robust manufacturing method that can potentially be used to scale up the production of composite nanoparticulate colon-targeted drug delivery systems.

Magnetic resonance imaging (MRI) was used to assess in situ swelling behaviors of spray-dried chitosan acetate (CSA) in 0.1 N HCl, pH 6.8 and pH 5.0 Tris–HCl buffers. The in vitro drug releases from CSA matrix tablets containing the model drugs, diclofenac sodium and theophylline were investigated in all media using USP-4 apparatus. The effect of chitosan molecular weight, especially in pH 6.8 Tris–HCl, was also studied. In 0.1 N HCl, the drug release from the matrix tablets was the lowest in relation to the highest swelling of CSA. The swelling kinetics in Tris–HCl buffers are Fickian diffusion according to their best fit to Higuchi’s model as well as the drug release kinetics in all the media. The high swelling rate ( k s ′ ) was found to delay the drug release rate (k′). The linear relationship between the swelling and fractions of drug release in Tris–HCl buffers was observed, indicating an important role of the swelling on controlling the drug release mechanism. Additionally, CSA of 200 and 800 kDa chitosan did not swell in pH 6.8 Tris–HCl but disintegrated into fractions, and the drug release from the matrix tablets was the highest.

The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin–olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.

The aim of this study was to improve enteric properties of shellac by the formation of succinate derivative through dry media reaction. Shellac and succinic anhydride were mixed and then co-ground by planetary ball mill. The ground mixture was then activated by heating for various times and washed for removal of excess succinic anhydride. The ground mixtures and the heat-activated mixtures were characterized by physical and chemical tests, including acid value, FTIR spectroscopy, (1)H NMR and (13)C NMR spectroscopy, thermal analysis and film properties. The results demonstrated that acid values of heat-activated shellac mixtures increased with the increase of annealing time, suggesting the presence of carboxylic acid moieties of succinate at shellac molecules. The results were in good agreement with the DSC thermograms. The melting peak of shellac disappeared after heating, while melting peak of succinic anhydride gradually decreased, suggesting the utilization of succinic anhydride for the esterification. The shellac succinate formation was also confirmed by (1)H NMR and (13)C NMR spectroscopies. Film prepared from shellac succinate showed improved solubility, especially at the pH of small intestine (5.8-6.7), as compared to native shellac. The shellac succinate film also demonstrated better mechanical property, in terms of increased flexibility. In conclusion, solid-state formation of shellac succinate ester, which had improved enteric properties, was easily accomplished under the concept of "green approach".

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1 N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

A multiple-unit floating drug delivery system based on gas formation technique was developed in order to prolong the gastric residence time and to increase the overall bioavailability of the dosage form. The system consists of the drug-containing core pellets prepared by extrusion-spheronization processes, which are coated with double layers of an inner effervescent layer (sodium bicarbonate) and an outer gas-entrapped polymeric membrane of an aqueous colloidal polymer dispersion (Eudragit) RL 30D, RS 30D, NE 30D). Only the system using Eudragit RL 30D as a gas-entrapped polymeric membrane could float. The time to float decreased as amount of the effervescent agent increased and coating level of gas-entrapped polymeric membrane decreased. The optimum system could float completely within 3min and maintained the buoyancy over a period of 24h. The drug release was sustained and linear with the square root of time. Increasing coating level of gas-entrapped polymeric membrane decreased the drug release. Both the rapid floating and the sustained release properties were achieved in the multiple-unit floating drug delivery system developed in this present study.

A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 microm in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solid-state (13)C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 degrees C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.

Eleven heavy metals in various products of Moringa oleifera were analyzed to determine eleven heavy metals (Al, As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, and Zn) using Inductively Coupled Plasma-Mass Spectrometry. The products of M. oleifera were purchased in Nakhon Pathom, Thailand. All products were digested with nitric acid solution before determining the concentrations of heavy metals. The recoveries of all heavy metals were found to be in the range of 99.89-103.05%. Several criteria such as linearity, limits of detection, limits of quantification, specificity, precision under repeatability conditions and intermediate precision reproducibility were evaluated. Results indicate that this method could be used in the laboratory for determination of eleven heavy metals in M. oleifera products with acceptable analytical performance. The results of analysis showed that the highest concentrations of As, Cr, Hg, and Mn were found in tea leaves while the highest concentrations of Al, Cd, Cu, Fe, Ni, Pb, and Zn were found in leaf capsules. Continuous monitoring of heavy metals in M. oleifera products is crucial for consumer health.