Diphenyl Carbonate Research Articles

Investigation of effect of complexing agent and processing method on solubility of Efonidipine

Nanosponges are versatile carriers due to their exceptional capability to improve the solubility of poorly water-soluble drugs, taste masking and enhancement of stability. This study investigates potential of nanosponges, prepared by crosslinking β-cyclodextrin with diphenyl carbonate in 1:4 ratio for enhancing solubility of Efonidipine. Nanosponges were characterized in terms of particle size. Phase solubility studies and solution state interaction studies were employed to understand the nature and strength of drug: nanosponge complexation. Complexes were prepared by kneading method and spray drying. Saturation solubility, in vitro dissolution studies and molecular modeling studies were performed. Complexes were characterized by differential scanning calorimetry (DSC), infrared spectroscopy, X ray powder diffraction (XRPD) and scanning electron microscopy. Phase solubility studies revealed 1:2 complexation between drug and carriers. Saturation solubility studies showed significant solubility increase with both beta CD and nanosponges. The increase was higher in case of spray dried complexes in all media. An 18 fold increase was observed in case of spray dried complexes in distilled water. DSC and PXRD confirmed amorphization of drug in the complexes. Thus solubility enhancement of EFD could be attributed to complexation and amorphization. Molecular modeling studies revealed the mode of entrapment of efonidipine in the carriers. In conclusion the versatility of nanosponges in encapsulating both hydrophilic and hydrophobic drug molecules holds immense promise for personalized medicine and targeted therapy, ultimately leading to improved patient outcomes. Moreover, the study introduces the efficacy of spray drying as a scalable and practical approach to maximize the solubility-enhancing benefits of nanosponges. This research highlights the potential of nanosponges to overcome a fundamental challenge in pharmaceuticals, opening new avenues for drug delivery and therapeutic advancement. Keywords: Nanosponges, β -cyclodextrin, inclusion complexes, solubility enhancement, molecular modelling

Anatase-Layered TiO2 for Selective Transesterification for Diphenyl Carbonate: A Study of the Active Site and Deactivation Mechanism

Anatase-Layered TiO₂ for Selective Transesterification for Diphenyl Carbonate: A Study of the Active Site and Deactivation Mechanism

Refined kinetic model for the simulation of polycarbonate synthesis via continuous melt transesterification

This paper establishes a kinetic model for the polymerization and condensation occurring during the melt transesterification of bisphenol A (BPA) and diphenyl carbonate (DPC). The model is based on molecular fragments and functional groups, treating polymers as an assembly of four types of chain segments. This study delves into the reaction mechanisms underlying the polycondensation of BPA and DPC, offering fresh perspectives on the process. Kinetic equations pertinent to the polycondensation mechanism were deduced from the analysis and then rigorously tested against experimental data to ascertain their validity. Kinetic constants emerged through the fitting of this experimental data, lending credence to the model’s accuracy. Utilizing the Aspen Plus software, the model was applied to simulate the annual production of 100,000 tons of polycarbonate (PC). The simulation facilitated the optimization of the operating conditions for each reactor, yielding valuable insights for scaling up to industrial production.

Multi-objective optimization for sustainable and economical polycarbonate production with reaction kinetics inference for real-world industrial process

Polycarbonate has a wide range of applications in electronic devices and medicine because of its remarkable properties such as transparency and mechanical strength. However, the polycarbonate production process using diphenyl carbonate leads to the inevitable generation of nitrogen oxide (NOx) from byproduct incineration. Therefore, it is essential to optimize the process conditions while simultaneously considering the production costs and NOx emissions. Herein, we propose a multi-objective optimization model for sustainable and economical polycarbonate production using a high-fidelity reaction model for real-world industrial processes. Additionally, a data-driven model was developed using industrial data to identify the operating conditions that minimize NOx emissions and maximize profitability. Four of the ten reaction parameters were selected through variance-based global sensitivity analysis, and the posterior distribution of each parameter was determined through Bayesian inference. In addition, NOx emissions were predicted using the data-driven model developed from industrial data. A process model with coefficients of determination above 0.7 and a data-driven model with R-squared value above 0.99 for pilot-scale experimental and industrial data were generated using our approach. The Pareto optimality, identified based on the developed models, suggested operating conditions that optimize both economic and environmental benefits. Consequently, NOx emissions could be reduced by 27.2%–27.4% and the unit costs of production could be reduced by 0.8%–1.6% compared with the base case.

Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic β-Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field.

A β-cyclodextrin (β-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the "Atkinson-Brezovich criterion". The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.

Diphenyl Carbonate: Recent Progress on Its Catalytic Synthesis by Transesterification

Diphenyl carbonate is one of the raw materials used for the synthesis of polycarbonate, and its green and clean production is of great importance to the non-phosgene process for polycarbonate. The production of diphenyl carbonate by transesterification is its representative process route and is considered to be one of the typical examples of a green and sustainable process for chemicals. Since the discovery of the transesterification catalyst for diphenyl carbonate in the 1970s, researchers have been committed to improving its catalytic activity and selectivity and, correspondingly, the reaction engineering process. However, thermodynamic limitations, low activity, low selectivity, and limited stability have been bottlenecks that the transesterification catalyst has not been able to completely overcome, and the improvement of the catalyst is still ongoing. Therefore, this review takes the transesterification reaction of dimethyl carbonate and phenol as a model reaction and, based on a review of the progress in catalyst research on catalytic reaction processes, tries to clarify the structure–activity relationship between catalytic active sites and catalytic performance in homogeneous and heterogeneous catalytic processes and provides an overview of the progress in catalyst synthesis and modification.

Mechanism Study on Synthesis of Biobased Polycarbonate from Diphenyl Carbonate and Isosorbide with Metal-Free Catalysts by Identifying Reactivity of endo-OH and exo-OH

Mechanism Study on Synthesis of Biobased Polycarbonate from Diphenyl Carbonate and Isosorbide with Metal-Free Catalysts by Identifying Reactivity of <i>endo</i>-OH and <i>exo</i>-OH

Synergistic treatment of androgenetic alopecia with follicular co-delivery of minoxidil and cedrol in metal–organic frameworks stabilized by covalently cross-linked cyclodextrins

Androgenetic alopecia seriously affects the physical and mental health of patients. The main clinical therapeutic agent, minoxidil tincture, is challenged by solvent irritation and dose-dependent side effects. Our recent work has identified a biosafety natural product, cedrol, that is synergistic in combination with minoxidil, thereby improving medication safety by substantially reducing the clinical dose of minoxidil. In addition, ccross-linked CD-MOF were designed as carriers for hair follicle delivery, and γ-CD in the carriers was cross-linked by diphenyl carbonate with covalent bonds to protect the CD-MOF from rapid disintegration in an aqueous environment. This improved nanocarrier has a drug loading of 25%, whereas nanocarriers increased drug delivery to the hair follicles through ratchet effect, and increased human dermal papilla cells uptake of drugs via endocytosis pathways mainly mediated by lattice proteins, energy-dependent active transport, and lipid raft-dependent, thus improved cell viability, proliferation, and migration, followed by significantly enhancing the anti-androgenetic alopecia effect, with cedrol focusing on inhibiting 5α-reductase and activating Shh/Gli pathway, and minoxidil, which up-regulated VEGF, down-regulated TGF-β, and activated ERK/AKT pathway. This drug combination provides a new therapeutic strategy for androgenetic alopecia, while the newly developed cross-linked CD-MOF has been shown to serve as a promising follicular delivery vehicle.

Energy saving design and control of side-streams reactive distillation configuration for diphenyl carbonate production process

Diphenyl carbonate (DPC), a phosgene-free precursor for polycarbonate production, has traditionally undergone industrial production through a well-established two-step transesterification process by a reactive distillation (RD) and a distillation column. Thermal enhancement techniques in RD, such as thermally coupled (TCRD) and hybrid heat-integrated (HIRD) methods, have consistently demonstrated significant improvements in energy efficiency, eliminating remixing effect and reducing total annual cost (TAC) during DPC synthesis. However, the combination of TCRD or HIRD with a side-stream configuration (SS) remains relatively underexplored, particularly in the context of DPC production. This study aims to address this gap by proposing a novel combination of TCRD/HIRD, incorporating both a one side-stream (SS1-TCRD and SS1-HIRD) and a two side-streams configuration (SS2-TCRD and SS2-HIRD). Employing a sequential iterative procedure for optimization, the study sought to minimize TAC. Results unveiled SS2-HIRD as the optimal configuration, showcasing a remarkable 47.27% reduction in energy consumption and a 31.46% decrease in TAC. Moreover, four proposed control structures (CS1∼CS4) were implemented for SS2-HIRD to ensure both product quality and process safety. Among all structures, CS4 exhibited remarkable efficacy in managing disturbances in feed and composition throughput, demonstrating the smallest integral of the absolute error (IAE) value.

Direct Functionalization of Polysaccharide-Based Xylan Phenyl Carbonate Nanoparticles with Tumor Cell Specific Antibodies.

An efficient and easy-to-use approach is presented for obtaining biocompatible polysaccharide-based nanoparticles (NP) that can act as tumor-specific drug delivery agents. Two antibodies are directly immobilized onto reactive xylan phenyl carbonate (XPC) NP; namely Cetuximab (CTX) that binds to human epidermal growth factor receptor (EGFR) and Atezolizumab (ATZ) that binds to programmed death-ligand 1 (PD-L1). High coupling efficiency (up to 100 %) are achieved without any pre-activation and no aggregation occurs during antibody immobilization. By quartz crystal microbalance experiments with dissipation monitoring (QCM-D), flow cytometry assays, and confocal laser scanning microscopy imaging it is demonstrated that the functionalized XPC-NP specifically bind to cells carrying the corresponding antigens. Moreover, the NP retain the antibody specific bioactivities (growth inhibition for CTX and induction of T-cell cytotoxicity for ATZ).

Preparation of high temperature resistant polycarbonate via ionic liquid activation of bisphenol fluorene under mild conditions

In this study, the melt polycondensation reaction of 9,9’- bis(4-hydroxyphenyl)fluoride (BHPF) and diphenyl carbonate (DPC) was catalyzed using three ionic liquids (ILs) and a conventional alkali metal as catalysts. The optimal IL catalysts were determined to be [BMmim][BF4] ionic liquid catalysts, and the catalytic mechanism was investigated. Furthermore, the optimum process conditions were identified: the optimal amount of [BMmim][BF4] was 0.05 mol% based on DPC, the polycondensation temperature was set at 200°C for a duration of 3 h, followed by polymerization at 280°C for another 3 h. As a result, the Mn value of poly(9,9-bis(4-hydroxyphenyl) carbonate) (PFC) reached up to 41387 g/mol with a glass transition temperature band of approximately 254°C and Td-5% value of around 436°C.

Potential of Nitrofurantoin Cyclodextrin Nanosponge Complex to Enhance Solubility and Masking Bitter Taste

This study aimed to produce b-cyclodextrin (β-CD) based nanosponges (NS) loaded with nitrofurantoin (NFN) to improve oral bioavailability, solubility, and dissolution rate while concealing bitter tastes. The cross-linker diphenyl carbonate and β-CD were reacted in various ratios (1:1, 1:2, 1:4, 1:6, and 1:8) to produce NFN-loaded NS. The developed NS were evaluated for phase solubility study, particle size, drug loading, polydispersity index, scanning electron microscope (SEM), zeta potential, fourier transform infrared (FTIR), differential scanning calorimetry (DSC), a study of phosphate buffer at pH 7.2 for in-vitro release and taste masking ability in human volunteers. Pure NFN showed nearly 100 mcg/mL solubility in ditilled water while at 1:8 (β-CD: DPC) ratio the solubility was found to be 250 mcg/mL, i.e., nearly 2.5 fold enhancement in solubility was observed. The SEM of the NFN-loaded NS (1:8 β-CD: DPC ratio) showed highly spherical surface morphology. For formulation containing a 1:8 proportion of β-CD to DPC, the average particle size was measured at 324.78 ± 10.45 nm, possessing a low polydispersity index of 0.196 ± 0.054. It was found that the zeta potential’s value was -20.59 ± 0.4 mV, indicating sufficient electrostatic repulsion to maintain particle dispersion. FTIR, DSC study reveled excellent drug and excipient compatability. As compared to pure NFN, NFN-loaded NS showed faster release in pH 7.2 phosphate buffer. Research conducted in-vitro showed a gradual release of NFN from pure NFN throughout a two-hour period. The plain NFN suspension was found to have a pronounced bitterness. With 3.95 ± 0.57 as the average score, while the NFN nanosponges (1:8 ratio) had a mean bitterness score of only 0.10 ± 0.00. These findings suggest that the NFN (1:8 ratio) has the capacity to thoroughly cover up the bitter taste of NF.

Synthesis and characterization of nucleophilic polysaccharide carbazates

A simple synthesis of amino polysaccharides (PS) could be developed. Phenyl carbonates (PC) of xylan, dextran, and cellulose were easily transferred into PS carbazates by conversion with hydrazine hydrate. The degree of substitution could be adjusted by varying the molar ratio of hydrazine to PS repeating unit, enabling the preparation of both pure PS carbazates and derivatives with bifunctional reactivity containing the reactive PC and the amino group of the carbazate moiety. Further functionalization of the derivatives is feasible with carbonyl compounds like aldehydes at the carbazate groups. The reactivity of carbazate groups is shown by the reaction with 4-fluorobenzaldehyde, resulting in the formation of Schiff base conjugates.

DEVELOPMENT, CHARACTERIZATION AND EVALUATION OF ENTRECTINIB NANOSPONGES LOADED TABLETS FOR ORAL DELIVERY

Objective: As Entrectinib is a lipophilic, basic, moderately permeable molecule with strongly pH-dependent solubility with antitumor activity in advanced and metastatic solid tumors, the current study was designed to improve the oral solubility of Entrectinib through incorporation into nanosponges tablets (NSs). Methods: Box-Behnken Design was used to optimize the independent variables of β-Cyclodextrin (β-CD) NSs formation. β-CD NSs were prepared by an ultrasound-assisted method using diphenyl carbonate as cross-linking agent, which were later characterized and formulated into tablets by wet granulation method. The prepared tablets were evaluated for the physico-chemical properties and in vitro release of the drug. Results: A series of fifteen experiments were performed based on the experimental runs generated from a three-factor, three-level Box–Behnken design (BBD). The range of mean particle size was 149-294 nm, the range for encapsulation efficiency % was 65.4%-87.3%, and the value for polydispersity index was 0.437. The zeta potential for the optimized formulation was found to be 38.1 Mv. The drug and excipients were compatibles as confirmed by Fourier Transformed Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC) studies. Scanning Electron Microscopic (SEM) analysis confirmed that the Entrectinib has successfully entrapped in the core of polymer. In vitro release of the Entrectinib-loaded NSs tablets (six compositions) were compared with a marked product and satisfactory results were obtained. It was observed that rapid dissolution occurred in 0.1 N HCl for first 2 h (15.64±1.52% vs. 12.67±1.89%) and 98.94±2.43% of drug release was observed in Entrectinib loaded NSs and 91.78±1.37% in marketed product in 24 h. The prepared formulations were stable during 6 mo stability study period. Conclusion: The study results studies of Entrectinib NS tablets indicated rapid dissolution due to changed solubility properties of the drug, compared to pure drug meeting the set objective of enhanced absorption. The formulated Entrectinib-loaded NSs can be beneficial in the treatment of cancers.

Synthesis and properties of bisphenol‐Z polycarbonate via melt transesterification

AbstractPolycarbonate (PC) is a thermoplastic engineering plastic with excellent properties, and its excellent dielectric properties have broad application prospects in the field of electronics. In this paper, bisphenol Z (BPZ) and diphenyl carbonate (DPC) are used as raw materials to synthesize special polycarbonate (BPZ‐PC) by melt transesterification. The effects of catalyst type, catalyst dosage, molar ratio of raw materials, transesterification reaction time and vacuum degree, polycondensation reaction temperature and time on the molecular weight of the product are investigated, and the optimal reaction conditions are obtained. The chemical structure of the product is verified by FTIR, 1H‐NMR and 13C‐NMR spectra tests. The thermal properties, mechanical properties, optical properties and dielectric properties of BPZ‐PC are evaluated. Therefore, due to its excellent performance, BPZ‐PC, a high‐performance low‐dielectric polycarbonate, can be widely used in high‐frequency communication, microelectronics, and aerospace industries.

Halide-free squaramide–phenolate organocatalyst for the cycloaddition of CO2 into epoxides

The cycloaddition of CO2 into epoxide (CCE) reaction was the few routes viable industrially in catalytic fixation of carbon dioxide into value-added chemicals in which cocatalyst halide was predominant. To obviate the harmful corrosion of halide anions to steel reactors, and to alleviate the environmental burden of halogen waste, halide-free catalyst was desirable. We propose a category of one-component H-bond donor (HBD) and nucleophilic anion (HBD–anion) bifunctional organocatalyst as representative halide-free catalyst in CCE reactions. Squaramide (Sq) in conjugation with phenolate constitutes a typical HBD–anion catalyst featured with the squaramide as the HBD moiety and the phenolate as the nucleophilic anion moiety. Series of pre-catalyst in structure of squaramide–phenol (Sq–PhOH) was designed and the active catalyst Sq–phenolate (Sq–PhO) was generated from the corresponding Sq–PhOH by deprotonating of the weakly acidic hydroxyl of the phenol by super strong Brønsted base. In an optimal N-benzyl squaramide para-phenol (Sq–PhOH-p) and P2 phosphazene (t-BuP2) combination, CCE reactions proceed under mild conditions of 120 °C, and atmospheric pressure of 0.1 MPa, by 2.5 mol % loading of catalyst Sq–PhOH-p/t-BuP2. Terminal epoxides were transformed with excellent conversions (86–99 %) and high selectivity (85–97 %) in 8 h. Bifunctional activations mechanisms were proposed and validated. 1H and 13C NMR titrations certified the coordination of H-bond donor squaramide to epoxide, and FT-IR spectra observed formation of phenyl carbonate anion from phenolate and carbon dioxide, these suggested unprecedent CCE reaction composed capture of CO2 in carbonate anion followed by its intramolecular nucleophilic attack on the HBD coordinated epoxide as the key catalytic steps. The squaramide–phenolate catalytic dyad exemplified halide-free HBD–anion organocatalyst of wide scope for carbon dioxide activation and fixation.

Enhanced stability of nitrogen-doped carbon-supported palladium catalyst for oxidative carbonylation of phenol

Enhancing the stability of supported noble metal catalysts emerges is a major challenge in both science and industry. Herein, a heterogeneous Pd catalyst (Pd/NCF) was prepared by supporting Pd ultrafine metal nanoparticles (NPs) on nitrogen-doped carbon; synthesized by using F127 as a stabilizer, as well as chitosan as a carbon and nitrogen source. The Pd/NCF catalyst was efficient and recyclable for oxidative carbonylation of phenol to diphenyl carbonate, exhibiting higher stability than Pd/NC prepared without F127 addition. The hydrogen bond between chitosan (CTS) and F127 was enhanced by F127, which anchored the N in the free amino group, increasing the N content of the carbon material and ensuring that the support could provide sufficient N sites for the deposition of Pd NPs. This process helped to improve metal dispersion. The increased metal-support interaction, which limits the leaching and coarsening of Pd NPs, improves the stability of the Pd/NCF catalyst. Furthermore, density functional theory calculations indicated that pyridine N stabilized the Pd2+ species, significantly inhibiting the loss of Pd2+ in Pd/NCF during the reaction process. This work provides a promising avenue towards enhancing the stability of nitrogen-doped carbon-supported metal catalysts.

2,2′‐Bis(arylamino)‐1,1′‐biaryls as Building Blocks for the Synthesis of Dibenzo[d,f][1,3]diazepines, Dibenzo[d,f][1,3]diazepinones, and Dibenzo[c,e][1,2,7]thiadiazepine 6‐Oxides

AbstractThe iron‐catalyzed oxidative C−C homocoupling of diarylamines affords 2,2′‐bis(arylamino)‐1,1′‐biaryls which represent crucial synthetic building blocks for an access to a range of seven‐membered heterocyclic ring systems. Reaction with paraformaldehyde, diphenyl carbonate, and diphenyl sulfite as efficient 1,1‐dielectrophiles led to dibenzo[d,f][1,3]diazepines, dibenzo[d,f][1,3]diazepinones, and dibenzo[c,e][1,2,7]thiadiazepine 6‐oxides. The synthetic procedures enable short and practical routes to these 1,3‐diazepine derivatives under mild reaction conditions and with a high tolerance of various functional groups.

Enhancement in the therapeutic potential of lapatinib ditosylate against breast cancer by the use of β-cyclodextrin based ternary nanosponge system

The present investigation was performed to demonstrate the therapeutic potential of lapatinib ditosylate (LD) loaded nanosponge for the treatment of breast cancer. The study reports the fabrication of nanosponge by reaction of β-cyclodextrin with a cross-linking agent, diphenyl carbonate, at several molar ratios using the ultrasound-assisted synthesis method. The drug was loaded into the rightest nanosponge by lyophilization with and without 0.25% w/w polyvinylpyrrolidone. The significantly reduced crystallinity of developed formulations was established by differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). Morphological changes of LD, and formulations were compared by scanning electron microscopic (SEM) technique. Fourier transform infrared (FT-IR), and nuclear magnetic resonance (NMR) spectroscopic analysis were performed to establish the interacting groups of the host and guest molecules. It revealed interaction of the quinazoline ring, furan ring, and chlorobenzene functionality of LD with the hydroxyl group of β-cyclodextrin based nanosponge. Similar predictions were also obtained during their in-silico analysis. Saturation solubility and in vitro drug release studies revealed a 4.03-fold, and 2.43-fold rise in aqueous solubility, and dissolution of LD in the optimized formula (F2). The MCF-7 cell line study, too, revealed the higher efficiency of nanosponge formulations. The in vivo pharmacokinetic studies of optimized formulation illustrated 2.76-times, and 3.34-times enhancements in Cmax and oral bioavailability, respectively. Concomitant results were obtained during the in vivo studies performed using DMBA-induced breast cancer models in female Sprague Dawley rats. The tumor burden was found to be reduced to approximately 60% by the use of F2. The hematological parameters of animals treated with F2 were also improved. Histopathology of breast tissue excised from an F2-treated rat showed a reduced size of ductal epithelial cells associated with shrunken cribriform structures and cross-bridges. The in vivo toxicity studies also showcased reduced hepatotoxicity of the formulation. Altogether, it can be concluded that encapsulation of lapatinib ditosylate in β-cyclodextrin nanosponge has improved aqueous solubility, bioavailability and, in turn, therapeutic efficacy.

Cyclodextrin based Nanosponges for the Oral Delivery of Actarit: Physicochemical Characterisation and Dissolution Studies

Introduction: The current research aims to formulate a controlled release formulation of Actarit utilizing cyclodextrin based nanosponges as a nanocarriers. β-Cyclodextrin built nanosponges were prepared by condensation reaction using diphenyl carbonate as crosslinking agent. Method: A 3-level, 3-factor Box-Behnken design was used to optimize the reaction conditions. The particle size, zeta potential and solubilization efficiency of prepared nanosponges were determined. Actarit was loaded into nanosponges by freeze drying method. Actarit loaded nanosponges were further evaluated for particle size, zeta potential, surface morphology, FTIR, DSC, XRD and Dissolution characteristics. The cyclodextrin nanosponges prepared under optimum conditions exhibited a particle size range of 143.42 to 152.76 nm with low polydispersity indices. FTIR spectra confirmed the formation of carbonyl bond between the β-Cyclodextrin molecules. Results and Discussion: Actarit loaded nanosponges exhibited a particle size range of 157.13 to 168.34 nm with minimum polydispersity index. The zeta potential value was sufficiently high to maintain the stability of colloidal nanosponges. TEM image exposed the spherical structure of drug loaded nanosponges that could be retained and released gradually over time. The FTIR, DSC and XRPD studies inveterate the interaction between Actarit and nanosponges. The drug loaded nanosponges displayed a significant progress in dissolution of drug when compared to plain Actarit. The initial rapid release of Actarit from nanosponges formulations was observed. After 24 h of study, around 90 % of the drug released from nanoformulation and only around 20 % of the drug from free drug suspension. Conclusion: Cyclodextrin based nanosponges displayed superior complexing capability with increased solubility of poorly soluble Actarit.