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Due to their potential adverse health effects, some N-nitrosamines in drug products are strictly regulated with very low maximum daily intake limits. Nitrosamines can be formed from the reaction of nitrite and secondary or tertiary amines when both species co-exist in the drug synthesis or formulation process. One key strategy to mitigate nitrosamine risk in drugs is to select low-nitrite containing pharma excipients for formulation. It is necessary to develop a sensitive method for trace nitrite determination in pharma excipients as it enables drug producers to study nitrosamine formation kinetics and select excipient suppliers. This study details the development and validation of a two-dimensional ion chromatography mass spectrometry (2D-IC/MS) method for trace nitrite determination in hydroxypropyl methylcellulose (HPMC), one of the most important pharmaceutical excipients used in many drug formulations. The 2D-IC system was operated in heart-cutting mode with a concentrator column coupling the two dimensions. A standard bore anion-exchange column was used in the first dimension ( 1 D) to enable a large volume injection for increased sensitivity and provide improved resolution between nitrite and the interfering chloride peak. A high efficiency microbore anion-exchange column with different selectivity was used in the second dimension ( 2 D) to resolve nitrite from other interfering species. The use of 2D-IC resulted in significantly improved resolution, solving the sensitivity loss issue due to ion suppression from an otherwise 1D separation. MS detection with selective ion monitoring and isotope labeled nitrite internal standard further improve the method specificity, accuracy, and ruggedness, as compared with conductivity detection. For trace determination, it is also extremely important to have a clean blank. For this purpose, a novel cleaning procedure using a strong anion wash was developed to remove nitrite contamination from labware. The optimized method was validated with linearity of nitrite in the concentration range of 18.5-5005.8 ng/g having a regression coefficient of >0.9999, precision with RSD at 3.5-10.1 % and recovery of 90.5-102.4 %. The limit of detection and limit of quantitation were 8.9 and 29.6 ng/g relative to the HPMC sample, or equivalent to 89 and 296 pg/g in the sample solution, respectively., 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.)

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Lamivudine (LMD), an enantiomer of 2'-deoxy-3'-thiacytidine, plays a crucial role in combatting HIV-1 and managing hepatitis B virus infections. Despite its effectiveness, challenges arise from its difficult flowability and tendency to agglomerate during storage, necessitating a granulation step before tablet compression, as direct compression has proven ineffective. This study aimed to optimize Lamivudine spherical agglomerates using response surface methodology, delving into the intricate relationship between design factors (concentration of tween, span, and acetone) and experimental outcomes (yield and particle size) through central composite design. Analysis of variance (ANOVA) was employed for optimization, with the Quasi-emulsion solvent-diffusion (QESD) crystallization technique utilized for the checkpoint batch. This technique, involving a single solvent and antisolvent with surfactants, showcased remarkable enhancements in flowability and reduced storage agglomeration. The impact of various surfactants [Hydroxy Propyl Methyl Cellulose (HPMC), polysorbate 80, and sorbitane monooleate] on particle morphology, flowability, and storage agglomeration during crystallization was thoroughly assessed. While achieving direct compression into tablets, the porous structure of LMD agglomerates presented challenges in tablet press production speeds, prompting adjustments such as reducing punch speed or implementing a precompression step. Positive outcomes were realized for disintegration and in vitro drug release in comparison to direct compression and wet granulation methods. In conclusion, the QESD crystallization technique successfully yielded hollow, spherical LMD agglomerates with enhanced properties, representing a significant milestone in pharmaceutical formulation., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed., Methods: Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer., Results: 45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1)., Significance: The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP). The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC). MN-loaded LP measured 284.7 ± 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 ± 3.3 %) and positive zeta potential (+47.4 ± 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, once-daily extended-release tablets with dual-phase release of oseltamivir phosphate were developed for the treatment of influenza. The goal was to improve patient adherence and offer more therapeutic choices. The tablets were manufactured using wet granulation, bilayer tablet compression, and enteric membrane-controlled coating processes. Various polymers, such as hydroxypropyl methylcellulose (HPMC K100MCR, K15MCR, K4MCR, K100LV), enteric polymers (HPMC AS-LF, Eudragit L100-55) and membrane-controlled polymers (OPADRY® CA), were used either individually or in combination with other common excipients. The formulations include enteric-coated extended-release tablet (F1), hydrophilic matrix extended-release tablet (F2), semipermeable membrane-controlled release tablet (F3) and a combination extended-release tablet containing both enteric and hydrophilic matrix (F4). The in vitro drug release profile of each formulation was fitted to the first-order model, and the Ritger-Peppas model suggested that Fickian diffusion was the primary mechanism for drug release. Comparative bioequivalence studies with Tamiflu® (oseltamivir phosphate) capsules revealed that formulations F1, F2, and F3 did not achieve bioequivalence. However, under fed conditions, formulation F4 achieved bioequivalence with a relative bioavailability of 95.30% (90% CI, 88.83%-102.15%). This suggests that the formulation F4 tablet could potentially be a new treatment option for patients with influenza., 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.)

In this study, berberine hydrochloride (Ber) was used as model drug to prepare a sustained-release cold sol using hydroxypropyl methyl cellulose (HPMC) to achieve superior drug dissolution and transdermal absorption effects. For comparison, a Ber cold sol without HPMC was also prepared using the same method. The preparation process was optimized based on the in vitro release and transdermal permeability of the drug. The results indicated that 1.67 wt% Carbomer 940 and 1.33 wt% HPMC K100M were selected as matrix components with the best sustained-release effect, and drug dissolution of cold sol prepared by combination of these two matrices was significantly slower than the cold sol without HPMC. In addition, transdermal absorption result demonstrated that 0.67 wt% glycerin and 1.33 wt% peppermint oil were the best osmotic enhancers for the optimization of Ber sustained-release cold sol. Herein, HPMC K100M performed important functions in the external application of Ber., Competing Interests: Declaration of competing interest There is no conflict of interest in the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Low-viscosity hydroxypropyl methylcellulose (HPMC) was obtained by electron beam irradiation, and its use as an excipient for improving the properties of spray dried pharmaceutical powders was investigated. The minimum molecular weight of HPMC which could maintain the capacity of encapsulation and powder modification was explored. As the irradiation dose was increased from 10 to 200 kGy, the molecular weight and viscosity of HPMC decreased linearly. However, its main structure and degrees of methoxy and hydroxypropyl substitution were not significantly affected. The irradiated HPMC could encapsulate particles during spray drying and, thus, modify powder properties. Furthermore, the water content of spray-dried powders with irradiated HPMC was lower than that with parent HPMC. After the spray-dried powder with irradiated HPMC was prepared into granules, their dissolution rate was also faster. However, in order to achieve high encapsulation, the molecular weight of HPMC should be ensured to be above 7.5 kDa. The designated low-viscosity HPMC obtained by electron beam irradiation is a suitable powder-modification material for use in spray drying, and it shows promise as a superior excipient in medicine, food, paint industries, among others., 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.)

Prion diseases are fatal transmissible neurodegenerative disorders. Among known anti-prions, hydroxypropyl methylcellulose compounds (HPMCs) are unique in their chemical structure and action. They have several excellent anti-prion properties but the effectiveness depends on the prion-infected mouse model. In the present study, we investigated the effects of stearoxy-modified HPMCs on prion-infected cells and mice. Stearoxy modification improved the anti-prion efficacy of HPMCs in prion-infected cells and significantly prolonged the incubation period in a lower HPMC-responding mouse model. However, stearoxy modification showed no improvement over nonmodified HPMCs in an HPMC-responding mouse model. These results offer a new line of inquiry for use with prion-infected mice that do not respond well to HPMCs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kenta Teruya reports financial support was provided by the Japan Society for the Promotion of Science [grant numbers 19K22479 and 23K05036]. Kenta Teruya has patent #P2017-93414 issued to Tohoku University. Katsumi Doh-ura has patent #P2017-93414 issued to Tohoku University. 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 Ltd.. All rights reserved.)

One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC-mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC-mannitol, and their respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance. It was found that co-processed HPMC-mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150-200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC-mannitol ratios. Co-processed HPMC-mannitol offers an interesting addition to the formulator's toolbox in the design of controlled release formulations for direct compression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christina Yong Xin Kang, Wen Chin Foo, Kwan Hang Lam, Keat Theng Chow, Yuan Siang Lui, Hui Ping Goh, Antoine Salome, Baptiste Boit, Philippe Lefevre, and Rajeev Gokhale are current/past employees of Roquette and may own Roquette stock. In addition, Baptiste Boit and Philippe Lefevre have patent issued to Roquette Freres SA., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC 0-12 h ) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment., 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.)

Prion diseases are fatal transmissible neurodegenerative disorders. Tremendous efforts have been made for prion diseases; however, no effective treatment is available. Several anti-prion compounds have a preference for which prion strains or prion-infected animal models to target. Styrylbenzoazole compound called cpd-B is effective in RML prion-infected mice but less so in 263K prion-infected mice, whereas hydroxypropyl methylcellulose is effective in 263K prion-infected mice but less so in RML prion-infected mice. In the present study, we developed a combination therapy of cpd-B and hydroxypropyl methylcellulose expecting synergistic effects in both RML prion-infected mice and 263K prion-infected mice. A single subcutaneous administration of this combination had substantially a synergistic effect in RML prion-infected mice but had no additive effect in 263K prion-infected mice. These results showed that the effect of cpd-B was enhanced by hydroxypropyl methylcellulose. The complementary nature of the two compounds in efficacy against prion strains, chemical properties, pharmacokinetics, and physical properties appears to have contributed to the effective combination therapy. Our results pave the way for the strategy of new anti-prion agents., (© 2023. The Author(s).)

Collagen (COL)-hydroxypropyl methylcellulose (HPMC) blended films with apple polyphenol (AP) as cross-linking agent and antioxidant compound were developed to produce biodegradable active packaging film. The effects of AP content on the rheological behavior of the blended solution, the structure, physicochemical and functional properties of the blended film were systematically investigated. The incorporation of AP increased the viscosity and reduced the fluidity of COL-HPMC solution. The results of rheological tests and FTIR analysis manifested the formation of hydrogen bonding interactions between collagen, HPMC and AP, which made the structures of COL-HP-AP films more compact. The mechanical strength, UV-blocking ability, water-resistance performance and thermostability were gradually enhanced as increasing AP content. DPPH free radical scavenging experiment showed that a small amount of AP could efficiently improve the antioxidant activity of COL-HP film, and with increasing AP content to 5 wt%, the scavenging rate was as high as 94.23 %. Active film containing 5 wt% AP showed obvious antibacterial effect on E. coli and S. aureus, and it could effectively prevent the oxidation of vitamin C and reduce the accumulation of MDA on green pepper during the storage. COL-HP-AP films have great potential in food packaging field for extending the shelf life of food., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recent work has shown that an amorphous drug-polymer salt can be highly stable against crystallization under hot and humid storage conditions (e.g., 40 °C/75% RH) and provide fast release and that these advantages depend on the degree of salt formation. Here, we investigate the salt formation between the basic drug lumefantrine (LMF) and several acidic polymers: poly(acrylic acid) (PAA), hypromellose phthalate (HPMCP), hypromellose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), Eudragit L100, and Eudragit L100-55. Salt formation was performed by "slurry synthesis" where dry components were mixed at room temperature in the presence of a small quantity of an organic solvent, which was subsequently removed. This method achieved more complete salt formation than the conventional methods of hot-melt extrusion and rotary evaporation. The acidic group density of a polymer was determined by nonaqueous titration in the same solvent used for slurry synthesis; the degree of LMF protonation was determined by X-ray photoelectron spectroscopy. The polymers studied show very different abilities to protonate LMF when compared at a common drug loading, following the order PAA > (HPMCP ∼ CAP ∼ L100 ∼ L100-55) > HPMCAS, but the difference largely disappears when the degree of protonation is plotted against the concentration of the available acidic groups for reaction. This indicates that the extent of salt formation is mainly controlled by the acidic group density and is less sensitive to the polymer architecture. Our results are relevant for selecting the optimal polymer to control the degree of ionization in amorphous solid dispersions.

Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of vinyl pyrrolidone/vinyl acetate copolymer (Kollidon® VA64, VA64) and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm 2 (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90% of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODF treatment group had a 100% reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7% higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group showed minimal oral irritation, scoring only 1 point and a 65% preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment product development., 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.)

The multifunctionality of advanced laundry detergents primarily relies on the inclusion of functional solid particles, such as pearlescent powder, enzymes, and perfume microcapsules. However, the high-content surfactants in these detergents can render most existing suspending rheology modifiers ineffective, making it challenging to achieve uniform suspension of these functional particles. This compromises the overall functionality of laundry products. To address this, we have developed a binary rheology modifier comprising cellulose microgel and HPMC (hydroxypropyl methylcellulose), acting as the "island" and "chain," respectively. Together, they form an interconnected dynamic network that effectively "encapsulates" the functional particles. Furthermore, the cellulose microgel/HPMC rheology modifier demonstrates versatility, proving effective with various surfactants. Despite its potential, the suspension mechanism of cellulose microgel/HPMC remains elusive. Therefore, we conducted a comprehensive investigation, fabricating cellulose microgels with varying nanofabrication degrees and surface charges through TEMPO oxidation. Our findings highlight the critical role of the surficial structure of T-Microgel, specifically its nanofabrication degree, in influencing the dynamic network's fabrication, thereby impacting yield and thixotropic properties. The surface charge of T-microgel does not significantly influence the process. This research not only elucidates the intricate dynamics of cellulose microgel/HPMC interaction but also provides fundamental insights essential for the development of innovative rheology modifiers tailored for high-content surfactant applications., 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. Published by Elsevier B.V.)

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss., 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 Ltd. All rights reserved.)

The requirement to improve the efficiency of pesticide utilization has led to the development of sustainable and smart stimuli-responsive pesticide delivery systems. Herein, a novel avermectin nano/micro spheres (AVM@HPMC-Oxalate) with sensitive stimuli-response function target to the Lepidoptera pests midgut microenvironment (pH 8.0-9.5) was constructed using hydroxypropyl methylcellulose (HPMC) as the cost-effective and biodegradable material. The avermectin (AVM) loaded nano/micro sphere was achieved with high AVM loading capacity (up to 66.8 %). The simulated release experiment proved the rapid stimuli-responsive and pesticides release function in weak alkaline (pH 9) or cellulase environment, and the release kinetics were explained through release models and SEM characterization. Besides, the nano/micro sphere size made AVM@HPMC-Oxalate has higher foliar retention rate (1.6-2.1-fold higher than commercial formulation) which is beneficial for improving the utilization of pesticides. The in vivo bioassay proved that AVM@HPMC-Oxalate could achieve the long-term control of Plutella xylostella by extending UV shielding performance (9 fold higher than commercial formulation). After 3 h of irradiation, the mortality rate of P. xylostella treated by AVM@HPMC-Oxalate still up to 56.7 % ± 5.8 %. Moreover, AVM@HPMC-Oxalate was less toxic to non-target organisms, and the acute toxicity to zebrafish was reduced by 2-fold compared with AVM technical., 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 Ltd. All rights reserved.)

Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing., 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. Published by Elsevier Ltd.)

Microparticles as a multicompartment drug delivery system are beneficial for poorly soluble drugs. Mucoadhesive polymers applied in microparticle technology prolong the contact of the drug with the mucosa surface enhancing drug bioavailability and extending drug activity. Sodium alginate (ALG) and hydroxypropyl methylcellulose (hypromellose, HPMC) are polymers of a natural or semi-synthetic origin, respectively. They are characterized by mucoadhesive properties and are applied in microparticle technology. Spray drying is a technology employed in microparticle preparation, consisting of the atomization of liquid in a stream of gas. In this study, the pharmaceutical properties of spray-dried ALG/HPMC microparticles with posaconazole were compared with the properties of physical mixtures of powders with equal qualitative and quantitative compositions. Posaconazole (POS) as a relatively novel antifungal was utilized as a model poorly water-soluble drug, and hard gelatin capsules were applied as a reservoir for designed formulations. A release study in 0.1 M HCl showed significantly prolonged POS release from microparticles compared to a mixture of powders. Such a relationship was not followed in simulated vaginal fluid (SVF). Microparticles were also characterized by stronger mucoadhesive properties, an increased swelling ratio, and prolonged residence time compared to physical mixtures of powders. The obtained results indicated that the pharmaceutical properties of hard gelatin capsules filled with microparticles were significantly different from hard gelatin capsules with mixtures of powders.

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets., 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.)

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future., 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.)

This study focuses on the combination of three-dimensional printing (3DP) and amorphous solid dispersion (ASD) technologies for the manufacturing of gastroretentive floating tablets. Employing hot melt extrusion (HME) and fused deposition modeling (FDM), the study investigates the development of drug-loaded filaments and 3D printed (3DP) tablets containing felodipine as model drug and hydroxypropyl methylcellulose (HPMC) as the polymeric carrier. Prior to fabrication, solubility parameter estimation and molecular dynamics simulations were applied to predict drug-polymer interactions, which are crucial for ASD formation. Physical bulk and surface characterization complemented the quality control of both drug-loaded filaments and 3DP tablets. The analysis confirmed a successful amorphous dispersion of felodipine within the polymeric matrix. Furthermore, the low infill percentage and enclosed design of the 3DP tablet allowed for obtaining low-density systems. This structure resulted in buoyancy during the entire drug release process until a complete dissolution of the 3DP tablets (more than 8 h) was attained. The particular design made it possible for a single polymer to achieve a zero-order controlled release of the drug, which is considered the ideal kinetics for a gastroretentive system. Accordingly, this study can be seen as an advancement in ASD formulation for 3DP technology within pharmaceutics., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Conventional spray drying using a 2-fluid nozzle forms matrix microparticles, where drug is distributed throughout the particle and may not effectively mask taste. In contrast, spray drying using a 3-fluid nozzle has been reported to encapsulate material. The objective of this study was to spray dry Eudragit® E-PO (EE) with acetaminophen (APAP), a water-soluble model drug with a bitter taste, using 2- and 3-fluid nozzles for taste masking. Spray drying EE with APAP, however, resulted in yields of ≤ 13 %, irrespective of nozzle configuration. Yields improved when Eudragit® L 100-55 (EL) or Methocel® E6 (HPMC) was used in the inner fluid stream of the 3-fluid nozzle or in place of EE for the 2-fluid nozzle. Drug release from microparticles prepared with the 2-fluid nozzle was relatively rapid. Using EE in the outer fluid stream of the 3-fluid nozzle resulted in comparatively slower drug release, although drug release was observed, indicating that encapsulation was incomplete. Results from these studies also show that miscible polymers used in the two fluid streams mix during the spray drying process. In addition, findings from this study indicate that the polymer used in the inner fluid stream can impact drug release., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Linda Felton reports financial support was provided by National Institutes of Health. Linda Felton has patent #17/111,645 pending to University of New Mexico. 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.)

The study involved preparing and applying edible nano-emulsion coatings containing hydroxypropyl methylcellulose (HPMC), beeswax (BW), and essential oils (thyme, cinnamon, clove, and peppermint) onto sweet cherries. The application was conducted at 4 °C, and the coated cherries were stored for 36 days. This research examines synthesized nano-emulsions physicochemical properties and antibacterial and antifungal activities (C 1 , C 2 , and C 3 ). Additionally, it evaluates the quality parameters of control and coated sweet cherry samples. The features of the three edible coatings were assessed, and the findings from the zeta sizer, zeta potential, FTIR, and SEM analyses were deemed satisfactory. It was observed that the application of nano-emulsion coating C 1 yielded positive results in maintaining quality attributes such as total suspended solids (TSS), total solids (TS), color, weight loss, respiration rate, firmness, total phenolic contents, and sensory evaluations. Nano-emulsion coating C 1 demonstrated efficacy as an antibacterial and antifungal agent against foodborne pathogens E. coli and A. niger, respectively. The current research results are promising and applicable in food industries. The implications suggest that composite nano-emulsion, specifically nano-emulsion edible coatings, can be extensively and effectively used to preserve the quality and shelf life of fruits and vegetables. Furthermore, the environmental waste from conventional food packaging will be minimized using edible packaging applications., 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.)

Solid dispersions (SDs) have emerged as a promising strategy to enhance the solubility and bioavailability of poorly soluble active pharmaceutical ingredients. However, SDs tend to recrystallize unless suitable excipients are utilized. This study aimed to facilitate the rational selection of polymers and formulation design by evaluating the impact of various polymers on the miscibility, and phase behavior of SDs using baloxavir marboxil (BXM) with a high crystallization tendency as a model drug. Meanwhile, the effects of these polymers on the solubility enhancement and recrystallization inhibition were also assessed. The results indicated that the miscibility limit of BXM for HPMCAS was around 40 % drug loading (DL), whereas for PVP, PVPVA, and HPMC approximately 20 % DL. The BXM-HPC system exhibited limited miscibility with DL of 10 % or higher. BXM SDs based on various polymers exhibited varying degrees of spontaneous phase separation once DL exceeded the miscibility limit. Interestingly, a correlation was discovered between the phase separation behavior and the ability of the polymer to inhibit recrystallization. BXM-HPMCAS SDs exhibited optimal dissolution performance, compared with other systems. In conclusion, the physicochemical properties of polymers significantly influence BXM SDs performance and the BXM-HPMCAS SDs might promote an efficient and stable drug delivery system., 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. Manuscript: Effects of hypromellose acetate succinate on recrystallization inhibition, miscibility, and dissolution enhancement of baloxavir marboxil solid dispersions. Authors: Lili Wang, Hengqian Wu, Zhengping Wang, Zhuang Ding, Yanna Zhao, Suye Li, Heng Zhang, Guangwei Jia, Lingfeng Gao, Jun Han., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Buccal mucosa administration is a promising method for insulin (INS) delivery with good compliance. However, buccal mucosa delivery systems still face challenges of long-term mucosal adhesion, sustained drug release, and mucosal drug penetration. To address these issues, a double-layer film consisting of a hydroxypropyl methylcellulose/polyacrylic acid interpolymer complex (IPC)-formulated mucoadhesive layer and an ethylcellulose (EC)-formulated waterproof backing layer (IPC/EC film) was designed. Protamine (PTM) and INS were co-loaded in the mucoadhesive layer of the IPC/EC film (PTM-INS-IPC/EC film). In ex vivo studies with porcine buccal mucosa, this film exhibited robust adhesion, with an adhesion force of 120.2 ± 20.3 N/m 2 and an adhesion duration of 491 ± 45 min. PTM has been shown to facilitate INS mucosal transfer. Pharmacokinetic studies indicated that the PTM-INS-IPC/EC film significantly improved the absorption of INS, exhibiting a 1.45 and 2.24-fold increase in the area under the concentration-time curve (AUC 0-∞ ) compared to the INS-IPC/EC film and free INS, respectively. Moreover, the PTM-INS-IPC/EC film effectively stabilized the blood glucose levels of type 1 diabetes mellitus (T 1 DM) rats with post oral glucose administration, maintaining lower glucose levels for approximately 8 h. Hence, the PTM-INS-IPC/EC film provides a promising noninvasive INS delivery system for diabetes treatment., 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.)

To improve the compatibility of gelatin (GA) and hydroxypropyl methylcellulose (HPMC), we investigated the effects of zein-pectin composite particles (ZCPs) with various zein/pectin ratios (1:0, 1:0.5, 1:1, 1:1.5, and 1:2) on the physical stability, microstructure, and rheological properties of the GA/HPMC water-water systems. With increasing pectin ratio, the particle size of the composite particles increased from 234.53 ± 1.48 nm to 1111.00 ± 26.91 nm, and their zeta potential decreased from 20.60 mV to below -34.77 mV. Macroscopic and microstructure observations indicated that pectin-modified ZCPs could effectively inhibit phase separation behavior between GA and HPMC. Compared to pure HPMC, the GA/HPMC water-water systems possessed a higher viscosity and dynamic modulus at room temperatures but lower gel temperatures (reduction of about 11 %). The viscosity and modulus of the water-water systems increased with increasing pectin ratio in ZCPs. However, the ratio had no impact on the gel-sol (sol-gel) transition temperatures (not statistically significant (P < 0.05)). This study may serve as a reference for advancing the processability of HPMC., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Amorphous solid dispersions (ASDs) represent an important approach for enhancing oral bioavailability for poorly water soluble compounds; however, assuring that these ASDs do not recrystallize to a significant extent during storage can be time-consuming. Therefore, various efforts have been undertaken to predict ASD crystallization levels with kinetic models. However, only limited success has been achieved due to limits on crystal content quantification methods and the complexity of crystallization kinetics. To increase the prediction accuracy, the accelerated stability assessment program (ASAP), employing isoconversion (time to hit a specification limit) and a modified Arrhenius approach, are employed here for predictive shelf-life modeling. In the current study, a model ASD was prepared by spray drying griseofulvin and HPMC-AS-LF. This ASD was stressed under a designed combinations of temperature, relative humidity and time with the conditions set to ensure stressing was carried out below the glass transition temperature (T g ) of the ASD. Crystal content quantification method by X-ray powder diffraction (XRPD) with sufficient sensitivity was developed and employed for stressed ASD. Crystallization modeling of the griseofulvin ASD using ASAPprime® demonstrated good agreement with long-term (40 °C/75 %RH) crystallinity levels and support the use of this type of accelerated stability studies for further improving ASD shelf-life prediction accuracy., 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. Published by Elsevier B.V.)

Oral dispersible films have received broad interest due to fast drug absorption and no first-path metabolism, leading to high bioavailability and better patient compliance. Saxagliptin (SXG) is an antidiabetic drug that undergoes first-path metabolism, resulting in a less active metabolite, so the development of SXG oral dispersible films (SXG-ODFs) improves SXG bioavailability. The formula optimisation included a response surface experimental design and the impact of three formulation factors, the type and concentration of polymer and plasticiser concentration on in-vitro disintegration time and folding endurance. Two optimised SXG-ODFs prepared using either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose were investigated. SXG-ODFs prepared with PVA demonstrated a superior rapid disintegration time, ranging from 17 to 890 s, with the fastest disintegration time recorded at 17 s. These short durations can be attributed to the hydrophilic nature of PVA, facilitating rapid hydration and disintegration upon contact with saliva. Additionally, PVA-based films displayed remarkable folding endurance, surpassing 200 folds without rupture, indicating flexibility and stability. The high tensile strength of PVA-based films further underscores their robust mechanical properties, with tensile strength values reaching up to 4.53 MPa. SXG exhibits a UV absorption wavelength of around 212 nm, posing challenges for traditional quantitative spectrophotometric analysis, so a polyaniline nanoparticles-based solid-contact screen-printed ion-selective electrode (SP-ISE) was employed for the determination of SXG release profile effectively in comparison to HPLC. SP-ISE showed a better real-time release profile of SXG-ODFs, and the optimised formula showed lower blood glucose levels than commercial tablets., (© 2024. The Author(s).)

Hydroxypropyl methyl cellulose (HPMC) is a type of cellulose derivative with properties that render it useful in e.g. food, cosmetics, and pharmaceutical industry. The substitution degree and composition of the β-glucose subunits of HPMC affect its physical and functional properties, but HPMC characterization is challenging due to its high structural heterogeneity, including many isomers. In this study, comprehensive two-dimensional liquid chromatography-mass spectrometry was used to examine substituted glucose monomers originating from complete acid hydrolysis of HPMC. Resolution between the different monomers was achieved using a C18 and cyano column in the first and second LC dimension, respectively. The data analysis process was structured to obtain fingerprints of the monomers of interest. The results revealed that isomers of the respective monomers could be selectively separated based on the position of substituents. The examination of two industrial HPMC products revealed differences in overall monomer composition. While both products contained monomers with a similar degree of substitution, they exhibited distinct regioselectivity., 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. Published by Elsevier B.V.)

Since ancient times, mouth fresheners in many different forms have been used throughout the world. Traditional knowledge describes the health benefits of mouth fresheners, and contemporary science is now investigating their benefits. Claims have been made that mouth fresheners not only improve digestion but also promote oral health. Similar, but in a more profound sense, probiotics offer astounding advantages in treating many disorders. In certain cases, probiotics also offer prophylactic effects. Numerous benefits for dental health are being studied for B. coagulans (MB-BCM9) and B. subtilis (MB-BSM12). In this current study, a probiotic and a mouth freshener were combined to ameliorate the impacts of both. The oral residence of probiotics was enhanced by employing mucoadhesive polymers. Numerous compositions were developed and evaluated for the unaltered growth of probiotics, along with other evaluations like microscopy, in vitro mucoadhesive strength, and stability studies. Xanthan gum and hydroxypropyl methylcellulose were used in the development of mucoadhesive probiotic powder by employing the lyophilization technique. More than five hours of residence time were observed in the in vitro study with goat oral mucosa. The enumeration study validated the label claims of MB-BCM9 and MB-BSM12. It also concluded that none of the components of the formulation had a detrimental effect on probiotics. In essence, the present work discloses the novel and stable formulation of a probiotic-based mouth freshener., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

The separation sheets for fruit leather are traditionally made of plastic film or wax paper, which not only leads to environmental issues but also is inconvenience to consumers. This study evaluated edible fruit leather separation sheets using food polymers, including hydroxypropyl methyl cellulose (HPMC) and incorporation of cranberry pomace water extract (CPE) for providing natural fruit pigment, flavor, and phenolics. HPMC CPE film was then further improved by incorporating hydrophobic compound (oleic acid, OA) and vitamin E (VE) via cellulose nanocrystal (CNC) Pickering emulsion (CNCP) for enhancing film hydrophobicity and nutritional benefit, respectively. The CNCP-HPMC CPE film exhibited reduced water vapor permeability (∼0.033 g mm/m 2  d Pa) compared to HPMC CPE film (∼0.59 g mm/m 2  d Pa) and had the least change in mass and moisture content when wrapping fruit leather for up to 2 weeks of ambient storage. The fruit leather wrapped by CNCP-HPMC CPE film showed lower weight change than those by films without CNCP due to low mass transfer between film and fruit leather. CNCP resulted in controlled release of VE into a food simulating solvent (ethanol). The developed colorful and edible fruit leather separation sheet satisfied the increased market demands on sustainable food packaging. PRACTICAL APPLICATION: Colorful and flavorful edible films made of edible polymers, fruit pomace water extract, and emulsified hydrophobic compounds with vitamin E were created. The films have the satisfactory performance to replace the conventional fruit leather separation sheet made of plastic or wax paper. The edible films can be eaten with packaged fruit leather for not only reducing packaging waste but also providing convenience and nutritional benefit to consumers. These functional edible films may also be utilized to package other food products for promoting packaging sustainability and nutritional benefit., (© 2024 Institute of Food Technologists.)

Edible films with modulated release of antimicrobial agents are important for food preservation. Herein, antimicrobial edible films were prepared using whey protein (WP) and hydroxypropyl methylcellulose (HM) as polymer matrix materials and cinnamaldehyde (CIN) as antimicrobial agent. The mass ratios of WP and HM were 100/0, 75/25, 50/50, 25/75 and 0/100. The release kinetics of CIN through the film was studied, applying the Fickian model, power law and Weibull model. The films were also characterized by physical and structural characteristics, and antibacterial activity. In comparison to other films, the CIN-loaded film with a WP/HM ratio of 50/50 had better moisture resistance, water vapor barrier properties and mechanical properties. High correlation factors were obtained by fitting the CIN release data with the power law (R 2  > 0.96) and Weibull model (R 2  > 0.97). The diffusion mechanism of CIN was pseudo-Fickian. The diffusion coefficients (D 1 and D 2 ) had a positive linear relationship with the HM ratio, suggesting that a high HM ratio was beneficial to the CIN release. Finally, the WH50-C film was successfully used to preserve Mongolian cheese. This research provides a new perspective on the design of active packaging film with sustained-release characteristics., 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.)

Despite the clinical success of tricalcium silicate (TCS)-based materials in endodontics, the inferior handling characteristic, poor anti-washout property and slow setting kinetics hindered their wider applications. To solve these problems, an injectable fast-setting TCS/β-tricalcium phosphate/monocalcium phosphate anhydrous (β-TCP/MCPA) cement was developed for the first time by incorporation of hydroxypropyl methylcellulose (HPMC) and β-TCP/MCPA. The physical-chemical characterization (setting time, anti-washout property, injectability, compressive strength, apatite mineralization and sealing property) of TCS/(β-TCP/MCPA) were conducted. Its hydration mechanism was also investigated. Furthermore, the cytocompatibility and osteogenic/odontogenic differentiation of stem cells isolated from human exfoliated deciduous teeth (SHED) treated with TCS/β-TCP/MCPA were studied. The results showed that HPMC could provide TCS with good anti-washout ability and injectability but slow hydration process. However, β-TCP/MCPA effectively enhanced anti-washout characteristics and reduced setting time due to faster hydration kinetics. TCS/(β-TCP/MCPA) obtained around 90 % of injection rate and high compressive strength whereas excessive additions of β-TCP/MCPA compromised its injectability and compressive strength. TCS/(β-TCP/MCPA) can induce apatite deposition and form a tight marginal sealing at the dentin-cement interface. Additionally, TCS/(β-TCP/MCPA) showed good biocompatibility and promoted osteo/odontogenic differentiation of SHED. In general, our results indicated that TCS/(β-TCP/MCPA) may be particularly promising as an injectable bioactive cements for endodontic treatment., 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.)

Herpetrione(HPE) is an effective compound that has been used in the treatment of liver diseases. To improve its dissolution and absorption, herpetrione nanosuspensions was prepared. Nanosuspensions were proved to achieve intact absorption in vivo. However, the transport mechanisms are not fully understood, especially lack of direct evidence of translocation of particulates. In this study, an environment-responsive dye, P4, was loaded into herpetrione amorphous nanoparticles (HPE-ANPs) to elucidate the absorption and transport mechanism of the nanoparticles. And the amount of HPE and nanoparticles in the samples were quantified using HPLC/LC-MS/MS and IVIS with the model of Caco-2 and Caco-2/HT29-MTX. Results demonstrated that HPE is mainly taken up by passive diffusion in the form of free drugs, while HPE-ANPs are internalized by an energy dependent active transport pathway or intracellular endocytosis. It is speculated that HPE-ANPs may change the original entry pathway of drug molecules. Furthermore, the presence of mucus layer and the use of HPMC E15 may contribute to drug absorption to some extent. Transcellular transport study indicates that HPE-ANPs has a poor absorption. In conclusion, the differences in the absorption behavior trends of HPE-ANPs are caused by the difference in particle properties and the form of existence of the drug., 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.)

The excessive water sensitivity of hydroxypropyl methylcellulose (HPMC) films prevent them from being used extensively. In order to overcome this limitation, superhydrophobic HPMC films were meticulously crafted through the utilization of a composite of polydimethylsiloxane (PDMS) and ball-milled rice starch, corn starch, or potato starch (RS/CS/PS) for the coating process. Initially possessing hydrophilic properties, the HPMC Film (CA = 49.3 ± 1.8°) underwent a transformative hydrophobic conversion upon the application of PDMS, resulting in a static contact angle measuring up to 103.4 ± 2.0°. Notably, the synergistic combination of PDMS-coated HPMC with ball-milled starch demonstrated exceptional superhydrophobic attributes. Particularly, the treated HPMC-based film, specifically the HP-CS-2 h film, showcased an impressive contact angle of 170.5° alongside a minimal sliding angle of 5.2°. The impact of diverse starch types and the ball milling treatment on the PDMS/starch coatings and HPMC film was thoroughly examined using scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXS), and particle size analysis. These studies demonstrated that the low surface energy and roughness required for the creation of superhydrophobic HPMC-based films were imparted by the hierarchical structure formed by the application of PDMS/ball-milled starch. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Polydimethylsiloxane (PubChem CID: 24764); Hydroxypropyl methylcellulose (PubChem CID: 671); Ethyl acetate (PubChem CID: 8857)., 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. Published by Elsevier B.V.)

Dairy products are highly susceptible to contamination from microorganisms. This study aimed to evaluate the efficacy of hydroxypropyl methylcellulose (HPMC) and propolis film as protective coatings for cheese. For this, microbiological analyses were carried out over the cheese' ripening period, focusing on total mesophilic bacteria, yeasts and moulds, lactic acid bacteria, total coliforms, Escherichia coli , and Enterobacteriaceae . Physicochemical parameters (pH, water activity, colour, phenolic compounds content) were also evaluated. The statistical analysis (conducted using ANOVA and PERMANOVA) showed a significant interaction term between the HPMC film and propolis (factor 1) and storage days (factor 2) with regard to the dependent variables: microbiological and physicochemical parameters. A high level of microbial contamination was identified at the baseline. However, the propolis films were able to reduce the microbial count. Physicochemical parameters also varied with storage time, with no significant differences found for propolis-containing films. Overall, the addition of propolis to the film influenced the cheeses' colour and the quantification of phenolic compounds. Regarding phenolic compounds, their loss was verified during storage, and was more pronounced in films with a higher percentage of propolis. The study also showed that, of the three groups of phenolic compounds (hydroxybenzoic acids, hydroxycinnamic acids, and flavonoids), hydroxycinnamic acids showed the most significant losses. Overall, this study reveals the potential of using HPMC/propolis films as a coating for cheese in terms of microbiological control and the preservation of physicochemical properties.

This paper reports a novel α-gel formulation technology referred to as polymer complexed lamella (PCL) that uses hydroxypropyl methyl cellulose (HPMC) and glycerol. The PCL method suppressed lipid crystallization even after drying. This effect was maximized by the addition of HPMC and glycerol at high temperature. HPMC and lipids coexisted when mixed at high temperature, which decreased the mobility of HPMC, an effect that was enhanced by the strong interaction of glycerol with HPMC. These results indicate that mixing of HPMC with glycerol directly regulates the lipid structure and suppresses crystallization. PCL also maintained the effect of occlusion related to the moisturization of skin, even if the membrane was repeatedly bent such as in facial expressions.

Background: Although nucleation kinetic data is quite important for the concept of supersaturation behavior, its part in rationalizing the crystallization inhibitor has not been well understood., Objective: This study aimed to investigate the nucleation kinetic profile of Dextromethorphan HBr (as an ideal drug, BCS-II) by measuring liquid-liquid phase segregation, nucleation induction time, and Metastable Zone width., Methods: Surfeit action was examined by a superfluity assay of the drug. The concentration was scrutinized by light scattering techniques (UV spectrum (novel method) and Fluorometer (CL 53))., Results: The drug induction time was 20 min without polymer and 90 and 110 min with polymers, such as HPMC K15M and Xanthan Gum, respectively. Therefore, the order of the polymer's ability to inhibit nucleation was Xanthan Gum > HPMC K15M in the medium (7.4 pH). Similarly, the drug induction time was 30 min without polymer and 20, 110, and 90 min with polymers, such as Sodium CMC, HPMC K15M, and Xanthan Gum, respectively. Therefore, the order of the polymer's ability to inhibit nucleation was HPMC K15M > Xanthan Gum > Sodium CMC in SIFsp (6.8 pH), which synchronizes the polymer's potentiality to interdict the drug precipitation., Conclusion: The HPMC K15M and xanthan Gum showed the best crystallization inhibitor effect for the maintenance of superfluity conditions till the drug absorption time. The xanthan gum is based on the "glider" concept, and this shows the novelty of this preliminary research. The screening methodology used for rationalizing the best polymers used in the superfluity formulations development successfully., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Oral film is a novel functional carrier, which can provide a new pathway for the efficient absorption of anthocyanin. However, anthocyanin homeostasis in oral film is a prerequisite for achieving efficient absorption and utilization of anthocyanin. Herein, three sulfated polysaccharides, including chondroitin sulfate (CS), fucoidin (FU) and λ-carrageenan (λ-CG), were complexed with blueberry anthocyanin (BA) to prepare oral film formulations using hydroxypropyl methylcellulose (HPMC) as a film-forming matrix. The addition of three sulfated polysaccharides improved the stability of BA in content and color, which were associated with interactions between BA and polysaccharides. The BA retention rate of CS-BA/HPMC system increased 5.5-fold after 8 d of light-accelerated storage compared with the control group, showing the best homeostasis effect. CS and λ-CG enhanced the elongation at break and prolonged disintegration time of oral films. The addition of FU made the oral film denser and smoother, and had the highest BA release (75.72 %) in the simulated oral cavity system. In addition, the oral films of three sulfated polysaccharides complexed with BA showed superior antioxidant capacity. The present study provides new insights into the application of anthocyanin in film formulation carriers., 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 © 2023 Elsevier B.V. All rights reserved.)

Aim: This study aimed to formulate and characterize aceclofenac buccal film formulations made of different polymers and evaluate the effects of polymer type on buccal film properties., Materials and Methods: Five polymer types, namely hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (SCMC), polyvinyl alcohol (PVA), Eudragit S100, and Eudragit SR100, were used to prepare aceclofenac buccal film formulation either separately or combined by solvent-casting method. These formulations were evaluated in terms of physical appearance, folding test, film weight and thickness, drug content, percentage of elongation, moisture uptake, water vapor permeability, and in vitro drug release., Results: The addition of Eudragit polymer in most of the produced buccal films was unacceptable with low folding endurance. However, the dissolution profile of buccal films made from PVA and Eudragit SR100 provided a controlled drug release profile., Conclusion: Buccal films can be formulated using different polymers either individually or in combination to obtain the drug release profile required to achieve a desired treatment goal. Furthermore, the property of the buccal films depends on the type and concentration of the polymer used., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Semi-solid extrusion (SSE) 3D printing has recently attracted increased attention for its pharmaceutical application as a potential method for small-batch manufacturing of personalised solid dosage forms. It has the advantage of allowing ambient temperature printing, which is especially beneficial for the 3D printing of thermosensitive drugs. In this study, the effects of polymeric compositions (single hydroxypropyl methylcellulose (HPMC) system and binary HPMC + polyvinylpyrrolidone (PVP) system), disintegrant (silicon oxide (SiO 2 )), and active pharmaceutical ingredients (tranexamic acid (TXA) and paracetamol (PAC)) on the printability of semisolid inks and the qualities of SSE printed drug-loaded tablets were investigated. Printability is defined by the suitability of the material for the process in terms of its physical properties during extrusions and post-extrusion, including rheology, solidification time, avoiding slumping, etc. The rheological properties of the inks were investigated as a function of polymeric compositions and drug concentrations and further correlated with the printability of the inks. The SSE 3D printed tablets were subjected to a series of physicochemical properties characterisations and in vitro drug release performance evaluations. The results indicated that an addition of SiO 2 would improve 3D printing shape fidelity ( e.g. , pore area and porosity) by altering the ink rheology. The pores of HPMC + PVP + 5PAC prints completely disappeared after 12 hours of drying (pore area = 0 mm 2 ). An addition of SiO 2 significantly improved the pore area of the prints which are 3.5 ± 0.1 mm 2 . It was noted that the drug release profile of PAC significantly increased ( p < 0.05) when additive SiO 2 was incorporated in the formulation. This could be due to a significantly higher porosity of HPMC + PVP + SiO 2 + PAC (70.3 ± 0.2%) compared to HPMC + PVP + PAC (47.6 ± 2.1%). It was also likely that SiO 2 acted as a disintegrant speeding up the drug release process. Besides, the incorporation of APIs with different aqueous solubilities, as well as levels of interaction with the polymeric system showed significant impacts on the structural fidelity and subsequently the drug release performance of 3D printed tablets.

Purpose: Croscarmellose sodium, generally used as a superdisintegrant in pharmaceutical formulations, is hydrolyzed to form the gel structure under basic pH conditions. Utilizing this property of croscarmellose sodium, we developed a novel sustained release (SR) system., Methods: Immediate release (IR) and SR tablets containing croscarmellose sodium, alkaline excipients and/or hydroxypropyl methylcellulose (HPMC) were prepared and examined for wet strength and in vitro drug release behavior. In vivo oral drug absorption was evaluated for IR tablets, HPMC tablets and our novel SR tablets in fasted Beagle dogs., Results: To form the gel structure even under the physiological condition, alkaline excipients were added into the formulation containing croscarmellose sodium. Furthermore, HPMC was used to make the gel structure strong enough against mechanical destructive forces. The novel alkalized croscarmellose sodium-HPMC (ACSH) SR tablet, consisting of croscarmellose sodium, alkaline excipients, and HPMC, successfully sustained the release of acetaminophen, ibuprofen, or nicardipine hydrochloride, compared with the IR tablets. The ACSH SR system provided a better release of acetaminophen than the HPMC tablet without croscarmellose sodium in the release study using a small volume of liquid, suggesting that substantial release and subsequent absorption would be expected in the distal intestinal segments after oral dosing. The in vivo oral absorption study revealed that the ACSH SR system successfully suppressed and prolonged the plasma concentrations of acetaminophen., Conclusion: This novel ACSH SR system prepared with croscarmellose sodium, alkaline excipients, and HPMC, would be a promising SR formulation for enabling substantial drug absorption in the distal intestinal segments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO 3 ) and ammonium bicarbonate (NH 4 HCO 3 ) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Hydroxypropyl methylcellulose (HPMC) belongs to the cellulose ether family that has hydroxyl groups substituted by hydrophobic methyl groups (DS) and hydrophilic hydroxypropyl groups (MS). Herein, the interactions between water molecules and cryogels prepared with HPMC in the presence and absence of a linear nonionic surfactant, as well as CaO 2 microparticles, which react with water producing O 2 , were systematically investigated by sorption experiments and Time-Domain Nuclear Magnetic Resonance. Regardless of the DS and MS, most water molecules presented transverse relaxation time t2 typical of intermediate water and a small population of more tightly bound water. HPMC cryogels with the highest DS of 1.9 presented the slowest swelling rate of 0.519 ± 0.053 g water /(g.s) and the highest contact angle values 85.250 o  ± 0.004 o , providing the best conditions for a slow reaction between CaO 2 and water. The presence of surfactant favored hydrophobic interactions that allowed the polar head of the surfactant to be exposed to the medium, resulting in a higher swelling rate and lower contact angle values. The HPMC with the highest MS presented the fastest swelling rate and the lowest contact angle. These findings are relevant for the formulations and reactions, where tuning the swelling kinetics is crucial for the final 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 © 2023 Elsevier Ltd. All rights reserved.)

In terms of delivery systems for active compounds, orally disintegrating films are a great option. The initial stage in creating an oral disintegrating film is selecting a film-forming polymer. The basic polymers combination Microcrystalline Cellulose (MCC), which is co-processed with Carboxymethylcellulose Sodium (CMC) and hydroxypropylmethyl cellulose were used to create an oral disintegrating film that contains cholecalciferol (Vitamin D3), a fat-soluble vitamin that aids in the body's absorption of calcium and phosphorus. The goal of the current inquiry was to develop orally disintegrating films of vitamin D3 to improve patient comfort and compliance for pediatric or elderly patients due to its simplicity of administration. Films containing drugs and made of the appropriate plasticizer and chosen polymers demonstrated outstanding film forming and folding endurance. The dissolution test showed that Vitamin D3 has a rapid disintegration property, with the majority of it dissolving in the medium (pH 6.8) in less than two minutes after being inserted. To verify that the films were successfully formed, a variety of procedures including HPLC, FT-IR and microscopic studies were employed. When kept at 40oC with humidity of 75%, the film showed good stability for at least three months.

Metformin is known to lower inflammation, independent of its anti-diabetic action. Thus, topical metformin can be a therapeutic strategy for managing ocular inflammation associated with diabetes. To achieve this and address the issues of ocular retention and controlled release an in situ gel of metformin was developed. The formulations were prepared using sodium hyaluronate, hypromellose, and gellan gum. The composition was optimized by monitoring gelling time/capacity, viscosity, and mucoadhesion. MF5 was selected as the optimized formulation. It showed both chemical and physiological compatibility. It was found to be sterile and stable. MF5 exhibited sustained release of metformin for 8h that fitted best with zero-order kinetics. Further, the release mode was found to be close to the Korsmeyer-Peppas model. Supported by an ex vivo permeation study, it showed potential for prolonged action. It showed a significant reduction in ocular inflammation that was comparable to that of the standard drug. MF5 shows translational potential as a safe alternative to steroids for managing ocular inflammation., Competing Interests: Declaration of Competing Interest The authors reveal no conflict of interest to declare., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

P-glycoprotein (P-gp) inhibitors, like zosuquidar, partly increase oral bioavailability of P-gp substrates, such as etoposide. Here, it was hypothesised that co-release of etoposide and zosuquidar from amorphous solid dispersions (ASDs) may further increase oral etoposide bioavailability. This was envisioned through simultaneous co-release and subsequent spatiotemporal association of etoposide and zosuquidar in the small intestinal lumen. To further achieve this, ASDs of etoposide and zosuquidar in polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) 5, and HPMC 4 k were prepared by freeze-drying. From these ASDs, etoposide release was fastest from PVP, then HPMC 5 and slowest from HPMC 4. Release from PVP and HPMC5 resulted in stable supersaturations of etoposide. In transcellular permeability studies across MDCKII-MDR1 cell monolayers, the accumulated amount of etoposide increased 3.7-4.9-fold from amorphous etoposide or when incorporated into PVP- or HPMC 5-based ASDs, compared to crystalline etoposide. In vivo, the oral bioavailability in Sprague Dawley rats increased from 1.0 to 2.4-3.4 %, when etoposide was administered as amorphous drug or in ASDs. However, when etoposide and zosuquidar were co-administered, the oral bioavailability increased further to 8.2-18 %. Interestingly, a distinct increase in oral etoposide bioavailability to 26 % was observed when etoposide and zosuquidar were co-administration in HPMC5-based ASDs. The supersaturation of etoposide as well as the simultaneous co-release of etoposide and zosuquidar in the small intestinal lumen may explain the observed bioavailability increase. Overall, this study suggested that simultaneous co-release of an amorphous P-gp substrate and inhibitor may be a novel and viable formulation strategy to increase the bioavailability P-gp substrates., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)