Current Issue : January-March Volume : 2025 Issue Number : 1 Articles : 5 Articles
A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release....
Background/Objectives: Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. Methods: Dry amorphization using a twin-screw extruder is presented in this paper. A blend of mesoporous silica particles and crystalline itraconazole was processed using a pharma-grade laboratory scale twinscrew extruder. The influence of different screw configurations and process parameters was tested. Particle size and shape are compared in scanning electron microscopy (SEM) images. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are used to determine the residual amount of crystalline itraconazole in the final product. Results: An optimized screw configuration for the process was found which leads to more than 90% amorphous API when processed at room temperature. Full amorphization was reached at 70 ◦C. The specific mechanic energy (SME) introduced into the material during twin-screw processing is crucial for the dry amorphization. The higher the SME, the lower the residual amount of crystalline API. Two months after processing, however, recrystallization was observed by XRD. Conclusions: Dry processing using a twin-screw extruder is continuous, free of solvents and can be performed at low temperatures. This study proves the concept of twin-screw processing with mesoporous silica for dry amorphization of itraconazole....
Objective: The aim of this study was to analyze the effects of different particle sizes of Tetrastigma hemsleyanum Diels et Gilg (TDG) powders on physical properties, dissolution, in vitro antioxidant activity, and in vivo hepatoprotective properties. Methods: The particle size of TDG coarse powders (TDG-CP), TDG fine powders (TDG-FP), and TDG micro powders (TDG-MP) were measured by a laser particle size analyzer. The physical properties were measured according to the latest version of the Chinese Pharmacopoeia (Committee Chinese Pharmacopoeia 2020). The content of the total flavonoids, total polysaccharides, kaempferol-3-O-rutinoside, and rutin of TDG powders were determined using the NaNO2-Al (NO3)3 colorimetric method, the sulphate-phenol colorimetric method, and HPLC, respectively. In vitro dissolution and antioxidant activity were determined by the paddle method in phosphate buffer (pH 6.8) and the DPPH radical scavenging method, respectively. In addition, the liver tissue pathology was evaluated by hematoxylin and eosin staining (H&E), and the AST and ALT activities were measured by automatic biochemical analyzer. The superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities were measured by using commercial analysis kits. Results: As the particle size decreases, the fluidity of TDG powders decreased and the porosity increased. In addition, there were no significant differences in physical properties between low temperature pulverized powders and room temperature pulverized powders. The final dissolution rates of the four bioactive ingredients in TDG-MP were found to be 85.06%, 85.61%, 83.88%, and 83.26%, respectively, whereas in TDG-CP, the dissolution rates were significantly lower at 18.79%, 17.96%, 22.46%, and 24.35%. The EC50 values of TDG-CP, TDG-FP, and TDG-MP on DPPH scavenging activity were 0.82, 0.31, and 0.10 mg/mL, respectively. The AST and ALT activities of the TDG-FP group and the TDG-MP group were significantly decreased and the SOD, CAT, and GSH activities were significantly increased when compared with that of the model group. The inflammatory cell infiltration and vacuolar degeneration of liver cells in the TDG-FP group and the TDG-MP group were significantly improved. Conclusions: The particle size of TDG powders had a significant effect on the physical properties and in vivo bioactivity. TDG pulverized to a fine particle size or smaller is a promising approach for clinical applications with improved physicochemical and biological properties....
Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH2) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future....
Background/Objectives: This study assessed the effects of formulation components on the long-term stability of a previously described tetraethyl orthosilicate-based drug delivery system. Early stability studies of a product concept are crucial not only to provide information on the overall system stability and individual components’ contributions to it, but also to identify opportunities for dosage form optimization and to define its use case. Methods: We assessed the time-dependent thixogel properties—specifically, mechanical strength, thixotropy, release of model drug, and dry substance—in both real-time and accelerated shelf-life determination set-ups. Results: Our findings indicate that the concentration and molecular weight of hyaluronic acid, one of the main constituents of the investigated thixotropic systems, are key determinants of formulation stability. We further showed that changes in both of these parameters reflect on the drug release properties and stiffness of the formulation and could inform subsequent product development based on several use cases. Conclusions: Overall, this study provides an understanding of some key factors that would need to be considered prior to and in the final product development process of thixogels in preparation for commercialization....
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