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Indomethacin (IND) as a non-selective cyclooxygenase 1 and 2 inhibitor administered orally causes numerous adverse effects, mostly related to the gastrointestinal tract. Moreover, when applied exogenously in topical preparations, there are obstacles to its permeation through the stratum corneum due to its low water solubility and susceptibility to photodegradation. In this work, solid dispersions (SDs) of IND with low-substituted hydroxypropyl cellulose (LHPC) were developed. The IND-SDs were incorporated into a hydroxypropyl guar (HPG) hydrogel to enhance drug solubility on the skin. The hydrogels were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), viscosity, drug release, and unspecific cytotoxicity in mammalian cells. SEM showed a highly porous structure for SD hydrogels. DSC and XRPD studies showed that amorphous IND species were formed; therefore, these hydrogels exhibited superior drug release in comparison with IND raw material hydrogels. FTIR evidenced the presence of the hydrogen bond in the SD hydrogel. The rheology parameter viscosity increased across gels formulated with SDs in comparison with hydrogels with pure IND. In addition, IND-SD hydrogels combine the advantages of a suitable viscosity for dermal use and no potentially hazardous skin irritation. This study suggests that the formulated IND-SD hydrogels represent a suitable candidate for topical administration.
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Photodynamic therapy (PDT) is an emerging treatment modality that utilizes light-sensitive compounds, known as photosensitizers, to produce reactive oxygen species (ROS) that can selectively destroy malignant or diseased tissues upon light activation. This study investigates the incorporation of two porphyrin structures, 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2.) and 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1.), into hydroxypropyl cellulose (HPC) hydrogels for potential use in topical photodynamic therapy (PDT). The structural and compositional properties of the resulting hydrogels were characterized using advanced techniques such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-Visible (UV-Vis) spectroscopy, and fluorescence spectroscopy. FTIR spectra revealed a slight shift of the main characteristic absorption bands corresponding to the porphyrins and their interactions with the HPC matrix, indicating successful incorporation and potential hydrogen bonding. XRD patterns revealed the presence of crystalline domains within the HPC matrix, indicating partial crystallization of the porphyrins dispersed within the amorphous polymer structure. TGA results indicated enhanced thermal stability of the HPC-porphyrin gels compared to 10% HPC gel, with additional weight loss stages corresponding to the thermal degradation of the porphyrins. Rheological analysis showed that the gels exhibited pseudoplastic behavior and thixotropic properties, with minimal impact on the flow properties of HPC by P2.1., but notable changes in viscosity and shear stress with P2.2. incorporation, indicating structural modifications. AFM imaging revealed a homogeneous distribution of porphyrins, and UV-Vis and fluorescence spectroscopy confirmed the retention of their photophysical properties. Pharmacotechnical evaluations showed that the hydrogels possessed suitable mechanical properties, optimal pH, high swelling ratios, and excellent spreadability, making them ideal for topical application. These findings suggest that the porphyrin-incorporated HPC hydrogels have significant potential as effective therapeutic agents for topical applications.
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This study introduces draw solutions for application in forward osmosis (FO) processes, combining mono propylene glycol propyl ether (PGPE) with the cellulose derivative hydroxypropyl cellulose (HPC). A total of 16 unique single-solute and ternary organic draw solutions were prepared and evaluated, leading to the selection of three promising solutions for further investigation. Notably, eight of the initial organic draw solutions demonstrated osmotic pressures exceeding 2.4 MPa. The dynamic viscosities of all draw solutions exhibited a significant reduction with increasing temperature. Among the investigated solutions, the 0.25HPC-3.75PGPE demonstrated the most favorable FO performance, achieving average experimental water fluxes of 11.062 and 9.852 Lm-2 h-1 (LMH) against a 1 g/L NaCl brackish feed solution across two FO runs. PRACTITIONER POINTS: Hydroxypropyl cellulose (HPC, MW ~100,000) was mixed with propylene glycol propyl ether (PGPE) as draw solutes for FO processes. Seven combinations of HPC and PGPE produced osmolalities greater than 1000 mOsm/kg. 0.5HPC-7.5PGPE ternary draw solution achieved experimental water fluxes of 11.062 and 9.852 LMH against 1 g/L NaCl brackish feed solution. Leveraging the LCSTs of these ternary organic solutions holds promise for improved separation and regeneration processes.
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Celulose , Osmose , Águas Salinas , Purificação da Água , Celulose/química , Celulose/análogos & derivados , Purificação da Água/métodos , Águas Salinas/química , Propilenoglicóis/químicaRESUMO
Dye wastewater poses a serious threat to the environment and human health, necessitating sustainable degradation methods. In this study, Na-based Montmorillonite (MMT) was exfoliated using different ionic liquids ([C16MIM][Cl], [C16MIM][BF4], [C16MIM][PF6]), and silver nanoparticles (Ag NPs) were green-synthesized using hydroxypropyl cellulose (HPC). The HPC significantly enhanced the dispersion of MMT in the hydrogel. By introducing lauryl methacrylate (LMA), a hydrophobic associative network was constructed in PAM/LMA/HPC/MMT@ILs&Ag NPs hydrogel. This hydrogel demonstrated outstanding mechanical properties, with a stress of 833.21 kPa, strain of 3300 %, and toughness of 14.36 MJ/m3. It also exhibited excellent catalytic activity, with a rate constant of 0.83 min-1 for 4-nitrophenol degradation at 28 °C. The effects of temperature and catalyst concentration on the catalytic reaction were systematically investigated. This study presents a simple green synthesis approach for Ag NPs using HPC, achieving superior mechanical performance and stable MMT dispersion in aqueous solutions.
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Bentonita , Celulose , Hidrogéis , Líquidos Iônicos , Nanopartículas Metálicas , Prata , Poluentes Químicos da Água , Celulose/química , Celulose/análogos & derivados , Líquidos Iônicos/química , Catálise , Bentonita/química , Hidrogéis/química , Poluentes Químicos da Água/química , Prata/química , Nanopartículas Metálicas/química , Ânions/química , Nitrofenóis/química , Química Verde , Purificação da Água/métodosRESUMO
Decreasing oil resources creates the need to search for raw materials in the biosphere, which can be converted into polyols suitable for obtaining polyurethane foams (PUF). One such low-cost and reproducible biopolymer is cellulose. There are not many examples of cellulose-derived polyols due to the sluggish reactivity of cellulose itself. Recently, cellulose and its hydroxypropyl derivatives were applied as source materials to obtain polyols, further converted into biodegradable rigid polyurethane foams (PUFs). Those PUFs were flammable. Here, we describe our efforts to modify such PUFs in order to decrease their flammability. We obtained an ester from diethylene glycol and phosphoric(III) acid and used it as a reactive flame retardant in the synthesis of polyol-containing hydroxypropyl derivative of cellulose. The cellulose-based polyol was characterized by infrared spectra (IR) and proton nuclear magnetic resonance (1H-NMR) methods. Its properties, such as density, viscosity, surface tension, and hydroxyl numbers, were determined. Melamine was also added to the foamed composition as an additive flame retardant, obtaining PUFs, which were characterized by apparent density, water uptake, dimension stability, heat conductance, compressive strength, and heat resistance at 150 and 175 °C. Obtained rigid PUFs were tested for flammability by determining oxygen index, horizontal flammability test, and calorimetric analysis. Obtained rigid PUFs showed improved flammability resistance in comparison with non-modified PUFs and classic PUFs.
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Foam granulation is a relatively newer wet granulation process whereby foamed binder solutions are added to the powders in the mixer to reduce localized over-wetting encountered during the wet granulation. This study is the first to investigate the effect of binder grade and foam quality on foam granulation process and granule properties of a high drug load formulation. Two different HPC grades, HPC LF (two times more viscous) and HPC EXF at an equivalent 7.4%w/w solution concentration, and foam quality of 50%, 90% and binder solution dripped were added to a high drug load (81%w/w) formulation for wet granulation. The granules were evaluated for compactibility and resultant compact strengths. The 50% foam quality of either HPC LF and HPC EXF resulted in lowest impeller power reading and water activity compared to 90% foam quality or dripped HPC solution. Granules prepared with 50% foam quality also exhibited smaller granule size, wider size distribution and higher specific surface area, resulting in higher compactibility. Whilst the granules prepared with different foamed HPC grades were not significantly different in compression behavior, they were higher in compact strengths, suggesting that foam mixing was more efficient in binder distribution compared to binder liquid penetration and distribution.
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Celulose , Composição de Medicamentos , Excipientes , Tamanho da Partícula , Pós , Celulose/química , Celulose/análogos & derivados , Pós/química , Excipientes/química , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Viscosidade , Água/químicaRESUMO
Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the -OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer-Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer.
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Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of hydroxypropyl cellulose as a technological feed additive for all animal species. In its previous opinions on the safety and efficacy of the product, the FEEDAP Panel could not conclude on proper identification and characterisation as required for a feed additive. The occurrence of potential toxic impurities could also not be assessed. Based on the new data provided, the feed additive hydroxypropyl cellulose was properly identified and characterised and was shown to meet the specifications set for the food additive. Therefore, the conclusions of the safety assessment reached in the previous opinion for hydroxypropyl cellulose meeting the food additive specifications, apply to the hydroxypropyl cellulose under assessment as a feed additive. The feed additive is considered safe for all animal species, the consumer and the environment. In the absence of data, the FEEDAP Panel is not in the position to conclude on the safety for the user.
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Hydroxypropyl cellulose (HPC) is a sustainable cellulose derivative valued for its excellent biocompatibility and solubility and is widely used in various fields. Recent scientific research on high-substituted HPC mainly focused on its efficient preparation and phase transition behavior. Herein, a novel strategy of high-substituted HPC synthesis was demonstrated by employing DMSO/TBAF·3H2O as a cellulose solvent, exhibiting more efficiency than traditional approaches. High-substituted HPC prepared has remarkable thermal stability, exceptional hydrophilicity, and satisfactory solubility. Phase transition behavior of HPC with varying molar degrees of substitution (MS) was delved and a notable negative correlation between MS and cloud point temperature (TCP), was revealed, particularly evident at an MS of 12.3, where the TCP drops to 33 °C. Moreover, a unique self-assembly behavior featuring structural color and responsiveness to force in a solvent-free environment emerged when the MS exceeded 10.4. These insights comprehensively strengthen the understanding and knowledge of high-substituted HPC, simultaneously paving the way for further HPC investigation and exploitation.
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A system based on poly(l-lactic acid) (PLLA) and hydroxypropyl cellulose (HPC) was considered in this study to achieve electrospun mats with outstanding properties and applicability in biomedical engineering. A novel binary solvent system of chloroform/N,N-dimethylformamide (CF/DMF:70/30) was utilized to minimize the probable phase separation between the polymeric components. Moreover, Response Surface Methodology (RSM) was employed to model/optimize the process. Finally, to scrutinize the ability of the complex in terms of drug delivery, Calendula Officinalis (Marigold) extract was added to the solution of the optimal sample (Opt.PH), and then the set was electrospun (PHM). As a result, the presence of Marigold led to higher values of fiber diameter (262 ± 34 nm), pore size (483 ± 102 nm), and surface porosity (81.0 ± 7.3 %). As this drug could also prohibit the micro-scale phase separation, the PHM touched superior tensile strength and Young modulus of 11.3 ± 1.1 and 91.2 ± 4.2 MPa, respectively. Additionally, the cumulative release data demonstrated non-Fickian diffusion with the Korsmeyer-Peppas exponent and diffusion coefficient of n = 0.69 and D = 2.073 × 10-14 cm2/s, respectively. At the end stage, both the Opt.PH and PHM mats manifested satisfactory results regarding the hydrophilicity and cell viability/proliferation assessments, reflecting their high potential to be used in regenerative medicine applications.
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Oxidation of polysaccharides can provide biomaterials with aldehyde and ketone functional groups, which are particularly useful in biomedical applications, like drug delivery, tissue adhesion and hydrogel preparation. However, despite their potential, only a few such methods have been reported, and achieving selective, quantitative oxidation of polysaccharides remains challenging. Herein we report utilization of a mild oxidant, Dess-Martin periodinane, for the chemoselective oxidation of hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC). Our findings reveal that the oxidation of HPC is fast, efficient and achieves near-quantitative conversion. Moreover, both Ox-HPC and Ox-HEC exhibit low cell toxicity, and readily form hydrogels by reaction with a polypeptide comprising amino acids with amine-containing a-substituents, α-poly-l-lysine. The peptide/polysaccharide hydrogels display self-healing properties, injectability, and antimicrobial activity, making them highly attractive for biomedical applications including in wound dressings.
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Celulose , Hidrogéis , Hidrogéis/química , Celulose/química , Polissacarídeos , Sistemas de Liberação de Medicamentos , Derivados da Hipromelose , PeptídeosRESUMO
Construction of biomimetic models for structural color evolution not only gives new photonic phenomena but also provide cues for biological morphogenesis. Here, a novel confined self-assembly method is proposed for the generation of hydroxypropyl cellulose (HPC)-based cholesteric liquid crystals (CLCs) microbubbles. The assembly process relies on the combination of droplet microfluidics, solvent extraction, and a volume confined environment. The as-prepared HPC structural color microbubbles have a transparent shell, an orderly arranged cholesteric liquid crystal (CLC) middle layer, and an innermost bubble core. The size of the microbubble, shell thickness, and the color of the CLC layer can be adjusted by altering the microfluidic parameters. Intriguingly, benefited from the compartmentalization effect provided by droplet microfluidics, microbubbles with multiple cores of different color combinations are generated under precise control. The self-assembled CLCs microbubbles have bright structural color, suspending ability, and good temperature-sensitive characteristics, making them ideal underwater sensors. The present confined assembly approach will shed light on creating novel photonic structures and the HPC microbubble will find widespread applications in multifunctional sensing, optical display, and other related fields are believed.
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Structural color is a fascinating optical phenomenon arising from intricate light-matter interactions. Biological structural colors from natural polymers are invaluable in biomimetic design and sustainable construction. Here, we report a renewable, abundant, and biodegradable cellulose-derived organic gel that generates stable cholesteric liquid crystal structures with vivid structural colors. We construct the chromatic gel using a 68 wt % hydroxypropyl cellulose (HPC) matrix, incorporating distinct polyethylene glycol (PEG) guest molecules. The PEGs contain peculiar end groups with tailored polarity, allowing for precise positioning on the HPC helical backbone through electrostatic repulsion between the PEG and HPC chains. This preserves the HPC's chiral nematic phase without being disrupted. We demonstrate that the PEGs' polarity tunes the HPC gel's reflective color. Additionally, gels with variable polarities are highly sensitive to temperature, pressure, and stretching, resulting in rapid, continuous, and reversible color changes. These exceptional dynamic traits establish the chiral nematic gel as an outstanding candidate for next-generation applications across displays, wearables, flexible electronics, health monitoring, and multifunctional sensors.
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Integrating optically active components into chiral photonic cellulose to fabricate circularly polarized luminescent materials has transformative potential in disease detection, asymmetric reactions, and anticounterfeiting techniques. However, the lack of cellulose-based left-handed circularly polarized light (L-CPL) emissions hampers the progress of these chiral functionalizations. Here, this work proposes an unprecedented strategy: incorporating a chiral nematic organization of hydroxypropyl cellulose with robust aggregation-induced emission luminogens to generate intense L-CPL emission. By utilizing N,N-dimethylformamide as a good solvent for fluorescent components and cellulose matrices, this work produces a right-handed chiral nematic structure film with a uniform appearance in reflective and fluorescent states. Remarkably, this system integrates a high asymmetric factor (0.51) and an impressive emission quantum yield (55.8%) into one fascinating composite. More meaningfully, this approach is versatile, allowing for the incorporation of luminogen derivatives emitting multicolored L-CPL. These chiral fluorescent films possess exceptional mechanical flexibility (toughness up to 0.9 MJ m-3) and structural stability even under harsh environmental exposures, making them promising for the fabrication of various products. Additionally, these films can be cast on the fabrics to reveal multilevel and durable anticounterfeiting capabilities or used as a chiral light source to induce enantioselective photopolymerization, thereby offering significant potential for diverse practical applications.
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Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.
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Canabidiol , Micelas , Humanos , Polímeros/química , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Géis , Água , Portadores de Fármacos , Poliésteres/químicaRESUMO
Along with the increased usage of cellulose in the manufacture of novel materials, those of its derivatives that have good solubility in water or organic solvents have become increasingly important. In this study, hydroxypropyl cellulose (HPC), a cellulosic derivative with distinct features, was utilized to investigate how two of the most-selective oxidation methods currently available in the literature act on the constituent OH groups of both the side chain and the anhydroglycosidic unit in HPC. The oxidation reactions were carried out first using TEMPO, sodium hypochlorite, and sodium bromide, then sodium periodate (NaIO4), for 5 h. A combination of these two protocols was applied. The amount of aldehyde and number of carboxylic groups introduced after oxidation was determined, while the changes in the morphological features of oxidized HPC were, additionally, assessed. Furthermore, utilizing Fourier-transform infrared spectra, X-ray diffraction, and thermogravimetric studies, the chemical structure, crystallinity, and thermal stability of the oxidized HPC samples were examined and compared.
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Inspired by ordered photonic crystals and structural color materials in nature, we successfully prepared hydroxypropyl cellulose (HPC) photonic films with ordered surface arrays by double-imprint soft lithography. Then we introduced another important material of the cellulose family, cellulose nanocrystals (CNC), which has liquid crystal nature and birefringent properties of the particles, into the system to realize the single-point shrinkage of the film array and the control of structural color. Through multi-component doping and concentration control, we further optimized the multi-scale structure of the materials, and obtained HPC/CNCs composite photonic films with excellent properties in color, stability and flexibility, whose elastic modulus and tensile properties are significantly higher than those of single-component. Further loading of SiO2@PDA enhances the color saturation and realizes the in-situ reduction of metal ions on the film surface. This plasma film can track a variety of substances with high sensitivity and long-term stability, showing potential application prospects in the field of surface-enhanced Raman scattering (SERS), which provides a potential possibility for chiral structures to be used in the field of biosensor detection and circularly polarized luminescence.
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Amorphous solid dispersion (ASD) formulations are preferred enabling formulations for poorly water soluble active pharmaceutical ingredients (API) as they reliably enhance the dissolution behavior and solubility. Balancing a high stability against unwanted transformations such as crystallization and amorphous phase separation during storage on the one hand and optimizing the dissolution behavior of the formulation (high supersaturation and maintenance for long time) on the other hand are essential during formulation development. This study assessed the potential of ternary ASDs (one API and two polymers) containing the polymers hydroxypropyl cellulose together with poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) or hydroxypropyl cellulose acetate succinate to stabilize the amorphously embedded APIs fenofibrate and simvastatin during storage and to enhance the dissolution performance. Thermodynamic predictions using the PC-SAFT model revealed for each combination of polymers the optimal polymer ratio, maximum API load that is thermodynamically stable as well as miscibility of the two polymers. The stability predictions were validated by three months enduring stability tests, followed by a characterization of the dissolution behavior. The thermodynamically most stable ASDs were found to be the ASDs with deteriorated dissolution performance. Within the investigated polymer combinations, physical stability and dissolution performance opposed each other.
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Amorphous solid dispersions (ASDs) based on water-insoluble hydrophilic polymers can sustain supersaturation in their kinetic solubility profiles (KSPs) compared to soluble carriers. However, in the limit of very high swelling capacity, the achievable extent of drug supersaturation has not been fully examined. This study explores the limiting supersaturation behavior of ASDs of poorly soluble indomethacin (IND) and posaconazole (PCZ) based on a high-swelling excipient, low-substituted hydroxypropyl cellulose (L-HPC). Using IND as a reference, we showed that the rapid initial supersaturation buildup in the KSP of IND ASD can be simulated through sequential IND infusion steps, however at large times the KSP of IND release from ASD appears more sustained than direct IND infusion. This has been attributed to potential trapping of seed crystals generated in the L-HPC gel matrix thus limiting their growth and rate of desupersaturation. Similar result is also expected in PCZ ASD. Furthermore, the current drug loading process for ASD preparation resulted in the agglomeration of L-HPC based ASD particles, producing granules of up to 300-500 µm (cf. 20 µm individual particle), with distinct kinetic solubility profiles. This feature makes L-HPC particularly suitable as ASD carriers for fine tuning of supersaturation to achieve enhanced bioavailability for poorly soluble drugs.
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Celulose , Indometacina , Preparações Farmacêuticas , Cristalização/métodos , Celulose/química , Solubilidade , Indometacina/química , Liberação Controlada de FármacosRESUMO
A novel hydroxypropyl cellulose (gHPC) hydrogel with graded porosity has been fabricated, in which pore size, shape, and mechanical properties vary across the material. The graded porosity was achieved by cross-linking different parts of the hydrogel at temperatures below and above 42 °C, which was found to be the temperature of turbidity onset (lower critical solution temperature, LCST) for the HPC and divinylsulfone cross-linker mixture. Scanning electron microscopy imaging revealed a decreasing pore size along the cross-section of the HPC hydrogel from the top to the bottom layer. HPC hydrogels demonstrate graded mechanical properties whereby the top layer, Zone 1, cross-linked below LCST, can be compressed by about 50% before fracture, whereas the middle and bottom layers (Zone 2 and 3, respectively) cross-linked at 42 °C, can withstand 80% compression before failure. This work demonstrates a straightforward, yet novel, concept of exploiting a graded stimulus to incorporate a graded functionality into porous materials that can withstand mechanical stress and minor elastic deformations.