Physiological pH Range Research Articles

Fibrous anion exchanger with ternary amino groups as a component of the substrate for plants growing

A set of studies necessary to determine the suitability of a fibrous anion exchanger with ternary amino groups based on industrial polyacrylonitrile fiber Nitron C as a component of ion substrates was carried out. A laboratory-prepared ion exchanger sample had a working exchange capacity equal to 0.9 meq/g for the nitrate anion, which limits the biological productivity of the substrate for growing plants, in the physiological pH range = 5.5–7.5 and the concentration of the equilibrium nutrient solution is 0.02 eq/l. This capacity is at the level of the best granular ion exchangers and significantly exceeds the capacity of the previously used fibrous ion exchangers for growing plants in zero gravity conditions on space stations in 1970–1994 (Mir, Soyuz TM-10 – TM-17). The synthesized ion exchanger is a polyampholyte and contains three types of ion exchange groups, has high hydrophilicity and mechanical properties that allow it to be processed into textiles and used for any purpose, in which fibrous ion exchangers can be used (air and water purification, human protection means, etc.).

On the pH-dependence of α-synuclein amyloid polymorphism and the role of secondary nucleation in seed-based amyloid propagation

The aggregation of the protein α-synuclein is closely associated with several neurodegenerative disorders and as such the structures of the amyloid fibril aggregates have high scientific and medical significance. However, there are dozens of unique atomic-resolution structures of these aggregates, and such a highly polymorphic nature of the α-synuclein fibrils hampers efforts in disease-relevant in vitro studies on α-synuclein amyloid aggregation. In order to better understand the factors that affect polymorph selection, we studied the structures of α-synuclein fibrils in vitro as a function of pH and buffer using cryo-EM helical reconstruction. We find that in the physiological range of pH 5.8–7.4, a pH-dependent selection between Type 1, 2, and 3 polymorphs occurs. Our results indicate that even in the presence of seeds, the polymorph selection during aggregation is highly dependent on the buffer conditions, attributed to the non-polymorph-specific nature of secondary nucleation. We also uncovered two new polymorphs that occur at pH 7.0 in phosphate-buffered saline. The first is a monofilament Type 1 fibril that highly resembles the structure of the juvenile-onset synucleinopathy polymorph found in patient-derived material. The second is a new Type 5 polymorph that resembles a polymorph that has been recently reported in a study that used diseased tissues to seed aggregation. Taken together, our results highlight the shallow amyloid energy hypersurface that can be altered by subtle changes in the environment, including the pH which is shown to play a major role in polymorph selection and in many cases appears to be the determining factor in seeded aggregation. The results also suggest the possibility of producing disease-relevant structure in vitro.

On the pH-dependence of α-synuclein amyloid polymorphism and the role of secondary nucleation in seed-based amyloid propagation.

The aggregation of the protein α-synuclein is closely associated with several neurodegenerative disorders and as such the structures of the amyloid fibril aggregates have high scientific and medical significance. However, there are dozens of unique atomic-resolution structures of these aggregates, and such a highly polymorphic nature of the α-synuclein fibrils hampers efforts in disease-relevant in vitro studies on α-synuclein amyloid aggregation. In order to better understand the factors that affect polymorph selection, we studied the structures of α-synuclein fibrils in vitro as a function of pH and buffer using cryo-EM helical reconstruction. We find that in the physiological range of pH 5.8-7.4, a pH-dependent selection between Type 1, 2, and 3 polymorphs occurs. Our results indicate that even in the presence of seeds, the polymorph selection during aggregation is highly dependent on the buffer conditions, attributed to the non-polymorph-specific nature of secondary nucleation. We also uncovered two new polymorphs that occur at pH 7.0 in phosphate-buffered saline. The first is a monofilament Type 1 fibril that highly resembles the structure of the juvenile-onset synucleinopathy polymorph found in patient-derived material. The second is a new Type 5 polymorph that resembles a polymorph that has been recently reported in a study that used diseased tissues to seed aggregation. Taken together, our results highlight the shallow amyloid energy hypersurface that can be altered by subtle changes in the environment, including the pH which is shown to play a major role in polymorph selection and in many cases appears to be the determining factor in seeded aggregation. The results also suggest the possibility of producing disease-relevant structure in vitro.

3D Hybrid branched carbon/ZnO core-shell nanostructure as biosensor for sensitive and selective detection of glucose

Reliable glucose monitoring at physiological pH and clinical practical range is critical for appropriate diabetes management which remains one of a major health concern. Herein, we describe the construction of flexible and 3D hybrid electrode for glucose sensing by successful immobilization of the GOx on branched carbon/ZnO core–shell nanostructures electrode. The microstructure, morphology and device properties of glucose sensor was systemically characterized by using HRTEM, SEM, FT-IR, and electrochemical analysis. The branched carbon/ZnO core–shell nanostructure sensor showed reliable stability, selectivity and remarkable sensitivity (i.e., 32.48 (±0.04) µA mM−1 cm−2) for glucose in clinical range at physiological pH conditions. The mediator less direct electron communication between the electrode surface and the redox center (FADH & FAD) was also analyzed comprehensively, which concludes an efficient direct electron communication (DET). This enhanced DET can be attributed to the larger surface area provided by the branched carbon/ZnO core–shell nanostructure and also favorable orientation of GOx which allows close proximity of the redox center and the electrode surface. It is believed that such kind of sensors could provide an ideal platform for continuous glucose monitoring (CGM) device fabrication which could perform glucose sensing in real-time and in-vivo analysis.

Formulation and Evaluation of Ketoconazole Nano-suspension

The use of antifungals that are widely used by the public is ketoconazole. Ketoconazole is included in the Biopharmaceutical Classification System (BCS) II category, where the drug is poorly soluble in water but has high permeability. In this study, ketoconazole was prepared in a nanosuspension formulato increase solubility. The method for preparing 2% ketoconazole nanosuspension used a sonicator bath with variations of tween 80 (F1 8%, F2 10%, F3 12%) and transcutol as surfactant and co-surfactant. The results showed that the particle size of the ketoconazole nanosuspension F1 was 102 ± 4.3 nm, F2 was 105 ± 3.2 nm, and F3 was 90 ± 2.4 nm on day 0. Testing on day 28 showed an increase in particle size in F1 115 ± 3.1 nm, F2 129±4.5nm, F3 97±2.4nm (p>0.05). In testing the morphology of the nanosuspension using Scanning Electron Microscopy (SEM), The results showed that the irregular spheres were scattered. Organoleptic testing showed clear and homogeneous preparations. pH testing for 28 days showed a pH range of 5.6-6 which is included in the physiological skin pH range (p>0.50). Nanosuspension preparations can be said to meet the physical evaluation requirements.

Biomimetic peroxidase MOF-Fe promotes bone defect repair by inhibiting TfR2 and activating the BMP2 pathway

BackgroundLarge bone defects pose a clinical treatment challenge; inhibiting transferrin receptor 2 (TfR2), which is involved in iron metabolism, can promote osteogenesis. Iron-based metal-organic frameworks (MOF-Fe) particles not only inhibit TfR2 but also serve as biomimetic catalysts to remove hydrogen peroxide in reactive oxygen species (ROS); excess ROS can disrupt the normal functions of osteoblasts, thereby hindering bone regeneration. This study explored the potential effects of MOF-Fe in increasing osteogenic activity and clearing ROS.MethodsIn vitro experiments were performed to investigate the osteogenic effects of MOF-Fe particles and assess their impact on cellular ROS levels. To further validate the role of MOF-Fe in promoting bone defect repair, we injected MOF-Fe suspensions into the femoral defects of SD rats and implanted MOF-Fe-containing hydrogel scaffolds in rabbit cranial defect models and observed their effects on bone healing.ResultsIn vitro, the presence of MOF-Fe significantly increased the expression levels of osteogenesis-related genes and proteins compared to those in the control group. Additionally, compared to those in the untreated control group, the cells treated with MOF-Fe exhibited a significantly increased ability to remove hydrogen peroxide from ROS and generate oxygen and water within the physiological pH range. In vivo experiments further confirmed the positive effect of MOF-Fe in promoting bone defect repair.ConclusionThis study supports the application of MOF-Fe as an agent for bone regeneration, particularly for mitigating ROS and activating the bone morphogenetic protein (BMP) pathway, demonstrating its potential value.

A pH-Responsive Topological Switch Based on a DNA Quadruplex-Duplex Hybrid.

A guanine-rich oligonucleotide based on a human telomeric sequence but with the first three-nucleotide intervening stretch replaced by a putative 15-nucleotide hairpin-forming sequence shows a pH-dependent folding into different quadruplex-duplex hybrids in a potassium containing buffer. At slightly acidic pH, the quadruplex domain adopts a chair-type conformation. Upon increasing the pH, a transition with a midpoint close to neutral pH to a major and minor (3+1) hybrid topology with either a coaxially stacked or orthogonally oriented duplex stem-loop occurs. NMR-derived high-resolution structures reveal that an adenine protonation is prerequisite for the formation of a non-canonical base quartet, capping the outer G-tetrad at the quadruplex-duplex interface and stabilizing the antiparallel chair conformation in an acidic environment. Being directly associated with interactions at the quadruplex-duplex interface, this unique pH-dependent topological transition is fully reversible. Coupled with a conformation-sensitive optical readout demonstrated as a proof of concept using the fluorescent dye thiazole orange, the present quadruplex-duplex hybrid architecture represents a potentially valuable pH-sensing system responsive in a physiological pH range of 7±1.

Controllable Fabrication of Polypyrrole Nanopillar/Hair Arrays by Oxygen Plasma Treatment and Their Applications as Antibacterial Flexible pH Sensors

AbstractFlexible pH sensors have attracted a great deal of attention in numerous applications, such as wearable healthcare devices, smart wound bandages, and other pH monitor sensors for chemical and bioprocess control. Herein, a facile approach to fabricate conducting polymer polypyrrole nanopillar arrays is proposed, and its potential as an advanced pH sensing interface is shown. Using oxygen plasma treatment as the etching tool, polypyrrole nanopillar/hair arrays can be prepared after etching 3D polypyrrole network structures. Conductive polypyrrole nanopillar arrays possessed unique advantages in sensing: their featured nanopillars has enhanced antibacterial properties; their structures showed excellent hydrophilicity and are favorable for interaction with analytes in small‐volume liquids. A flexible polypyrrole nanopillar array‐based potentiometric pH sensor integrated with a solid‐state reference electrode is further designed and fabricated. Superior performance with a near‐Nernstian response of 60.1±1.0 mV pH−1, excellent repeatability, high stability, and reproducibility is verified in the physiological pH range. The reliabilities of flexible and small‐volume sample testing, as well as the applicability for artificial sweat sample pH sensing, are examined. Provided with the advantages of antibacterial properties and hydrophilicity, the proposed flexible pH sensor is promising for trace analysis in biological, medical, and healthcare applications.

An Ortho-modification Strategy to Develop Brooker's Merocyanine Probe for Precise Monitoring of pH Changes in Urine.

As a non-invasive body fluid, urine pH is one of the important biomarkers for diseases such as the kidneys. Therefore, rapid and accurate detection of urine pH is of great clinical significance. A novel fluorescent probe (SPPH-Cl) was developed based on Brooker's merocyanine skeleton for pH detection. The pKa of SPPH-Cl was adjusted to 6.55 using a phenolic hydroxyl ortho substitution strategy, therefore, the fluorescence response range of SPPH-Cl to pH covers the urine physiological pH range (4.6-8.0). SPPH-Cl has excellent water solubility, stable recoverability, wide anti-interference capability, and sensitive reactions to pH fluctuations in pure aqueous solutions. SPPH-Cl has succeeded in applying to monitor the pH of volunteer urine samples based on a standard curve established in artificially simulated urine, and the detection results have accuracy comparable to pH meters. Therefore, this work provided a powerful molecule tool for detecting pH in urine samples.

Intrinsic dual emissive insulin capped Au/Ag nanoclusters as single ratiometric nanoprobe for reversible detection of pH and temperature and cell imaging

pH and temperature are two important characteristics in cells and the environment. These, not only in the well-done regulation of cell functions but also in diagnosis and treatment, have a key role. Protein-protected bimetallic nanoclusters are abundantly used in the building of biosensors. However, insulin-stabilized Au–Ag nanoclusters with dual intrinsic emission have not been investigated yet. In this work, Dual emissive insulin templated Au–Ag nanocluster (Ins(Au/Ag)NCs) were first synthesized in a simple and green one-put manner. The two emission wavelengths of, as-prepared NCs centered at 410 and 630 nm, excited in one excitation wavelength (330 nm). These two emission peaks were assigned to the di-Tyrosine cross-linked formation and bimetallic nanoclusters respectively. Further analysis displayed that each emission band of Ins(Au/Ag)NCs responded to one variable whilst another peak remained constant; For blue and red emission wavelengths, pH dependency and thermo-responsibility were observed respectively. As-prepared nanoprobe with the intrinsic dual emissive feature was used for ratiometric determination of these parameters, each with a discrete response from another. The linear range of 6.0–9.0 for pH and 1 to 71 °C for temperature was obtained, which comprises the physiological range of pH and temperature and afforded intracellular sensing and imaging capability. As-prepared NCs probe show excellent biocompatibility and cell membrane permeability, and so were successfully applied as direct ratiometric pH and temperature probes in HeLa and HFF cells. More interestingly, this dual emissive nanoprobe is capable of distinguishing cancer cells from normal ones.

A novel fluorescent probe based on carbazole-thiophene for the recognition of hypochlorite and its applications

A carbazole thiophene-aldehyde and 4-methylbenzenesulfonhydrazide conjugate CSH was synthesized by introducing 5-thiophene aldehyde at the 3-position of the carbazole group as the precursor and then condensing it with 4-methylbenzenesulfonhydrazide. CSH has high selectivity and sensitivity towards ClO−, which can specifically identify ClO− by UV–Vis and fluorescence spectroscopy. CSH can rapidly respond to ClO− in the physiological pH range through a fluorescence quenching pattern, accompanied by the color of CSH changing markedly from turquoise to yellowish green under the 365 nm UV light. Probe CSH exhibits a quantitative response to ClO− (0–11 μM) with a low detection limit (1.16 × 10−6 M). Cell imaging experiments have shown that CSH can capture fluorescent signals in the cyan and yellow channels of HeLa cells through fluorescence confocal microscopy, and can successfully identify exogenous ClO− in HeLa cells. In addition, probe CSH can also be used to detect ClO− in environmental water samples. These results indicate that CSH has potential application prospects in the environmental analysis and biological aspects.

A Conformable Holographic Sensing Bandage for Wound Monitoring

AbstractChronic wound monitoring can provide personalized pathophysiological information for wound management and treatment. Continuously monitoring the wound milieu via the holographic pH sensor can reflect the wound healing processes. However, the integration with wearable devices is hindered by its inherently restricted interrogation angle dependency within 5°. Herein, a ball bearing‐based double photopolymerization method is developed to fabricate holographic pH sensors with a broader interrogation angle range of 15°–60° in wound exudates. The fabricated holographic pH sensor is then integrated with the flexible ultrathin polyurethane substrate, which replays a total Bragg peak shift of approximately 150 nm with physiological pH changes from 7.00 to 8.75. The conformable holographic pH sensing bandages demonstrate the ability to quantify the pH value under various bending manipulations, simulating the mounting on the body surface. The reversibility in artificial wound exudate demonstrates the durability and capability of real‐time pH monitoring in the wound milieu with minimal effect on the replay wavelength. The addition of electrolytes, albumin, urea, uric acid, lactate, and glucose does not interfere with the readout over the physiological pH range of wound exudates. The obtained conformable holographic sensing bandage benefits the wound healing process monitoring through colorimetric interrogation at point‐of‐care (POC) settings.

Fabrication of High-Performance pH Sensor Based on NiO/Mxene/PANI Modified Sensing Platform

Accurate pH measurement is a fundamental cornerstone in various scientific and industrial processes, playing a pivotal role in ensuring the quality and efficiency of countless applications. There is a significant demand for pH sensors with versatile applications across various sectors, including agriculture, healthcare, food processing, textiles, leather, wet laboratories, and environmental remediation [1-3]. In this study, we embark on a journey of innovation and precision, focusing on the development of a cutting-edge pH sensor. Our research endeavors to address the critical need for enhanced pH sensing capabilities through a meticulously designed sensing platform, combining the unique attributes of nickel oxide (NiO) nanoparticles (NPs), polyaniline (PANI), and MXene, all ingeniously integrated onto a nickel foam (NF) electrode. The fabrication process involved a series of steps, including the synthesis of NiO NPs via the sol-gel method, following by mixing NiO and MXene, followed by further mixing with PANI and electrodeposited onto the nickel foam electrode. Fig 1 represents the fabrication process of NF electrodes with NiO/MXene/PANI composites.The performance of the electrode was evaluated using cyclic voltammetry (CV) across various buffer solutions where NiO-PANI-MXene modified NF electrode, pt wire, and Ag/AgCl electrode were used as a working electrode, counter electrode, and reference electrode respectively. MXene are layered materials composed of transition metal carbides, nitrides, or carbonitrides. What makes MXene attractive for pH sensing is its surface functionalization, that often includes hydroxyl (-OH) and oxygen (-O) groups. These groups are responsive to variations in hydronium ion (H₃O⁺) concentration. In acidic solutions with high H₃O⁺ concentrations, these groups undergo protonation, modifying MXene's electrical properties, and affecting conductivity and potential. This alteration forms the basis for MXene's pH sensing ability, detectable through methods like open circuit potential (OCP), where changes in current at specific voltages correlate with pH levels, enabling precise pH measurements. To characterize the composites, various analytical techniques were employed. SEM-EDX, TEM and XRD were used for comprehensive structural analysis. In parallel, cyclic voltammetry (CV), amperometry, and OCP were employed to monitor shifts in potential corresponding to different pH levels within the buffer solution. The results revealed that the NiO/MXene/PANI sensor exhibited remarkable sensitivity over the pH range from 3 to 11. The pH sensor exhibits a sensitivity of 46.00 mV/pH (R2 = 0.99) and maintains consistent performance within the physiological pH range spanning from 3 to 11. This prototype currently undergoing testing alongside a commercially available pH meter using real samples, such as orange and a baking powder etc. solution. The durability and repeatability assessments have yielded encouraging outcomes. Thus, the presented NiO/MXene/PANI based pH sensor represents a significant advancement in pHsensing technology, offering improved sensitivity and stability. The incorporation of MXene within the sensing platform holds a promise for the future developments of solid-state pH sensors.Reference Jamal, T. K. Dey, T. Nasrin, A. Khosla, & K. M. Razeeb, 2022, Journal of The Electrochemical Society, 169(5), 057517.Islam, H. Shao, M. M. R. Badal, K. M. Razeeb, & M. Jamal, 2021, PloS one, 16 (3), e0248142.V. Mun’delanji, and E. Tamiya, 2015, Nanobiosensors and nanobioanalyses: A Review(pp. 3-20). Tokyo, Japan: Springer. Fig. 1. Fabrication process of NiO/MXene/PANI modified nickel foam electrode. Figure 1

Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms invivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug-drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended-release formulations, where systemic exposure of nifedipine was increased in subjects after multiple-dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well-understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically-based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in invitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two-stage invitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple-dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4-mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH-dependent formulation. The reported model-based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations.

Integrated spectroscopic and MD simulation approach to decipher the effect of pH on the structure function of Staphylococcus aureus thymidine kinase

Staphylococcus aureus is a major human pathogen responsible for a variety of clinical infections, becoming increasingly resistant to antibiotics. To address this challenge, there is a need to identify new cellular targets and innovative approaches to expand treatment options. One such target is thymidine kinase (TK), a crucial enzyme in the pyrimidine salvage pathway, which plays a key role in the phosphorylation of thymidine, an essential component in DNA synthesis and repair. In this study, we have successfully cloned, expressed, and purified the TK protein. A comprehensive investigation into how different pH levels affect the structure and functional activity of TK, using a combination of spectroscopy, classical molecular dynamics simulations, and enzyme activity assays was conducted. Our study revealed that variation in pH disrupts secondary and tertiary structures of TK with noticeable aggregate formation at pH 5.0. Enzyme activity studies demonstrated that TK exhibited its maximum kinase activity within the physiological pH range. These findings strongly suggest a connection between structural changes and enzymatic activity, which was further supported by the agreement between the spectroscopic features we measured and the results of our MD simulations. Our study provides a deeper insight into the structural features of TK, which could potentially be harnessed for the development of therapeutic strategies aimed at combatting infectious diseases. Conformational dynamics plays an essential role in the design and development of effective inhibitors. Considering the effects of pH on the conformational dynamics of TK, our findings may be implicated in the development of potent and selective inhibitors. Communicated by Ramaswamy H. Sarma

New Complexes of Isoniazid Derivative with 3d Metals: Synthesis, Structure and Molecular Docking

This article reports the results of our study aimed at synthesizing and describing the structure and properties of new transition metal complexes with potential anti-tuberculosis and other related activities. For the first time, five bis-complexes of the ligand N’-(1-(6-methylpyridine-2-yl)ethylidene)isonicotinohydrazide (LH) with ions of five 3d metals (Cu(II), Mn(II), Co(II), Ni(II), and Zn(II)) were synthesized. The structures of all synthesized complexes in crystalline form were identified by X-ray diffraction (XRD) analysis. The resulting compounds were characterized by NMR, mass spectrometry, and electron spectroscopy. DFT/PCM calculations were performed on the structures of the five ML(OH) hydroxocomplexes formed during the hydrolysis of ML2 complexes in an aqueous medium within the physiological pH range. The binding energies of the ML(OH) complexes with the biotarget, the InhA protein of the Mycobacterium tuberculosis strain, were determined by molecular docking. The data obtained suggest that the studied complexes have high biological activity and warrant further biomedical research.

Cu-doped bioactive glass with enhanced in vitro bioactivity and antibacterial properties

This work aimed to optimize, produce and characterize Cu-doped bioactive glasses which are antibacterial without the addition of antibiotics obtained via ion exchange in an aqueous solution. According to morphological, compositional and structural analyses, 0.001 M was selected as the most optimal concentration of the ion exchange solution. The doped glass was then compared to the undoped one to investigate the effect of Cu-doping on the glass surface composition and bioactivity. Cu-doping was found to enhance the bioactivity kinetics and the following hydroxyapatite formation, evidenced by X-ray diffraction, energy dispersive X-ray spectroscopy, and zeta potential measurements. Besides that, the zeta potential titration measurements confirmed that the Cu-doping did not alter the surface chemical stability of the glass both in the inflammatory and physiological pH range. Moreover, the leaching ability of Cu2+-ions, both in physiological and inflammatory-mimicking conditions, was measured, followed by an in-depth study of the antibacterial properties, using two protocols to distinguish between the antiadhesive, antibacterial, and antibiofilm effects. For both protocols, a reduction of metabolic activity and Colony-Forming Unit after 24 h against Staphylococcus aureus Multi-Drug resistance strain was evidenced. These results showed that Cu-doped glass could show potential as a bioactive and antibacterial surface for bone surgery applications.

Flurbiprofen cataplasms: Development and validation of in-vitro dissolution methods and evaluation of multimedia dissolution profiles

The investigation of the systemic release performance of dosage forms using in vitro tools is a crucial objective in the realm of pharmaceutical development. The dissolution methodology is an effective tool for monitoring batch-to-batch variabilities in quality control and gaining insight into the release mechanisms of pharmaceutical drugs. The majority of the dissolution techniques that have been approved are primarily intended for solid oral dosage forms. Nevertheless, these techniques have also been applied to various other dosage forms, including transdermal drug delivery systems. The administration of medication through cataplasm, a transdermal application, poses challenges in understanding the characteristics of drug release. Flurbiprofen is classified as a class II drug according to the Biopharmaceutics Classification System and is commonly administered in the form of a cataplasm for its analgesic properties. A dissolution method was developed to assess the in vitro release profile of the flurbiprofen transdermal delivery system. This method utilized a United States Pharmacopeia dissolution apparatus V, with a disc assembled over the paddle. Additionally, a method for quantification was developed using liquid chromatography. The discriminatory aspect of the developed method has faced criticism due to substantial alterations in excipient composition. Furthermore, we have developed clearly defined multimedia release profiles within the physiological pH range. The validation of the dissolution and chromatography systems was conducted.

Stir casting technology for fabrication of biodegradable magnesium metal matrix composites containing different percentages of hydroxyapatite reinforcement material for biomedical purposes

Due to the superior biocompatibility and strength of magnesium and its alloys compared to other metallic alloys, such as those used in orthopaedics as a bone-implant material, they have recently been considered a breakthrough material for biomedical applications. However, before tissues have fully adjusted to the high chloride environment and physiological pH range of the physiological system, pure magnesium might lose its mechanical integrity. Therefore, it is believed that the development of magnesium matrix composites is an approach to decrease corrosion rates and improve their mechanical properties that are similar to those of natural bone. They are not required to be taken out once the wound has entirely healed because they are biodegradable as well, which might reduce the need for additional surgeries in the future. The stir casting technique has been employed in this workto produce samples of magnesium-based biodegradable metal matrix composites, referred to as M2H (Magnesium & 2.0 wt% Hydroxyapatite powder) and M4H (Magnesium & 4.0 wt% Hydroxyapatite powder), with varying amounts of hydroxyapatite powder as a reinforcement material. In this worktensile test samples (M2H-T1,T2 & M4H-T1,T2) andcompression test samples (M2H-C1,C2,C3& M4H-C1,C2,C3,C4)along with microstructural and SEM test samples (M2H-MS & M4H-MS)were prepared and cut to a suitable shape and size in accordance with ASTM standards. This paper mainly focuses on the samples preparation for mechanical testing and SEM characterisation.

Vitamin-E TPGS Based Microemulsion: An Approach for Solubility Enhancement of Poorly Water-Soluble Drugs

Poor aqueous solubility is the primary concern for dissolving new drug substances during early development. Several novel solubility enhancement techniques such as particle size reduction, salt formation, making solid dispersion, complex formation, use of cosolvent techniques, use of surfactants, physical and chemical modification, and PH adjustment using buffering agents have been explored extensively to resolve the issue of poor aqueous solubility of drug substances. Drug delivery in micro and nano-sized formulations is one of the ways to improve the solubility of these drug candidates over the physiological pH range. In recent years, combination methods have also been considered an interesting approach where more than one solubility enhancement technique is used. The present review focuses on the feasible approach for improving the solubility by forming Vitamin E TPGS-based suspension in micro or nano form by particle size reduction. Further, by granulation or spray drying techniques, these suspensions converted to a solid dosage form for oral drug delivery for patient compliance are being explore