A novel mucoadhesive film containing probiotic extract for oral candidiasis treatment: Formulation and antifungal evaluation.

Probiotic strains offer a novel and potentially effective approach to treat oral candidiasis. Buccal mucoadhesive films have attracted considerable attention in recent years due to their unique ability to adhere and persist on the oral mucosa, while gradually releasing their encapsulated drug content. Therefore, the aim of the study was to develop mucoadhesive films containing probiotic extract for treatment of oral candidiasis. Mucoadhesive films were fabricated with hydrophilic polymers, such as polyvinyl alcohol (PVA) and hydroxy propyl methyl cellulose (HPMC). Then, films were evaluated regarding their thickness, pH, tensile strength and elongation, swelling, in vitro release and antifungal activity. The type of polymer used had an impact on the mechanical properties, swelling and release of the films. Films prepared using PVA showed significantly higher tensile strength and elongation at break values compared to those prepared using HPMC. However, swelling index increased with enhancing HPMC concentration in the films. The release of probiotic extract from the film prepared with HPMC occurred slowly. Based on these results, films containing 54 % HPMC and 26 % PVA were selected as optimal formulation. Moreover, it was found that optimal film containing probiotic extract could inhibit the growth of Candida albicans. Regarding to the obtained results, probiotic oral adhesive mucoadhesive films can be considered as a promising alternative to traditional methods in the treatment of candidiasis.

Starch-based films affected by the addition of collagen from Prochilodus magdalenae residues and HPMC: Application in Andean blackberry (Rubus glaucus Benth) coatings.

Starch-based films offer the advantages of biodegradability, edibility, barrier properties, flexibility, and adaptability. This study compared the physicochemical properties of starch-based films by adding raw fish collagen and hydroxypropylmethylcellulose (HPMC). The tensile properties were evaluated, and the interaction with water was analyzed. Barrier properties, such as water vapor and oxygen permeability, were examined, and optical properties, such as gloss and good internal transmittance, were evaluated. The films were evaluated as coatings on Andean blackberries (Rubus glaucus Benth) for 2 weeks at 85% RH and 25°C. The results showed that the inclusion of collagen caused a reduction in the tensile strength and elastic modulus of the films. Also, the formulation with the highest collagen concentration (F7) exhibited the lowest weight loss and water vapor permeability, also it had the highest collagen concentration and showed the highest reduction in Xw and WAC, with values of 0.048 and 0.65 g water/g dry film, respectively. According to analyzing the optical properties, F1 presented the highest bright-ness and transmittance values, with 18GU and 82 nm values, respectively. In general, the films and coatings are alternatives to traditional packaging materials to prolong the shelf life of these fruits.

An empirical predictive model for determining the aqueous solubility of BCS class IV drugs in amorphous solid dispersions.

CONTEXT: Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities. OBJECTIVE: This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices. METHODS: ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation. RESULTS: The ASDs' drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%. CONCLUSION: The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%.

Microbiological and Physicochemical Evaluation of Hydroxypropyl Methylcellulose (HPMC) and Propolis Film Coatings for Cheese Preservation.

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.

Formulation, Optimization and In-Vivo Characterization of Thermosensitive In-Situ Nasal Gel Loaded with Bacoside a for Treatment of Epilepsy.

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.

Bacteriophage ɸPT1b-Based Hand Sanitizer Gel for Reducing Pathogenic Escherichia coli Infection.

Foodborne disease is caused by consuming pathogenic microorganism-contaminated food that generates poisoning. Escherichia coli is a bacterium that causes foodborne disease, which is neutralized using gel hand sanitizer containing a bacteriophage with hydroxypropyl methylcellulose (HPMC) and active glycerin ingredients. Phages are viruses that infect bacteria naturally. This study aims to examine the effect of HPMC and glycerin on the physical properties and activity of bacteriophage ɸPT1b-based hand sanitizer gel, as well as determining the optimum composition of the combination of HPMC and glycerin in the same. The results of the study shows that the HPMC and glycerin factors show a positive value for inhibitory response, with the HPMC factor showing the best results. The optimum formula results using Design Expert 12.0 software were 0.75% for HPMC and 7.5% for glycerin, while the values for viscosity, dispersal power, and inhibitory power were 32,500 dPas, 7,737 cm, and 1.300 cm, respectively. In conclusion, an increase in HPMC concentration affects the increment of the viscosity score and decreases spread response. However, the glycerin concentration increment reduces the viscosity score but raises the spread value.

Development of Sustained Release System Based on High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose Sodium as a Gel Former.

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.

Hot Melt Extrusion as an Effective Process in the Development of Mucoadhesive Tablets Containing Scutellariae baicalensis radix Extract and Chitosan Dedicated to the Treatment of Oral Infections.

Hot Melt Extrusion (HME) technology was developed to obtain blends containing lyophilized Scutellariae baicalensis root extract and chitosan in order to improve the rheological properties of the obtained blends, including tableting and compressibility properties. (Hydroxypropyl)methyl cellulose (HPMC) in 3 different ratios was used as amorphous matrix formers. The systems were characterized using X-ray powder diffraction (PXRD), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR), and in vitro release, permeability, and microbiological activity studies. Then, the extrudates were used to prepare tablets in order to give them the appropriate pharmaceutical form. HPMC-based systems released baicalin more slowly, resulting in delayed peaks in the acceptor fluid. This behavior can be explained by the fact that HPMC swells significantly, and the dissolved substance must have diffused through the polymer network before being released. The best tabletability properties are provided by the formulation containing the extrudate with lyophilized extract HPMC 50:50 w/w. These tablets offer a valuable baicalin release profile while maintaining good mucoadhesive properties that condition the tablet's retention in the application site and the effectiveness of therapy.

Modified celluloses improve the proofing performance and quality of bread made with a high content of resistant starch.

BACKGROUND: Adding resistant starch (RS) to bread formulations is a promising way of increasing fiber content of white bread. However, the partial replacement of wheat flour (WF) by RS can lead to a decrease in technological quality. The objective of this study was to analyze the performance of hydroxypropylmethylcellulose and carboxymethylcellulose as improvers of wheat bread with a high level of replacement (30%) with maize RS. The levels of the modified celluloses were 1% and 1.5% (WF + RS basis), and a formulation without modified celluloses was used as control. Proofing time, loaf volume, crumb characteristics (porosity, texture), and bread staling parameters (hardness increase, moisture loss), among other attributes, were analyzed, and principal component analysis was applied to compare samples. RESULTS: The use of both modified celluloses was effective in improving the quality of breads. Specific volume and crumb porosity were enhanced, particularly at the 1.5% level. Breads with modified celluloses also allowed a higher retention of water and a better preservation of mechanical properties during storage. The principal component analysis projection graph for the first two principal components showed that samples with modified celluloses were clustered by the level of hydrocolloid addition rather than by the type of hydrocolloid used, although all the samples with modified celluloses were close to each other and distant from the control sample without hydrocolloids. CONCLUSION: The quality decrease resulting from the replacement of WF by a high level of RS can be greatly compensated by the use of structuring agents such as hydroxypropylmethylcellulose and carboxymethylcellulose. © 2022 Society of Chemical Industry.

Novel Sprayable Thermosensitive Benzydamine Hydrogels for Topical Application: Development, Characterization, and In Vitro Biological Activities.

Benzydamine hydrochloride (BZD) having analgesic, anesthetic, and anti-inflammatory effects is used orally or topically in the treatment of disorders such as joint inflammation and muscle pain. Within the scope of this study, sprayable thermosensitive BZD hydrogels were developed using thermoresponsive poloxamers to avoid systemic side effects and to provide better compliance for topical administration. Also, hydroxypropyl methyl cellulose (HPMC) was employed to improve the mechanical strength and bioadhesive properties of the hydrogel. The addition of BZD generally decreased the viscosity of the formulations (p < 0.05), while increasing the gelation temperature (p < 0.05). The formulations that did not have any clogs or leaks in the nozzle of the bottle during the spraying process were considered lead formulations. To spray the formulations easily, it was found that the viscosity at RT should be less than 200 mPa·s, and their gelation temperature should be between 26 and 34°C. Increasing HPMC and poloxamer improved bioadhesion. The amount of HPMC and poloxamers did not cause a significant change in the release characteristics of the formulations (p > 0.05); the release profiles of BZD from the formulations were similar according to model-independent kinetic (f2 > 50). HPMC and poloxamers had important roles in the accumulation of BZD in the skin. In vitro biological activity studies demonstrated that the formulations presented their anti-inflammatory activity with TNF-α inhibition but did not have any effect on the inhibition of COX enzymes as expected. As a result, thermosensitive hydrogels containing BZD might be an appropriate alternative, providing an advantage in terms of easier application compared to conventional gels.

Influence of Poloxamer on the Dissolution and Stability of Hot-Melt Extrusion-Based Amorphous Solid Dispersions Using Design of Experiments.

The current study aimed to see the effects of poloxamer P407 on the dissolution performance of hydroxypropyl methylcellulose acetate succinate (AquaSolve™ HPMC-AS HG)-based amorphous solid dispersions (ASD). A weakly acidic, poorly water-soluble active pharmaceutical ingredient (API), mefenamic acid (MA), was selected as a model drug. Thermal investigations, including thermogravimetry (TG) and differential scanning calorimetry (DSC), were conducted for raw materials and physical mixtures as a part of the pre-formulation studies and later to characterize the extruded filaments. The API was blended with the polymers using a twin shell V-blender for 10 min and then extruded using an 11-mm twin-screw co-rotating extruder. Scanning electron microscopy (SEM) was used to study the morphology of the extruded filaments. Furthermore, Fourier-transform infrared spectroscopy (FT-IR) was performed to check the intermolecular interactions of the components. Finally, to assess the in vitro drug release of the ASDs, dissolution testing was conducted in phosphate buffer (0.1 M, pH 7.4) and hydrochloric acid-potassium chloride (HCl-KCl) buffer (0.1 M, pH 1.2). The DSC studies confirmed the formation of the ASDs, and the drug content of the extruded filaments was observed to be within an acceptable range. Furthermore, the study concluded that the formulations containing poloxamer P407 exhibited a significant increase in dissolution performance compared to the filaments with only HPMC-AS HG (at pH 7.4). In addition, the optimized formulation, F3, was stable for over 3 months when exposed to accelerated stability studies.

Pharmacobezoar Formation From HPMC-AS-Containing Spray-Dried Formulations in Nonclinical Safety Studies in Rats.

Changing the physical state from crystalline to amorphous is an elegant method to increase the bioavailability of poorly soluble new chemical entity (NCE) drug candidates. Subsequently, we report findings from repeat-dose toxicity studies of an NCE formulated as a spray-dried amorphous solid dispersion (SD-ASD) based on hydroxypropyl methylcellulose acetate succinate (HPMC-AS) in rats. At necropsy, agglomerates of SD-ASD were found in the stomach and small intestine, which in reference to literature were termed pharmacobezoars. We interpreted the pH-dependent insolubility of HPMC-AS in the acidic gastric environment to be a precondition for pharmacobezoar formation. Gastric pharmacobezoars were not associated with clinical signs or alterations of clinical pathology parameters. Pharmacobezoar-correlated histopathological findings were limited to the stomach and consisted of atrophy, erosion, ulcer, and inflammation, predominantly of the nonglandular mucosa. Pharmacobezoars in the small intestines induced obstructive ileus with overt clinical signs which required unscheduled euthanasia, prominent alterations of clinical pathology parameters indicative of hypotonic dehydration, degenerative and inflammatory processes in the gastrointestinal tract, and secondary renal findings. The incidence of pharmacobezoars increased with dose and duration of dosing. Besides the relevance of pharmacobezoars to animal welfare, they limit the non-observed adverse effect level in nonclinical testing programs and conclusively their informative value.

HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm.

PURPOSE: Abdominal aortic aneurysm (AAA) rupture is one of the most common causes of mortality in cardiovascular diseases, but currently there is no approved drug for AAA treatment or prevention in the clinic. Naringenin (NGN) has been reported to have anti-AAA effects. However, water solubility and in vivo absorption of NGN are not satisfactory, which leads to its low bioavailability, thus affecting its pharmacological effects. In this project, the improving effects of isonicotinamide (INT) co-crystal and hydroxy propyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP) on the solubility, in vivo absorption, and anti-AAA effects of NGN were evaluated. METHODS: In the current study, co-crystals of naringenin-isonicotinamide (NGN-INT) were prepared, and effects of PVP or HPMC on precipitation rate, supersaturation, and bioavailability of NGN were explored. In addition, with or without HPMC supply, the effects of NGN-INT co-crystal on anti-AAA efficacy of NGN were investigated on an elastase-induced AAA mouse model, and the results were compared with the efficacy of the NGN crude drug. RESULTS: Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased Cmax and AUC(0-∞) of NGN by 18 times and 1.97 times, respectively. Addition of PVP or HPMC in NGN-INT co-crystal further increased bioavailability of NGN in NGN-INT. The in vivo pharmacodynamic study showed that NGN-INT with HPMC significantly improved the inhibitory effects of NGN against AAA. CONCLUSION: NGN-INT significantly improved the absorption and aortic protective effects of NGN. The supersaturation-prolonging effect of HPMC further enhanced bioavailability and anti-AAA effects of NGN-INT.

Azelaic acid loaded chitosan and HPMC based hydrogels for treatment of acne: formulation, characterization, in vitro-ex vivo evaluation.

In this study, hydrogels containing azelaic acid were developed using chitosan or HPMC (1-7%) for local treatment of acne vulgaris. Physicochemical properties such as viscosity, pH and mechanical properties were evaluated. In vitro release and ex vivo permeability studies were performed using the Franz diffusion cell system. The pH of the hydrogels was highly compatible with the skin pH and varied between 4.38 and 5.84. The cumulative release percentages of the hydrogels at the end of 6 hours were 65-78%, whereas the marketed product yielded 50% drug release. According to the ex vivo permeability results, azelaic acid accumulated in the skin was found to be 9.38 ± 0.65% (marketed cream), 19.53 ± 1.06% (K3), 10.96 ± 1.91% (H6). The antiacne studies with Cutibacterium acnes revealed that K3 (29.45 ± 0.95) and H6 (32.35 ± 0.15) had higher inhibition zones compared to the marketed cream (24.50 ± 0.90). Additionally, the gels were found to be highly stable as a result of the stability studies for 6 months. Among the hydrogels that were prepared based on experimental findings, K3 (3% Chitosan) and H6 (6% HPMC) represented elevated in vitro release profile, higher permeability and increased antiacne activity. The findings of this research suggest that the developed hydrogels might be an alternative to the marketed product.

Optimization of Spray-Drying Process Parameters to Study Anti-Sticking Effect of Hydroxypropyl Methyl Cellulose-VLV on Corni fructus Extracts.

To prevent the sticking of Corni fructus extract (CFE) during spray drying, the anti-sticking effects of different excipients were compared. Hydroxypropyl methylcellulose (HPMC)-VLV showed a higher powder yield at a lower dosage (8% of total solids), and a lower solution viscosity, compared with HPMC-E5. Therefore, HPMC-VLV is a more effective excipient for reducing CFE sticking during spray drying. The spray-drying process parameters were optimized by central composite rotatable design/response surface methodology, and spray drying was conducted under the following conditions: Inlet air temperature, 126 °C; atomization pressure, 1.05 bar; pump speed, 7.7 mL/min. Scanning electron microscopy showed that the powder comprised shrunken spherical particles with particle sizes in the range of 2-30 µm. Analysis of dynamic surface tension and chemical elements on the powder surface showed that HPMC-VLV rapidly moved to the droplet surface owing to its surface activity. HPMC covered the droplet surface and reduced surface tension, achieving an anti-sticking effect. In conclusion, HPMC-VLV at a solid content of 8% significantly improved the spray drying and reduced sticking of CFE. The spray-drying process parameters were nonlinearly related to the dry product yield. Graphical Abstract.

Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties.

Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug.

Gastroretentive Sustained-Release Tablets Combined with a Solid Self-Micro-Emulsifying Drug Delivery System Adsorbed onto Fujicalin®.

Gastroretentive drug delivery systems (GRDDS) get retained in the stomach for a long time, thus facilitating the absorption of drugs in the upper gastrointestinal tract. However, drugs that are difficult to dissolve or unstable in an acidic environment are not suitable for GRDDS. The current study designs GRDDS combined with a self-micro-emulsifying drug delivery system (SMEDDS) for drugs with solubility or stability problems in the stomach. The model drug fenofibrate was formulated into the optimized liquid SMEDDS composed of 50 w/w% Capryol® PGMC, 40 w/w% Kolliphor® RH40, and 10 w/w% Transcutol® HP and solidified through adsorption on several porous adsorbents. In a dissolution medium at pH 1.2, the powdered SMEDDS using Fujicalin® dissolved quickly and achieved higher drug dissolution than other adsorbents. Based on these results, a gastroretentive bilayer tablet consisting of a drug release layer and a swelling layer was designed. The drug release layer was formulated with the powdered SMEDDS and hydroxypropyl methylcellulose (HPMC) as a release modifier. HPMC was also added to the swelling layer as a water-swellable polymer. The dissolution rate depended on the viscosity of the HPMC in the drug release layer. The time for 90% drug release was extended from 3.7 to 12.0 h by increasing the viscosity grade of HPMC from 0.1 to 100 K. Moreover, the tablet swelled and maintained a size comparable to a human pylorus diameter or more for at least 24 h. This GRDDS could apply to a broader range of drug candidates.

Improvement of the Bioavailability and Anti-hepatic Alveolar Echinococcosis Effect of Albendazole-Isethionate/Hypromellose Acetate Succinate (HPMC-AS) Complex.

Maximizing the pharmacodynamics of albendazole (ABZ), which is used to treat echinococcoses, is essential for the long-term treatment of echinococcosis patients. ABZ is a weak base whose solubility depends on the pH value of the solvent. After it has been orally administered, its solubility drops sharply from when it is in gastric juices (pH 1.4) to when it is in intestinal juices (pH 6.5) and is subsequently absorbed in the ileum and jejunum. This results in low solubility and poor bioavailability of the drug. In this study, we developed an orally administered albendazole-isethionate (ABZ-HES)/hypromellose acetate succinate (HPMC-AS) complex tablet (TABZ-HES-H) with improved solubility and bioavailability. Previous studies demonstrated that ABZ-HES has a higher intrinsic dissolution rate under pH 1.4 than the ABZ free base used in the commercial product Albenda and that HPMC-AS can effectively inhibit ABZ crystallization, which could be due to the hydrophobic interaction between ABZ and HPMC-AS in an aqueous environment. In this study, the dissolution behavior of TABZ-HES-Hin vitro was studied by the two-step pH conversion method. Our results demonstrated that the oral bioavailability of TABZ-HES-H was approximately 2.6 times higher than that of ABZ. More importantly, in the rat model of secondary hepatic alveolar echinococcosis, the anti-hepatic alveolar echinococcosis effect of TABZ-HES-H was 3.4 times higher than that of a commercial product. The improved preparation with salt and polymer has proven to be a feasible method of improving the oral bioavailability and pharmacodynamics of ABZ.

Nanostructured Valsartan Microparticles with Enhanced Bioavailability Produced by High-Throughput Electrohydrodynamic Room-Temperature Atomization.

The high-throughput drying and encapsulation technique called electrospraying assisted by pressurized gas (EAPG) was used for the first time to produce nanostructured valsartan within microparticles of excipients. Valsartan, a poorly absorbed and lipid-soluble drug, was selected since it is considered a good model for BCS class II drugs. Two different polymeric matrices were selected as excipients, i.e., hydroxypropyl methylcellulose (HPMC) and lactose monohydrate, while Span 20 was used as a surfactant. The produced 80% valsartan loading formulations were characterized in terms of morphology, crystallinity, in vitro release, in vitro Caco-2 cells' permeability, and in vivo pharmacokinetic study. Spherical microparticles of ca. 4 µm were obtained within which valsartan nanoparticles were seen to range from 150 to 650 nm. Wide-angle X-ray scattering and differential scanning calorimetry confirmed that valsartan had a lower and/or more ill-defined crystallinity than the commercial source, and photon correlation spectroscopy and transmission electron microscopy proved that it was dispersed and distributed in the form of nanoparticles of controlled size. In vitro dissolution tests showed that the HPMC formulation with the lowest API particle size, i.e., 150 nm, dissolved 2.5-fold faster than the commercial valsartan in the first 10 min. This formulation also showed a 4-fold faster in vitro permeability than the commercial valsartan and a 3-fold higher systemic exposure than the commercial sample. The results proved the potential of the EAPG processing technique for the production of safe-to-handle microparticles containing high quantities of a highly dispersed and distributed nanonized BCS class II model drug with enhanced bioavailability.

Ternary Amorphous Solid Dispersions Containing a High-Viscosity Polymer and Mesoporous Silica Enhance Dissolution Performance†.

The aim of this study was to evaluate the benefits of a ternary amorphous solid dispersion (ASD) that was designed as an immediate-release tablet with a high drug load (e.g., 40% w/w) to produce heightened maintenance of drug supersaturation during dissolution testing, which will be henceforth referred to as the "maintenance ability". Ternary ASD granules were produced by hot melt extrusion (HME) and were comprised of itraconazole (ITZ) 50%, hypromellose (HPMC) 20%, and mesoporous silica (XDP) 30%, where amorphous ITZ incorporated into HPMC was efficiently absorbed in XDP pores. The ternary ASD granules containing a high-viscosity HPMC (AF4M) produced a significantly heightened maintenance ability of drug supersaturation in neutral pH dissolution media in which crystalline ITZ solubility is below 1 µg/mL. The final tablet formulation contained 80% w/w of the ASD granules (40% w/w ITZ), had an acceptable size, and exhibited both sufficient tablet hardness and disintegration. The dissolution behavior of the ternary ASD tablet exhibited a supersaturation maintenance ability similar to that of the ASD granules. Under neutral conditions, the ternary ASD tablet showed immediate and higher ITZ release compared with the binary ASD tablets, and this phenomenon could be explained by the difference in ITZ/AF4M particle size in the tablet. In high-resolution scanning electron microscopy (SEM), it was observed that ITZ and AF4M in the ternary formulation could easily form nano-sized particles (<1 µm) during the absorption process into/onto XDP pores prepared by HME, which contributed to the immediate ITZ release from the ternary ASD tablet under neutral pH conditions. Therefore, the ternary ASD containing high-viscosity HPMC and mesoporous silica prepared by HME made it possible to design a high ASD content, small-size tablet with an ideal dissolution profile in biorelevant media, and we expect that this technology can be applied for continuous HME ASD manufacturing.