Correction: Shakir et al. Exorbitant Drug Loading of Metformin and Sitagliptin in Mucoadhesive Buccal Tablet: In Vitro and In Vivo Characterization in Healthy Volunteers. Pharmaceuticals 2022, 15, 686.

In the original publication, a mistake was observed in Figure 5 as published [...].

Development and characterization of pH-responsive Delonix regia/mucin co-poly (acrylate) hydrogel for controlled drug delivery of metformin HCl.

This study introduces a pH-responsive hydrogel developed from Delonix regia and mucin co-poly(acrylate) through free radical polymerization to enhance controlled drug delivery systems. Characterization using FTIR, DSC, TGA, SEM, PXRD, and EDX spectroscopy detailed the hydrogel's amorphous and crystalline structures, thermal stability, surface characteristics, and elemental composition. Tested at a pH of 7.4-mimicking intestinal conditions-the hydrogel demonstrated significant swelling, indicating its capability for targeted drug release. With Metformin HCl as a model drug, the hydrogel exhibited a promising sustained release profile, underscoring its potential for oral administration. Safety and biocompatibility were assessed through acute oral toxicity studies in albino rabbits, encompassing biochemical, hematological, and histopathological evaluations. X-ray imaging confirmed the hydrogel's navigability through the gastrointestinal tract, affirming its application in drug delivery. By potentially mitigating gastrointestinal side effects, enhancing patient compliance, and improving therapeutic efficacy, this Delonix regia/mucin co-poly(acrylate) hydrogel represents a step in pharmaceutical sciences, exploring innovative materials and methodologies for drug delivery.

Sustained release delivery of favipiravir through statistically optimized, chemically cross-linked, pH-sensitive, swellable hydrogel.

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir.

Development and evaluation of a pH-responsive Mimosa pudica seed mucilage/ß- cyclodextrin-co-poly(methacrylate) hydrogel for controlled drug delivery: In vitro and in vivo assessment.

In this comprehensive investigation, a novel pH-responsive hydrogel system comprising mimosa seed mucilage (MSM), ß-cyclodextrin (ß-CD), and methacrylic acid (MAA) was developed via free radical polymerization technique to promote controlled drug delivery. The hydrogel synthesis involved strategic variations in polymer, monomer, and crosslinker content in fine-tuning its drug-release properties. The resultant hydrogel exhibited remarkable pH sensitivity, selectively liberating the model drug (Capecitabine = CAP) under basic conditions while significantly reducing release in an acidic environment. Morphological, thermal, and structural analyses proved that CAP has a porous texture, high stability, and an amorphous nature. In vitro drug release experiments showcased a sustained and controlled release profile. Optimum release (85.33 %) results were recorded over 24 h at pH 7.4 in the case of MMB9. Pharmacokinetic evaluation in healthy male rabbits confirmed bioavailability enhancement and sustained release capabilities. Furthermore, rigorous toxicity evaluations and histopathological analyses ensured the safety and biocompatibility of the hydrogel. This pH-triggered drug delivery system can be a promising carrier system for drugs involving frequent administrations.

Chitosan-based intelligent polymeric networks for site-specific colon medication delivery: A comprehensive study on controlled release of diloxanide furoate and network formation dynamics.

Oral medications are prone to gastric degradation and enzymatic inactivation, diminishing their efficacy. This study investigates a solution by developing intelligent polymeric networks, incorporating chitosan, methacrylic acid, N, N, methylene bisacrylamide, and montmorillonite clay, to enable the controlled release of Diloxanide Furoate (DF), an anti-protozoal drug. Employing a swelling-assisted diffusion technique, drug loading percentages varied from 63.96 % to 76.82 % among different formulations. Increased chitosan and methacrylic acid content enhanced drug loading, while N, N, methylene bisacrylamide and montmorillonite clay demonstrated an inverse relationship affecting diffusion and swelling. Equilibrium swelling studies unveiled formulation-dependent behaviors, with chitosan reducing swelling and methacrylic acid promoting it. Higher N, N, methylene bisacrylamide concentrations decreased swelling, indicating a denser cross-linked structure, while montmorillonite clay reduced hydrophilicity and swelling capacity. Further analyses confirmed successful gel formation, particularly in formulations with higher chitosan, methacrylic acid, and N, N, methylene bisacrylamide content, while montmorillonite clay limited gel fraction due to restricted polymer chain mobility. Techniques such as Fourier transform infrared spectroscopy, Differential scanning calorimetry, and thermal gravimetric analyses supported network development, enhancing thermal stability and cross-linking density. This research underscores the flexibility of polymeric networks for precise drug delivery, offering potential advancements in targeted therapies for various medical conditions.

Statistically Optimized Polymeric Buccal Films of Eletriptan Hydrobromide and Itopride Hydrochloride: An In Vivo Pharmacokinetic Study.

A migraine is a condition of severe headaches, causing a disturbance in the daily life of the patient. The current studies were designed to develop immediate-release polymeric buccal films of Eletriptan Hydrobromide (EHBR) and Itopride Hydrochloride (ITHC) to improve their bioavailability and, hence, improve compliance with the patients of migraines and its associated symptoms. The prepared films were evaluated for various in vitro parameters, including surface morphology, mechanical strength, disintegration test (DT), total dissolving time (TDT), drug release and drug permeation, etc., and in vivo pharmacokinetic parameters, such as area under curve (AUC), mean residence time (MRT), half-life (t1/2), time to reach maximum concentration (Tmax), and time to reach maximum concentration (Cmax). The outcomes have indicated the successful preparation of the films, as SEM has confirmed the smooth surface and uniform distribution of drugs throughout the polymer matrix. The films were found to be mechanically stable as indicated by folding endurance studies. Furthermore, the optimized formulations showed a DT of 13 ± 1 s and TDT of 42.6 ± 0.75 s, indicating prompt disintegration as well as the dissolution of the films. Albino rabbits were used for in vivo pharmacokinetics, and the outcomes were evident of improved pharmacokinetics. The drug was found to rapidly permeate across the buccal mucosa, leading to increased bioavailability of the drug: Cmax of 130 and 119 ng/mL of ITHC and EHBR, respectively, as compared to 96 (ITHC) and 90 ng/mL (EHBR) of oral solution. The conclusion can be drawn that possible reasons for the enhanced bioavailability could be the increased surface area in the form of buccal films, its rapid disintegration, and faster dissolution, which led toward the rapid absorption of the drug into the blood stream.

Fast dissolving microneedle patch for pronounced systemic delivery of an antihyperlipidemic drug.

Fast dissolving microneedles (F-dMN) are quite a novel approach delivering specific drug molecules directly into the bloodstream, bypassing the first-pass effect. The present study reported an F-dMN patch to enhance systemic delivery of simvastatin in a patient-friendly manner. The F-dMN patch was developed using polyvinyl pyrrolidone and polyvinyl alcohol and characterized using light microscopy, SEM, XRD, FTIR, mechanical strength, drug content (%), an ex-vivo penetration study, an ex-vivo drug release study, a skin irritation test, and a pharmacokinetics study. The optimized F-dMN patch exhibited excellent elongation of 35.17%, good tensile strength of 9.68 MPa, an appropriate moisture content of 5.65%, and good penetrability up to 560 µm. Moreover, it showed 93.4% of the drug content within the needles and 81.75% in-vitro release. Histopathological findings and a skin irritation study proved that the F-dMN patch was biocompatible and did not cause any sort of irritation on animal skin. Pharmacokinetic parameters of F-dMN patches were improved (Cmax 6.974 µg/ml, tmax 1 hr and AUC 19. 518 µg.h/ml) as compared to tablet Simva 20 mg solution (Cmax 2.485 µg/ml, tmax 1.4 hr and AUC 11.199 µg.h/ml), thus confirming bioavailability enhancement. Moreover, stability studies confirmed the stability of the developed F-dMN patch, as investigated by axial needle fracture force and drug content.

Quince seed mucilage/ß-cyclodextrin/Mmt-Na+-co-poly (methacrylate) based pH-sensitive polymeric carriers for controlled delivery of Capecitabine.

In current work, quince seed mucilage and ß-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system's stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %-93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine. Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t1/2 (10.57 h), AUC (121.52 µg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system's safety, non-toxicity, and biocompatibility.

Validation of a Novel RP-HPLC Technique for Simultaneous Estimation of Lignocaine Hydrochloride and Tibezonium Iodide: Greenness Estimation Using AGREE Penalties.

Herein, we reported an HPLC method for the simultaneous determination of tibezonium iodide (TBN) and lignocaine hydrochloride (LGN). The method was developed according to the International Conference for Harmonization guidelines (ICH) Q2R1 using Agilent® 1260 with a mobile phase consisting of acetonitrile and phosphate buffer (pH 4.5) in a volumetric ratio of 70:30 and flowing through a C8 Agilent® column at 1 mL/min. The results revealed that TBN and LGN peaks were isolated at 4.20 and 2.33 min, respectively, with a resolution of 2.59. The accuracy of TBN and LGN was calculated to be 100.01 ± 1.72% and 99.05 ± 0.65% at 100% concentration, respectively. Similarly, the respective precision was 100.03 ± 1.61% and 99.05 ± 0.48%. The repeatability for TBN and LGN was found to be 99.05 ± 0.48% and 99.19 ± 1.72%, respectively, indicating that the method was precise. The respective regression co-efficient (r2) for TBN and LGN was found to be 0.9995 and 0.9992. Moreover, the LOD and LOQ values for TBN were 0.012 and 0.037 µg/mL, respectively, while for LGN, they were 0.115 and 0.384 µg/mL, respectively. The calculated greenness of the method for ecological safety was found to be 0.83, depicting a green contour on the AGREE scale. No interfering peaks were found when the analyte was estimated in dosage form and in volunteers' saliva, depicting the specificity of the method. Conclusively, a robust, fast, accurate, precise and specific method was successfully validated to estimate TBN and LGN.

Development of Tofacitinib Loaded pH-Responsive Chitosan/Mucin Based Hydrogel Microparticles: In-Vitro Characterization and Toxicological Screening.

Tofacitinib is an antirheumatic drug characterized by a short half-life and poor permeability, which necessitates the development of sustained release formulation with enhanced permeability potential. To achieve this goal, the free radical polymerization technique was employed to develop mucin/chitosan copolymer methacrylic acid (MU-CHI-Co-Poly (MAA))-based hydrogel microparticles. The developed hydrogel microparticles were characterized for EDX, FTIR, DSC, TGA, X-ray diffraction, SEM, drug loading; equilibrium swelling (%), in vitro drug release, sol-gel (%) studies, size and zeta potential, permeation, anti-arthritic activities, and acute oral toxicity studies. FTIR studies revealed the incorporation of the ingredients into the polymeric network, while EDX studies depicted the successful loading of tofacitinib into the network. The thermal analysis confirmed the heat stability of the system. SEM analysis displayed the porous structure of the hydrogels. Gel fraction showed an increasing tendency (74-98%) upon increasing the concentrations of the formulation ingredients. Formulations coated with Eudragit (2% w/w) and sodium lauryl sulfate (1% w/v) showed increased permeability. The formulations equilibrium swelling (%) increased (78-93%) at pH 7.4. Maximum drug loading and release (%) of (55.62-80.52%) and (78.02-90.56%), respectively, were noticed at pH 7.4, where the developed microparticles followed zero-order kinetics with case II transport. Anti-inflammatory studies revealed a significant dose-dependent decrease in paw edema in the rats. Oral toxicity studies confirmed the biocompatibility and non-toxicity of the formulated network. Thus, the developed pH-responsive hydrogel microparticles seem to have the potential to enhance permeability and control the delivery of tofacitinib for the management of rheumatoid arthritis.

Development and Evaluation of Cellulose Derivative and Pectin Based Swellable pH Responsive Hydrogel Network for Controlled Delivery of Cytarabine.

In the present study, pH-sensitive, biodegradable, and biocompatible Na-CMC/pectin poly(methacrylic acid) hydrogels were synthesized using an aqueous free radical polymerization technique and encapsulated by cytarabine (anti-cancer drug). The aim of the project was to sustain the plasma profile of cytarabine through oral administration. Sodium carboxymethyl cellulose (Na-CMC) and pectin were cross-linked chemically with methacrylic acid (MAA) as a monomer, using methylene bisacrylamide (MBA) as cross-linker and ammonium per sulfate (APS) as an initiator. Prepared hydrogel formulations were characterized for their texture, morphology, cytarabine loading efficiency, compositional and structural properties, thermal nature, stability, swelling response, drug release profile (pH 1.2 and pH 7.4), and in-vivo pharmacokinetic evaluation. Cytarabine-loaded hydrogels were also evaluated for their safety profile by carrying out toxicity studies in rabbits. Results demonstrated efficient encapsulation of cytarabine into the prepared network with loading ranging from 48.5-82.3%. The highest swelling ratio of 39.38 and maximum drug release of 83.29-85.27% were observed at pH 7.4, highlighting the pH responsiveness of the grafted system. Furthermore, cytarabine maximum release was noticed over 24 h, ensuring a sustained release response for all formulations. Histopathological studies and hemolytic profiles confirmed that the prepared hydrogel system was safe, biocompatible, and non-irritant, showing no symptoms of any toxicities and degeneration in organs. Moreover, pharmacokinetic estimation of the cytarabine-loaded hydrogel showed a remarkable increase in the plasma half-life from 4.44 h to 9.24 h and AUC from 22.06 µg/mL.h to 56.94 µg/mL.h. This study revealed that the prepared hydrogel carrier system has excellent abilities in delivering the therapeutic moieties in a controlled manner.

Development and Optimization of Tamarind Gum-ß-Cyclodextrin-g-Poly(Methacrylate) pH-Responsive Hydrogels for Sustained Delivery of Acyclovir.

Acyclovir has a short half-life and offers poor bioavailability. Its daily dose is 200 mg five times a day. A tamarind gum and ß-cyclodextrin-based pH-responsive hydrogel network for sustained delivery of acyclovir was developed using the free-radical polymerization technique. Developed networks were characterized by FTIR, DSC, TGA, PXRD, EDX, and SEM. The effect of varying feed ratios of polymers, monomers, and crosslinker on the gel fraction, swelling, and release was also investigated. FTIR findings confirmed the compatibility of the ingredients in a new complex polymer. The thermal stability of acyclovir was increased within the newly synthesized polymer. SEM photomicrographs confirmed the porous texture of hydrogels. The gel fraction was improved (from 90.12% to 98.12%) with increased reactant concentrations. The pH of the dissolution medium and the reactant contents affected swelling dynamics and acyclovir release from the developed carrier system. Based on the R2 value, the best-fit model was zero-order kinetics with non-Fickian diffusion as a release mechanism. The biocompatibility of the developed network was confirmed through hematology, LFT, RFT, lipid profile, and histopathological examinations. No sign of pathology, necrosis, or abrasion was observed. Thus, a pH-responsive and biocompatible polymeric system was developed for sustained delivery of acyclovir to reduce the dosing frequency and improve patient compliance.

pH Responsive Hydrogels for the Delivery of Capecitabine: Development, Optimization and Pharmacokinetic Studies.

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45-83.54% and 50.13-72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents.

The Development of Eletriptan Hydrobromide Immediate Release Buccal Films Using Central Composite Rotatable Design: An In Vivo and In Vitro Approach.

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 ± 1.13), while a maximum of 92.87 ± 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 µm. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t½) of 4.54 ± 0.18 h and a Cmax of 128 ± 0.87 (ng/mL); Tmax was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively.

Evaluation of Renessans (Iodine Complex Molecule) Safety in Human Beings: An Open-Labeled Clinical Study.

Extensive studies on evaluation of effectiveness/toxicity of different oral doses of iodine have not been explored yet. An open-labeled phase I clinical studies were conducted using iodine complex based research compound called Renessans. Study groups were observed for development of any adverse/serious adverse events and alteration in laboratory values of vital organs, TSH and T4 hormones before and after the administration of the products. Out of 31 consented individuals, 24 healthy individuals participated in the study. Rate of occurrence of mild Adverse Events (AEs) in group A was 8.3% while in Group B it was 33.33% but these Adverse Events were self-resolving. After completion of study treatment blood serum iodine was reported to 3522.88 µg/l while mean urine iodine concentration (MUIC) was greater than 2000 µg/l. Hormonal and vital organ's testing revealed that all parameters of TSH and T4, LFT, CBC, RFT remained unaltered except from ALT-SGPT (P-value = .006) and AST-SGOT (P-value = .02). From all of these findings, it can be inferred that the use of Renessans formulations did not pose any sort of risk to human body and can be considered safe through this pilot study.

Simvastatin Loaded Dissolvable Microneedle Patches with Improved Pharmacokinetic Performance.

Microneedle patches (MNPs) are one of the emerging approaches for drug delivery involving minimal invasion and improved skin penetration of macro- and micro-entities. Herein, we report dissolvable microneedle patches (dMNPs) as a novel tool for better systemic delivery of Simvastatin in the management of hypocholesteremia. Thiolated chitosan (TC), polyvinyl pyrolidone (PVP) and polyvinyl alcohol (PVA) were employed in the development of dMNPs. Developed patches were characterized through SEM, FTIR, DSC, TGA, PXRD, dissolution testing, tensile strength, elongation (%), skin irritation studies, moisture content and pharmacokinetic evaluation. dMNP F26 exhibited excellent tensile strength (9.85 MPa), penetration potential (~700 µm), moisture content (5.95%), elongation (35.54%) and Simvastatin release of 77.92%. Pharmacokinetic properties were also improved, i.e., Cmax 1.97 µg/mL, tmax 9 h, MRT 19.9 h and AUC 46.24 µg·h/mL as compared to Simvastatin solution displaying Cmax 2.55 µg/mL, tmax 3 h, MRT 5.91 h and AUC 14.20 µg·h/mL thus confirming higher and improved bioavailability. Kinetic modelling revealed zero order as the best fit model based on regression coefficient. Histopathological findings proved the biocompatibility of the developed dMNPs.

Exorbitant Drug Loading of Metformin and Sitagliptin in Mucoadhesive Buccal Tablet: In Vitro and In Vivo Characterization in Healthy Volunteers.

The aim of the proposed study is to develop a mucoadhesive buccal delivery system for the sustained delivery of metformin (MET) and sitagliptin (SIT) against diabetes mellitus (DM) with improved bioavailability. Polymeric blend of Carbopol® 940 (CP), agarose (AG) or polyvinylpyrrolidone K30 (PVP) as mucoadhesive agents in formulations (R1-R15) were compressed via the direct compression technique. Tablets were characterized for solid state studies, physicochemical and in vivo mucoadhesion studies in healthy volunteers. Outcomes did not reveal any unusual peak or interaction between the drugs and polymers in the physical mixture through Fourier Transform Infrared Spectroscopy (FTIR) and DSC analysis. The mucoadhesive blend of CP and PVP was superior compared to other blends. The formulation R4 revealed exorbitant loading of drugs with complete drug release for 6 h with ex vivo mucoadhesive strength and time of 26.99 g and 8.1 h, respectively. It was further scrutinized to evaluate it as an optimized formulation where it was found to be stable for up to 6 months. The formulation R4 depicted Korsmeyer-Peppas model and first-order mode of release correspondingly for SIT and MET. Moreover, it showed hemocompatibility, biocompatibility and stability with non-significant changes in the dissolution profile. Overall, the CP blend with PVP was found appropriate to yield the desired release coupled with the optimized mucoadhesive properties of the buccal tablets, ensuring sufficient pharmaceutical stability.

Orally Administered, Biodegradable and Biocompatible Hydroxypropyl-ß-Cyclodextrin Grafted Poly(methacrylic acid) Hydrogel for pH Sensitive Sustained Anticancer Drug Delivery.

In the current study, a pH sensitive intelligent hydroxypropyl-ß-cyclodextrin-based polymeric network (HP-ß-CD-g-MAA) was developed through a solution polymerization technique for site specific delivery of cytarabine in the colonic region. Prepared hydrogel formulations were characterized through cytarabine loading (%), ingredient's compatibility, structural evaluation, thermal integrity, swelling pattern, release behavior and toxicological profiling in rabbits. Moreover, the pharmacokinetic profile of cytarabine was also determined in rabbits. New polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 37.17-79.3%. Optimum swelling ratio of 44.56 was obtained at pH 7.4. Cytarabine release was persistent and in a controlled manner up to 24 h. In vitro degradation of hydrogels was more pronounced at intestinal pH as compared to acidic pH. Toxicity studies proved absence of any ocular, skin and oral toxicity, thus proving biocompatibility of the fabricated network. Hydrogels exhibited longer plasma half-life (8.75 h) and AUC (45.35 µg.h/mL) with respect to oral cytarabine solution. Thus, the developed hydrogel networks proved to be excellent and biocompatible cargo for prolonged and site-specific delivery of cytarabine in the management of colon cancer.

Press-Coated Aceclofenac Tablets for Pulsatile Drug Delivery: Formulation and In Vitro Evaluations.

The symptoms of some diseases show circadian rhythms, such as the morning stiffness associated with pain at the time of awakening in rheumatoid arthritis. Therapy for such diseases doesn't require immediate release or sustained release of medicament. In such therapies, pulsatile drug release is more suitable with a programmed drug release. The purpose of this research was to formulate press-coated aceclofenac tablets for pulsatile drug delivery with a distinct delay time of no drug release and release of the drug when it is more likely desired (i.e., after 5 to 6 h). Immediate release core tablets having aceclofenac were formulated. Three formulations, F1, F2, and F3, were prepared with variable concentrations of sodium croscarmellose. Pre- and post-compression tests were performed on the core tablets. The selection criteria included the lowest disintegration time as a requirement of pulsatile drug delivery with an immediate release core and a delayed release coat. The disintegration times of F1, F2, and F3 were 120 s, 60 s, and 15 s, respectively. Therefore, the F3 formulation was selected as the core tablet formulation because it had the shortest disintegration time (15 s). The core tablets were press-coated using different polymers, such as HPMC K100M, Eudragit L100, HEC, and HPMC E5. The polymers were used in the coatings to hinder the release of the core for the desired time. 36 formulations of polymer were prepared: A1 to A10 had HPMC K100M and Avicel PH102; formulations B1 to B6 had HPMC K100M, Eudragit L100, and Avicel PH102; formulations C1 to C7 had HPMC K100M and hydroxyethyl cellulose; formulations D1 to D7 had HPMC K100M and HPMC E5; and formulations E1 to E6 had changed the coating weight of the formulation used for D6 (having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5%). Evaluations of the press-coated tablets were carried out through thickness, hardness, weight variation, friability, and in vitro dissolution tests. These parameters concluded that the formulation of E6, having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5% at 600 mg weight, was the most optimum formulation as it showed 3.5% drug release after 4 h, 21.4% drug release after 5 h, and 99.27% drug release after 6 h.

Fenugreek seed mucilage grafted poly methacrylate pH-responsive hydrogel: A promising tool to enhance the oral bioavailability of methotrexate.

This study aimed to develop the Fenugreek seed mucilage-based pH-responsive hydrogel system in order to improve the oral bioavailability of methotrexate (MTX). Fenugreek seed mucilage (FSM) was extracted from Trigonella foenum-graecum seeds. F1-F9 formulations of pH-responsive hydrogels were prepared using various FSM ratios, methacrylic acid (MAA), and methylene bis acrylamide (MBA) via free radical polymerization technique. Swelling behavior and in vitro drug release studies of prepared hydrogels were evaluated. Toxicity studies of prepared hydrogels were performed on normal cells and on Wistar rats (n = 6). Moreover, in vivo pharmacokinetics parameters were studied on albino rabbits. Hydrogels formation was confirmed by FTIR analysis, thermal analysis and SEM studies. The maximum swelling of hydrogel was found to be 384.7% at pH 7.4. MTX-loaded hydrogel showed the controlled release of MTX up to 24 h following Super Case II transport. Prepared hydrogels exhibited no toxicity in normal cells as well as in experimental subjects. MTX loaded hydrogels exhibited less inhibition compared to free MTX on Hela cells. In Vivo studies revealed 7.5-fold improved oral bioavailability of MTX with higher Cmax (928 ng/mL). These results indicate that the pH-responsive hydrogel system based on FSM is a promising tool for the controlled delivery of MTX.