Search

[Display omitted] Dressings should protect wounds, promote healing, absorb fluids, and maintain moisture. Bacterial cellulose is a biopolymer that stands out in biomaterials due to its high biocompatibility in several applications. In the area of dressings, it is already marketed as an alternative to traditional dressings. However, it lacks any intrinsic activity; among these, the need for antimicrobial activity in infected wounds stands out. We developed a cationic cellulose film by modifying cellulose with 1-(5-carboxypentyl)pyridin-1-ium bromide, enhancing its wettability (contact angle: 26.6°) and water retention capacity (2714.37 %). This modified film effectively retained oxacillin compared to the unmodified control. Liposomal encapsulation further prolonged oxacillin release up to 11 days. Both oxacillin-loaded films and liposomal formulations demonstrated antimicrobial activity against Staphylococcus aureus. Our findings demonstrate the potential of chemically modified cellulose as a platform for controlled anionic antibiotics and/or their formulations delivery in wound care. [ABSTRACT FROM AUTHOR]

Nanoemulsion based nanomaterial (NE) was carried out in the present study to evaluate the efficacy and its antitumor potential of the gastric cancer cells. NE was prepared with astaxanthin/alpha-tocopherol- cellulose nanocrystals/cellulose nanofibrils based nanoemulsions for gastric cancer treatment. The cytotoxic potential was tested against cancer cells and evaluated in terms of its cell proliferation, migration, and cellular uptake by the standard methods. NE was examined for its synergetic effect with photodynamic therapy (PDT) in a xenograft mouse model. The results confirmed the synergetic effect of PDT and NEs in the in vivo animal model. The regulated expression of proteins manifested the reduced toxicity and inhibition of cell proliferation and migration. The antitumor study showed that NE inhibited the growth of human colon cancer in vivo. Immunohistological analysis confirmed the regulation of PI3K/AKT signaling pathway. The present study demonstrates that NEs can enhance anti-cancer effect against human gastric cancer through the immunomodulatory signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85-90 % of all lymphomas. Clinical treatment of NHL is based on the "4-drug regimen" known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erem Bilensoy reports financial support was provided by Scientific and Technological Research Council of Turkey. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

[Display omitted] The influence of hydroxypropyl cellulose type (HPC-SSL SFP, HPC-SSL), concentration (2 %, 3.5 %, 5 %) and filler (lactose, calcium hydrogen phosphate (DCP)/microcrystalline cellulose (MCC)) on twin-screw wet granulation and subsequent tableting was studied. The aim was to identify the formulation of the highest tabletability which still fulfills the requirements of the disintegration. Lactose combined with 5 % binder enabled a higher tabletability and a faster disintegration than DCP/MCC. It was found that tabletability of lactose formulations can be increased by higher binder concentration and higher compression pressure while tabletability of DCP/MCC formulations can be only increased by higher compression pressure. It was observed that batches containing DCP/MCC failed the disintegration test, if the highest binder concentration and the highest compression pressure were used. To ensure a fast disintegration, the compression pressure or at least the binder concentration had to be low. Changing the disintegrant and its localization improved the DCP/MCC formulation, resulting in faster disintegration than lactose tablets. However, it also resulted in a lower tabletability. In this study best tablets were achieved with 3.5 % or 5 % binder and lactose as filler. These tablets presented the highest tabletability but still disintegrated in less than 500 s. [ABSTRACT FROM AUTHOR]

[Display omitted] The objective of this research is to explore the impact of sinkers on the dissolution rate of tablets exhibiting coning in paddle dissolution tests. The ICH M9 guideline refers to the use of sinkers to mitigate coning issues. However, the effectiveness of sinkers on coning phenomena has not been comprehensively investigated. Therefore, this study evaluated whether applying sinkers of different shapes could alleviate coning problems. The dissolution profiles of amlodipine tablet formulations which had been clinically demonstrated to be bioequivalent were assessed in a USP2 Apparatus with and without sinkers. Moreover, the effects of artificially induced coning formed by adding cellulose particles of various sizes on dissolution profiles, and the impacts of sinkers on the dissolution delay caused by the cellulose particles were investigated. Our study suggested that the CLIPS sinker was effective in obtaining in vivo relevant dissolution profiles by facilitating the dispersion of coning. The effect of sinkers varied depending on their shapes and the characteristics of the particles that constituted the coning. These findings enhance our understanding of the effectiveness of sinkers in addressing coning issues and aid in predicting the in vivo dissolution performance of tablet formulations that exhibit coning during dissolution testing. [ABSTRACT FROM AUTHOR]

Amorphous solid dispersions enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the link between polymer properties and formulation performance has not been fully clarified yet. We studied the effect of hydroxypropyl cellulose (HPC) polymers molecular weight (M w ) on the storage stability, dissolution kinetics and supersaturation stability of spray-dried amorphous glibenclamide (GLB) formulations. The solid-state stability of amorphous GLB during storage was significantly enhanced by both the 40 kDa (HPC-SSL) and 84 kDa (HPC-L) polymers, regardless of M w differences. In contrast, HPC-SSL maintained significantly higher aqueous drug concentrations during dissolution, compared to HPC-L (its higher M w analogue). Dedicated dissolution experiments, in situ optical microscopy and solid-state characterization revealed that aqueous drug concentrations were determined by the interplay between crystallization inhibition, drug ionization, wetting and solubilization effects: (1) HPC prevents surface nucleation, hence inhibiting crystallization, (2) intestinal colloids (bile salts and phospholipids) increase supersaturated drug concentrations via wetting and solubilization effects and (3) pH and drug ionization severely impact the degree of supersaturation. The better performance of the lower M w HPC-SSL was due to its superior inhibition of surface crystallization during dissolution. These insights into the molecular mechanisms of dissolution and crystallization of amorphous solids provide foundation for rational formulation development., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zahari Vinarov reports financial support was provided by Bulgarian National Science Fund. Vladimir Petkov reports equipment, drugs, or supplies was provided by European Union. Slavka Tcholakova reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

There is a growing and urgent need for developing novel biomaterials and therapeutic approaches for efficient wound healing. Microneedles (MNs), which can penetrate necrotic tissues and biofilm barriers at the wound and deliver active ingredients to the deeper layers in a minimally invasive and painless manner, have stimulated the interests of many researchers in the wound-healing filed. Among various materials, polymeric MNs have received widespread attention due to their abundant material sources, simple and inexpensive manufacturing methods, excellent biocompatibility and adjustable mechanical strength. Meanwhile, due to the unique properties of nanomaterials, the incorporation of nanomaterials can further extend the application range of polymeric MNs to facilitate on-demand drug release and activate specific therapeutic effects in combination with other therapies. In this review, we firstly introduce the current status and challenges of wound healing, and then outline the advantages and classification of MNs. Next, we focus on the manufacturing methods of polymeric MNs and the different raw materials used for their production. Furthermore, we give a summary of polymeric MNs incorporated with several common nanomaterials for chronic wounds healing. Finally, we discuss the several challenges and future prospects of transdermal drug delivery systems using nanomaterials-based polymeric MNs in wound treatment application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

[Display omitted] Extemporaneous preparation (EP) formulation is an attractive strategy to accelerate the formulation development of new chemical entities for first entry into human study. In this work, an EP suspension formulation for a development drug candidate GDC-6599 was successfully developed. The formulation spanned a wide concentration range from 0.1 to 2.0 mg/mL. A non-solubilizing vehicle, 0.6 % (w/v) methylcellulose solution was used to suspend GDC-6599. An aversive agent denatonium benzoate at an extremely low level (6 ppm) was applied as a taste masking agent. This enabled a simple matrix for the analysis of related substances from GDC-6599 during all stability studies. Microcrystalline cellulose at 10 mg/mL concentration was added to the EP formulation to generate a suspension appearance, leading to the success of using a single placebo for matching active formulation at all concentrations. The developed formulation demonstrated excellent homogeneity, sufficient stability and passed microbiological enumeration test. Rinsing performance test demonstrated that greater than 99.8 % amount of drug was successfully recovered by rinsing with water twice, providing guidance for clinical dosing. Biopharmaceutical assessment was conducted by both in silico simulation and in vitro tests. Greater than 90 % bioaccessibility of the EP suspension formulation was obtained via an in vitro system mimicking the human gastrointestinal absorption, consistent with the result from the in silico modeling. The developed EP formulation was successfully used to support the early single ascending dose (SAD) cohorts of GDC-6599 Phase I clinical study. The formulation matrix and assessment workflow developed in this work are generalizable as a platform for EP formulation development of new chemical entities for early phase clinical studies. [ABSTRACT FROM AUTHOR]

[Display omitted] The majority of tablets manufactured contain lubricants to reduce friction during ejection. However, especially for plastically deforming materials, e.g., microcrystalline cellulose (MCC), the internal addition of lubricants is known to reduce tablet tensile strength. This reduction is caused by the surface coverage by lubricant particles, the extent of which depends on both process and formulation parameters. Previously published models to predict the lubrication effect on mechanical strength do not account for changes in the excipient particle size. In this study, the impact of both lubricant concentration and mixing time on the tensile strength of tablets consisting of three different grades of MCC and four grades of magnesium stearate (MgSt) was evaluated. By taking into account the particle size of the applied excipients, a unifying relationship between the theoretically estimated surface coverage and compactibility reduction was identified. Evaluating the dispersion kinetics of MgSt as a function of time reveals a substantial impact of the initial surface coverage on the dispersion rate, while the minimal tensile strength was found to be comparable for the majority of formulations. In summary, the presented work extends the knowledge of lubricant dispersion and facilitates the reduction of necessary experiments during the development of new tablet formulations. [ABSTRACT FROM AUTHOR]

Cellulose is a natural homopolymer, composed of β-1,4- anhydro- d -glucopyranose units. Unlike plant cellulose, bacterial cellulose (BC), obtained from species belonging to the genera of Acetobacter, Rhizobium, Agrobacterium, and Sarcina through various cultivation methods and techniques, is produced in its pure form. BC is produced in the form of gel-like, never dry sheet with tremendous mechanical properties. Containing up to 99% of water, BC hydrogel is considered biocompatible thus finding robust applications in the health industry. Moreover, BC three-dimensional structure closely resembles the extracellular matrix (ECM) of living tissue. In this review, we focus on the porous BC morphology particularly suited to host oxygen and nutrients thus providing conducive environment for cell growth and proliferation. The remarkable BC porous morphology makes this biological material a promising templet for the generation of 3D tissue culture and possibly for tissue-engineered scaffolds. [ABSTRACT FROM AUTHOR]

The management of pain and inflammation arising from wounds is essential in obtaining effective healing rates. The application of a wound dressing loaded with an anti-inflammatory drug would enable both issues to be ameliorated, and the aim of this work was to fabricate such a dressing by electrospinning. Fibers comprising ethyl cellulose (EC) and poly(vinyl pyrrolidone) (PVP) loaded with naproxen (Nap) were developed to be used in the early stages of wound care. A family of PVP/EC/Nap systems was prepared by varying the PVP: EC ratio. In all cases, the products of electrospinning comprise non-woven mats of fibers which generally have smooth and cylindrical morphologies. The formulations exist as amorphous solid dispersions, and there appear to be intermolecular interactions between the three components. Adjusting the polymer ratios results in tunable drug release, and formulations have been produced which give zero-order drug release over 20 and 80 h. The fiber mats generated in this work thus have great potential to be used as dressings for the treatment of wound pain and inflammation. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The use of non-aqueous cellulose-based formulations for extrusion-spheronisation (E-S) is investigated. A 10 wt% hydroxypropyl cellulose/isopropyl alcohol solution (HPC/IPA) was identified as a suitable sticky liquid binder for preparing non-aqueous pastes. Preliminary tests were performed on a series of pastes using a ram as well as a laboratory roller screen extruder, since the former is commonly used in batch testing and the latter replicates the shear range in a manufacturing screen extruder. Pellets with acceptable size and shape distributions were obtained with Avicel® HFE-102 NF/HPC/IPA for ram E-S, and with Avicel® RC-591/HPC/IPA for screen E-S. Further investigation was performed with calcium carbonate added as a model active pharmaceutical ingredient. Both formulations were able to generate pellets with acceptable size and shape characteristics at up to 50 wt% carbonate loading: further work is required to optimise yields. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract A novel amorphous solid dispersion (ASD) of poorly water-soluble nobiletin (Nob) with highly water-soluble methyl hesperidin (MeHes) was developed. Mixtures of Nob and excipients (MeHes, cellulose derivatives, and synthetic polymers) were processed by hot-melt extrusion (HME). Powder X-ray diffraction analysis proved that most of the HME products were fully amorphized. In dissolution studies, Nob-MeHes ASD showed a prominently higher Nob concentration than other HME products with polymeric excipients. Nob concentration upon dissolution of Nob-MeHes ASD was 400 and 7.5 times higher than that upon dissolution of crystalline Nob and a Nob-MeHes physical mixture, respectively. In addition, Nob-MeHes ASD showed good preservation stability for 6 months under an accelerated condition of 40 °C and 80% relative humidity. Permeation studies using a Caco-2 cell monolayer showed that Nob-MeHes ASD markedly increased the amount of Nob transported. In mice, the plasma Nob concentration and accumulated amount of Nob in various tissues drastically increased after administration of Nob-MeHes ASD. This is the first successful application of MeHes, with a relatively low glass-transition temperature, as an excipient for an ASD formulation prepared by hot-melt extrusion. The drastic improvement in Nob concentration with a small-molecule excipient may be an important finding. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Crystalline nanodispersions of naproxen stabilized with hydroxypropyl cellulose were prepared at different pHs both below and above the pK a of the drug. After spray drying together with lactose, the measured particle size of the rehydrated dispersions using laser light scattering/Mie analysis was found to depend strongly on the pH of the original, processed nanodispersion. The pH-dependent solubility of this weak acid resulted in formation of a dissolved fraction of drug in the nanodispersions, this being higher as the pH increases. There was therefore a loss of crystalline naproxen during processing at higher pH, with fewer and/or smaller nanoparticles in the nanodispersion after nanomilling. After spray drying, the dissolved naproxen fraction formed an amorphous solid, as shown by differential scanning calorimetry and X-ray powder diffraction. The amorphous fraction re-dissolves on re-hydration. An improved disaggregation and smaller particle size of the nanoparticles at higher pH was observed because of the lower amount of crystalline nanoparticles now present. If the pH of the nanodispersion during processing is kept below the pK a for a weak acid, then a high yield of nanoparticles should be expected with little formation of an amorphous phase of the drug. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The purpose of this study was to explore the potential of a quantitative structure–property relationship (QSPR) model to predict tablet density. First, we calculated 3381 molecular descriptors for 81 active pharmaceutical ingredients (API). Second, we obtained data that were merged with a dataset including powder properties that we had constructed previously. Next, we prepared 81 types of tablet, each containing API, microcrystalline cellulose, and magnesium stearate using direct compression at 120, 160, and 200 MPa, and measured the tablet density. Finally, we applied the boosted-tree machine learning approach to construct a QSPR model and to identify crucial factors from the large complex dataset. The QSPR model achieved statistically good performance. A sensitivity analysis of the QSPR model revealed that molecular descriptors related to the average molecular weight and electronegativity of the API were crucial factors in tablet density, whereas the effects of powder properties were relatively insignificant. Moreover, we found that these descriptors had a positive linear relationship with tablet density. This study indicates that a QSPR approach is possibly useful for in silico prediction of tablet density for tablets prepared using more than a threshold compression pressure, and to allow a deeper understanding of tablet density. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Polyphosphates are important polyanionic electrolytes that play a major role in stabilization and consolidation of colloids surface and interior microstructures. In this study, the polyelectrolyte complexes (PEC) microcapsules (sodium cellulose sulfate-chitosan hydrochloride, sample 1), and the patched ones via sodium tripolyphosphate (sample 2), sodium pyrophosphate (sample 3) and sodium hexametaphosphate (sample 4) were fabricated under mild conditions. The effects of polyphosphates on the formation of the PEC microcapsules were investigated systematically. Scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM) observation showed that both of the sample 2 and sample 3 had more compact interior microstructures with higher fluorescence intensity, compared with the sample 4 with macroporous ones and sample 1 with irregular ones. Fourier transform-infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) showed the electrostatic interactions occurred among the –NH 3 + groups, –SO 3 − groups, HP 3 O 10 4− groups, P 2 O 7 4− groups and H 2 PO 4 − groups, and the sample 2 and sample 3 had a more thermal stability comparatively. The sample microcapsules showed good capacity of drug loading and encapsulation efficiency (max. 66.9 ± 4.6% and 74.2 ± 5.1%). In the in vitro release studies showed that the sample 2 and sample 3 had a larger accumulative drug release rate of 5-aminosalicylic acid (5-ASA) at the same time point and released completely at 12 h; the drug release mechanisms analysis indicated that the sample 1 and sample 3 were mainly diffusion controlled, while the sample 2 and sample 4 were followed the mechanism of non-Fickian transport. Under the polyphosphate's consolidation, the PEC microcapsules fabricated with sustained drug release profiles could be used as the promising drug vehicles. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract 3D-printing is a promising tool to pave the way to the widespread adaption of individualized medicine. Several printing techniques have been investigated and introduced to pharmaceutical research. Until now, only one 3D-printed medicine is approved on the US market. The medicine is manufactured via drop-on-powder deposition, which uses inkjet printing to jet a liquid binder on a powder bed to create 3D objects. However, inkjet processes are prone to nozzle clogging when binders or active pharmaceutical ingredients (APIs) are included in the printing ink. This renders the formulation development of the ink the most challenging step. In this study, different hydroxypropyl cellulose (HPC) grades were investigated as solid binders in the powder formulation on a commercially available DoP printer. The printed ink only consisted of a water/ethanol mixture. Formulations containing 70% caffeine as model API were developed and tablets printed. It was found that the friability of the tablets greatly depends on the particle size of the employed binder, whereas disintegration time and dissolution properties mainly depend on the viscosity of the employed binders. Higher viscous binders led to slower disintegration and dissolution whereas lower viscous binders led to faster disintegration and dissolution. The study demonstrates that HPC is a suitable solid binder for DoP printing and that 3D-DoP printing can be used to print robust dosage forms. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Curcuma comosa (C. comosa) is a Thai medicinal herb that provides numerous pharmacologic activities due to its estrogen-like action. This study aimed to investigate the use of liquisolid technique to prepare tablets containing oleoresin-like crude extract of C. comosa, and to improve the dissolution profiles of its major compounds, diarylheptanoids (DAs). Free flowing powders of C. comosa extract were obtained by adsorption onto solid carriers, microcrystalline cellulose, with colloidal silica as coating material. FTIR results ruled out possible interactions between C. comosa extract and excipients. The results indicated that all of liquisolid tablets met the USP requirements. The release of DAs were significantly increased through liquisolid formulations, compared to crude extract. By decreasing the ratio of carrier to coating from 20 to 10, an improvement in dissolution rate was observed. Addition of additives - namely polymer (polyvinyl pyrrolidone) and/or nonvolatile liquid (propylene glycol) affected tablet properties which involved longer disintegration time and lower DA dissolution. Optimized C. comosa liquisolid formulation was prepared in a carrier to coating ratio of 10 without additives. Stability studies showed that physical properties of liquisolid tablet were not affected by aging, but percent remaining and dissolution profiles of DAs were influenced by storage temperature. In vivo pharmacokinetic behavior of the optimized C. comosa liquisolid tablets was investigated following a single oral administration to rabbits. The results proved that the method used for preparation of liquisolid led to C. comosa tablets with low variation in content uniformity and tablet properties, as well as enhanced dissolution behavior. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Wound healing can be a painful and time-consuming process in patients with diabetes mellitus. In light of this, the use of wound healing devices could help to accelerate this process. Here, cellulose-based films loaded with vitamin C (VitC) and/or propolis (Prop), two natural compounds with attractive properties were engineered. The starting materials and the cellulose-based films were characterized in detail. As assessed, vitamin C can be released from the Cel-PVA/VitC and Cel-PVA/VitC/Prop films in a controlled manner. In vitro antibacterial activity studies showed a reduction of bacteria counts (Escherichia coli and Staphylococcus aureus) after Cel-PVA/VitC, Cel-PVA/Prop, and Cel-PVA/VitC/Prop treatments. Moreover, we examined the antibacterial and wound healing properties of the cellulose-based films in a streptozotocin (STZ)-induced diabetic animal model. Diabetic mice exhibited impaired wound healing while the Cel-PVA/VitC/Prop treatment increased the wound closure. A marked reduction in bacterial counts present in the wound environment of diabetic mice was observed after Cel-PVA/VitC, Cel-PVA/Prop and Cel-PVA/VitC/Prop treatment. Histological analysis demonstrated that the non-treated diabetic mice group did not exhibit adequate wound healing while the treated group with Cel-PVA/VitC and Cel-PVA/VitC/Prop films presented good cicatricial response. Furthermore, these novel eco-friendly films may represent a new therapeutic approach to accelerate diabetic wound healing. [ABSTRACT FROM AUTHOR]

[Display omitted] In this study, a novel multifunctional nanocomposite wound dressing was developed, consisting of TEMPO-oxidized bacterial cellulose (TOBC) nanofibers functionalized with donut-like copper-based metal–organic frameworks (CuVB3 MOFs). These CuVB3 MOFs were constructed using copper nodes linked by vitamin B3 molecules, resulting in a copper nicotinate crystal structure as confirmed by X-ray diffraction. Electron microscopy confirmed the presence of donut-like microstructures with uniform element distribution in the synthesized MOFs. Through the incorporation of CuVB3 MOFs into the TOBC nanofibers, innovative TOBC-CuVB3 nanocomposites were created. Biocompatibility testing using the MTT assay demonstrated enhanced cell viability of over 115% for the TOBC-CuVB3 nanocomposite. Acridine Orange staining revealed a ratio of 88–92% live cells on the wound dressings. Furthermore, fibroblast cells cultured on TOBC-CuVB3 exhibited expanded morphologies with long filopodia. The agar diffusion method exhibited improved antibacterial activity against both Gram-positive and Gram-negative bacterial strains, correlating with increased CuVB3 concentration in the samples. In vitro cellular scratch assays demonstrated excellent wound healing potential, with a closure rate of over 98% for wounds treated with the TOBC-CuVB3 nanocomposite. These findings underscore the synergistic effects of copper, vitamin B3, and TOBC nanofibers in the wound healing process. [ABSTRACT FROM AUTHOR]

[Display omitted] Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. Water-soluble HPC leaches out and forms a porous structure that controls the drug transport. Industrially, the pellets are coated using a fluidized bed spraying device, and a layered film exhibiting varying porosity and structure after leaching is obtained. A detailed understanding of the formation of the multilayered, phase-separated structure during production is lacking. Here, we have investigated multilayered EC/HPC films produced by sequential spin-coating, which was used to mimic the industrial process. The effects of EC/HPC ratio and spin speed on the multilayer film formation and structure were investigated using advanced microscopy techniques and image analysis. Cahn-Hilliard simulations were performed to analyze the mixing behavior. A gradient with larger structures close to the substrate surface and smaller structures close to the air surface was formed due to coarsening of the layers already coated during successive deposition cycles. The porosity of the multilayer film was found to vary with both EC/HPC ratio and spin speed. Simulation of the mixing behavior and in situ characterization of the structure evolution showed that the origin of the discontinuities and multilayer structure can be explained by the non-mixing of the layers. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract This study was undertaken to prepare films by solvent evaporation method comprising well-known polymers in order to investigate their potential for buccal suitability. Mucoadhesive films were manufactured using different polymers such as ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose as well as carboxymethyl cellulose. Buccal films were evaluated in regards of mucoadhesiveness, swelling and physico-chemical properties. Furthermore rheological measurement and adhesion study were carried out on the buccal porcine mucosa. Moreover, allantoin as humectant was incorporated and trans -mucosal water loss was determined. The results showed that physico-chemical, buccal adhesive and swelling properties varied depending on the composition of the polymers. The findings indicated films containing allantoin to be suitable for buccal application. In completion, adhesive films are appropriate and promising formulations in the treatment of various disease in the intraoral cavity. [ABSTRACT FROM AUTHOR]

The size and speed of release of proteins of different sizes from standard cellulose sulphate capsules (Cell-in-a-Box®) was investigated. Proteins with molecular weights of up to around 70kD can be released. The conformation, charge and concentration of the protein being released play a role in the release kinetics. Small proteins such as cytokines can be easily released. The ability to produce cytokines at a sustained and predefined level from encapsulated cells genetically engineered to overexpress such cytokines and implanted into patients may aid immunotherapies of cancer as well as infectious and other diseases. It will also allow allogeneic rather than autologous cells to be used. We show that cells encapsulated in polymers of cellulose sulphate are able to release cytokines such as interleukin-2 (IL-2) in a stimulated fashion e.g. using phorbol 12-myristate 13-acetate (PMA) plus ionomycin. Given the excellent documented safety record of cellulose sulphate in patients, these data suggest that clinical usage of the technology may be warranted for cancer treatment and other diseases. [ABSTRACT FROM AUTHOR]

Drug release from a new type of matrix material consisting of partially fibrillated microcrystalline cellulose was investigated. A mechanical treatment of novel AaltoCell™ cellulose microcrystals caused partial opening of the nanofibrillary structure of the cellulose particles and entanglement of individual particles led into formation of an elastic network of microcrystalline cellulose. The rheological properties of the stable hydrogel-like materials were characterised by shear rheometry. Model compounds metronidazole and lysozyme were successfully employed in drug release experiments carried out by delignified (bleached) and lignin-containing matrices. The viscosity as well as the lignin-content played a role in the release dynamics of the drugs. Microcrystalline AaltoCell™ was proven as high-performing material for diffusion controlled release of the chosen model compounds and can be seen as a safe and economical alternative for novel matrix materials such as nanocellulose or cellulose derivatives. [ABSTRACT FROM AUTHOR]

Layer weight control, delamination and cross-contamination are major challenges in the production of compacted multilayer tablets (MLT). In this work, we describe a novel approach to manufacturing MLT: the Gluing Pills Technology (GPT). High loads of ibuprofen free acid and caffeine anhydrate were blended with microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCPD) and compacted into monolayer tablets. They were glued together via the GPT using solutions of either fish gelatin or polyvinylpyrrolidone K90 as gluing agents with defined viscosity. Factors that have a substantial impact on the deformation behavior of blends (i.e., elastic recovery, tensile strength and porosity) of monolayer tablets were investigated in terms of bilayer tablets manufactured via the GPT. The results indicated that high levels of elastic recovery negatively affected the robustness of GPT bilayer tablets and that the type of gluing agent was critical. Raman microscopy analysis was successfully applied to qualitatively assess the function of gluing layer as a barrier to cross-contamination between two monolayer tablets. This study shows the feasibility of the GPT for manufacturing of robust MLT, emphasizing its potential in terms of real-time production of individualized fixed-dose combinations and application in both translational pharmaceutics and personalized medicine. [ABSTRACT FROM AUTHOR]

Compressibility and tablet forming ability (compactibility) of bimodal mixtures of differently sized granules formed from microcrystalline cellulose were studied experimentally and numerically with the discrete element method (DEM). Compression data was analysed using the Kawakita equation. A multi-body contact law that accounts for contact dependence resulting from plastic incompressibility/geometric hardening was used in the DEM simulations. The experimental Kawakita a and 1 / b parameters both depended non-monotonically on composition (weight fraction of large particles). For the a parameter, this dependence was explained by variations in the porosity of the initial granule beds; for the 1 / b parameter, other factors were found to be of importance as well. The numerical results generally compared favourably with the experiments, demonstrating the usefulness of the DEM at high relative densities, provided that a suitable multi-particle contact model is used. For all mixtures, the tensile strength of the formed tablets increased with increasing applied pressure. The tensile strength generally decreased with increasing fraction of large particle, and this decrease was more rapid for large differences in particle size. A possible interpretation of these findings was proposed, in terms of differences in lateral support of small particles in the vicinity of large particles. [ABSTRACT FROM AUTHOR]

The compression physics of powders must be considered when developing a suitable tablet formulation. In the present study, the gravitation-based high-velocity method was utilized to analyze mechanical properties of eight common pharmaceutical excipients: two grades of lactose, anhydrous glucose, anhydrous calcium hydrogen phosphate, three grades of microcrystalline cellulose and starch. Samples were compressed five times consecutively with varying pressure and speed so that Setup A produced higher pressure and longer contact time than Setup B . The important parameters obtained from samples were porosity profiles, compaction pressure, contact time, internal energy change and the amount of elastic recovery. All acquired data was only based on distance-time profile of the compression event. Lactose and glucose fragmented effectively while calcium hydrogen phosphate remained in rearrangement phase, due to its hardness and insufficient pressure applied. Microcrystalline cellulose samples showed plastic behaviour and starch was most elastic of all the samples. By utilizing the method, examined excipients could be categorized according to their compression behaviour in an accurate and cost-efficient manner. [ABSTRACT FROM AUTHOR]

Excipients with good flowability, bulk density as well as compaction properties are desired for use in tableting since they play important roles in formulation development and processing, including, handling, mixing, feeding and compaction. The objective of this paper is to examine the feasibility of using dry coating based surface modification of microcrystalline cellulose, Avicel PH-105, to produce an engineered fine grade (<30 μm) excipient that has all three desired properties. Using a material sparing high-intensity vibrational mixer, Avciel PH-105 is dry coated with 1 wt% Aerosil 200, selected due to its relatively higher dispersive surface energy and lower particle size amongst other silica choices. The results indicated that as expected, the bulk density and flowability are significantly improved, while there was an appreciable loss of compaction. To minimize the loss of compaction, attributed to decreased surface energy after coating, while maintaining improved bulk density and flowability, the effect of reduced silica amount was examined. Remarkably, at reduced levels (0.5 wt% to 0.7 wt%) of Aerosil 200, significant improvements in bulk density and flowability were attained with only 9%–12% compaction reduction. The properties of the surface-engineered excipients were compared with several other commercially available pharmaceutical excipients using two different processibility or regime maps; tablet tensile strength versus bulk density or flow function coefficient (FFC). The surface engineered excipients exhibited the best overall performance establishing a promising pathway to engineer excipients using dry processing instead of complex processes such as spray drying. [ABSTRACT FROM AUTHOR]

[Display omitted] Pellet coat damage in multi-unit pellet system (MUPS) tablets has previously been studied and addressed with limited success. The effects of lactose filler material attributes on pellet coat damage have been relatively well-studied but a similar understanding of microcrystalline cellulose (MCC) is lacking notwithstanding its high cushioning potential. Hence, the relationships between MCC attributes and pellet coat damage were investigated. Single pellet in minitablets (SPIMs) were used to isolate pellet-filler effects and reveal the under-unexplored impact of risk factors found in MUPS tablets. MUPS tablets and SPIMs were prepared with various grades of MCC and pellets with an ethylcellulose or acrylic coat at various compaction pressures. Subsequently, the extent of pellet coat damage was determined by dissolution test and quantified using two indicators to differentiate the nature of the damage. A multi-faceted analytical approach incorporated linear regression, correlations and a classification and regression tree algorithm and evaluated how MCC attributes, such as flowability, particle size and plastic deformability, exert various influences on the extent of ethylcellulose and acrylic pellet coat damage. This analysis improved the understanding of the different mechanisms by which pellet coat damage to these two polymer types occurs which can help enhance future pellet coat damage mitigation strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydroxyethylcellulose (HEC) is a non-ionic water-soluble polymer with poor mucoadhesive properties. The mucoadhesive properties of hydroxyethylcellulose can be improved by modifying it through conjugation with molecules containing maleimide groups. Maleimide groups interact with the thiol groups present in cysteine domains in the mucin via Michael addition reaction under physiological conditions to form a strong mucoadhesive bond. This will prolong the residence time of a dosage form containing this modified polymer and drug on mucosal surfaces. In this study HEC was modified by reaction with 4-bromophenyl maleimide in varying molar ratios and the successful synthesis was confirmed using 1H NMR and FTIR spectroscopies. The safety of the newly synthesised polymer derivatives was assessed with in vivo planaria assays and in vitro MTT assay utilising Caco-2 cell line. The synthesized maleimide-functionalised HEC solutions were sprayed onto blank tablets to develop a model dosage form. The physical properties and mucoadhesive behavior of these tablets were evaluated using a tensile test with sheep buccal mucosa. The maleimide-functionalised HEC exhibited superior mucoadhesive properties compared to unmodified HEC. [ABSTRACT FROM AUTHOR]

The wetting and dissolution of a BCS class II drug (Ibuprofen) is enhanced by solventless solid dispersion technique using co-milling. The co-milling is performed in a planetary ball mill using 1:1 wt. ratio of Ibuprofen (drug) and Microcrystalline cellulose, MCC (excipient). The improvement in wettability and dissolution after co-milling are compared with the raw ibuprofen, ball-milled ibuprofen without any excipient and v-blend mixture of ibuprofen with an excipient. The changes in crystal level properties and reduction in crystallinity due to co-milling are measured using Powder X-ray diffraction (P-XRD) and Differential Scanning Calorimetry (DSC) respectively. The increased interaction between ibuprofen and MCC as well as hydrogen bond formation is confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The morphological changes are observed by optical microscopy and Field Emission Scanning Electron Microscopy (FESEM). The miscibility of drug and excipient and evidence of formation of glassy solutions are demonstrated by Modulated Temperature Differential Scanning Calorimetry (MTDSC) and Raman microscopy. The surface energy and wetting properties are determined using Inverse Gas Chromatography (IGC) and sessile drop method respectively. The results show that co-milling generates defects, strain, and reduction in crystallite size (changes in crystal level properties) which are responsible for the improvement of wetting and dissolution (96% in 90 min). Also, with increase in co-milling time, the polar surface energy increases and the hydrophobic ibuprofen drug surface transforms into hydrophilic surface due to increase in OH groups of MCC on the ibuprofen surface. The present work quantified all the above-mentioned parameters including the acidic and basic parameters of co-milled ibuprofen using IGC. The technique improves the wetting and dissolution of hydrophobic drugs. It can be very well extended to BCS class II and IV drugs in the presence of different hydrophilic excipients. [ABSTRACT FROM AUTHOR]

Poor aqueous solubility of drugs is becoming an increasingly pronounced challenge in the formulation and development of drug delivery systems. To overcome the limitations associated with these problematic drugs, formulation scientists are required to use enabling strategies which often demands the use of new excipients. Cellulose nanofibers (CNFs) is such an excipient and it has only recently been described in the pharmaceutical field. In this review, the use of CNF in drug formulation with a focus on poorly soluble drugs is featured. In particular, the aim is to describe and discuss the many unique properties of CNFs, which make CNFs attractive as excipients in pharmaceutical sciences. Furthermore, the use of CNF as stabilizers for crystalline drug nanoparticles, as a matrix former to obtain a long-lasting sustained drug release over several weeks and as a film former with immediate release properties for poorly soluble drug are reported. Finally, the preparation of pharmaceutical CNF foams together with poorly soluble drugs is highlighted; foams, which offer a sustained drug delivery system with positive buoyancy. [ABSTRACT FROM AUTHOR]

Microcrystalline cellulose (MCC) is one of the most important excipients due to its outstanding binding and tableting properties. Owing to the absence of high resolution characterization techniques at the single particle scale, 3D (three dimension) microstructure of MCC and its effects on formulation performance remain unexamined. The aim of this work was to establish a methodology for single particles of MCC type 102 based on synchrotron radiation X-ray micro computed tomography (SR-μCT), principal component analysis (PCA) and partial least square discriminant analysis (PLSDA). Scanning electron microscopy, SR-μCT, powders properties together with tensile strength (TS), disintegration time (DT), Kawakita plots and force/displacement profiles of tablets were measured. PCA-PLSDA was applied to evaluate the structural classification of MCC particles on the basis of 2D and 3D SR-μCT derived images. The studied MCCs were found to differ in the TS, DT, Kawakita plot and force/displacement, while box ratio and Feret ratio had major influence on the principal components, but the angle of repose, bulk and tapped density did not exhibit significantly. These findings verified that different samples of MCCs from alternative suppliers have morphological diversity when assessed at the individual particle level, which could result into variation in powder properties and tableting performance. [ABSTRACT FROM AUTHOR]

A new model to predict the compressibility and compactability of mixtures of pharmaceutical powders has been developed. The key aspect of the model is consideration of the volumetric occupancy of each powder under an applied compaction pressure and the respective contribution it then makes to the mixture properties. The compressibility and compactability of three pharmaceutical powders: microcrystalline cellulose, mannitol and anhydrous dicalcium phosphate have been characterised. Binary and ternary mixtures of these excipients have been tested and used to demonstrate the predictive capability of the model. Furthermore, the model is shown to be uniquely able to capture a broad range of mixture behaviours, including neutral, negative and positive deviations, illustrating its utility for formulation design. [ABSTRACT FROM AUTHOR]

With modern tableting machines large amounts of tablets are produced with high output. Consequently, methods to examine powder compression in a high-velocity setting are in demand. In the present study, a novel gravitation-based method was developed to examine powder compression. A steel bar is dropped on a punch to compress microcrystalline cellulose and starch samples inside the die. The distance of the bar is being read by a high-accuracy laser displacement sensor which provides a reliable distance-time plot for the bar movement. In-die height and density of the compact can be seen directly from this data, which can be examined further to obtain information on velocity, acceleration and energy distribution during compression. The energy consumed in compact formation could also be seen. Despite the high vertical compression speed, the method was proven to be cost-efficient, accurate and reproducible. [ABSTRACT FROM AUTHOR]

With increasing importance of continuous manufacturing, the interest in integrating dry granulation into a continuous manufacturing line is growing. Residence time distribution measurements are of importance as they provide information about duration of materials within the process. These data enable traceability and are highly beneficial for developing control strategies. A digital image analysis system was used to determine the residence time distribution of two materials with different deformation behavior (brittle, plastic) in the milling unit of dry granulation systems. A colorant was added to the material (20% w/w iron oxide), which did not affect the material properties excessively, so the milling process could be mimicked well. Experimental designs were conducted to figure out which parameters effect the mean residence time strongly. Moreover, two types of dry granulation systems were contrasted. Longer mean residence times were obtained for the oscillating mill (OM) compared to the conical mill (CM). For co-processed microcrystalline cellulose residence times of 19.8–44.4 s (OM) and 11.6–29.1 s (CM) were measured, mainly influenced by the specific compaction force, the mill speed and roll speed. For dibasic calcium phosphate anhydrate residence times from 17.7–46.4 (OM) and 5.4–10.2 s (CM) were measured, while here the specific compaction force, the mill speed and their interactions with the roll speed had an influence on the mean residence time. [ABSTRACT FROM AUTHOR]

The aim of this study was to provide a systematic evaluation of various compression models (Percolation, Kawakita, Exponential model) in respect to predict tablet́s solid fraction for direct compression mixtures, based on single component compression analysis. Four mixtures were compressed over a wide pressure range at various fractions of microcrystalline cellulose (MCC) and pre-agglomerated lactose monohydrate (LAC) to compare an adjusted Percolation, Kawakita and a simple Exponential model. Based on single compression analysis of the pure excipients and application of these models, it was possible to predict the solid fraction of all mixtures. The Kawakita model showed overall superior prediction accuracy, whereas the Percolation model resulted in the best fit for mixtures containing microcrystalline cellulose in a range of 72%–48%. Both models were in good agreement at residuals below 3%. [ABSTRACT FROM AUTHOR]

[Display omitted] • Electrospun mats were prepared based on polymeric components of PCL and HPC. • n -ZnO and MO extract were added to conduct antibacterial/anti-inflammatory activity. • The optimized samples were obtained by Response Surface Methodology. • Final mats had desirable hydrophilicity and did not show any cytotoxicity. • Final wound dressings based on PCL/HPC/ZnO/MO led to a high level of wound closure. Nanofibrous wound dressing is one of the most prominent stratagems for wound caring/management. This research is an approach for designing an electrospun wound dressing based on poly(ε-caprolactone)/hydroxypropyl cellulose/zinc oxide nanoparticles (PCL/HPC/ n -ZnO), in which response surface methodology (RSM) was utilized to ascertain the optimum sample. It was observed that the addition of n -ZnO and Melilotus Officinalis (MO) extract could increase the fibers mean diameter, pore size, and crystallinity of mats. The mentioned quantities for a sample with the highest MO content (PHZM10) were equal to 469 ± 105 nm, 544 ± 370 nm, and 49.67 % , respectively. Moreover, enhancing the amount of MO led to an increase in mechanical properties. In this respect, the PHZM10 sample had the modulus, strength, and toughness of 82.41 ± 0.61 , 20.45 ± 0.30 MPa, and 4194.86 mJ, respectively. Also, according to the MTT assay, no cytotoxicity was reported from any of the manufactured samples. Besides, it was concluded that the antibacterial activity and nanofibrous structure of mats, and also their potential for release of MO extract could accelerate the wound healing. Hence, the wound closure index for the PHZM10 group was 99.3 ± 1.1 %. Based on all noted results, the PCL/HPC/ n -ZnO/MO electrospun mats can be proposed as reassuring wound dressing candidates. [ABSTRACT FROM AUTHOR]

Nanocapsules and nanoparticles play an essential role in the delivery of pharmaceutical agents in modern era, since they can be delivered in specific tissues and cells. Natural polymers, such as cellulose acetate, are becoming very important due to their availability, biocompatibility, absence of toxicity and biodegradability. In parallel, essential oils are having continuous growth in biomedical applications due to the inherent active compounds that they contain. A characteristic example is lemongrass oil that has exceptional antimicrobial properties. In this work, nanocapsules of cellulose acetate with lemongrass oil were developed with the solvent/anti-solvent method with resulting diameter tailored between 95 and 185 nm. Various physico-chemical and surface analysis techniques were employed to investigate the formation of the nanocapsules. These all-natural nanocapsules found to well bioadhere to mucous membranes and to have very good antimicrobial properties at little concentrations against Escherichia coli and Staphylococcus aureus . [ABSTRACT FROM AUTHOR]