Polymer Hydroxypropyl Methylcellulose Research Articles

MgO nanofiller reinforced biodegradable, flexible, tunable energy gap HPMC polymer composites for eco-friendly electronic applications

This study explores the development and characterization of eco-friendly Magnesium Oxide (MgO) nanofiller reinforced hydroxypropyl methylcellulose (HPMC) polymer composites for eco-friendly electronic applications. The prepared nanocomposites are biodegradable and flexible without any additional plasticizer. MgO nanoparticles were synthesized using the solution combustion method and incorporated into HPMC matrix through solution casting method. The structural, mechanical, optical, AC and DC electrical, and degradation properties of the prepared nanocomposites were systematically investigated. X-ray diffraction (XRD) confirmed the successful integration of MgO nanoparticles into the HPMC matrix, with noticeable interactions affecting the crystallinity. Mechanical testing revealed an optimal MgO concentration of 0.2 g, which provided the best balance of strength and ductility, while higher concentrations led to increased brittleness. UV–Vis spectroscopy results evident that the energy gap of nanocomposites can be tuneable with MgO incorporation. The photoresponsivity study indicated that higher MgO content reduce the photocurrent due to agglomeration and defect states. Dielectric studies showed a typical frequency-dependent behaviour, with enhanced dielectric constants at lower frequencies attributed to interfacial polarization. However, increasing MgO content decreased the dielectric constant and loss due to reduced polymer chain mobility and increased resistive pathways. Current-Voltage (I-V) characteristics demonstrated a non-ohmic conduction behaviour with Poole-Frenkel emission identified as the predominant conduction mechanism. Degradation tests in both tap water and soil, demonstrated that the MgO incorporation significantly slowed the degradation rate of the composites, enhancing their durability. These findings suggest that MgO-HPMC nanocomposites hold promise for sustainable and flexible eco-friendly electronic applications.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection

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.

The investigation on targeted micro-surface treatment methods for waste tires recycling in cementitious construction materials

Defects in the interfacial transition zone (ITZ) between recycled tire rubber and cement matrix obstacle to the large-scale application of sustainable rubberized cementitious materials. This paper proposed and evaluated different targeted treatment methods for micro-surface properties enhancement of rubber aggregate by the Polyvinyl Alcohol (PVA), Polyethylene Glycol-200 (PEG), and Hydroxypropyl methylcellulose (HY) polymer solutions through copolymerization and drafting processes. The optimum modification condition was determined through the FT-IR analysis, contact angle, and surface free energy of treated rubber aggregates and the micro-surface morphology and element distribution were analyzed by using ESEM and EDX, respectively. The flexural strength and pore size distribution of steel fiber-reinforced rubberized mortar with relatively high replacing volumes (20%, 40%, and 60%) were evaluated to validate the targeted micro-surface modification efficiency. The surface microstructure and hydrophilic properties of rubber aggregate were significantly improved and the mechanism for enhancing the interface adhesion between rubber and cement matrix was revealed.

Opportunities and Challenges: Process Raman for the Real-Time Release Testing (RTRT) of Extended-Release Formulations

The use of a process analytical technology has been demonstrated using near-infrared spectroscopy for continuous manufacturing of pharmaceutical formulations and is within the scope of the U.S. Food and Drug Administration's real-time release testing initiative. While effective for simple formulations, this preliminary study investigates whether such a spectroscopic surrogate application can replace pharmaceutical dissolution testing for extended-release formulations. In this study, we will assess the use of process Raman spectroscopy for real-time dissolution testing. Extended-release tablet formulations often accomplish the release rate delay through the addition of gelling agents. In this work, hydroxypropyl methylcellulose (HPMC) polymers were used to formulate extended-release niacin tablets. Process Raman spectroscopy was evaluated as a tool to effectively model dissolution profiles to determine if the optical technique has the ability to differentiate HPMC polymers from the background and be selective for the polymer type employed. Our preliminary work indicates that while Raman can effectively detect and monitor the niacin response of the tablet formulations, there are not enough unique spectral features between the different HPMC polymers to selectively resolve their responses. Additional measurements and chemometric analysis might suggest otherwise. Thus, for extended-release tablet applications with continuous manufacturing, further dissolution surrogate development is needed.

Development and Characterization of Enteric Polymer-based Solid Dispersion for Cholecalciferol Delivery

Background: The deficiency of vitamin D is a global concern affecting individuals of all age groups. Insufficient exposure to sunlight and disease conditions can lead to cholecalciferol (vitamin D3) deficiency. Objective: Cholecalciferol is a lipophilic crystalline molecule, and it is highly susceptible to degradation under environmental conditions, including light, temperature, and oxygen, and its degradation rate is high in the low pH range. Therefore, an enteric solid dispersion-based formulation was developed in the present study for the oral delivery of cholecalciferol. Method: Enteric polymer hydroxypropylmethylcellulose acetate succinate (HPMCAS)-based solid dispersion was developed and characterized by Fourier transform-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction analysis. The effect of various concentrations of cholecalciferol formulations on the viability of Caco-2 cells was determined using an MTT assay. A dissolution and stability study of the product was also performed. Result: An amorphous form of cholecalciferol in the solid dispersion was reported. The drug content of solid dispersions was in the order of 90%. The viability assay indicated that the surfactant used in the developed solid dispersion of cholecalciferol had no cytotoxic effect on Caco-2 cells. A dissolution study on enteric solid dispersion in two-stage dissolution under a biomimetic medium indicated the pHdependent release of cholecalciferol from the HPMCAS-based solid dispersion. Moreover, the stability study showed no significant changes in the cholecalciferol content in the developed formulation under storage at experimental conditions. Conclusion: The enteric solid dispersion of cholecalciferol was developed, which exhibited compatibility with Caco-2 cells, improved dissolution, and acceptable stability profile, and represented a potential option for efficient delivery of cholecalciferol.

The Exploitation of Sodium Deoxycholate-Stabilized Nano-Vesicular Gel for Ameliorating the Antipsychotic Efficiency of Sulpiride.

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 33 Box-Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects.

Development of active packaging material based on polycaprolactone/hydroxypropyl methylcellulose nanofibers containing carbon dot nanoparticles for meat preservation

This work demonstrates the feasibility of using a combination of biodegradable polycaprolactone (PCL) and natural-based hydroxypropyl methylcellulose (HPMC) polymers containing carbon dots (CDs) for food packaging applications. CDs were synthesized using the insoluble portion of Zedo gum. The 5% and 15% concentrations of bare Zedo CDs (Z-CD) and nitrogen and sulfur co-doped CDs (TZ-CD) were chosen for incorporation into PCL/HPMC nanofibers (NFs). The PCL/HPMC/Z-CD15% and PCL/HPMC/TZ-CD15% demonstrated improved tensile strength (12.88 and 15.01 MPa), water solubility (30.20 and 42.36%), and water vapor transmittance (0.62 and 0.71 g mm/m2 h kPa)), respectively. When comparing the release of CDs in 10%, 50%, and 95% ethanolic solutions, it was found that TZ-CD released more rapidly than Z-CD from NFs in all three simulants. The CDs-added NFs exhibited potent antioxidant activity (80.5%). More significant antimicrobial activity against S. aureus was observed compared to E. coli. Additionally, reductions in total volatile basic nitrogen and thiobarbituric acid values indicated that beef covered with PCL/HPMC/TZ-CD15% and PCL/HPMC/Z-CD15% NFs had an extended shelf life of more than five days. In conclusion, PCL/HPMC/Z-CD15% and PCL/HPMC/TZ-CD15% NFs can be used as promising biodegradable packaging materials to enhance the shelf life of meat products.

Formulation and Evaluation of Verapamil Hydrochloride Sustain Release Tablet

Verapamil hydrochloride, a calcium channel blocker, is used to treat hypertension, supraventricular arrhythmia and myocardial infarction Verapamil hydrochloride (VPH) sustain release tablets were developed for this study in order to maintain plasma concentrations, enhance bioavailability, and avoid repeated dosing. Materials and procedures Tablets containing a fixed amount of VPH were made using the direct compression method and various combinations and ratios of the polymers hydroxypropyl methyl cellulose (HPMC K15) and ethyl cellulose. The tablets were then tested for thickness, weight variation, hardness, uniformity of the drug content, drug release, and potential ingredient interactions. Regarding thickness, weight variation, hardness, and medication content, all tablets were satisfactory. It may be determined from formulations comprising HPMCK15 and ethyl cellulose that the two polymers functioned well together, controlling the first burst and improving the drug's release throughout the first three hours. A study of in vitro drug release followed the formulation of the 32 factorial planned batches. The formulations F5, F6, and F8 demonstrated better drug release up to 24hours and minimal burst release with more than 80% release in 24hours. They were composed of HPMC K15 60mg, 60 mg, and 75mg, respectively, and ethyl cellulose 30mg, 45mg, and 30mg, respectively. Thus, the F5 formulation with somewhat lower polymer content was chosen as the optimal formulation and they contained HPMC K15 60mg and ethyl cellulose 30mg.

Solution blow spun flexible zirconia nanofibers toward high-performance 2D and 3D nanostructures

Polymer templates are critical in the preparation of ceramic fibers from precursor solutions, but the available options are limited. Here, ZrO2 nanofiber films and aerogels are developed by solution blow spinning method using hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) as templates. The effects of HPMC ratio, polymer concentration, and calcination temperature on the morphology and structure of the ZrO2 nanofibers are investigated. The nanofiber films with an areal density of 20 mg cm−2 exhibit excellent filtration property, achieving a filtration efficiency of 94.94% and a pressure drop of 136 Pa at an airflow velocity of 32 L min−1. The nanofiber aerogels display low density of 50 mg cm−3, low thermal conductivity of 0.039 W m−1 K−1, as well as superior compressibility, demonstrating significant potential for thermal protection applications. This work expands the formation template option of ceramic fibers, offering significant guidance in the development of flexible, high-temperature-resistant ceramic fiber materials.

Enhancing the solubility and dissolution rate of piperine via preparation of piperine–hydroxypropyl methylcellulose 2910 solid dispersion system using freeze-drying method

Context: Piperine is the main secondary metabolite isolated from the family Piperaceae. This biologically active ingredient has many pharmacological effects, though its low water solubility limits its absorption in gastrointestinal fluid. Aims: To improve piperine’s solubility and dissolution rate by incorporating it into a solid dispersion system with the hydrophilic polymer hydroxypropyl methylcellulose (HPMC) 2910 via the freeze-drying method. Methods: Three different piperine:polymer ratios – 1:1, 1:2, and 2:1 (w/w) – were prepared. A physical mixture was also prepared in a 1:1 (w/w) ratio for comparison. The physicochemical properties of the samples were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The solubility and dissolution tests were conducted in distilled water. Results: The solid dispersion characterization indicated a decrease in the melting points and endothermic peaks in the DSC analysis, a decrease in peak intensity in the PXRD patterns, no chemical interactions between active substances and polymers in the FTIR analysis, and significant morphological changes in the SEM analysis. The solubility test revealed the highest increase in piperine solubility (7.88-fold increase) for the 1:2 solid dispersion. Moreover, the 1:2 solid dispersion in the dissolution test led to the greatest amount of dissolved piperine (56.445 ± 1.13%). Conclusions: The piperine–HPMC solid dispersion system improved the solubility and dissolution rate of piperine.

Improvement of in vitro dissolution profile of poorly aqueous soluble anti-parasitic agent ivermectin using novel hydrophilic polymeric carriers

Ivermectin (IVM), a BCS Class II drug with weak water solubility, has minimal oral absorption and dissolution. This study aims to enhance the dissolution profile of IVM by performing solid dispersion methods using four hydrophilic polymers: Kollicoat IR, Kollidon 90F, poloxamer 407, and hydroxypropyl methylcellulose (HPMC). The solid dispersion formulations (SDF) were made through physical mixing, solvent evaporation, and melt solvent/fusion. Using three ratios of IVM and hydrophilic carriers (1:1, 1:2, and 1:3), the cumulative release rate of IVM from formulations formed by physical mixing, solvent evaporation, and fusing was much larger than pure IVM (10%). IVM release rates from formulations including Poloxamer 407, Kollicoat IR, and HPMC polymers were 76% (fusion technique), 69% (physical mixing), and 47% (solvent evaporation method). The research demonstrated that fusion optimized drug solubility better than physical mixing and solvent evaporation. The research found that SD of weakly water-soluble IVM with Kollicoat IR/Poloxamer 407 improves its in vitro dissolving profile much better. Bangladesh J. Sci. Ind. Res. 58(4), 209-220, 2023

Multivariate Analysis and Computational Predictability of Modified Release Formulation of Chirally Pure Metoprolol Succinate

This study employs computational techniques to predict the performance of a modified-release matrix formulation of chirally pure S (-) Metoprolol Succinate, using a Quality by Design (QbD) approach. The research defines the Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQAs) of the S (-) Metoprolol Succinate matrix formulation. To assess risks, an Ishikawa diagram and Failure Mode Effect Analysis (FMEA) following ICH Q8 guidelines were conducted. The formulation screening process utilized Plackett–Burman design, followed by optimization through Box–Behnken design. The modified-release formulation was developed using high shear granulation, incorporating a combination of high and low viscosity Hydroxypropyl Methylcellulose (HPMC) polymers along with other excipients. The impact of polymer composition and stearic acid on the release profile of S (-) Metoprolol Succinate was investigated, revealing their significant influence on the drug delivery system's desired effect. Specifically, the variables X1: HPMC K4M and X2: HPMC K100M were identified as key factors affecting drug release (Y1). Statistical analysis (ANOVA) confirmed the significance of the selected model, with predicted outcomes aligning well with observed results, comparable to the reference product Seleken® XL range. Both drug content and release performance were found to be similar to the innovator formulation. In summary, this investigation underscores the potential of employing a QbD approach with a combination of low and high viscosity HPMC polymers to achieve precise single-dose delivery of S (-) Metoprolol Succinate.

Preparation and In Vitro Evaluation of Levofloxacin-Loaded Floating Tables Using Various Rate-Controlling Agents.

Floating tablets are a new approach to extending the time a drug is in the stomach to improve therapy outcomes. Floating tablets were formulated with the drug, the polymers hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), and starch, fillers, and lubricants. The tablets were prepared using the direction compression method. The tablets' physical quality control tests were found to be within acceptable limits. The tablets extended drug release up to 12 h and were uniform in their drug contents. The swelling index of the tablets ranged from 60 ± 0.11 to 66 ± 0.14%, and the tablets were less dense than water. The floating lag time (10 ± 0.23 to 16 ± 0.09 s) and total floating time (>12 h) showed good floating behaviors. The kinetic modeling showed that the drug was released from the tablets by pseudo-diffusion, swelling, erosion, or anomalous non-Fickian diffusion. F6 (starch and CMC) showed higher n values (0.994 ± 0.04), exhibiting pseudo-zero-order drug release kinetics compared to those of other tablets. The dissolution data of the test and reference tables were not similar (P > 0.05). In terms of antimicrobial activity, the zones of inhibition of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) were found to be significantly similar (P > 0.05). The study concluded that these floating tablets can improve the gastric residence time and therapeutic outcomes.

Development and Evaluation of Topical Zinc Oxide Nanogels Formulation Using Dendrobium anosmum and Its Effect on Acne Vulgaris.

Zinc oxide nanoparticles have high levels of biocompatibility, a low impact on environmental contamination, and suitable to be used as an ingredient for environmentally friendly skincare products. In this study, biogenically synthesized zinc oxide nanoparticles using Dendrobium anosum are used as a reducing and capping agent for topical anti-acne nanogels, and the antimicrobial effect of the nanogel is assessed on Cutibacterium acne and Staphylococcus aureus. Dendrobium anosmum leaf extract was examined for the presence of secondary metabolites and its total amount of phenolic and flavonoid content was determined. Both the biogenically and chemogenic-synthesized zinc oxide nanoparticles were compared using UV-Visible spectrophotometer, FE-SEM, XRD, and FTIR. To produce the topical nanogel, the biogenic and chemogenic zinc oxide nanoparticles were mixed with a carbomer and hydroxypropyl-methyl cellulose (HPMC) polymer. The mixtures were then tested for physical and chemical characteristics. To assess their anti-acne effectiveness, the mixtures were tested against C. acne and S. aureus. The biogenic zinc oxide nanoparticles have particle sizes of 20 nm and a high-phase purity. In comparison to chemogenic nanoparticles, the hydrogels with biogenically synthesized nanoparticles was more effective against Gram-positive bacteria. Through this study, the hybrid nanogels was proven to be effective against the microbes that cause acne and to be potentially used as a green product against skin infections.

Polymer Tablet Matrix Systems for the Controlled Release of Dry Betula pendula Leaf Extract.

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 33 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Sustained Delivery of the Antiviral Protein Griffithsin and Its Adhesion to a Biological Surface by a Silk Fibroin Scaffold.

The protein Griffithsin (Grft) is a lectin that tightly binds to high-mannose glycosylation sites on viral surfaces. This property allows Grft to potently inhibit many viruses, including HIV-1. The major route of HIV infection is through sexual activity, so an important tool for reducing the risk of infection would be a film that could be inserted vaginally or rectally to inhibit transmission of the virus. We have previously shown that silk fibroin can encapsulate, stabilize, and release various antiviral proteins, including Grft. However, for broad utility as a prevention method, it would be useful for an insertable film to adhere to the mucosal surface so that it remains for several days or weeks to provide longer-term protection from infection. We show here that silk fibroin can be formulated with adhesive properties using the nontoxic polymer hydroxypropyl methylcellulose (HPMC) and glycerol, and that the resulting silk scaffold can both adhere to biological surfaces and release Grft over the course of at least one week. This work advances the possible use of silk fibroin as an anti-viral insertable device to prevent infection by sexually transmitted viruses, including HIV-1.

Studies on Morphological Parameters, Radius of Gyration, Correlation Length and Invariant of HPMC Polymer Doped with Ferrous (II) Oxide Using SAXS Method

It shed light on morphological parameters which influence radius of gyration, correlation length and invariant of Hydroxy Propyl Methyl Cellulose (HPMC) polymer doped with ferrous (II) oxide (FeO) using small angle X-ray scattering (SAXS) method. SAXS patterns have been recorded for different composition and gives an information about the structure of the polymer on a scale of about 800Ǻ, in which the variation of scattered intensity with angles from 0o to 2.5o has been measured for different composition of FeO with host polymer of HPMC. Employing para-crystalline model and exponential distribution function of phase lengths (amorphous and crystalline), we find a good agreement between the measured and predicted scattering except for a very small range of angles on the low angle side of the peak intensity. The method enabled quantitative parameters describing morphology of the two phases, amorphous and crystalline, consistent with the SAXS intensity distribution. A stepping procedure has been employed to compute the final parameters which gave the best fit between the calculated and experimental data. This was done by minimizing the statistical goodness-of-fit parameter chi-square. It is observed that there are significant changes in distribution of phase lengths due to different percentage weight of FeO in HPMC contents. Additionally, SAXS data has been used to estimate (i) radius of gyration (Rg), ii) correlation length (Lcor) and (iii) invariant (Q) parameters. A functional representation of the long period and also radius of gyration at different dopant concentrations is adopted by viewing them as realizations of a continuous-time stochastic process observed with measurement error. This allows one to estimate the mean functional relationship between long period and the dopant concentration.

Effect of Polymer Additives on the Crystal Habit of Metformin HCl.

The crystal habit can have a profound influence on the physical properties of crystalline materials, and thus controlling the crystal morphology is of great practical relevance across many industries. Herein, this work investigates the effect of polymer additives on the crystal habit of metformin HCl with both experiments and computational methods with the aim of developing a combined screening approach for crystal morphology engineering. Crystallization experiments of metformin HCl are conducted in methanol and in an isopropanol-water mixture (8:2V/V). Polyethylene glycol, polyvinylpyrrolidone, Tween80, and hydroxypropyl methylcellulose polymer additives are used in low concentrations (1-2% w/w) in the experiments to study the effect they have on modifying the crystal habit. Additionally, this work has developed computational methods to characterize the morphology "landscape" and quantifies the overall effect of solvent and additives on the predicted crystal habits. Further analysis of the molecular dynamics simulations is used to rationalize the effect of additives on specific crystal faces. This work demonstrates that the effects of additives on the crystal habit are a result of their absorption and interactions with the slow growing {100} and {020} faces.

Evaluation of Pharmacobezoar Formation from Suspensions of Spray-Dried Amorphous Solid Dispersions: An MRI Study in Rats

Spray-dried amorphous solid dispersions of new chemical entities and pH-dependent soluble polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were found to form solid agglomerates in the gastrointestinal tract of rodents after oral administration. These agglomerates, referring to descriptions of intra-gastrointestinal aggregated oral dosage forms termed pharmacobezoars, represent a potential risk for animal welfare. Previously, we introduced an in vitro model to assess the agglomeration potential of amorphous solid dispersions from suspensions and how it can be reduced. In this work, we investigated if the in vitro effective approach of viscosity enhancement of the vehicle used to prepare suspensions of amorphous solid dispersions could reduce the pharmacobezoar formation potential following repeated daily oral dosing to rats as well. The dose level of 2400 mg/kg/day used in the main study was determined in a dose finding study carried out in advance. In the dose finding study, MRI investigations were carried out at short time intervals to gain insights into the process of pharmacobezoar formation. Whereas MRI investigations underlined the importance of the forestomach for the formation of pharmacobezoars, viscosity enhancement of the vehicle reduced the incidence of pharmacobezoars, delayed the onset of pharmacobezoar formation and reduced the overall mass of pharmacobezoars found at necropsy.

Development of denture-fitting, palate-mucoadhesive miconazole nitrate films for denture stomatitis

Denture stomatitis commonly affects denture users. Most available antifungal buccal formulations cannot maintain adequate drug levels in the mouth cavity for a sufficient time unless applied frequently. In the present study, denture-fitting, palate-mucoadhesive buccal miconazole nitrate films were developed and assessed for the management of upper denture stomatitis, caused by Candida albicans, in comparison to a commercial oral gel. Three films were prepared by solvent casting; the common film ingredients apart from miconazole nitrate, included propylene glycol as plasticizer, and hydroxypropyl methylcellulose polymer as mucoadhesive film-forming agent (F1–F3). The second and third film (F2 & F3) also contained sodium carboxy methyl cellulose as an additional mucoadhesive polymer. In films F1 and F2, miconazole nitrate was dissolved in the plasticizer propylene glycol. The third film (F3) contained miconazole nitrate-loaded chitosan nanoparticles dispersed in the film matrix. Films were characterized. Performance-related tests assessed in vitro drug release, in vitro mucoadhesion, in-vitro antifungal efficiency and in vivo clinical efficacy in denture stomatitis patients (colony counts following palate swabs and pain scoring during treatment). Attachment of film to denture was also investigated in vitro. Film F3 proved statistically more effective compared to films F1 & F2 and to the commercial oral gel, based on patients’ pain scoring at three days (P ≤ 0.05) and colony count at ten days (P ≤ 0.05) post treatment initiation, in spite of reduced amount of miconazole applied per day in case of films compared to gel. Differences in fungi inhibition zones, tested under equivalent amount of miconazole per agar well, were also statistically significant (P ≤ 0.05). Film (F3) can be promoted for effective local treatment of denture-related candidiasis with reduced application frequency, and less daily amount of applied miconazole compared to a commercial oral gel application.