Orthodontic pain with fixed appliances and clear aligners: A 6-month comparison.

INTRODUCTION: This prospective study compared pain perception, intensity, and analgesic use among patients treated with fixed appliances (FAs) and clear aligners (CAs) over 6 months. METHODS: Digital surveys were collected from 87 adult patients treated with CA or FA from 2 orthodontic offices. The 7-item survey was sent at 3-time points (preappointment, 2-day postappointment, and 7-day postappointment) for each appointment. Wilcoxon, t test, and Fisher exact chi-square tests were performed with significance set at 0.05. RESULTS: The FA group had a higher rate and intensity of pain 2 days after the second, third, and fifth appointments (P <0.030). At 7 days postappointment, the FA group had a higher rate and intensity of pain for the first and fifth appointments. Dull pain was reported the most in both groups, with a proportion of FA patients reporting throbbing (31%) or sharp (20%) pain (P = 0.035) at 2 days postappointment. The CA group reported the most pain at rest, whereas the FA group reported chewing as the most painful (P = 0.002). The FA group had a higher rate of analgesic consumption after the first appointment (P = 0.037). CONCLUSIONS: Both the FA and CA groups experienced similar rates and intensities of pain 2 days after the delivery of appliances at the first appointment. Although CA pain intensity remained minimal, FA pain peaked 2 days postappointment whenever a new orthodontic stimulus was introduced and remained elevated 7 days postappointment when that stimulus was a new archwire material.

Design, synthesis and evaluation the bioactivities of novel 1,3-dimethyl-6-amino-1H-indazole derivatives as anticancer agents.

Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site. We further examined their anticancer activity on hypopharyngeal carcinoma cells (FaDu), squamous cell carcinoma of the oral tongue (YD-15), breast cancer cells (MCF7), and human dental pulp stem cells (HDPSC). Of them, compound N-(4-bromobenzyl)-1,3-dimethyl-1H-indazol-6-amine (7) remarkably suppressed IDO1 expression in a concentration - dependent manner. In addition, 7 was the most potential anticancer compound with inducing apoptosis activity as well as selectively activated extracellular signal-regulated kinases (ERK) in mitogen-activated protein kinase (MAPK) pathways on FaDu cells. Finally, compound 7 suppressed cell mobility in wound healing assay with the reduced expression of matrix metalloproteinase MMP9. Taken together, we believe that 7 is the most promising compound, which may be applied to treatment of hypopharyngeal carcinoma.

Cultural competence of Australian dental students.

BACKGROUND: Australia possesses a highly multicultural demographic, and thus dental practitioners are likely to regularly encounter culturally and linguistically diverse individuals. It is important for dental practitioners to be culturally competent, however, cultural competency education is highly variable in the curricula of dentistry and oral health courses in Australia, and research is largely limited to dentistry students. This study aims to investigate and compare perceived attitudes, beliefs and practices of cultural competence amongst first and final year Doctor of Dental Surgery (DDS) and Bachelor of Oral Health (BOH) students at the University of Melbourne Dental School. METHODS: Following ethics approval, anonymous questionnaires were completed by 213 participants. The questionnaire was adapted from Schwarz's Healthcare Provider Cultural Competence Instrument and consisted of five scales. Data was analysed using SPSS V 24.0 software. RESULTS: A total of 213 students participated in this study (response rate = 88%) The majority of participants were female (n = 114, 53.5%) and the mean age of 23.5 years (range 18-40). The majority of participants were Australian born (n = 110) with 74.6% (n = 159) first generation Australians. Participants who identified as Australian represented 35.7% (n = 76) with 66.1% (n = 141) identified as partly Australian. Multivariate analysis indicated that, after controlling for other independent variables in the model, those who had the highest cultural competence score were female, who self-identify as "Australian", who were in the final year. Furthermore, those who were in the final BOH year scored significatively higher than final year DDS students. CONCLUSION: The findings of this study suggest that there is a significant difference in students self-reported cultural competence at different stages of their education. This may be attributed to differences in cultural competence education, scope of practice and the type of patient encounters and role modelling that students may experience. Future research should involve follow up to create longitudinal data, as well as research at other dental schools in Australia and overseas.

Formulation of solid dispersion to improve dissolution and oral bioavailability of poorly soluble dexibuprofen.

Dexibuprofen (DEXI) belongs to BCS class II drug with poor aqueous solubility resulting in poor bioavailability. To enhance solubility and bioavailability of DEXI, DEXI-loaded solid dispersion (SD) was formulated. DEXI-SDs were prepared by melting method and solvent evaporation method. Amphipathic polymer poloxamer 407 (pol 407) was selected based on solubility and dissolution tests. The ratio of DEXI:pol 407 was optimized as 1:2. The physicochemical properties, dissolution, and oral bioavailability of SD3 and SD6 were evaluated to compare preparation methods. The dissolution rate of DEXI from SD formulations was higher at pH 6.8 and pH 7.2 than at pH 1.2. Following oral administration in rats, the Cmax and AUClast of SD3 and SD6 formulations were significantly higher compared with raw DEXI. In addition, the SD6 formulation showed increased Cmax and AUClast by 1.34- and 1.33-fold, compared with those of SD3 formulation, respectively. These results demonstrated that SD formulation has excellent potential as a formulation for poorly soluble drug DEXI.

Development of film-forming gel containing nanoparticles for transdermal drug delivery.

Despite several studies on film-forming systems with the advantages of both the film and the hydrogel, there are still no effective systems for fast film formation with a high level of control over permeability. In this study, a film-forming system for the delivery of nanomedicine, termed a film-forming nanogel (FFN), was produced and investigated for the first time to meet this need. The objective of this research was to study a new generation of film-forming hydrogels (FFHs) loaded with curcumin nanoparticles (CUR-GNPs) for transdermal applications. FFHs were prepared by employing zein and HPMC 4000 as film-forming polymers. Meanwhile, CUR-GNPs were obtained by sonoprecipitation. The film-forming time, particle characteristics and FFN drug release profile were assessed. The optimized FFH had a smooth surface and a fast drying time of 6 min and 4.5 min in vitro and ex vivo, respectively. Additionally, high, sustained drug permeation from the FFN was observed after 24 h. The FFH containing CUR-GNPs showed potential for application in transdermal drug delivery with a fast film-forming time, uniform particle dispersion and high, sustained drug permeation.

Development of a Sustained Release Solid Dispersion Using Swellable Polymer by Melting Method.

PURPOSE: This study is to design a sustained release solid dispersion using swellable polymer by melting method. METHODS: Polyethylene glycol 6000 (PEG 6000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were used in solid dispersion for not only enhancing drug dissolution rate but also sustaining drug release. HPMC 4000 is a common swellable polymer in matrix sustained release dosage form, but could not be used in preparation of solid dispersion by melting method. However, the current study utilized the swelling capability of HPMC 4000 accompanied by the common carrier PEG 6000 in solid dispersion to accomplish the goal. RESULTS: While PEG 6000 acted as a releasing stimulant carrier and provided an environment to facilitate the swelling of HPMC 4000, this swellable polymer could act as a rate-controlling agent. This greatly assisted the dissolution enhancement by changing the crystalline structure of drug to more amorphous form and creating a molecular interaction. CONCLUSIONS: These results suggested that this useful technique can be applied in designing a sustained release solid dispersion with many advantages.

Impact of aluminum chloride on process performance and microbial community structure of granular sludge in an upflow anaerobic sludge blanket reactor for natural rubber processing wastewater treatment.

In this study, granular sludge formation was carried out using an aluminum chloride supplement in an upflow anaerobic sludge blanket (UASB) reactor treating natural rubber processing wastewater. Results show that during the first 75 days after the start-up of the UASB reactor with an organic loading rate (OLR) of 2.65 kg-COD·m(-3)·day(-1), it performed stably with a removal of 90% of the total chemical oxygen demand (COD) and sludge still remained in small dispersed flocs. However, after aluminum chloride was added at a concentration of 300 mg·L(-1) and the OLR range was increased up to 5.32 kg-COD·m(-3)·day(-1), the total COD removal efficiency rose to 96.5 ± 2.6%, with a methane recovery rate of 84.9 ± 13.4%, and the flocs began to form granules. Massively parallel 16S rRNA gene sequencing of the sludge retained in the UASB reactor showed that total sequence reads of Methanosaeta sp. and Methanosarcina sp., reported to be the key organisms for granulation, increased after 311 days of operation. This indicates that the microbial community structure of the retained sludge in the UASB reactor at the end of the experiment gave a good account of itself in not only COD removal, but also granule formation.

Effects of Bone Vibrator Position on Auditory Spatial Perception Tasks.

OBJECTIVE: This study assessed listeners' ability to localize spatially differentiated virtual audio signals delivered by bone conduction (BC) vibrators and circumaural air conduction (AC) headphones. BACKGROUND: Although the skull offers little intracranial sound wave attenuation, previous studies have demonstrated listeners' ability to localize auditory signals delivered by a pair of BC vibrators coupled to the mandibular condyle bones. The current study extended this research to other BC vibrator locations on the skull. METHOD: Each participant listened to virtual audio signals originating from 16 different horizontal locations using circumaural headphones or BC vibrators placed in front of, above, or behind the listener's ears. The listener's task was to indicate the signal's perceived direction of origin. RESULTS: Localization accuracy with the BC front and BC top positions was comparable to that with the headphones, but responses for the BC back position were less accurate than both the headphones and BC front position. CONCLUSION: This study supports the conclusion of previous studies that listeners can localize virtual 3D signals equally well using AC and BC transducers. Based on these results, it is apparent that BC devices could be substituted for AC headphones with little to no localization performance degradation. APPLICATION: BC headphones can be used when spatial auditory information needs to be delivered without occluding the ears. Although vibrator placement in front of the ears appears optimal from the localization standpoint, the top or back position may be acceptable from an operational standpoint or if the BC system is integrated into headgear.

Polymer conjugate-based nanomaterials for drug delivery.

The structure of polymeric amphiphiles with both hydrophilic and hydrophobic groups forming self-assembled nanoparticles have attracted increasing attention in studies of delivery systems of therapeutic agents. An amphiphilic carrier for self-assembly in an aqueous solution is preferable because of its structure with a hydrophobic core and hydrophilic outer shell, which can be applied to many biotechnological and pharmaceutical fields with numerous types of drugs. An amphiphilic carrier for self-assembly also represents the most appealing delivery system owing to its exceptional advantages in selectively delivering drugs to tumor cells and thus, reduction of side effects. This paper reviews two types of self-assembled nanoparticles/micelles of conjugated polymeric amphiphiles: (1) self-assembled micelles/nanoparticles of amphiphilic conjugates followed by drug loading and (2) self-assembled micelles/nanoparticles of polymer-drug conjugates where a conjugation reaction occurs between the polymer and drug. The development of the research has been addressed in this review with up-to-date references. In conclusion, the challenges and remaining difficulties for the future development are discussed.

Bioresorbable Multilayer Organic-Inorganic Films for Bioelectronic Systems.

Bioresorbable electronic devices as temporary biomedical implants represent an emerging class of technology relevant to a range of patient conditions currently addressed with technologies that require surgical explantation after a desired period of use. Obtaining reliable performance and favorable degradation behavior demands materials that can serve as biofluid barriers in encapsulating structures that avoid premature degradation of active electronic components. Here, this work presents a materials design that addresses this need, with properties in water impermeability, mechanical flexibility, and processability that are superior to alternatives. The approach uses multilayer assemblies of alternating films of polyanhydride and silicon oxynitride formed by spin-coating and plasma-enhanced chemical vapor deposition , respectively. Experimental and theoretical studies investigate the effects of material composition and multilayer structure on water barrier performance, water distribution, and degradation behavior. Demonstrations with inductor-capacitor circuits, wireless power transfer systems, and wireless optoelectronic devices illustrate the performance of this materials system as a bioresorbable encapsulating structure.

Sialic acid-decorated liposomes enhance the anti-cancer efficacy of docetaxel in tumor-associated macrophages.

Tumor-associated macrophages (TAMs) in the tumor microenvironment potentially enhance tumor growth and invasion through various mechanisms and are thus an essential factor in tumor immunity. The highly expressed siglec-1 receptors on the surfaces of TAMs are potential targets for cancer drug delivery systems. Sialic acid (SA) is a specific ligand for siglec-1. In this study, the sialic acid-polyethylene glycol conjugate (DSPE-PEG2000-SA) was synthesized to modify the surface of liposomes and target TAMs by interacting with the siglec-1 receptor. Three docetaxel (DTX)-loaded liposomes, conventional (DTX-CL), DSPE-PEG2000-coated (DTX-PL), and DSPE-PEG2000-SA-coated (DTX-SAPL) liposomes, were prepared, with a particle size of <100 nm, uniform polydispersity index (PDI) values, negative zeta potential, and % encapsulation efficiency (EE) exceeding 95 %. Liposomes showed high stability after 3 months of storage at 4 °C without significant changes in particle size, PDI, zeta potential, or % EE. DTX was released from liposomes according to the Weibull model, and DTX-SAPL exhibited more rapid drug release than other liposomes. In vitro studies demonstrated that DTX-SAPL liposome exhibited a higher uptake and cytotoxicity on RAW 264.7 cells (TAM model) and lower toxicity on NIH3T3 cells (normal cell model) than other formulations. The high cell uptake ability was demonstrated by the role of the SA-SA receptor. Biodistribution studies indicated a high tumor accumulation of surface-modified liposomal formulations, particularly SA-modified liposomes, showing high signal accumulation at the tumor periphery, where TAMs were highly concentrated. Ex vivo imaging showed a significantly higher accumulation of SA-modified liposomes in the tumor, kidney, and heart than conventional liposomes. In the anti-cancer efficacy study, DTX-SAPL liposomes showed effective inhibition of tumor growth and relatively low systemic toxicity, as evidenced by the tumor volume, tumor weight, body weight values, and histopathological analysis. Therefore, DSPE-PEG2000-SA-coated liposomes could be promising carriers for DTX delivery targeting TAMs in cancer therapy.

Magnetic resonance imaging of pancreatic islets using tissue-adhesive particles containing iron oxide nanoparticles.

Post-transplantation tracking of pancreatic islets is a prerequisite for advancing cell therapy to treat type 1 diabetes. Magnetic resonance imaging (MRI) has emerged as a safe and non-invasive technique for visualizing cells in clinical applications. In this study, we proposed a novel MRI contrast agent formulation by encapsulating iron oxide nanoparticles (IONPs) in poly(lactic-co-glycolic acid) (PLGA) particles functionalized with a tissue adhesive polydopamine (PD) layer (IONP-PLGA-PD MS). Intriguingly, our particles facilitated efficient and robust labeling through a one-step process, allowing for the incorporation of a substantial amount of IONPs without detrimental impacts on the viability and functionality of pancreatic islets. The MRI signals emanating from islets labeled using our particles were found to be stable over 30 days in vitro and 60 days when transplanted under kidney capsules of diabetic mice. These results suggest that our approach provides a potential platform for monitoring the fate of pancreatic islets after transplantation.

Recent Approaches in the Catalytic Transformation of Biomass-Derived 5-Hydroxymethylfurfural into 2,5-Diformylfuran.

The conversion of biomass into a great variety of valuable chemicals, polymers, and fuels gives a sustainable alternative for the insufficiency of non-renewable fossil fuel resources and reduces environmental pollution. 5-Hydroxymethylfurfural (HMF), converted from sustainable carbohydrates, is a significant building block chemical, and the selective oxidation of HMF into 2,5-diformylfuran (DFF) presents an ongoing challenge. DFF is a versatile platform molecule derived from biomass and has promising application in pharmaceuticals and polymers. This Review provides an overview of the latest developments of efficient catalytic systems for the sustainable conversion of HMF to DFF.

Development and characterisation of hybrid composite skin simulants based on short polyethylene fibre and bioactive glass particle-reinforced silicone.

Silicone elastomers are widely recognised as artificial skins for medical prosthesis and cranial injury assessment. Since silicone is not an ideal skin simulant due to the lack of mechanical stiffness and a fibrous structure, the present study aimed to tailor the mechanical and structural characteristics of silicone by integrating biocompatible reinforcements (namely, short polyethylene fibres and bioglass particles) to develop suitable bio-integrative skin simulant candidates. The influences of short polyethylene fibres and bioglass particles in the selected platinum silicone on the mechanical properties of silicone-based composite skin simulants were investigated with various factors, including filler concentration, KMnO4 surface treatment of the polyethylene fibre, and particle size. A comprehensive assessment of the tensile, compressive, and hardness properties of the examined composites was conducted, and they were compared with the properties of human biological skin. The results exhibited that the elastic moduli and the hardness of all composites increased with the concentration of both reinforcements. While integrating only the bioglass particles had the advantage of an insignificant effect on the hardness change of the silicone matrix, the composite with polyethylene fibres possessed superior tensile elastic modulus and tensile strength compared to those of the bioglass reinforced composite. The composites with 5% untreated polyethylene fibres, KMnO4 surface-treated fibres, and bioglass reinforcements enhanced the tensile elastic moduli from the pure silicone up to 32%, 44%, and 22%, respectively. It reflected that the surface treatment of the fibres promotes better interfacial adhesion between the silicone matrix and the fibres. Moreover, the smaller bioglass particle had a greater mechanical contribution than the larger glass particle. Systematically characterised for the first time, the developed composite skin simulants demonstrated essential mechanical properties within the range of the human skin and constituted better skin alternatives than pure silicone for various biomedical applications.

Automated segmentation of head CT scans for computer-assisted craniomaxillofacial surgery applying a hierarchical patch-based stack of convolutional neural networks.

PURPOSE: Computer-assisted techniques play an important role in craniomaxillofacial surgery. As segmentation of three-dimensional medical imaging represents a cornerstone for these procedures, the present study was aiming at investigating a deep learning approach for automated segmentation of head CT scans. METHODS: The deep learning approach of this study was based on the patchwork toolbox, using a multiscale stack of 3D convolutional neural networks. The images were split into nested patches using a fixed 3D matrix size with decreasing physical size in a pyramid format of four scale depths. Manual segmentation of 18 craniomaxillofacial structures was performed in 20 CT scans, of which 15 were used for the training of the deep learning network and five were used for validation of the results of automated segmentation. Segmentation accuracy was evaluated by Dice similarity coefficient (DSC), surface DSC, 95% Hausdorff distance (95HD) and average symmetric surface distance (ASSD). RESULTS: Mean for DSC was 0.81 ± 0.13 (range: 0.61 [mental foramen] - 0.98 [mandible]). Mean Surface DSC was 0.94 ± 0.06 (range: 0.87 [mental foramen] - 0.99 [mandible]), with values > 0.9 for all structures but the mental foramen. Mean 95HD was 1.93 ± 2.05 mm (range: 1.00 [mandible] - 4.12 mm [maxillary sinus]) and for ASSD, a mean of 0.42 ± 0.44 mm (range: 0.09 [mandible] - 1.19 mm [mental foramen]) was found, with values < 1 mm for all structures but the mental foramen. CONCLUSION: In this study, high accuracy of automated segmentation of a variety of craniomaxillofacial structures could be demonstrated, suggesting this approach to be suitable for the incorporation into a computer-assisted craniomaxillofacial surgery workflow. The small amount of training data required and the flexibility of an open source-based network architecture enable a broad variety of clinical and research applications.

Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets.

Pancreatic islet transplantation holds great potential as a curative therapy for treating type 1 diabetes. However, the need for lifelong systemic immunosuppression with inevitable side effects is an obstacle to clinical success. Here we devised a strategy for the site-specific delivery of an immunosuppressant (tacrolimus) using layer-by-layer assembly of polymeric particles and collagen on the islet surface. This approach aims to provide a continuous and sustained supply of tacrolimus in the vicinity of transplanted cells while avoiding systemic drug exposure. The dose and release rate of tacrolimus can be tunable to achieve therapeutic windows by varying layer-by-layer construction and chemistry of polymers. Transplanting 400 IEQ of pancreatic islets coated with particles containing ∼3 µg of TAC per recipient provided controlled drug release and rectified diabetes for up to 5 months in a xenogeneic rodent model of type 1 diabetes. We anticipate that the findings of this study will be found useful by those developing local immunomodulation strategies aimed at improving the outcomes and safety of cell therapies for curing type 1 diabetes.

Release Kinetics of Hydroxypropyl Methylcellulose Governing Drug Release and Hydrodynamic Changes of Matrix Tablet.

BACKGROUND: Hydrophilic Hydroxypropyl Methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet. METHODS: Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-Nuclear Magnetic Resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive Near-Infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process. RESULTS: High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC. CONCLUSION: The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release- modulating mechanism in the hydrophilic matrix system.

Dissolution-enhancing mechanism of alkalizers in poloxamer-based solid dispersions and physical mixtures containing poorly water-soluble valsartan.

The purpose of this study was to investigate the effects of alkalizers in dissolution rate and crystal structure of valsartan (VAL) in Poloxamer 407 (POX)-based solid dispersions (SD). VAL, a poorly-water soluble drug was selected as a model drug because of its low solubility at low pH. The POX-based SDs containing alkalizers (Na2CO3, MgO, meglumine and arginine) were prepared by melting method. The dissolution tests were performed using the United States Pharmacopeia (USP) paddle II method in enzyme-free simulated gastric fluid (pH 1.2) for 2 h. Microenvironmental pH (pH(M)) was examined potentiometrically by using a surface pH electrode. Dissolution rate of SD incorporating Na2CO3 was drastically increased. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) data indicated that crystalline structure of VAL in SD was transformed to amorphous form by the addition of alkalizers but could not explain the differences in the dissolution rates. The molecular interaction between VAL and Na2CO3 was observed in the Fourier transform infrared spectroscopy (FT-IR) spectra by the shift of C=O band from 1732 to 1719 cm⁻¹ and the disappearance of carbonyl group at 1598 cm⁻¹. Furthermore, Na2CO3 efficiently modulated pH(M) by providing a favorable microenvironment for drug dissolution. A combination of SD method and use of alkalizer is a promising approach to modulate release rate of poorly water-soluble and ionizable drug with an aid of changes of drug crystallinity, molecular interaction and pH(M).

Design and mechanism of on-off pulsed drug release using nonenteric polymeric systems via pH modulation.

The aim was to design a pH-sensitive pulsatile drug delivery system that allows for an on-off pulsed release of a drug using polyacrylic acid (PAA) blended with ethyl cellulose (EC) in different ratios. PAA, a polyelectrolyte polymer, exhibits a highly coiled conformation at low pH but a highly extended structure at high pH. Fumaric acid, which is an internal acidifying agent, was incorporated into the hydroxypropyl methylcellulose-based core tablets to create an acidic microenvironmental pH (pH(M)). The concentration of fumaric acid inside the core tablet and the ratio of PAA/EC in the coating layer were very crucial in modulating drug release behaviors. When the fumaric acid was retained in the core tablet, it gave a more acidic pH(M), so that the PAA was kept in a highly coiled state in the coated film, which hindered drug release ("off" release pattern). Interestingly, the release profiles of the drug and fumaric acid from coated tablets showed the on-off pulsed pattern upon dissolution. Imaging analyses using scanning electron microscopy, near-infrared imaging, confocal laser scanning microscopy, and Fourier transform infrared spectroscopy confirmed this on-off release behavior of the drug and fumaric acid from coated tablets.

Fast-Dissolving Solid Dispersions for the Controlled Release of Poorly Watersoluble Drugs.

Solid dispersions offer many advantages for oral drug delivery of poorly water-soluble drugs over other systems, including an increase in drug solubility and drug dissolution. An improvement in drug absorption and the higher bioavailability of active pharmaceutical ingredients in the gastrointestinal tract have been reported in various studies. In certain circumstances, a rapid pharmacological effect is required for patients. Fastdissolving solid dispersions provide an ideal formulation in such cases. This report will provide an overview of current studies on fast-dissolving solid dispersions, including not only solid dispersion powders with fast dissolution rates but also specific dose form for the controlled release of poorly water-soluble drugs. Specifically, the applications of fast-dissolving solid dispersions will be described in every specific case. Moreover, pharmaceutical approaches and the utilization of polymers will be summarized. The classification and analysis of fastdissolving solid dispersions could provide insight into strategies and potential applications in future drug delivery developments.