Particle agglomeration of chitosan–magnesium aluminum silicate nanocomposites for direct compression tablets

Exfoliated nanocomposites of chitosan-magnesium aluminum silicate (CS-MAS) particles are characterized by good compressibility but poor flowability. Thus, the aims of this study were to investigate agglomerates of CS-MAS nanocomposites prepared using the agglomerating agents water, ethanol, or polyvinylpyrrolidone (PVP) for flowability enhancement and to evaluate the agglomerates obtained as direct compression fillers for tablets. The results showed that the addition of agglomerating agents did not affect crystallinity, but slightly influenced thermal behavior of the CS-MAS nanocomposites. The agglomerates prepared using water were larger than those prepared using 95% ethanol because high swelling of the layer of chitosonium acetate occurred, allowing formation of solid bridges and capillary force between particles, leading to higher flowability and particle strength. Incorporation of PVP resulted in larger agglomerates with good flowability and high strength due to the binder hardening mechanism. The tablets prepared from agglomerates using water showed lower hardness, shorter disintegration times and faster drug release than those using 95% ethanol. In contrast, greater hardness and more prolonged drug release were obtained from the tablets prepared from agglomerates using PVP. Additionally, the agglomerates of CS-MAS nanocomposites showed good carrying capacity and provided desirable characteristics of direct compression tablets.     

Investigation of novel alginate-magnesium aluminum silicate microcomposite films for modified-release tablets.

Physicochemical properties of sodium alginate-magnesium aluminum silicate (SA-MAS) composite films were investigated and a potential as a film former of SA-MAS dispersion for modifying drug release from tablets was evaluated as well. Interaction between SA and MAS in the composite films was revealed using FTIR spectroscopy. Thermal behavior of the composite films was changed due to the complexation of SA and MAS. Powder X-ray diffractometry data suggested that a higher crystallinity of the composite film and a phase-separated microcomposite were formed. The composite films in the ratios of 1:0.5 and 1:1 showed the increases of tensile strength and percentage of elongation when compared with SA films. Water vapor permeability of the composite films tended to increase with increasing ratio of MAS. The decreases in water uptake and drug permeability in 0.1 M HCl were found in the composite films. A positive charge drug, propranolol HCl, provided a higher affinity on the composite films than a weakly acidic nonelectrolyte, acetaminophen, resulting in a longer lag time and a higher partition coefficient depending on the content of MAS in the composite films. This was due to the complex formation of propranolol HCl and MAS. Using SEM, the tablets coated with SA-MAS dispersion had a smooth surface, while those with SA dispersion showed a pinholing on the surface, resulting in a faster drug release. The drug release profiles of the tablets could be modified by coating with the composite film at different coating levels. This finding suggests that MAS could improve physicochemical properties of the SA films, leading to a novel coating material of the SA-MAS dispersion for modifying drug release from tablets.     

Alginate-magnesium aluminum silicate composite films: effect of film thickness on physical characteristics and permeability

The different film thicknesses of the sodium alginate-magnesium aluminum silicate (SA-MAS) microcomposite films were prepared by varying volumes of the composite dispersion for casting. Effect of film thickness on thermal behavior, solid-state crystallinity, mechanical properties, water uptake and erosion, and water vapor and drug permeability of the microcomposite films were investigated. The film thickness caused a small change in thermal behavior of the films when tested using DSC and TGA. The crystallinity of the thin films seemed to increase when compared with the thick films. The thin films gave higher tensile strength than the thick films, whereas % elongation of the films was on the contrary resulted in the lower Young's modulus of the films when the film thickness was increased. This was due to the weaker of the film bulk, suggesting that the microscopic matrix structure of the thick films was looser than that of the thin films. Consequently, water uptake and erosion, water vapor permeation and drug diffusion coefficient of the thick films were higher than those of the thin films. The different types of drug on permeability of the films also showed that a positive charge and large molecule of drug, propranolol HCl, had higher lag time and lower diffusion coefficient that acetaminophen, a non-electrolyte and small molecule. This was because of a higher affinity of positive charge drug on MAS in the films. The findings suggest that the evaporation rate of solvent in different volumes of the composite dispersion used in the preparation method could affect crystallinity and strength of the film surface and film bulk of the microcomposite films. This led to a change in water vapor and drug permeability of the films.     

Quaternary polymethacrylate–sodium alginate films: effect of alginate block structures and use for sustained release tablets

The objectives in this study were to characterize quaternary polymethacrylate–sodium alginate (QPM–SA) films prepared using high G block or high M block SA (GSA or MSA, respectively), and to investigate the effects of QPM–SA ratios, film-coating levels and SA block structures on propranolol HCl (PPN) released from coated tablets. The results demonstrated that GSA and MSA shared a similar interaction mechanism with QPM. The QPM–GSA films had higher puncture strength than the QPM–MSA films in dry and wet states, whereas the % elongations were not different. The drug permeability of the QPM–GSA films was lower than that of the QPM–MSA films in both acidic and neutral media, but higher water uptake of the QPM–GSA films was found at neutral pH. Moreover, the QPM–MSA-coated tablets had a greater PPN release rate than the QPM–GSA-coated tablets, and drug release was dependent on the film-coating levels. In addition, the QPM–SA films at a ratio of 4:0.5 produced a stronger film and could sustain PPN release. These results indicate that the QPM–GSA films had greater film strength and lower drug permeability than the QPM–MSA films. Additionally, the QPM–SA films have a strong potential for use in sustained-release tablets.     

Tetrahedral DNA nanostructures as drug delivery and bioimaging platforms in cancer therapy

Structural DNA nanotechnology enables DNA to be used as nanomaterials for novel nanostructure construction with unprecedented functionalities. Artificial DNA nanostructures can be designed and generated with precisely controlled features, resulting in its utility in bionanotechnological and biomedical applications. A tetrahedral DNA nanostructure (TDN), the most popular DNA nanostructure, with high stability and simple synthesis procedure, is a promising candidate as nanocarriers in drug delivery and bioimaging platforms, particularly in precision medicine as well as diagnosis for cancer therapy. Recent evidence collectively indicated that TDN successfully enhanced cancer therapeutic efficiency both in vitro and in vivo. Here, we summarize the development of TDN and highlight various aspects of TDN applications in cancer therapy based on previous reports, including anticancer drug loading, photodynamic therapy, therapeutic oligonucleotides, bioimaging platforms, and other molecules and discuss a perspective in opportunities and challenges for future TDN‐based nanomedicine.     

Alginate-magnesium aluminum silicate films: importance of alginate block structures

Sodium alginate-magnesium aluminum silicate (SA-MAS) composite dispersions were prepared and characterized for the flow behavior and morphology of their dispersed phase before casting. The high G block and high M block SA (GSA and MSA, respectively) were used. The physicochemical properties and permeabilities of the films were investigated using non-electrolyte and amine compounds in an acidic medium. The results showed that incorporation of MAS into the GSA and MSA dispersions gave identical flow behaviors and morphologies of MAS flocculates. FTIR spectroscopy revealed that the GSA and MSA presented similar molecular interactions with MAS in the films. However, the crystallinity of the GSA-MAS films was possibly higher than that of the MSA-MAS films. This indicated a higher density of matrix structure formed between GSA and MAS, resulting in lower water uptake in an acidic medium. Consequently, the permeability of the GSA-MAS films was lower than that of the MSA-MAS films. The diffusion and partition coefficients were directly related to the molecular weight of the non-electrolyte and amine compounds. This study suggested that transport of non-electrolyte compounds was predominantly controlled by diffusion in aqueous-filled microchannels, whereas both partition via adsorption onto MAS and diffusion in microchannels occurred concurrently for amine compounds.     

Novel chitosan-magnesium aluminum silicate nanocomposite film coatings for modified-release tablets

To find out potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX in O/W emulsion and liposome selected as candidates of nanocarriers for PTX. Surface modification of these nanoparticles with polyethylene glycol (PEG) improved their in vivo behavior, but the effect of PEGylation on the pharmacokinetics of emulsion was not so remarkable and the release of PTX from emulsion was found to be very fast in blood circulation, indicating that emulsion would not be an adequate formulation for PTX. On the other hand, AUC of PEG liposome was 3.6 times higher than that of naked liposome after intravenous injection into normal rats due to the lower disposition into the reticuloendothelial system tissues such as liver and spleen. Since PEG liposome was able to stably encapsulate PTX in blood, AUC of PTX was also extensively enhanced after intravenous dosing of PTX-PEG liposome into normal rats. In the in vivo studies utilizing Colon-26 solid tumor-bearing mice, it was confirmed that PTX-PEG liposome delivered significantly larger amount of PTX to tumor tissue and provided more excellent anti-tumor effect than PTX-naked liposome. These results suggest that PEG liposome would serve as a potent PTX delivery vehicle for the future cancer chemotherapy.     

Optimization of minoxidil microemulsions using fractional factorial design approach

The objective of this study was to apply fractional factorial and multi-response optimization designs using desirability function approach for developing topical microemulsions. Minoxidil (MX) was used as a model drug. Limonene was used as an oil phase. Based on solubility, Tween 20 and caprylocaproyl polyoxyl-8 glycerides were selected as surfactants, propylene glycol and ethanol were selected as co-solvent in aqueous phase. Experiments were performed according to a two-level fractional factorial design to evaluate the effects of independent variables: Tween 20 concentration in surfactant system (X₁), surfactant concentration (X₂), ethanol concentration in co-solvent system (X₃), limonene concentration (X₄) on MX solubility (Y₁), permeation flux (Y₂), lag time (Y₃), deposition (Y₄) of MX microemulsions. It was found that Y₁ increased with increasing X₃ and decreasing X₂, X₄; whereas Y₂ increased with decreasing X₁, X₂ and increasing X₃. While Y₃ was not affected by these variables, Y₄ increased with decreasing X₁, X₂. Three regression equations were obtained and calculated for predicted values of responses Y₁, Y₂ and Y₄. The predicted values matched experimental values reasonably well with high determination coefficient. By using optimal desirability function, optimized microemulsion demonstrating the highest MX solubility, permeation flux and skin deposition was confirmed as low level of X₁, X₂ and X₄ but high level of X₃.     

Influence of magnesium aluminium silicate on rheological, release and permeation characteristics of diclofenac sodium aqueous gels in-vitro

The effect of magnesium aluminium silicate (MAS) on rheological, release and permeation characteristics of diclofenac sodium (DS) aqueous gels was investigated. DS aqueous gels were prepared using various gelling agents, such as 15% w/w poloxamer 407 (PM407), 1% w/w hydroxypropylmethylcellulose (HPMC), and 1% w/w high and low viscosity grades of sodium alginate (HV-SA and LV-SA, respectively). Different amounts of MAS (0.5, 1.0 and 1.5% w/w) were incorporated into the DS gels. Incorporation of MAS into the DS gels prepared using SA or PM407 caused a statistical increase in viscosity (P<0.05) and a shift from Newtonian flow to pseudoplastic flow with thixotropic property. The DS release rates of these composite gels were significantly decreased (P<0.05) when compared with the control gels. This was due to an interaction between MAS and PM407 or SA, and adsorption of DS onto MAS particles. Moreover, a longer lag time and no change in DS permeation flux were found when MAS was added to the gels. The findings suggest that the rheological characteristics of gels prepared using PM407 or SA could be improved by incorporating MAS. However, the use of MAS could retard the DS release and extend the lag time of DS permeation.