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1.
Int J Pharm ; 658: 124204, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38710297

ABSTRACT

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.


Subject(s)
Antimalarials , Artesunate , Delayed-Action Preparations , Drug Liberation , Povidone , Printing, Three-Dimensional , Tablets , Artesunate/administration & dosage , Artesunate/chemistry , Artesunate/pharmacokinetics , Animals , Rabbits , Antimalarials/administration & dosage , Antimalarials/chemistry , Antimalarials/pharmacokinetics , Povidone/chemistry , Hypromellose Derivatives/chemistry , Excipients/chemistry , Drug Delivery Systems , Administration, Oral , Carboxymethylcellulose Sodium/chemistry , Poloxamer/chemistry , Gastric Mucosa/metabolism
2.
Int J Pharm ; 658: 124215, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38740104

ABSTRACT

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.


Subject(s)
Drug Liberation , Felodipine , Hypromellose Derivatives , Printing, Three-Dimensional , Solubility , Tablets , Felodipine/chemistry , Felodipine/administration & dosage , Hypromellose Derivatives/chemistry , Drug Compounding/methods , Molecular Dynamics Simulation , Drug Carriers/chemistry , Delayed-Action Preparations/chemistry , Chemistry, Pharmaceutical/methods , Hot Melt Extrusion Technology/methods , Technology, Pharmaceutical/methods
3.
Int J Pharm ; 658: 124191, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38701909

ABSTRACT

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.


Subject(s)
Acetaminophen , Drug Liberation , Polymethacrylic Acids , Taste , Acetaminophen/chemistry , Acetaminophen/administration & dosage , Polymethacrylic Acids/chemistry , Spray Drying , Drug Compounding/methods , Hypromellose Derivatives/chemistry , Particle Size , Solubility , Desiccation/methods , Acrylic Resins
4.
Int J Biol Macromol ; 269(Pt 1): 132050, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38777690

ABSTRACT

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.


Subject(s)
Crystallization , Hypromellose Derivatives , Solubility , Hypromellose Derivatives/chemistry , Polymers/chemistry , Pyridones/chemistry , Pyridones/pharmacology
5.
Int J Pharm ; 657: 124189, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38701906

ABSTRACT

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 (Tg) 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.


Subject(s)
Crystallization , Drug Stability , Griseofulvin , Griseofulvin/chemistry , Hypromellose Derivatives/chemistry , X-Ray Diffraction/methods , Solubility , Drug Compounding/methods , Chemistry, Pharmaceutical/methods , Temperature , Humidity
6.
Molecules ; 29(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731432

ABSTRACT

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.


Subject(s)
Cheese , Food Preservation , Hypromellose Derivatives , Propolis , Cheese/microbiology , Cheese/analysis , Propolis/chemistry , Hypromellose Derivatives/chemistry , Food Preservation/methods , Phenols/chemistry , Phenols/analysis , Food Microbiology , Escherichia coli/drug effects
7.
Carbohydr Polym ; 337: 122163, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710557

ABSTRACT

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.


Subject(s)
Hypromellose Derivatives , Prion Diseases , Animals , Hypromellose Derivatives/chemistry , Mice , Prion Diseases/drug therapy , Disease Models, Animal
8.
Int J Pharm Compd ; 28(3): 249-259, 2024.
Article in English | MEDLINE | ID: mdl-38768505

ABSTRACT

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.


Subject(s)
Hypromellose Derivatives , Mouth Mucosa , Polysaccharides, Bacterial , Probiotics , Probiotics/administration & dosage , Animals , Hypromellose Derivatives/chemistry , Polysaccharides, Bacterial/chemistry , Goats , Adhesiveness , Freeze Drying , Drug Compounding , Powders , Drug Stability
9.
AAPS PharmSciTech ; 25(5): 116, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769223

ABSTRACT

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.


Subject(s)
Adamantane , Aniline Compounds , Dipeptides , Drug Liberation , Nanoparticles , Polyvinyl Alcohol , Adamantane/chemistry , Adamantane/analogs & derivatives , Dipeptides/chemistry , Dipeptides/pharmacokinetics , Dipeptides/administration & dosage , Aniline Compounds/chemistry , Nanoparticles/chemistry , Administration, Oral , Polyvinyl Alcohol/chemistry , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Humans , Hypromellose Derivatives/chemistry , Tensile Strength , Chemistry, Pharmaceutical/methods , Biological Availability , Solubility , Electrodes
10.
Int J Pharm ; 658: 124180, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38705246

ABSTRACT

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.


Subject(s)
Drug Delivery Systems , Drug Liberation , Flavonoids , Hypromellose Derivatives , Nanofibers , Povidone , Solvents , Nanofibers/chemistry , Animals , Solvents/chemistry , Povidone/chemistry , Flavonoids/chemistry , Flavonoids/administration & dosage , Flavonoids/pharmacokinetics , Drug Delivery Systems/methods , Hypromellose Derivatives/chemistry , Solubility , Skin Absorption , Male , Rats
11.
J Chromatogr A ; 1722: 464874, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38598893

ABSTRACT

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 ß-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.


Subject(s)
Hypromellose Derivatives , Mass Spectrometry , Hydrolysis , Hypromellose Derivatives/chemistry , Mass Spectrometry/methods , Chromatography, Liquid/methods , Isomerism , Glucose/chemistry , Glucose/analysis , Liquid Chromatography-Mass Spectrometry
12.
Int J Biol Macromol ; 267(Pt 1): 131580, 2024 May.
Article in English | MEDLINE | ID: mdl-38688788

ABSTRACT

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/ß-tricalcium phosphate/monocalcium phosphate anhydrous (ß-TCP/MCPA) cement was developed for the first time by incorporation of hydroxypropyl methylcellulose (HPMC) and ß-TCP/MCPA. The physical-chemical characterization (setting time, anti-washout property, injectability, compressive strength, apatite mineralization and sealing property) of TCS/(ß-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/ß-TCP/MCPA were studied. The results showed that HPMC could provide TCS with good anti-washout ability and injectability but slow hydration process. However, ß-TCP/MCPA effectively enhanced anti-washout characteristics and reduced setting time due to faster hydration kinetics. TCS/(ß-TCP/MCPA) obtained around 90 % of injection rate and high compressive strength whereas excessive additions of ß-TCP/MCPA compromised its injectability and compressive strength. TCS/(ß-TCP/MCPA) can induce apatite deposition and form a tight marginal sealing at the dentin-cement interface. Additionally, TCS/(ß-TCP/MCPA) showed good biocompatibility and promoted osteo/odontogenic differentiation of SHED. In general, our results indicated that TCS/(ß-TCP/MCPA) may be particularly promising as an injectable bioactive cements for endodontic treatment.


Subject(s)
Calcium Compounds , Calcium Phosphates , Hypromellose Derivatives , Silicates , Silicates/chemistry , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Calcium Compounds/chemistry , Humans , Hypromellose Derivatives/chemistry , Osteogenesis/drug effects , Materials Testing , Cell Differentiation/drug effects , Compressive Strength , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Dental Cements/chemistry , Dental Cements/pharmacology , Stem Cells/drug effects , Stem Cells/cytology
13.
Int J Biol Macromol ; 268(Pt 1): 131744, 2024 May.
Article in English | MEDLINE | ID: mdl-38663711

ABSTRACT

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.


Subject(s)
Hypromellose Derivatives , Nanoparticles , Nanoparticles/chemistry , Humans , Caco-2 Cells , Hypromellose Derivatives/chemistry , Drug Carriers/chemistry , Biological Transport
14.
Int J Biol Macromol ; 269(Pt 1): 131846, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663702

ABSTRACT

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.


Subject(s)
Gelatin , Hypromellose Derivatives , Pectins , Rheology , Water , Zein , Pectins/chemistry , Gelatin/chemistry , Hypromellose Derivatives/chemistry , Zein/chemistry , Water/chemistry , Viscosity , Particle Size
15.
Int J Biol Macromol ; 269(Pt 2): 131876, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38685543

ABSTRACT

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 ±â€¯20.3 N/m2 and an adhesion duration of 491 ±â€¯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 (AUC0-∞) 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 (T1DM) 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.


Subject(s)
Acrylic Resins , Diabetes Mellitus, Experimental , Hypromellose Derivatives , Insulin , Mouth Mucosa , Mouth Mucosa/metabolism , Animals , Acrylic Resins/chemistry , Insulin/administration & dosage , Insulin/pharmacokinetics , Rats , Hypromellose Derivatives/chemistry , Swine , Diabetes Mellitus, Experimental/drug therapy , Drug Delivery Systems , Male , Adhesives/chemistry , Drug Liberation , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Administration, Buccal , Adhesiveness , Blood Glucose/drug effects , Drug Carriers/chemistry
16.
Int J Pharm ; 654: 123965, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38442796

ABSTRACT

The oral bioavailability of paclitaxel is limited due to low solubility and high affinity for the P-glycoprotein (P-gp) efflux transporter. Here we hypothesized that maximizing the intestinal paclitaxel levels through apparent solubility enhancement and controlling thesimultaneous release of both paclitaxel and the P-gp inhibitor encequidar from amorphous solid dispersions (ASDs) would increase the oral bioavailability of paclitaxel. ASDs of paclitaxel and encequidar in polyvinylpyrrolidone K30 (PVP-K30), hydroxypropylmethylcellulose 5 (HPMC-5), and hydroxypropylmethylcellulose 4 K (HPMC-4K) were hence prepared by freeze-drying. In vitro dissolution studies showed that both compounds were released fastest from PVP-K30, then from HPMC-5, and slowest from HPMC-4K ASDs. The dissolution of paclitaxel from all polymers resulted in stable concentration levels above the apparent solubility. The pharmacokinetics of paclitaxel after oral administration to male Sprague-Dawley rats was investigated with or without 1 mg/kg encequidar, as amorphous solids or polymer-based ASDs. The bioavailability of paclitaxel increased 3- to 4-fold when administered as polymer-based ASDs relative to solid amorphous paclitaxel. However, when amorphous paclitaxel was co-administered with encequidar, either as an amorphous powder or as a polymer-based ASD, the bioavailability increased 2- to 4-fold, respectively. Interestingly, a noticeable increase in paclitaxel bioavailability of 24-fold was observed when paclitaxel and encequidar were co-administered as HPMC-5-based ASDs. We, therefore, suggest that controlling the dissolution rate of paclitaxel and encequidar in order to obtain simultaneous and timed release from polymer-based ASDs is a strategy to increase oral paclitaxel bioavailability.


Subject(s)
Polymers , Povidone , Rats , Male , Animals , Biological Availability , Rats, Sprague-Dawley , Hypromellose Derivatives , Solubility
17.
Int J Biol Macromol ; 263(Pt 2): 130539, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432263

ABSTRACT

Hydroxypropyl methylcellulose (HPMC) was employed as an intermediate layer to enhance interfacial interaction between chitosan (CS) coating and tangerine fruits, thereby improving the preservation effect. Owing to the low surface tension of tangerine fruit (26.04 mN/m), CS coating solutions showed poor wetting properties on fruit peels (contact angle > 100°). However, by applying a 1.0 % (w/v) HPMC coating on fruits, the contact angle of CS solutions with concentrations of 0.5 %, 1.0 %, and 1.5 % (w/v) decreased to 47.0°, 47.4°, and 48.5°, respectively, whereas the spreading coefficient increased to -16.0 mN/m, -17.6 mN/m and -19.8 mN/m, respectively. Subsequently, the effects of the coatings on fruit quality were investigated. The results demonstrated the promising performance of HPMC-CS two-layer coating in inhibiting fruit respiration, reducing decay rate, and maintaining nutrient content. Notably, HPMC-1.5%CS coating not only reduced the decay rate of tangerine fruit by 45 % and 31 %, in comparison to the uncoated group (CK) and pure CS coating respectively, but also maintained a high content of ascorbic acid. Therefore, this study confirmed that the use of amphiphilic polymers for improving the surface properties of fruits can effectively facilitate the wetting of hydrophilic coatings on fruits, and significantly improve the fresh-keeping performance of edible coatings.


Subject(s)
Chitosan , Citrus , Wettability , Hypromellose Derivatives , Fruit , Food Preservation/methods , Methylcellulose
18.
Int J Biol Macromol ; 266(Pt 1): 131061, 2024 May.
Article in English | MEDLINE | ID: mdl-38521296

ABSTRACT

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 (R2 > 0.96) and Weibull model (R2 > 0.97). The diffusion mechanism of CIN was pseudo-Fickian. The diffusion coefficients (D1 and D2) 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.


Subject(s)
Acrolein , Acrolein/analogs & derivatives , Cheese , Edible Films , Hypromellose Derivatives , Whey Proteins , Whey Proteins/chemistry , Acrolein/chemistry , Kinetics , Hypromellose Derivatives/chemistry , Food Preservation/methods , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Food Packaging/methods
19.
Int J Biol Macromol ; 266(Pt 1): 131191, 2024 May.
Article in English | MEDLINE | ID: mdl-38552680

ABSTRACT

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).


Subject(s)
Dimethylpolysiloxanes , Hydrophobic and Hydrophilic Interactions , Hypromellose Derivatives , Starch , Starch/chemistry , Dimethylpolysiloxanes/chemistry , Hypromellose Derivatives/chemistry , Water/chemistry
20.
J Food Sci ; 89(5): 2857-2866, 2024 May.
Article in English | MEDLINE | ID: mdl-38532702

ABSTRACT

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. HPMCCPE 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-HPMCCPE film exhibited reduced water vapor permeability (∼0.033 g mm/m2 d Pa) compared to HPMCCPE film (∼0.59 g mm/m2 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-HPMCCPE 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.


Subject(s)
Edible Films , Food Packaging , Fruit , Plant Extracts , Vaccinium macrocarpon , Vitamin E , Vaccinium macrocarpon/chemistry , Vitamin E/analysis , Plant Extracts/chemistry , Fruit/chemistry , Food Packaging/methods , Hydrophobic and Hydrophilic Interactions , Permeability , Hypromellose Derivatives/chemistry , Food, Fortified/analysis , Oleic Acid/analysis , Oleic Acid/chemistry
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