Direct Compression Research Articles

Orientation of inertialess spheroidal particles in turbulent channel flow with spanwise rotation

The orientation dynamics of inertialess prolate and oblate spheroidal particles in a directly simulated spanwise-rotating turbulent channel flow has been investigated by means of an Eulerian–Lagrangian point-particle approach. The channel rotation and the particle shape were parameterized using a rotation number Ro and the aspect ratio λ, respectively. Eleven particle shapes 0.05 ≤ λ ≤ 20 and four rotation rates 0 ≤ Ro ≤ 10 have been examined. The spheroidal particles retained their almost isotropic orientation in the core region of the channel, despite the significant mean shear rate set up by the Coriolis force. Irrespective of channel rotation rate Ro, rod-like spheroids tend to align in the streamwise direction, while disk-like particles are oriented in the wall-normal direction. These trends were accentuated with increasing departure from sphericity λ = 1. The changeover from the isotropic orientation mode in the centre to the highly anisotropic near-wall orientation mode commenced further away from the suction-side wall with increasing Ro, whereas the particle orientations on the pressure side of the rotating channel remained essentially unaffected by Ro. We observed that the alignments of the fluid rotation vector with the Lagrangian stretching direction were similarly unaffected by the imposed system rotation, except that the de-alignment set in deeper into the core at high Ro. This contrasts with the well-known substantial impact of system rotation on the velocity and vorticity fields. Similarly, slender rods and flatter disks were aligned with the Lagrangian stretching and compression directions, respectively, for all Ro considered, except in the vicinity of the walls. The typical near-wall de-alignment extended considerably further away from the suction-side wall at high Ro. We conjecture that this phenomenon reflects a change in the relative importance of mean shear and small-scale turbulence caused by the Coriolis force. Preferential particle alignment with Lagrangian stretching and compression directions are known from isotropic and anisotropic turbulence in inertial reference systems. The present results demonstrate the validity of this principle also in a non-inertial system.

Development and characterisation of orally disintegrating flurbiprofen tablets using SeDeM-ODT tool.

In this study, SeDeM-ODT parametric tests were performed to determine the use of ludipress as a directly compressible tableting excipient for the development of a flurbiprofen orally disintegrating tablet. The preformulation features of different formulations (F1 -F9) were analyzed by the SeDeM-ODT tool which showed that all the powder blends were appropriate for direct compression since all the blends had index of good compressibility and bucodispersibility (IGCB) values above 5, signifying direct compression is the most appropriate method. The powder blend of the optimized formulation was assessed by the DSC-TGA technique. The optimization of nine different formulations blends of orally disintegrating tablets (ODTs) was prepared in various ratios by the implementation of design of experiments (DoE), using the central composite design by selecting ludipress (X1) (49-55%) and croscarmellose sodium (X2) (1-5%) while hardness, friability, and disintegration tests were selected as responses. The optimized formulations were evaluated by various tests and the results indicated that all the formulations were found to be in adequate range. Formulations were subjected to stability studies at accelerated states following ICH guidelines. Shelf life was found to be 51.144-56.186 months. Results of multiple-point dissolution studies revealed that formulations followed the Higuchi kinetic model. This study revealed that the SeDeM-ODT tool has been successfully used to determine the compression behavior of active compounds and their powder blends for the direct compression (DC) method in formulating flurbiprofen-ODT tablets.

Prediction of Femoral Bone Strength in the Presence of Tumors and Tumor-like Lesions Using Finite Element Analysis.

Patients with bone tumors in their femurs are at risk of developing pathological fractures. Tumors with high fracture risk, especially fragile malignant lesions, are treated surgically. However, it is difficult to estimate bone strength based on clinical and radiographic findings. This study aimed to determine whether finite element analysis (FEA) provides useful information on the bone strength of femurs with tumors and tumor-like lesions. Total femoral computed tomography (CT) data (slice thickness, 0.5 mm) were retrospectively obtained from 18 patients with femoral bone tumors. Three-dimensional FEA of femurs were developed using CT data. The virtual femoral head compression test and direct three-point bending test were performed on the femurs using FEA to predict bone strength and fracture location. The compression direction was parallel to the mechanical axis, whereas that of the three-point bending test was applied to the tumor itself. In the femoral head compression test using FEA, 13 out of 18 femurs with bone tumors fractured at the femoral head, while 14 out of 18 femurs fractured at the tumor site during the virtual direct three-point bending test. The median loads predicted using the femoral head compression test were significantly higher than those predicted by the direct three-point bending test. The FEA results indicated that pathological fractures are unlikely to occur during normal walking. Direct external forces applied to the tumor body may lead to fractures.

Effect of Disintegrating Agents on Red Ginger (Zingiber officinale Roxb) Dry Extract Fast Disintegrating Tablets Using Direct Compression Method

Red ginger (Zingiber officinale Roxb) is one of the medicinal plants that is effective as a medicine for nausea and vomiting. One of the techniques for developing traditional medicinal products is to make fast disintegrating tablets (FDT). This research aims to compare the effect of these various disintegrating materials on the physical properties of FDT. FDT red ginger extract is made using the direct compression method. The tablets obtained were physically evaluated including weight uniformity, hardness, friability, and disintegration time. The statistical results using the one-way ANOVA test show that between tablet formulas there are significant differences in tablet disintegration time with differences in the type of disintegrating agent. The data obtained shows that all formulas meet the physical properties test requirements for tablets. The tablet formula using crospovidone produces tablets with high hardness, low friability, and fast disintegration time

Evaluation on tension-compression anisotropic behavior of recycled asphalt mixture

The utilization of recycled asphalt pavement (RAP) is the effective way to improve resource conservation and reduce energy consumption. The asphalt mixture is a kind of typical anisotropic pavement materials due to its heterogeneity in composition and microstructure. This could lead to the differences of mechanical response between the tensile and compressive direction. However, there are limited researches to study the effect of RAP on the tension-compression anisotropic behavior of asphalt mixture. The strength, modulus and fatigue resistance tests are carried out and different loading modes are adopted. The results show that the tension-compression anisotropic behavior is more prominent with the increase of RAP content. The regenerant served as a kind of typical additive could alleviate this effect. In addition, the result of dynamic modulus test shows that the tension-compression anisotropic behavior has an increasing trend with the decrease of frequency and the increment of temperature. The ranking of fatigue life is opposite for the direct tensile and compressive loading mode, and the fatigue life ratio of compression to tension also show positive relation with the RAP content. Due to the difference in the stress mode, the fatigue life between the indirect tensile loading and four-point bending loading also show opposite trend, and the indirect tensile fatigue life has a larger discreteness.

Coating Tablets, Compositions, Recent Advancement and Current Status: A Comprehensive Review

Conventional Tablets are solid oral dosage forms that contain an active pharmaceutical ingredient (API) along with excipients. These tablets are typically prepared through direct compression, wet granulation, or dry granulation. They are designed to disintegrate and release the API in a controlled or immediate manner, depending on the formulation. Tablet coating is a vital process in pharmaceutical technology, designed to improve the therapeutic efficacy, patient compliance, and stability of oral dosage forms. This comprehensive review explores the key aspects of tablet coating, including the types, compositions, and recent advancements. Coating materials such as polymers, plasticizers, and pigments are discussed in detail, along with their roles in controlling drug release, masking taste, and enhancing aesthetic appeal. The recent advancements focus on innovative coating techniques like film coatings, enteric coatings, and the application of nanotechnology to improve precision and functionality. Additionally, the current status of tablet coating is analyzed in terms of regulatory compliance and industry trends. The review highlights the future potential of personalized coatings, smart coatings, and environmentally friendly approaches, showcasing the evolving landscape of tablet coating technologies/pans in modern pharmaceutical manufacturing and development. Keywords: Table coating; dosage form; enteric; coating pans; formulation; advancement; polymers

Minimally invasive management of a spinal arachnoid cyst with ultrasound-assisted catheter placement: illustrative case.

Spinal arachnoid cysts are cerebrospinal fluid-filled sacs that are frequently located within the thoracic spine and can lead to symptoms due to direct compression of the thoracic spinal cord. These lesions are typically treated with laminectomy and fenestration of the cyst, with or without shunting. However, with recurrence, treatment is often more complex and sometimes requires re-exposure and fenestration or shunting. Here, the authors describe a 57-year-old female with a thoracic intradural arachnoid cyst that recurred despite extensive and initially successful fenestration. Given the failure of fenestration, the authors instead attempted to place a cystoperitoneal shunt. Given how extensive her laminectomy was, the authors elected to perform the procedure under ultrasonic guidance to avoid the large incision required for open shunt placement. The procedure was successful, with gradual improvement in the size of the arachnoid cyst as well as symptomatic improvement. Here, the authors present a unique minimally invasive technique to treat recurrent spinal arachnoid cysts. They successfully demonstrated the feasibility and safety of this approach in shunting the cyst while avoiding the extensive re-exposure often required in such complex cases. https://thejns.org/doi/10.3171/CASE24461.

Influence of different wrought processes on the microstructure and texture evolution in AZ31 magnesium alloy

AZ31 magnesium alloys were deformed by five wrought processes (forging, rolling, extrusion, equal-channel-angular-extrusion (ECAE), and caliber rolling) under the condition of an introduced equivalent plastic strain of approximately 1.5 at 573 K. The strain components induced by these wrought processes were computed using the finite element method (FEM). By combining the calculation results with the microstructure observations, the texture and microstructure evolution were discussed from the viewpoint of the strain state. The FEM showed that approximately the same equivalent strain was induced at the center of the alloys where observations were performed. Therefore, as the values of the equivalent plastic strain were fixed in all wrought processes, the effect of the strain component could be compared. The forged and rolled alloys had an intensive basal texture perpendicular to the compression and normal directions, respectively. In the others, a basal fiber texture parallel to the material flow direction was observed. These basal textures were oriented perpendicular to the compressive strain, and their intensities strengthened with an increase in the strain component. The microstructure became more refined and homogenized as the magnitude of the minimum principal strain decreased. This decrease corresponds to the transition of the deformation mode from the uniaxial compression mode to the multidirectional deformation mode as long as the same equivalent strain is induced. This result demonstrates that the microstructure obtained through dynamic recrystallization depends on the deformation mode, separately from the effect of the conventionally reported equivalent plastic strain.

Hot deformation behavior and microstructural evolutions of a Mg-Gd-Y-Zn-Zr alloy prepared by hot extrusion

The hot deformation behavior of extruded Mg-9.5Gd-4Y-2Zn-0.5Zr alloy was studied through hot compression tests conducted at deformation temperatures of 350–500 °C and strain rates of 0.001–1 s−1. Under most deformation conditions, the flow stress first reached a maximum before decreasing to a stable value, demonstrating characteristics of dynamic recrystallization (DRX). The constitutive equation of the alloy was established as ε.=1.03*1011sinh0.01287*σp2.422exp(−171150/RT) through calculations and derivation. The influences of the deformation temperature and strain rate on the microstructure and DRX of the alloy during the hot compression process were investigated using electron backscatter diffraction. It was found that at temperatures between 350 °C and 450 °C, the alloy texture exhibited multiple {0001} peak rings distributed around the normal axis of the compression direction. When the strain rate was 0.001 s−1, the average equivalent grain diameter significantly increased from 3.3 μm to 22.4 μm with the rise in deformation temperature, whereas when the deformation temperature was 450 °C, the volume fraction of DRX grains noticeably decreased from 87.6 % to 13.2 % with the increasing strain rate. Further research revealed that due to the restriction of strain rate on grain boundary migration, discontinuous dynamic recrystallization and continuous dynamic recrystallization were the predominant DRX mechanisms at low and high strain rates, respectively.

Analysis of Thermoelectric Properties of Hot-deformed Bismuth Telluride Sintered Materials

Bismuth telluride (Bi2Te3)-based alloys are widely used for thermoelectric cooling and power generation at low temperatures, and they are the only commercially available materials for thermoelectric applications below 500 K. The rhombohedral unit cell with a large c/a lattice constant ratio consisting of - Te-Bi-Te-Bi-Te- stacked layers inevitably brings about a large anisotropy in transport properties, which is why texturing is very important in polycrystalline Bi2Te3</sub alloys for maximum performance. In this report, p and n-type polycrystalline Bi2Te3</sub alloys were synthesized and hot-deformed to investigate the effects of texturing on thermoelectric properties. Hot deformation (HD) induces the strong alignment of (001) orientations along the compression direction, and a remarkable increase in the orientation factor F of (001) orientations is observed after HD in both p and n-type materials. All of the hot-deformed polycrystalline samples showed increased electrical conductivity (σ), power factor (PF), and thermal conductivity (k) in the in-plane (IP) direction, and vice versa in the out-of-plane (OOP) direction, which makes the IP direction of the hot-deformed bodies more favorable for module fabrication in terms of power factor, for both p and n-type Bi2Te3</sub-based alloys. However, due to the different degree of anisotropy of k and σ, the figures of merit (zT) were maximized in the OOP direction in the p-type materials after HD, whereas the zTs of the n-type materials were higher in the IP direction. This occurs because the anisotropy factor of electron conduction is higher than that of hole conduction, which more than offsets the advantage of the smaller k in the c-direction of n-type Bi2Te3</sub. The maximum zT of 1.33 (OOP) and 0.90 (IP) were obtained after HD from the p and n-type Bi2Te3 alloys, respectively, which were 9.3% and 18.4% higher than those of as-sintered materials.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 2. Validation of calibration workflow

This paper is the second in a series of two that describes the application of discrete element method (DEM) and reduced order modeling to predict the effect of disturbances in the concentration of drug substance at the inlet of a continuous powder mixer on the concentration of the drug substance at the outlet of the mixer. In the companion publication, small-scale material characterization tests, a careful DEM parameter calibration and DEM simulations of the manufacturing process were used to develop a reliable RTD models. In the current work, the same calibration workflow was employed to evaluate the predictive ability of the resulting reduced-order model for an extended design space. DEM simulations were extrapolated using a relay race method and the cumulative RTD was accurately parameterized using the n-CSTR model. By performing experiments and simulations, a calibrated DEM model predicted the response of a continuous powder mixer to step changes in the inlet concentration of an API. Thus, carefully calibrated DEM models was used to guide and reduce experimental work and to establish an adequate control strategy. In addition, a further reduction in the computational effort was obtained by using the relay race method to extrapolate results. The predicted RTD curves were then parameterized to develop reduced order models and used to simulate the process in a matter of seconds. Overall, a control strategy evaluation tool based on high-fidelity DEM simulations was developed using material-sparing small-scale characterization tests.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 1. Calibration workflow

In this work, a high-fidelity digital twin was developed to support the design and testing of control strategies for drug product manufacturing via direct compression. The high-fidelity digital twin platform was based on typical pharmaceutical equipment, materials, and direct compression continuous processes. The paper describes in detail the material characterization, the Discrete Element Method (DEM) model and the DEM model parameter calibration approach and provides a comparison of the system’s response to the experimental results for stepwise changes in the API concentration at the mixer inlet. A calibration method for a cohesive DEM contact model parameter estimation was introduced. To assure a correct prediction for a wide range of processes, the calibration approach contained four characterization experiments using different stress states and different measurement principles, namely the bulk density test, compression with elastic recovery, the shear cell, and the rotating drum. To demonstrate the sensitivity of the DEM contact parameters to the process response, two powder characterization data sets with different powder flowability were applied. The results showed that the calibration method could differentiate between the different material batches of the same blend and that small-scale material characterization tests could be used to predict the residence time distribution in a continuous manufacturing process.

To Enhance the Performance of CI Engine with Using of Additives Based Hybrid Bio Fuel—A Review

AbstractThe growing demand of sustainable and environment friendly energy sources has spurred research and development efforts towards the integration of biofuels in various applications, particularly in internal combustion engines. Microemulsion technique is a new and innovative alternative to traditional fossil fuel that has gained a significant attention in recent years. This type of bio fuel is made by blending of small amount of biofuel and large amount of conventional diesel fuel. This review paper explores the potential of enhancing the performance of Compression ignition (CI) engines by incorporating additives into hybrid biofuels. The study focuses on the synergistic effects of combining traditional fossil fuels with bio‐derived components, such as ethanol, biodiesel, and other bio‐based additives. This review paper aim is to explore the performance of a 4‐stroke, single‐cylinder, direct injection Compression Ignition (CI) engine at different loads using different fuels blends like CNWEDB, BFNP150, PPNP150, and ME Diesel/Colza oil. The review outlines recent advancements in biofuel technology, including novel production methods and feedstock options, aiming to overcome limitations associated with conventional biofuels. The article aims to investigate the potential of vegetable oil in formulating MHBF, analyzing its performance and emissions in CI engines. The engine performance parameters viz., brake thermal efficiency brake specific fuel consumption have been reviewed and found that these values are comparable to the biodiesel blends with pure petrodiesel. At 60%, 80%, and full load condition the BTE of microemulsion diesel/colza oil is increasing while at 40%, 80%, and full load the BSFC is decreasing. Emissions reported by the various researchers, however, have a positive attribute with respect to NOx, CO, and UHC. At full load CO is decreasing and at all load conditions the value of UHC is decreasing. The paper concludes with a discussion on future research directions, emphasizing the need for continued innovation to address emerging issues and optimize the performance of CI engines for a sustainable and energy‐efficient future.

Evaluation of compression behaviour of 316L SS Gyroid and Diamond structures using SLM process – Experimental programme under static and dynamic compression loadings

The relative comparison in terms of energy absorption efficiency for a set of 4 structures made of various Triply Periodic Minimal Surfaces (TPMS) topologies is experimentally investigated. These TPMS structures are printed by Selective Laser Melting AM process using 316L SS. The study is carried out in consideration of the effect of parameters such as relative density, compressive loading directions and loading rates, number of unit cells for Diamond and Gyroids TPMS both declined for Sheet and Skeletal topologies. The objective is to quantify their structural responses in terms of apparent stress and strain, dynamic enhancement and Specific Energy Absorbed (SEA) and to evaluate their structural integrity in terms of collapse stability. The results reveal that the Sheet pattern of TPMS structures with its constant wall thickness and uniform geometry exhibits better energy absorption capabilities than the Skeletal pattern. The Diamond family shows greater interest rather than the Gyroid family only in the case of the Sheet pattern. The increase in relative density from 20 to 30% is characterized by improved manufacturing quality, an increase in energy absorption capacity and more homogeneous progressive deformations during compression. On the whole, the set of TPMS geometries exhibits energy absorption capacities prior to those of other conventional cellular materials currently used for impact engineering applications. Finally, in a first approach, an original design methodology using charts can be developed to establish a link between the energy absorption capabilities and the design geometric parameters of TPMS structures.

Crust and Mantle Flow From Central Tibetan Plateau to the Indo‐Burma Subduction Zone

AbstractThe extremely oblique Indo‐Burma subduction zone exhibits dextral strike‐slip faulting along the Sagaing, Kabaw, and Churachandpur‐Mao Faults as well as east‐west shortening between the Sagaing Fault and Bengal Basin. Through regional stress analysis, considering areas from central Tibet, around the eastern Himalaya Syntaxis, to Burma, it has been determined that the principal compressive stress directions align with the principal strain rates. The northeast‐southwest oriented compressive stress direction from the western Shan Plateau continues into Burma. Notably, P axes align with the topographic gradients, and T axes are sub‐parallel to the topographic contours in the Shan Plateau region south of 27°N. These stress patterns are consistent with a gravitational potential energy induced crustal and mantle flow. The alignment of the fast shear wave with the maximum strain rate and the colinear NW‐SE to E‐W fast direction of the SKS wave and T axis determined from focal mechanisms in the Shan Plateau suggest that the mantle lithosphere deforms in concert with the crust. We suggest crust and mantle flow south of the Red River Fault has resulted in widening of the lithosphere in the Shan Plateau in an east‐west direction. Therefore, the Sagaing Fault has bowed approximately 50–100 km westward if we assume that the Sagaing Fault was originally straight. Our results of regional stress inversion are consistent with late Miocene to present E‐W shortening in the Indo‐Burma subduction zone resulting from the release of gravitational potential energy from the central Tibetan Plateau.

Revolutionizing fast disintegrating tablets: Harnessing a dual approach with porous starch and sublimation technique

This study investigates the transformation of neat starch (NS) from mung beans into porous starch (PS) for the formulation of fast-disintegrating tablets (FDTs) using the sublimation technique, contrasting their performance with superdisintegrants such as sodium starch glycolate (SSG) and croscarmellose sodium (CS). Camphor was used as a sublimating agent. The interaction between drug and excipients was analyzed using Fourier-transform infrared spectroscopy (FTIR), while preformulation assessments were conducted on powder blends. Model drug Diclofenac sodium (DL)-loaded FDTs were prepared via direct compression technique. Thermal behavior and crystalline properties were evaluated using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), respectively. Compressibility of tablets was assessed through Heckel and Kawakita analyses. Post-compression evaluations encompassed hardness, thickness, in vitro disintegration, and dissolution studies. FTIR analysis indicated the absence of chemical interactions among constituents, while precompression analyses confirmed favorable flow properties of the blends. Heckel analysis supported the material's notable compressibility. Microscopic examination revealed the formation of pores on the tablet surface due to the sublimation process. Integration of PS significantly accelerated the disintegration time of FDTs, with durations ranging from 50 to 82 s, compared to 76–104 s for NS-FDTs. While PS-FDTs exhibited a longer disintegration time compared to SSG, they demonstrated faster disintegration compared to croscarmellose sodium. A significant disparity (p<0.01) in drug release at 60 min was observed between SSG and PS-FDTs, with DP3 achieving 97.65 % drug release. Most batches followed the Korsmeyer-Peppas model, except for DN2 and DN3, which adhered to Higuchi-matrix drug release kinetics. Stability assessments after 90 days revealed no significant differences (p>0.05). Conclusively, this study highlights the effectiveness of PS and the sublimation method in creating FDTs with enhanced drug release properties.

Investigating the effects of formulation variables on the disintegration of spray dried amorphous solid dispersion tablets

Amorphous solid dispersion (ASD) tablets based on hydrophilic polymer carriers may encounter disintegration challenges. In this work, the effect of different formulation composition variables on the ASD tablet disintegration performance was systematically studied. GDC-0334: copovidone (PVPVA) 60: 40 ASD prepared by spray drying was selected as the model ASD system. The effects of ASD loading, filler type and ratio, disintegrant type and level were then investigated using tablets made by direct compression process. Tablet disintegration time increased with the increase of ASD loading, especially when ASD loading exceeded 50 %. At the same tablet solid fraction, when lactose was used as the soluble filler, faster tablet disintegration time was observed compared to the tablets with mannitol as the soluble filler. Among the three tested disintegrants, croscarmellose sodium performed the best in facilitating the ASD tablet disintegration, followed by sodium starch glycolate, and crospovidone was the poorest. When croscarmellose sodium was used as the disintegrant, 5 % level was sufficient to enable ASD tablet disintegration at 60 % ASD loading and further increase of croscarmellose sodium level to 8 % did not provide additional benefit. Water uptake experiments were performed on selected tablets and the results demonstrated a positive correlation with tablet disintegration time, indicating water penetration is a major contributing step for the disintegration of our ASD tablets. Overall, this work provides a rationale for excipient selection and insights into building a platform formulation approach for developing immediate-release ASD tablets.

Implementing Sediment Delivery Model-Orodispersible Tablet (SeDeM-ODT) Expert System in Cetirizine Dihydrochloride Orally Disintegrating Mini-Tablets (ODMTs) Formulation

In recent years, pediatric medicine has shifted towards solid oral dosage forms, moving away from liquid formulations to create tailored platforms for children. Orally disintegrating mini-tablets (ODMTs), with a diameter below 3 mm, dissolve rapidly in the mouth and represent a promising option. This study aimed to develop ODMTs using various co-process excipients, assessing their suitability with the Sediment Delivery Model-Orally Disintegrating Tablet (SeDeM-ODT) expert system. Favorable Index of Good Compressibility and Bucodispersibility (IGCB) values (&gt; 5) were found for F-MELT® and co-process rice starch (CR), utilizing for ODMT formulation. Cetirizine dihydrochloride (CET) was evaluated for direct compression suitability, revealing flowability deficiencies. Therefore, co-process excipient quantities were adjusted based on flowability compensation. CET-ODMTs containing F-MELT® exhibited higher drug loading capacity than CR (5 and 2.5 mg/table, respectively). Uniformity of mass, content uniformity, and friability met acceptance criteria with no significant differences between formulations. F-MELT®-based CET-ODMTs showed slower wettability due to magnesium stearate lubrication. Ultimately, the SeDeM-ODT expert system facilitated the excipient selection and formulation development, resulting in ODMTs meeting requirements with minimal experimentation.

Enhanced Anti-Inflammatory Activity of Kaempferia galanga Extract by Solid Self-Nanoemulsifying Drug Delivery System and Its Development in Fast Disintegrating Tablet

The increasing global incidence of osteoarthritis (OA) emphasizes the need for effective treatments, particularly for the elderly. Conventional OA treatments pose administration challenges, leading to patient discomfort due to difficulties in administration. Herbal formulations offer an alternative to mitigate these issues. Kaempferia galanga (KG) contains ethyl p-methoxycinnamate, a compound displaying anti-inflammatory properties that hold promise for OA treatment. This study explores the formulation of a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Kaempferia galanga extract (KGE) and evaluates its anti inflammatory efficacy, subsequently developing it into a fast disintegrating tablet (FDT) dosage form. Initially, a liquid SNEDDS (L-SNEDDS) was prepared with varying surfactant and co surfactant concentrations. The optimal formula of L-SNEDDS (FL2) using tween 80: cremophor RH 40: PEG 400 in a ratio of 1:1:2 demonstrated favorable characteristics, including transmittance of 86.93 ± 1.16%, emulsification time of 28 ± 2.65 s, particle size of 27.79 ± 2.00 nm, PDI of 0.21 ± 0.014, and zeta potential of -12.57 mV. FL2 was solidified using aerosil 200 to produce S-SNEDDS and tested for anti-inflammatory efficacy in vivo using a carrageenan induced rat model. Results showed enhanced anti-inflammatory efficacy of KGE via S-SNEDDS, marked by reduced edema volume. Afterward, FDT S-SNEDDS were prepared using the direct compression method by comparing different types of superdisintegrants. The formulation using the combination of crospovidone and croscarmellose sodium (FT2) demonstrated excellent flow properties, tablet disintegration time of 63 s, wetting time of 34.01 ± 7.87 s, friability of 0.19%, and hardness of 3.53 ± 6.16 kg/cm2. The dissolution test indicated a better dissolution profile for FT2 compared to other formulations. In conclusion, this research presents the potential of FDT S-SNEDDS as a promising drug delivery system for enhancing the therapeutic effects of Kaempferia galanga extract in treating inflammatory conditions such as osteoarthritis.

Development of intestinal colonic drug delivery systems for diverticular disease: A QbD approach

This study aimed to advance the development of intestinal colon-coated sustained-release matrix tablets of metronidazole for diverticulitis treatment, employing the Quality by Design (QbD) methodology. Comprehensive Risk analysis and Risk evaluation were conducted to assess the potential risks associated with Critical Material Attributes (CMA) and Critical Process Parameters (CPP). Ishikawa diagram, color-coded risk classification and the Risk Priority Number (RPN) were used as tools for risk evaluation. A Design of Experiments (DoE) was executed using a fractional factorial design, incorporating five key factors derived from the Risk analysis and Risk evaluation. Two levels and a central point were established for each factor, resulting in 28 batches of coated tablets. The manufacturing process involved direct compression, followed by a coating process using pH-dependent or time-dependent polymers. Characterization and dissolution studies were conducted on all batches, and the obtained results underwent analysis of variance (ANOVA).The findings demonstrated the robustness and reproducibility of both the direct compression and coating processes. Statistical analysis identified HPMC/chitosan ratio, blending time, coating polymer, and coating weight gain as factors significantly impacting drug release. A Design Space was established to delineate the interplay of these factors, offering insights into various combinations influencing drug release behavior. Thus, the design space for 10 % weight gain formulations includes a range of HPMC/CH ratios between 2.7–3 and mixing times between 10 and 12 min; for 20 % weight gain formulations it includes a range of HPMC/CH ratios up to 2 and mixing times between 10 and 16 min. Multiple Linear Regression between technological and biopharmaceutical variables were optimized facilitating scale-up operations. Batches with a 10 % weight increase and varied HPMC viscosity grades and coating polymers achieve ∼50 % drug release at 24 h; however, batches with a 20 % weight increase along, with either high proportions of HPMC and short blending times or low proportions of HPMC and longer blending times, achieve slow release of metronidazole. This study contributes to optimizing metronidazole colonic delivery systems, enhancing their potential efficacy in diverticulitis treatment.