Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release.

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Implications of Pharmacokinetic Potentials of Pioglitazone Enantiomers in Rat Plasma Mediated through Glucose Uptake Assay.

Pioglitazone, a PPAR-gamma activator used to diagnose hyperglycemia, was studied for its stereoselective deposition and active enantiomers in female albino Wistar rats. In accordance with USFDA recommendations, a bioanalytical technique was employed to assess the segregation of pioglitazone enantiomers in rat plasma with glimepiride as an internal standard. A Phenomenox i-Amylose-3 column (150 mm × 4.6 mm) of 5 µm was used for high-performance liquid chromatography (HPLC) with a mobile phase of 10 mM ammonium acetate buffer in Millipore water and acetonitrile in 60:40 (v/v) admixture with column temperature 35 °C, wavelength 265 nm, and flow rate 0.6 mL/min, respectively. Pioglitazone-S, Pioglitazone-R, and the internal standard had retention times of 3.1, 7.4, and 1.7 min, respectively. The study found that within-run and between-run precision ranged from 0.1606-0.9889% for Pioglitazone-R and from 0.2080-0.7919% for Pioglitazone-S, while the accuracy ranged from 99.86 to 100.36% for Pioglitazone-R and 99.84 to 99.94% for Pioglitazone-S. In addition, a non-radioactive glucose uptake assay was employed to examine the enantiomers in 3T3-L1 cell lines by flow cytometry. Significant differences were demonstrated in Cmax, AUClast (h*µg/mL), AUCINF obs (h*µg/mL), and AUC%Extrap obs (%) of Pioglitazone-R and S in female albino Wistar rats, suggesting enantioselectivity of pioglitazone.

The Use of Nanoneedles in Drug Delivery: an Overview of Recent Trends and Applications.

Nanoneedles (NN) are growing rapidly as a means of navigating biological membranes and delivering therapeutics intracellularly. Nanoneedle arrays (NNA) are among the most potential resources to achieve therapeutic effects by administration of drugs through the skin. Although this is based on well-established approaches, its implementations are rapidly developing as an important pharmaceutical and biological research phenomenon. This study intends to provide a broad overview of current NNA research, with an emphasis on existing approaches, applications, and types of compounds released by these systems. A nanoneedle-based delivery device with great spatial and temporal accuracy, minimal interference, and low toxicity could transfer biomolecules into living organisms. Due to its vast potential, NN has been widely used as a capable transportation system of many therapeutic active substances, from cancer therapy, vaccine delivery, cosmetics, and bio-sensing nanocarrier drugs to genes. The use of nanoneedles for drug delivery offers new opportunities for the rapid, targeted, and exact administration of biomolecules into cell membranes for high-resolution research of biological systems, and it can treat a wide range of biological challenges. As a result, the literature has analyzed existing patents to emphasize the status of NNA in biological applications.

Development and Optimization of Hybrid Polymeric Nanoparticles of Apigenin: Physicochemical Characterization, Antioxidant Activity and Cytotoxicity Evaluation.

Breast cancer is the most common cancer in females and ranked second after skin cancer. The use of natural compounds is a good alternative for the treatment of breast cancer with less toxicity than synthetic drugs. The aim of the present study is to develop and characterize hybrid Apigenin (AN) Nanoparticles (NPs) for oral delivery (AN-NPs). The hybrid AN-NPs were prepared by the self-assembly method using lecithin, chitosan and TPGS. Further, the NPs were optimized by Box-Behnken design (3-factor, 3-level). The hybrid NPs were evaluated for particle size (PS), entrapment efficiency (EE), zeta potential (ZP), and drug release. The optimized hybrid NPs (ON2), were further evaluated for solid state characterization, permeation, antioxidant, cytotoxicity and antimicrobial study. The formulation (ON2) exhibited small PS of 192.6 ± 4.2 nm, high EE 69.35 ± 1.1%, zeta potential of +36.54 mV, and sustained drug release (61.5 ± 2.5% in 24 h), as well as significantly (p < 0.05) enhanced drug permeation and antioxidant activity. The IC50 of pure AN was found to be significantly (p < 0.05) lower than the formulation (ON2). It also showed significantly greater (p < 0.05) antibacterial activity than pure AN against Bacillus subtilis and Salmonella typhimurium. From these findings, it revealed that a hybrid AN polymeric nanoparticle is a good carrier for the treatment of breast cancer.

Formulation of Isopropyl Isothiocyanate Loaded Nano Vesicles Delivery Systems: In Vitro Characterization and In Vivo Assessment.

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment.

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box−Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.

Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines.

Abemaciclib (AC) is a novel, orally available drug molecule approved for the treatment of breast cancer. Due to its low bioavailability, its administration frequency is two to three times a day that can decrease patient compliance. Sustained release formulation are needed for prolong the action and to reduce the adverse effects. The aim of current study was to develop sustained release NSs of AC. Nanosponges (NSs) was prepared by emulsion-solvent diffusion method using ethyl-cellulose (EC) and Kolliphor P-188 (KP-188) as sustained-release polymer and surfactant, respectively. Effects of varying surfactant concentration and drug: polymer proportions on the particle size (PS), polydispersity index (PDI), zeta potential (ζP), entrapment efficiency (%EE), and drug loading (%DL) were investigated. The results of AC loaded NSs (ACN1-ACN5) exhibited PS (366.3-842.2 nm), PDI (0.448-0.853), ζP (-8.21 to -19.7 mV), %EE (48.45-79.36%) and %DL (7.69-19.17%), respectively. Moreover, ACN2 showed sustained release of Abemaciclib (77.12 ± 2.54%) in 24 h Higuchi matrix as best fit kinetics model. MTT assay signified ACN2 as potentials cytotoxic nanocarrier against MCF-7 and MDA-MB-231 human breast cancer cells. Further, ACN2 displayed drug release property without variation in the % release after exposing the product at 25 °C, 5 °C, and 45 °C storage conditions for six months. This investigation proved that the developed NSs would be an efficient carrier to sustain the release of AC in order to improve efficacy against breast cancer.

Development and Characterization of Calcium-Alginate Beads of Apigenin: In Vitro Antitumor, Antibacterial, and Antioxidant Activities.

The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for particle size, drug loading, percentage yield, and in vitro drug release. Particle size was found to decrease, and drug entrapment efficiency was enhanced with an increase in the polymer concentration. The dissolution study showed sustained drug release from the apigenin-loaded alginate beads with an increase in the polymer proportion. Based on the dissolution profiles, BD6 formulation was optimized and characterized for FTIR, DSC, XRD, and SEM, results of which indicated successful development of apigenin-loaded Ca alginate beads. MTT assay demonstrated a potential anticancer effect against the breast cancer MCF-7 cell lines. The antimicrobial activity exhibited effective inhibition in the bacterial and fungal growth rate. The DPPH measurement revealed that the formulation had substantial antioxidant activity, with EC50 value slightly lowered compared to pure apigenin. A stability study demonstrated that the BD6 was stable with similar (f2) drug release profiles in harsh condition. In conclusion, alginate-based beads could be used for sustaining the drug release of poorly water-soluble apigenin while also improving in vitro antitumor, antimicrobial, and antioxidant activity.

Brigatinib loaded poly(d,l-lactide-co-glycolide) nanoparticles for improved anti-tumoral activity against non-small cell lung cancer cell lines.

OBJECTIVE: The aim of the current investigation was to develop poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to sustain the brigatinib (BTB) release for prolong time period and to examine the antitumor effect of the optimized NPs. SIGNIFICANCE: Optimized PLGA-based NPs of BTB could be potentially used as a promising nanocarrier for the treatment of non-small cell lung cancer. METHODS: BTB-loaded NPs were fabricated with core-shell of PLGA by solvent evaporation technique using different proportions of PLGA polymer and poly-vinyl alcohol (PVA) stabilizer. The prepared NPs were evaluated for particle characterizations; size, polydispersity index (PDI), zeta-potential, entrapment efficiency (EE), and drug loading (DL), Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction studies. The optimized NPs (BN5) were further evaluated for morphology, stability, and cytotoxicity studies against A549 cell-lines. RESULTS: Among the nine different NPs formulae (BN1-BN9), BN5 was optimized with composition of BTB (30 mg), PLGA (75 mg), PVA (0.55% w/v), represents an average particle size of (267.1 ± 1.01 nm), PDI (0.101 ± 0.007), and zeta potential (-42.1 ± 0.75 mV), high EE (66.83 ± 0.06%), and DL (6.17 ± 0.69%). SEM image of selected NPs was spherical with smooth surface. In vitro drug release profile in phosphate buffers (pH 5 and pH 7.4) showed a biphasic release with initial burst phase followed by sustained release for prolong time. Furthermore, optimized NPs (BN5) exhibited excellent cytotoxic activity against A549 cell-lines with IC50 value of 5.25 ± 0.23 µg/mL. CONCLUSION: The overall results suggest that BTB-loaded PLGA NPs could be a potential nanocarrier for lung cancer treatment.

Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability.

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (-36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer-Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.

Formulation and in vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection.

In the current study, four formulae (BNS1-BNS4) of butenafine (BTF) loaded nanosponges (NS) were fabricated by solvent emulsification technology, using different concentration of ethyl cellulose (EC) and polyvinyl alcohol (PVA) as a rate retarding polymer and surfactant, respectively. Prepared NS were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). Nanocarrier BNS3 was optimized based on the particle characterizations and drug encapsulation. It was further evaluated for physicochemical characterizations; FTIR, DSC, XRD and SEM. Selected NS BNS3 composed of BTF (100 mg), EC (200 mg) and 0.3% of PVA showed, PS (543 ± 0.67 nm), PDI (0.330 ± 0.02), ZP (-33.8 ± 0.89 mV), %EE (71.3 ± 0.34%) and %DL (22.8 ± 0.67%), respectively. Fabricated NS also revealed; polymer-drug compatibility, drug-encapsulation, non-crystalline state of the drug in the spherical NS as per the physicochemical evaluations. Optimized NS (BNS3) with equivalent amount of (1%, w/w or w/v) BTF was incorporated into the (1%, w/w or w/v) carbopol gel. BTF loaded NS based gel was then evaluated for viscosity, spreadability, flux, drug diffusion, antifungal, stability and skin irritation studies. BNS3 based topical gels exhibited a flux rate of 0.18 (mg/cm2.h), drug diffusion of 89.90 ± 0.87% in 24 h with Higuchi model following anomalous non-Fickian drug release. The BNS3 based-gel could be effective against pathogenic fungal strains.

Antioxidant and Anti-inflammatory Applications of Aerva persica Aqueous-Root Extract-Mediated Synthesis of ZnO Nanoparticles.

In the present study, ZnO nanoparticles were synthesized by using aqueous extracts of Aerva persica roots. Characterization of as-prepared ZnO nanoparticles was carried out using different techniques, including powder X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and BET surface area analysis. Morphological analysis confirmed the small, aggregated flake-shaped morphology of as-synthesized ZnO nanostructures. The as-prepared ZnO nanoparticles were analyzed for their potential application as anti-inflammatory (using in vivo inhibition of carrageenan induced paw edema) and antioxidant (using in vitro radical scavenging activity) agents. The ZnO nanoparticles were found to have a potent antioxidant and anti-inflammatory activity comparable to that of standard ascorbic acid (antioxidant) and indomethacin (anti-inflammatory drug). Therefore, due to their ecofriendly synthesis, nontoxicity, and biocompatible nature, zinc oxide nanoparticles synthesized successfully from roots extract of the plant Aerva persica with potent efficiencies can be utilized for different biomedical applications.

Quality by design aided self-nano emulsifying drug delivery systems development for the oral delivery of Benidipine: Improvement of biopharmaceutical performance.

The primary objective of the research effort is to establish efficient solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for benidipine (BD) through the systematic application of a quality-by-design (QbD)-based paradigm. Utilizing Labrafil M 2125 CS, Kolliphor EL, and Transcutol P, the BD-S-SNEDDS were created. The central composite design was adopted to optimize numerous components. Zeta potential, drug concentration, resistance to dilution, pH, refractive index, viscosity, thermodynamic stability, and cloud point were further investigated in the most efficient formulation, BD14, which had a globule size of 156.20 ± 2.40 nm, PDI of 0.25, zeta potential of -17.36 ± 0.18 mV, self-emulsification time of 65.21 ± 1.95 s, % transmittance of 99.80 ± 0.70%, and drug release of 92.65 ± 1.70% at 15 min. S-SNEDDS were formulated using the adsorption process and investigated via Fourier transform infrared spectroscopy, Differential scanning calorimeter, Scanning electron microscopy, and powder X-ray diffraction. Optimized S-SNEDDS batch BD14 dramatically decreased blood pressure in rats in contrast to the pure drug and the commercial product, according to a pharmacodynamics investigation. Accelerated stability tests validated the product's stability. Therefore, the development of oral S-SNEDDS of BD may be advantageous for raising BD's water solubility and expanding their releasing capabilities, thereby boosting oral absorption.

Formulation and Evaluation of pH-Modulated Amorphous Solid Dispersion-Based Orodispersible Tablets of Cefdinir.

Cefdinir (CEF) is a semi-synthetic third-generation broad-spectrum oral cephalosporin that exhibits poor solubility at lower pH values. Considering this, pH-modulated CEF solid dispersions (ASDs) were produced by solvent evaporation method employing various hydrophilic carriers and alkalizers. Among different carriers, ASDs produced using PEG 6000 with meglumine as alkalizer were found to significantly increase (p < 0.005) the drug solubility (4.50 ± 0.32 mg/mL) in pH 1.2. Fourier transform infrared spectrophotometry confirmed chemical integrity of CEF while differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) indicated CEF was reduced to an amorphous state in ASD8. Antimicrobial assay performed by well diffusion method against Staphylococcus aureus (MTCC96) and Escherichia coli (MTCC118) demonstrated significantly superior (p < 0.001) efficacy of CEFSD compared to CEF. The porous orodispersible tablets (ODTs) of ASD8 (batch F5) were developed by incorporating ammonium bicarbonate as a subliming agent by direct compression, followed by vacuum drying displayed quick disintegration (27.11 ± 1.96 s) that met compendial norms and near-complete dissolution (93.85 ± 1.27%) in 30 min. The ODTs of ASD8 appear to be a promising platform to mitigate the pH-dependent solubility and dissolution issues associated with CEF in challenging physiological pH conditions prevalent in stomach. Thus, ODTs of ASD8 are likely to effectively manage various infections and avoid development of drug-resistant strains, thereby improving the curing rates.

Simvastatin-Encapsulated Topical Liposomal Gel for Augmented Wound Healing: Optimization Using the Box-Behnken Model, Evaluations, and In Vivo Studies.

Statins function beyond regulating cholesterol and, when administered systemically, can promote wound healing. However, studies have yet to explore the topical use of statins for wound healing. The present study demonstrated the topical administration of SIM and aimed to formulate, evaluate, and optimize Simvastatin (SIM)-encapsulated liposome gel carrier systems to facilitate successful topical wound healing. Liposomes containing SIM were formulated and optimized via a response surface methodology (RSM) using the thin-film hydration method. The effects of formulation variables, including the 1,2-dioleoyloxy-3-trimethylammoniumpropan (DOTAP) concentration, Span 80 concentration, and cholesterol concentration, on zeta potential (mV), entrapment efficacy (%), and particle size (nm) were studied. The optimized liposome formulation (F-07) exhibited a zeta potential value of 16.56 ± 2.51 mV, revealing robust stability and a high SIM encapsulation efficiency of 95.6 ± 4.2%, whereas its particle size of 190.3 ± 3.3 nm confirmed its stability and structural integrity. The optimized liposome gel demonstrated pseudoplastic flow behavior. This property is advantageous in topical drug delivery systems because of its ease of application, improved spreadability, and enhanced penetration, demonstrating prolonged SIM release. The assessment of the wound healing efficacy of the optimized liposomal gel formulation demonstrated a substantial decrease in wound size in mice on the sixteenth day post-wounding. These findings suggest that the use of liposomal gels is a potential drug delivery strategy for incorporating SIM, thereby augmenting its effectiveness in promoting wound healing.

Box-Behnken Design-Based Optimization and Evaluation of Lipid-Based Nano Drug Delivery System for Brain Targeting of Bromocriptine.

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson's disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.

Development of Diphenyl carbonate-Crosslinked Cyclodextrin Based Nanosponges for Oral Delivery of Baricitinib: Formulation, Characterization and Pharmacokinetic Studies.

Background: The aim of the present investigation is to prepare baricitinib (BAR)-loaded diphenyl carbonate (DPC) ß-cyclodextrin (ßCD) based nanosponges (NSs) to improve the oral bioavailability. Methods: BAR-loaded DPC-crosslinked ßCD NSs (B-DCNs) were prepared prepared by varying the molar ratio of ßCD: DPC (1:1.5 to 1:6). The developed B-DCNs loaded with BAR were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), % yield and percent entrapment efficiency (%EE). Results: Based on the above evaluations, BAR-loaded DPC ßCD NSs (B-CDN3) was optimized with mean size (345.8±4.7 nm), PDI (0.335±0.005), Yield (91.46±7.4%) and EE (79.1±1.6%). The optimized NSs (B-CDN3) was further confirmed by SEM, spectral analysis, BET analysis, in vitro release and pharmacokinetic studies. The optimized NSs (B-CDN3) showed 2.13 times enhancement in bioavailability in comparison to pure BAR suspension. Conclusion: It could be anticipated that NSs loaded with BAR as a promising tool for release and bioavailability for the treatment of rheumatic arthritis and Covid-19.

Fused Deposition Modelling 3D-Printed Gastro-Retentive Floating Device for Propranolol Hcl Tablets.

Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product.

3D Printed Pharmaceutical Systems for Personalized Treatment in Metabolic Syndrome.

The current healthcare system is widely based on the concept of "one size fit for all", which emphasizes treating a disease by prescribing the same drug to all patients with equivalent doses and dosing frequency. This medical treatment scenario has shown varied responses with either no or weak pharmacological effects and exaggerated adverse reactions preceded by more patient complications. The hitches to the concept of "one size fits all" have devoted the attention of many researchers to unlocking the concept of personalized medicine (PM). PM delivers customized therapy with the highest safety margin for an individual patient's needs. PM has the potential to revolutionize the current healthcare system and pave the way to alter drug choices and doses according to a patient's clinical responses, providing physicians with the best treatment outcomes. The 3D printing techniques is a solid-form fabrication method whereby successive layers of materials based on computer-aided designs were deposited to form 3D structures. The 3D printed formulation achieves PM goals by delivering the desired dose according to patient needs and drug release profile to achieve a patient's personal therapeutic and nutritional needs. This pre-designed drug release profile attains optimum absorption and distribution, exhibiting maximum efficacy and safety profiles. This review aims to focus on the role of the 3D printing technique as a promising tool to design PM in metabolic syndrome (MS).

Eluxadoline-Loaded Eudragit Nanoparticles for Irritable Bowel Syndrome with Diarrhea: Formulation, Optimization Using Box-Behnken Design, and Anti-Diarrheal Activity.

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study's goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box-Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment.