Drug Solution Research Articles

Recent Advances in Transdermal Drug Delivery System (TDDS): A Review

Abstract: The transdermal route of administration has many advantages over more traditional routes of drug administration. They contain high bioavailability, lack of first-pass hepatic metabolism, stable plasma drug concns., and fact that the treatment is non-invasive. The biggest barrier to the penetration of medicinal molecules is the outer layer of the skin, stratum corneum. Thus, research to improve transdermal drug delivery (TDD) is worthwhile this layer is the area of interest. This review article is written to provide coverage commentary recent advances in TDD improvement techniques. Techniques that improve the permeability of the skin have been used developed to improve bioavailability and increase the choice of topical and transdermal drugs is a viable option. This review describes enhancement techniques based on drug/vehicle optimization, e.g selection of drugs, prodrugs and ion pairs, supersaturated drug solutions, eutectic systems, complexes, liposomes, vesicles and particles. Strengthening by changing the shell with moisturizing chemical enhancers partitioning and solubility effects affecting crustal lipid and keratin structure discussed Mechanism of action of penetration enhancers and retarders and their potential for clinical use application is described.

An experimentally validated cavitation inception model for spring-driven autoinjectors

Cavitation, the formation and collapse of vapor-filled bubbles, poses a problem in spring-driven autoinjectors (AIs). It occurs when the syringe accelerates abruptly during activation, causing pressure fluctuations within the liquid. These bubbles expand and then collapse, generating shock waves that can harm both the device and the drug molecules. This issue stems from the syringe’s sudden acceleration when the driving rod hits the plunger. To better understand cavitation in AIs, we explore how design factors like drive spring force, air gap size, and fluid viscosity affect its likelihood and severity. We use a dynamic model for spring-driven autoinjectors to predict and analyze the factors contributing to cavitation initiation and severity. This model predicts the motion of AI components, such as the displacement and velocity of the syringe barrel, and allows us to investigate pressure wave propagation and the subsequent dynamics of cavitation under various operating conditions. We investigated different air gap heights (from 1 to 4 mm), drive spring forces (from 8 to 30 N), and drug solution viscosities (from 1 to 18 cp) to assess cavitation inception based on operational parameters. Results reveal that AI dynamics and cavitation onset and severity strongly depend upon AI operating parameters, namely drive spring force and air gap height. The maximum syringe acceleration increases with spring stiffness and decreases with air gap height; increases in air gap height prolong the time interval of syringe acceleration but diminish the maximum syringe acceleration. From actuation to injection, air gap pressure peaks twice, first due to impact with the rod/plunger and secondly due to the deacceleration event upon injection. The maximum air gap pressure increases with spring stiffness and decreases with air gap height. Results show that maximum cavitation bubble radii and collapse-driven extension rates occur with higher driver spring forces, smaller air gap heights, and less viscous solutions. A cavitation criterion is developed for cavitation in autoinjectors that concludes that cavitation in autoinjectors depends on the peak syringe acceleration.

Formulation, Optimization, and Evaluation of Gliclazide loaded Nanosuspension for Dissolution Rate Enhancement

Diabetes mellitus is a prolonged metabolic condition categorized through elevated blood glucose levels. To treat this condition, oral antihyperglycemic medications like gliclazide, a second-generation sulfonylurea insulin secretagogue, are commonly used. Gliclazide comes into the biopharmaceutical classification system (BCS) class-II types, known for its lower solubility. To enhance its solubility, gliclazide was integrated into nanosuspensions. This study focused on formulating these gliclazide nanosuspensions using Kollicoat IR and Soluplus through the anti-solvent-precipitation method, through optimization achieved using the Box Behnken Design. Key parameters assessed included particle size (224 ± 1.23 nm) and entrapment efficiency (95.65 ± 0.12%). The drug release studies conducted on pH 7.4 indicated that over 95% of the drug was released within 30 minutes for the nanosuspension, whereas the pure drug solution released less than 70% in the same time frame, indicating immediate release with the nanosuspension. The morphology was examined using scanning electron microscopy (SEM), while fourier transform infrared (FTIR), X-Ray diffractometers (XRD), and differential scanning calorimeter (DSC) analyses confirmed the presence of the drug within the nanosuspension. In summary, the incorporation of gliclazide into nanosuspensions proved successful, resulting in enhanced release characteristics and ameliorated solubility.

Bioinspired labrum-shaped stereolithography (SLA) assisted 3D printed hollow microneedles (HMNs) for effectual delivery of ceftriaxone sodium

Microneedles (MNs), a microsystem having needle height in micrometers, have gained significant attention due to their minimum invasiveness, painless, and easy-to-administer nature. Here, we introduce a hollow microneedle (HMNs) array with bio-inspired labrum tip for low insertion force and desired mechanical strength, fabricated using vat-photopolymerization mediated stereolithography (SLA) assisted 3D printing technology utilizing biocompatible photo-crosslinkable and curable resin as feedstock. Fabricated HMNs was used for the effective transdermal delivery of a broad-spectrum antibiotics i.e., ceftriaxone sodium (CEF) with a high molecular weight of 554.58 g mol−1, possessing gastro-intestinal (GI) instability and low oral bioavailability (BA). The bio-inspired labrum tip structure of the fabricated HMNs was evaluated by digital microscopy and scanning electron microscopy (SEM) to ensure the printed prototype's superiority in terms of dimensions and array uniformity. The HMN microchannels were then characterized by X-ray microcomputer tomography (µCT) to ascertain the quality of internal channels and ensure even distribution of drug solution. Further, HMNs was also characterized for mechanical and penetration analysis. Suggesting a low force of 1.54 N was required for its effective penetration with a sufficient fracture force of around 171.82 N. The ex vivo skin permeation profile of CEF from the HMNs revealed 100 ± 0.80 % CEF permeation through porcine skin within 18 hr. Finally, a pre-clinical efficacy assessment of CEF-reservoir HMNs was performed in an experimental animal model, revealing efficient penetrability and desired BA of CEF. Overall results demonstrated the active transdermal drug delivery potential of these fabricated bio-inspired HMNs as a unique device for customized and personalized treatment.

The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions.

The growing interest in high-energy emulsification is a result of its scalability, which is important from an industrial perspective and allows for a more reproducible and efficient production of pharmaceutical formulations. The aim of this study was to evaluate the effect of composition, mainly a fixed surfactant/cosurfactant (Smix) ratio, their concentration, and the parameters of high-pressure homogenization (HPH) processing on the quality and stability of ophthalmic fluconazole-loaded nanoemulsions. After a physicochemical analysis of nanoemulsions containing 20% w/w of oil, as optimal conditions for the HPH process, three cycles at a pressure of 1000 bar were established, obtaining formulations with an average droplet diameter size in the range of 80.63-129.68 nm and PDI values below 0.25. While it was expected that an increasing cosurfactant concentration decreased the droplet size, in the case of formulations containing Tween 20 and 10% w/w of cosurfactants, "over-processing" was observed, identified by the droplet size and polydispersity index increase. Consecutively, the selected formulations were evaluated for in vitro drug release in Franz's cell, antifungal activity, and 30-day stability using NMR spectroscopy. An antifungal activity test showed no significant difference in the antifungal activity between optimal fluconazole-loaded nanoemulsions and a 0.3% aqueous drug solution, but previously, research showed that prepared formulations were characterized by a higher viscosity and satisfactory prolonged release compared to a control. In a 30-day stability study, it was observed that higher HLB values of the used surfactants decreased the stability of the formulations in the following order: Kolliphor EL, Tween 80, Tween 20. The NMR spectra confirmed that Kolliphor EL-based formulations ensured the higher stability of the nanoemulsion composition in comparison to Tween 80 and a better stabilizing effect of propylene glycol as a cosurfactant in comparison to PEG 200. Therefore, the optimization of HPH technology should be focused on the selection of Smix and the Smix:oil ratio in order to prepare stable formulations of high quality.

Antibody-decorated chitosan-iodoacetamide-coated nanocarriers for the potential delivery of doxorubicin to breast cancer cells

Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti–HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.

Investigation of intermolecular interactions of l-Valine and l-Phenylalanine with muscle relaxant drug mephenesin molecule prevalent in aqueous solution by various physico-chemical methods at T=298.15K–313.15K

A complete chemical analysis of significant intermolecular interactions of l-Valine (L-Val) and l-Phenylalanine (L-Phe) with Mephenesin (MEPN) molecules in aqueous solution has been studied by different physicochemical methodologies at various temperatures (T = 298.15 K–313.15 K at an interval of 5 K) and concentrations (0.001 mol kg−1, 0.003 mol kg−1, 0.005 mol kg−1) of aqueous MEPN solution. The limiting apparent molar volume (φV0) and experimental slope (SV*) values are found from the equation of Masson, viscosity A and B-coefficient determined using the equation of Jones-Doles, molar refraction (RM) and limiting molar refraction (RM0) derived by the Lorentz-Lorenz equation, express that in our experimental solution of amino acids (AAs) in aqueous MEPN, the solute-solvent interaction predominates over the solute-solute and solvent-solvent interactions for these ternary solutions. These are also justified by the measurement of various thermodynamic parameters, free energy of activation of viscous flow per mole of solvent(Δμ1°#) and solute (Δμ2°#), activation of viscous flow of enthalpies (ΔH°#) and entropies (ΔS°#). The characteristics of structure-breaking of solutes in the aqueous drug solution have been identified by Hepler's method and dB/dT value. The spectroscopic methods like UV–visible and proton-NMR studies help to explicate the strong AA-MEPN interactions in the solution phase and obtain a good correlation with theoretical studies. Theoretical investigations are checked to authenticate the experimental observations and according to both studies, L-Phe-MEPN interaction is greater than L-Val-MEPN interaction. The experimental and correlated research data are useful for the development of model combinations of AAs with drug molecules in pharmaceutical and medicinal chemistry.

Drugs in dental biofilm and enamel – A pilot study

ObjectiveEnamel and dental biofilm might serve as alternative matrices for determination of illicit and medical drugs. Thus, this study aims at evaluating possible correlations between detected drug concentrations in the matrices and simulated drug use in situ. DesignEleven subjects wore intraoral splints with embedded demineralized bovine enamel samples. Drug use was simulated by mouth rinsing with a 1.0 μg/ml drug solution three times daily for 1 min (study A) or by incubation of the splints in a 10 μg/ml drug solution once a day for 30 min (study B). Amphetamines, opiates, cocaine and benzoylecgonine were used as drugs. After 11 days, biofilm and enamel samples of the intraoral splints were analyzed by liquid chromatography mass spectrometry after drying and extraction via ultrasonication with acetonitrile (biofilm) or methanol (enamel). ResultsIn study A, median and mean drug concentration ± standard deviation were 1.3 pg/mg and 6.4 ± 11 pg/mg in biofilm and 0.2 pg/mg and 0.5 ± 0.9 pg/mg in enamel. In study B, median and mean drug concentration ± standard deviation were 350 pg/mg and 1100 ± 1600 pg/mg in biofilm and 5.8 pg/mg and 9.9 ± 10 pg/mg in enamel. ConclusionsOverall, there were considerable interindividual concentration differences. Correlations between concentrations in the two sample materials were shown. The results of this pilot study revealed a dependence of concentrations on intensity and duration of drug contact. Thus, important information on past drug use might be provided in forensic cases by analysis of dental biofilm and enamel.

Amorphous solid dispersions of triclabendazole: Keeping the supersaturated drug solution using poloxamers

The dissolution performance of amorphous solid dispersions often leads to the formation of supersaturated drug solutions. However, in many cases, the drugs can recrystallize from those solutions and precipitate. Thus, this study evaluates whether two selected poloxamers, as carriers of amorphous solid dispersions, could avoid the recrystallization and further precipitation of the hydrophobic triclabendazole. Different systems were prepared by the melting method and then characterized in solid and liquid states. The findings indicated that the drug solubility increased more than twenty times, from 0.3 μg/mL (raw drug) to 3.53 μg/mL and 7.28 μg/mL in the presence of P188 and P237, respectively. A similar finding was observed for the drug dissolution, and P188 and P237 increased the drug dissolution to 90 and 100 %, respectively. This study also confirmed that P237 was more effective than P188 in avoiding drug precipitation. As seen by X-ray diffraction analysis, an almost complete amorphization of the drug was observed by increasing the ratio of the poloxamers. Thus, these findings help to understand the dissolution behavior and supersaturated state of triclabendazole from amorphous solid dispersions, which could be applied to other hydrophobic drugs.

New Ion Selective Electrodes for Analysis of Metformin Based on Molecularly Imprinted Polymers

Metformin (MEF) imprinted polymer liquid electrodes arecreated using a precipitation polymerization process. The MEF served as a template for the creation of molecularly imprinted (MIP) materials using benzoyl peroxide (BPO) as an initiator, allyl methacrylate (AMA) crosslinkers, and glycidyl methacrylate (GMA) as a monomer. UtilizingDi-octyl-phthalate (DOPH) and di-butyl phthalate (DBPH) as plasticizers in a PVC matrix, the molecularly imprinted membranes arecreated. The reaction time is approximately 50 seconds, and the limits of detection for liquid electrodes, as determined by the calibration curves, are 55.6 to 58.4 mV/decadeat 5×10-5M and 8×10-5M respectively. The liquid electrodes demonstrated good selectivity over a variety of species and a consistent reaction when filled with a typical 0.1 M drug solution across the pH range of 1 to 11. Modern electrodes can detect MEF without the need for time-consuming pre-treatment procedures in pharmaceutical samples.

Unraveling the influence of solvent composition on Drop-on-Demand binder jet 3D printed tablets containing calcium sulfate hemihydrate

Recently, binder jet printed modular tablets were loaded with three anti-viral drugs via Drop on Demand (DoD) technology where drug solutions prepared in ethanol showed faster release than those prepared in water. During printing, water is used as a binding agent, whereas ethanol is added to maintain the porous structure of the tablets. Thus, the hypothesis is that the porosity would be controlled by manipulating the percentage of water and ethanol. In this study, Rhodamine 6G (R6G) was selected as a model drug due to its high solubility in water and ethanol, visualization function as a fluorescent dye, and potential therapeutic effects for cancer treatment. Approximately, 10 mg/ml R6G solutions were prepared with five different water–ethanol ratios (0–100, 75–25, 50–50, 75–25, 100–0). The ink solutions were printed onto blank binder jet 3D-printed tablets containing calcium sulphate hemihydrate using DoD technology. The tablets were dried at room temperature and then characterized using SEM-EDX, fluorescent microscope, TGA, XRD, FTIR, and DSC as well as in vitro release studies to investigate the impact of water–ethanol ratio on the release profile of R6G. Results indicated that the solution with higher ethanol ratio penetrated the tablets faster than the lower ethanol ratio, while the solution prepared with pure water was first accumulated onto the tablets' surface and then absorbed by the tablets. Moreover, tablets with more water content gained more weight and thickness. The EDX analysis and fluorescent microscope showed the uniform surface distribution of the drug. The SEM images revealed the difference in the tablet surface among the five formulations. Furthermore, the TGA data presents a notable increase in water loss, with XRD analysis suggesting the formation of gypsum in tablets containing elevated water content. The release study exhibited that the fastest release was from WE0-100, whereas the release rate decreases as the content of water increases. The WE0-100 releases more than 40 % drug within the first hour which is almost twice as high of the WE100-0 formulation. This DoD technology could distribute drugs onto the tablet's surface uniformly. The calcium sulfate would transform from hemihydrate to dihydrate form in the presence of water and therefore, those tablets treated with higher water content led to slower release. In conclusion, this study underscores the substantial impact of the water–ethanol ratio on drug release from binder jet printed tablets and highlights the potential of DoD technology for uniform drug distribution and controlled release.

Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics.

This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and AUCtotal (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl.

The inherent AIE feature revealed the drug molecular state in cyclodextrin metal–organic framework for enhanced stability and absorption

The amorphous form of a drug can greatly improve the solubility and rates of dissolution for enhancing oral bioavailability. However, amorphous drugs tend to crystallize thus negating their solubility advantages. Here, we use a nanoconfinement strategy to prevent the crystallization of amorphous solids by loading the poorly soluble drug indomethacin (IMC) into a porous γ-cyclodextrin-based metal–organic framework (CD-MOF). The inherent aggregation-induced emission (AIE) property of IMC was successfully applied as a sensitive fluorescence imaging tool to visualize its molecular state in the solid form. A distinct high-energy, non-aggregated molecular state of IMC in CD-MOF was revealed by the AIE turn-off phenomenon together with other solid-state characterization methods. The IMC@CD-MOF exhibited excellent physical stability even when stored at high temperature or humidity. The high supersaturated drug solutions were immediately generated and maintained during the dissolution of IMC@CD-MOF, resulting in a great enhancement of in vivo bioavailability. The inherent AIE feature of drugs can facilitate the understanding of the structure–property relationship in complex delivery systems, which is essential for the design and optimization of drug carriers with desired stability and biopharmaceutical performance.

Simultaneous Quantification of Mometasone Furoate and Formoterol Fumarate in Bulk and Formulations by RP-HPLC Method

A simple and robust reversed-phase high pressure liquid chromatographic method was developed and validated for the quantification of Mometasone and Formoterol in bulk and fixed dosage forms. The column utilized for study was Inertsil C18, ODS was chosen for good peak shape. Ambient temperature was found to be suitable for the nature of drug solution. The mobile phase was streamlined with a ratio of 35:65 Methanol: Water was optimized for symmetrical peaks and good resolution. The flow rate was streamlined at 1.0 ml/min because of good peak area, satisfactory retention time and good resolution. Common λ-max was found to be at 278 nm and Injection volume was 20 µl which gave a good peak area. The percentage recovery was found to be 98.0-101.50 was linear and precise over the same range. Both system and method precision was found to be accurate and well within the acceptable limits. Detection limit was found to be 0.25 Mometasone and 0.34 for Formoterol. The analytical method was found linearity over the range of 20-80 ppm of the target concentration for both the drugs. The LOD and LOQ values for Mometasone, was observed to be 0.25 and 0.77 and for Formoterol was in the range of 0.34 and 1.05 consecutively. The analytical method passed both intermediate precision and robustness tests. On both cases, relative standard deviation was well satisfactory. The validation experiments met ICH standards. It inferred the method found to be simple, accurate, precise and linear. The method was found to be having suitable application in routine laboratory analysis with high degree of accuracy and precision.

Accurate Estimation of Some Pharmaceutical Compounds Using HPLC Technology

For the assessment of different chemical components in pharmaceutical and biological samples, High Performance Liquid Chromatography (HPLC) can be defined as a commonly utilized analytical method in pharmaceutical samples. HPLC offers high sensitivity, specificity, and accuracy, making it a preferred method for the analysis of complex samples. In this technique, the sample is prepared by extracting, purifying, and concentrating the target analyte from the matrix. Mobile and stationary phases are after that used in chromatographic separation of the prepared sample. Several detectors, including fluorescence, UV-vis, and mass spectrometry, are used to identify and measure the eluted compounds. HPLC is capable of estimating a wide range of elements, including small molecules, peptides, and proteins, making it an essential tool in pharmaceutical research and development. The theoretical plates, peak tailing, and % assay have not been significantly impacted by the deliberate alterations made to the method. This implies that the existing technique is robust. The low values of LOQ and LOD show how sensitive the suggested approach is. The current research used a standard drug solution with six replicates to examine the system suitability parameters. It was discovered that the computed parameters fell under the acceptable criteria. The theoretical plate count, tailing factor, and HETP parameters are all within acceptable ranges. The results of this work are compared with those of earlier research. Upon analyzing the chart, it can be inferred that the proposed method presents certain benefits. The investigation employed a Kromasil C18 column. The obtained retention time is comparatively lower than that of all other methodologies. The maximum quantifiable threshold is 600 μg/mL, surpassing or equating all of the aforementioned techniques. The duration of the execution is also minimal. Therefore, the author draws the conclusion that the HPLC method proposed exhibits sensitivity and reproducibility in analysis of etodolac and thiocolchicoside in combined tablet dosage form, while also requiring a short analysis time.

Nanostructured lipid carriers loaded into in situ gels for breast cancer local treatment

In this study, nanostructured lipid carriers (NLC) were developed and employed to obtain in situ thermosensitive formulations for the ductal administration and prolonged retention of drugs as a new strategy for breast cancer local treatment. NLC size was influenced by the type and concentration of the oil phase, surfactants, and drug incorporation, ranging from 221.6 to 467.5 nm. The type of liquid lipid influenced paclitaxel and 5-fluorouracil cytotoxicity, with tributyrin-containing NLC reducing IC50 values by 2.0–7.0-fold compared to tricaprylin NLC in MCF-7, T-47D and MDA-MB-231 cells. In spheroids, the NLCs reduced IC50 compared to either drug solution (3.2–6.2-fold). Although a significant reduction (1.26 points, p < 0.001) on the health index of Galleria mellonella larvae was observed 5 days after NLC administration, survival was not significantly reduced. To produce thermosensitive gels, the NLCs were incorporated in a poloxamer (11 %, w/w) dispersion, which gained viscosity (2-fold) at 37 °C. After 24 h, ∼53 % of paclitaxel and 83 % of 5-fluorouracil were released from the NLC; incorporation in the poloxamer gel further prolonged release. Intraductal administration of NLC-loaded gel increased the permanence of hydrophilic (2.2–3.0-fold) and lipophilic (2.1–2.3-fold) fluorescent markers in the mammary tissue compared to the NLC (as dispersion) and the markers solutions. In conclusion, these results contribute to improving our understanding of nanocarrier design with increased cytotoxicity and prolonged retention for the intraductal route. Tributyrin incorporation increased the cytotoxicity of paclitaxel and 5-fluorouracil in monolayer and spheroids, while NLC incorporation in thermosensitive gels prolonged tissue retention of both hydrophilic and hydrophobic compounds.

In situ co-crystallization synthesis of the direct Z-scheme Bi5O7I/Bi2SiO5 heterojunction for enhanced photocatalytic rhodamine B and ciprofloxacin degradation

Semiconductor photocatalysis has driven considerable interests for its desirable potential to tackle the worldwide energy shortage and environmental pollution. In this paper, a novel Bi5O7I/Bi2SiO5 Z-scheme heterojunction photocatalyst was in situ synthesized via a co-crystallization process and partial anion exchange strategy. The XRD and FT-IR pattern validated the successful preparation of the heterojunction. The optimal Bi5O7I/Bi2SiO5 heterojunction displayed an excellent photocatalytic activity towards the ciprofloxacin under the simulated solar light, and the rate constant (0.46021 h−1) was 2 and 7.8 times higher than that of pure BiOI (0.22967 h−1) and Bi2SiO5 (0.05877 h−1). Similarly, the degradation efficiency on rhodamine B (RhB) reached 94%, which was much higher than that of the single photocatalysis. The enhanced photocatalytic performance of the heterojunction photocatalyst could be attributed to the formation of the direct Z-scheme heterojunction between the Bi5O7I and Bi2SiO5, which was favorable for retarding the recombination of photoinduced electron-hole pairs. Moreover, the bacteriostatic activity testing illustrated the toxicity of drug solutions decreased sharply after the photocatalytic degradation with the Bi5O7I/Bi2SiO5-3. The ESR characterization analysis and the free radical trapping experiments synergistically determined the Z-scheme electron transfer path of the heterojunction. The possible photocatalytic mechanism of Bi5O7I/Bi2SiO5 heterojunction was proposed. Overall, the well-designed Bi5O7I/Bi2SiO5 heterojunction depicted great practical promise in efficient treatment of organic pollutants.

Nanocrystallization - A Tool for Enhancement of Solubility and Dissolution Rate for Water Insoluble Drugs

An innovative method to increase the solubility of water insoluble drug by using Nanocrystallization. Various factor like solubility, dissolution drug release, temperature, ph, have its effect on these process. Solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Solutes are classified as highly soluble, sparingly soluble, or insoluble based on the concentration. Dissolution is ability of molecule to get break down in it. There are seven different types of dissolution apparatus defined in the United States Pharmacopeia (USP)-basket type, paddle type, reciprocating cylinder, and flow through cell, paddle over disc, rotating cylinder, and reciprocating disc. Drug release is when drug solutes migrate from the initial position in the polymeric system to the polymer's outer surface and then to the release medium. It is directly related to the drug stability. There are many mechanisms by which the drug release can be controlled in a system: dissolution, diffusion, osmosis, partitioning, swelling, erosion, and targeting. Drug Stabilizers are compounds, usually polysaccharides, which are added to products to provide and preserve structure, stability, and viscosity. Broadly there are 3 methods for the nanocrystallizationi.e. Bottom up technique, Top down technique and combination technique.

An Ultraswelling Microneedle Device for Facile and Efficient Drug Loading and Transdermal Delivery.

The advancement and extensive demand for transdermal therapies can benefit from a safe, and efficient and user-friendly transdermal technology with broad applicability in delivering various hydrophilic drugs. Here the design and proof of concept applications of an ultraswelling microneedle device that enables the facile and efficient loading and transdermal delivery of hydrophilic drugs with different molecular weights is reported. The device consists of a super-hydrophilic hydrogel microneedle array and a resin base substrate. Using a special micromolding technique that involves hydrated crosslinking and cryogenic-demolding, the microneedle part displays a rapid swelling ratio of ≈3800%, enabling the loading of drugs up to 500kDa in molecular weight. The drug loading process using the device just involves incubating the microneedle part in a drug solution for 1min, followed by 15min of drying. The microneedles can easily penetrate the skin under press and detach from the base substrate under shear, thereby releasing the payload. Administration of desired therapeutic agents using the device outperformed conventional administration methods in mitigating psoriasis and eliciting immunity. This biocompatible device, capable of withstanding ethylene oxide sterilization, can enhance the efficacy and accessibility of transdermal therapies in research institutes, hospitals, and even home settings.

Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer

Irinotecan (IRT), a classic clinical chemotherapeutic agent for treating colorectal cancer, has been found to induce immunogenic cell death (ICD) while exerting cytotoxicity in tumor cells. This effect is likely to be amplified in combination with immune modulators. Unfortunately, free drugs without targeting capacity would receive poor outcomes and strong side effects. To address these issues, in this work, an acid-sensitive micelle based on an amphiphilic poly(β-amino ester) derivative was constructed to co-deliver IRT and the immune adjuvant imiquimod (IMQ), termed PII. PII kept stable under normal physiological conditions. After internalization by tumor cells, PII dissociated in acidic lysosomes and released IRT and IMQ rapidly. In the CT26 tumor mouse model, PII increased the intra-tumoral SN38 (the active metabolite of IRT) and IMQ concentrations by up to 9.39 and 3.44 times compared with the free drug solution. The tumor inhibition rate of PII achieved 87.29%. This might profit from that IRT induced ICD, which promoted dendritic cells (DCs) maturation and intra-tumoral infiltration of CD8+ T cells. In addition, IMQ enhanced the antigen presenting ability of DCs and stimulated tumor associated macrophages to secrete tumor-killing cytokines. PII provided an effective strategy to combat colorectal cancer by synergy of chemotherapy and immunoregulation.