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Ketoconazole (K) is a poorly water-soluble drug that faces significant challenges in achieving therapeutic efficacy. This study aimed to enhance the dissolution rate of ketoconazole by depositing spray-dried ketoconazole (SK) onto the surface of ground trehalose dihydrate (T) using spray drying. Ketoconazole-trehalose surface solid dispersions (SKTs) were prepared in ratios of 1:1 (SK1T1), 1:4 (SK1T4), and 1:10 (SK1T10), and characterized them using particle size analysis, scanning electron microscopy, powder X-ray diffraction, and in vitro dissolution studies. Results showed that the dissolution rates of the dispersions were significantly higher than those of pure ketoconazole, with the 1:10 ratio showing the highest dissolution rate. The improved dissolution was attributed to the formation of a new crystalline phase and better dispersion of ketoconazole particles. These findings suggest that the surface solid dispersion approach could be a valuable method for enhancing the bioavailability of poorly water-soluble drugs., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus ® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

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

Hypericum perforatum (HP) contains valuable and beneficial bioactive compounds that have been used to treat or prevent several illnesses. Encapsulation technology offers protection of the active compounds and facilitates to expose of the biologically active compounds in a controlled mechanism. Microcapsulation of the hydroalcoholic gum arabic and maltodextrin have hot been used as wall materials in the encapsulation of HP extract. Therefore, the optimum microencapsulation parameters of Hypericum perforatum (HP) hydroalcoholic extract were determined using response surface methodology (RSM) for the evaluation of HP extract. Three levels of three independent variables were screened using the one-way ANOVA. Five responses were monitored, including total phenolic content (TPC), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), carr index (CI), hausner ratio (HR), and solubility. Optimum drying conditions for Hypericum perforatum microcapsules (HPMs) were determined: 180 °C for inlet air temperature, 1.04/1 for ratio of maltodextrin to gum arabic (w/w), and 1.98/1 for coating to core material ratio (w/w). TPC, antioxidant activity, CI, HR, and solubility values were specified as 316.531 (mg/g GAE), 81.912%, 6.074, 1.066, and 35.017%, respectively, under the optimized conditions. The major compounds of Hypericum perforatum (hypericin and pseudohypericin) extract were determined as 4.19 μg/g microcapsule and 15.09 μg/g microcapsule, respectively. Scanning electron microscope (SEM) analysis revealed that the mean particle diameter of the HPMs was 20.36 µm. Based on these results, microencapsulation of HPMs by spray drying is a viable technique which protects the bioactive compounds of HP leaves, facilitating its application in the pharmaceutical, cosmetic, and food industries., (© 2024. The Author(s).)

This study aimed to develop the solid astaxanthin-encapsulated self-microemulsifying delivery system (S-AST SMEDS) spray-dried particles and investigate the effect of materials in formulations on product characteristics. The optimized liquid AST SMEDS incorporated with a polymeric precipitation inhibitor (PI) was solidified with a solid carrier by spray drying. Physicochemical properties of S-AST SMEDS spray-dried powders including morphology, particle size and distribution, flowability, solid-state characters, moisture content, yield, loading capacity of AST, and reconstitution properties were examined. Polymeric PIs seemed to have an impact on particles' size, surface smoothness, and flowability while solid carriers had an effect on the particles' moisture content and droplet size of microemulsions obtained after reconstitution. The amount of AST encapsulated in S-SMEDS powder was influenced by both polymer and solid carriers. Dissolution and short-term stability of S-AST SMEDS were also studied. Our developed spray-dried solid SMEDS particles helped enhance AST dissolution rate., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Aqueous colloidal dispersions of water-insoluble polymers (APDs) avoid hassles associated with the use of organic solvents and offer processing advantages related to their low viscosity and short processing times. Therefore, they became the main vehicle for pharmaceutical coating of tablets and multiparticulates, a process commonly employed using pan and fluidized-bed machinery. Another interesting although less common processing approach is co-spray drying APDs with drugs in aqueous systems. It enables the manufacture of capsule- and matrix-type microspheres with controllable size and improved processing characteristics in a single step. These microspheres can be further formulated into different dosage forms. This systematic review is based on published research articles and aims to highlight the applicability and opportunities of co-spray drying drugs with APDs in drug delivery., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

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., (© 2021. The Author(s).)

Galeterone, a novel prostate cancer candidate treatment, was discontinued after a Phase III clinical trial due to lack of efficacy. Galeterone is weakly basic and exhibits low solubility in biorelevant media (i.e., ~ 2 µg/mL in fasted simulated intestinal fluid). It was formulated as a 50-50 (w/w) galeterone-hypromellose acetate succinate spray-dried dispersion to increase its bioavailability. Despite this increase, the bioavailability of this formulation may have been insufficient and contributed to its clinical failure. We hypothesized that reformulating galeterone as an amorphous solid dispersion by KinetiSol® compounding could increase its bioavailability. In this study, we examined the effects of composition and manufacturing technology (Kinetisol and spray drying) on the performance of galeterone amorphous solid dispersions. KinetiSol compounding was utilized to create galeterone amorphous solid dispersions containing the complexing agent hydroxypropyl-β-cyclodextrin or hypromellose acetate succinate with lower drug loads that both achieved a ~ 6 × increase in dissolution performance versus the 50-50 spray-dried dispersion. When compared to a spray-dried dispersion with an equivalent drug load, the KinetiSol amorphous solid dispersions formulations exhibited ~ 2 × exposure in an in vivo rat study. Acid-base surface energy analysis showed that the equivalent composition of the KinetiSol amorphous solid dispersion formulation better protected the weakly basic galeterone from premature dissolution in acidic media and thereby reduced precipitation, inhibited recrystallization, and extended the extent of supersaturation during transit into neutral intestinal media., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The present study adopted a Quality by Design (QbD) approach to spray dry indomethacin nanosuspension (IMC-NS) consisting of HPC-SL, poloxamer 407, and lactose monohydrate. The Box-Behnken Design was used to systematically evaluate the effects of inlet temperature, aspiration rate, and feed rate on the critical quality attributes (CQAs) [redispersibility index (RDI; minimize), % yield (maximize), and % release at 15 min (maximize)] of the indomethacin spray dried nanosuspension (IMC-SD-NS). To identify significant main and quadratic effects, two-way interactions, and create a predictive model for the spray drying process, regression analysis and ANOVA were utilized. Following optimization, the IMC-SD-NS was analyzed for its physicochemical properties using X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. Statistical analysis revealed significant independent variables, including inlet temperature, feed rate, and aspiration rate, that critically impacted the solidified end product's RDI, % yield, and % release at 15 min. The models developed for critical quality attributes (CQAs) were significant at a p-value of 0.05. The crystalline state of IMC was maintained in the solidified product, as confirmed by XRPD, and no interactions were observed between IMC and the excipients as evaluated by FTIR. In vitro dissolution studies showed improved dissolution rate for the IMC-SD-NS (3.82-fold increase in overall drug release), which may be attributed to the readily redispersible nanosized drug particles. The implementation of a well-designed study, utilizing Design of Experiments (DoE) methodology, played a crucial role in the development of a highly effective spray drying process., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The aim of this study was to prepare HY-038 solid dispersions (SDs) with single carrier at high drug loading and then forming a tablet to enhance solubility, dissolution, and bioavailability via spray drying technology. At the same time, we hope to develop a more convenient in vitro method to predict the absorption behavior of different formulations in vivo. Different solid dispersions, varying in drug/polymer ratios, were prepared. Infrared spectroscopy, differential scanning calorimetry, scanning electron microscope, and X-ray diffraction were used to perform solid-state characterizations of the pure drug and SDs. Contact angle of water, dissolution in pH = 6.8 phosphate buffer, and in vivo absorption in dogs were studied. As a result, solid-state characterization demonstrated the transformation of the crystalline HY-038 to an amorphous state in the solid dispersions, and the in vivo exposure followed with the trend of the dissolution curve combined with contact angle. Compared with the prototype formulation, the C max and AUC 0-∞ of optimized formulation SD2 (HY-038-HPMCAS 3:1) increased by about 5 ~ 9 times at the same dose. More importantly, the SD2 formulation showed approximately linear increases in C max and AUC 0-∞ as the dose increased from 50 to 100 mg, while the prototype formulation reached absorption saturation at 50 mg. SD2 (HY-038-HPMCAS 3:1) was selected as the best formulation for the downstream development., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

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., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Spray-drying dispersion (SDD) is a well-established manufacturing technique used to prepare amorphous solid dispersions (ASDs), allowing for poorly soluble drugs to have improved bioavailability. However, the process of spray-drying with multiple factors and numerous variables can lead to a lengthy development timeline with intense resource requirements, which becomes the main obstacle limiting spray-drying development at the preclinical stage. The purpose of this work was to identify optimized preset parameters for spray-drying to support the early development of ASDs suitable for most circumstances rather than individual optimization. First, a mini-DoE (Design of Experiment) study was designed to evaluate the critical interplay of two key variables for spray-drying using a BUCHI B-290 mini spray dryer: solid load and atomizing spray gas flow. The critical quality attributes (CQAs) of the ASDs, including yield, particle size, morphology, and in vitro release profile, were taken into account to identify the impact of the key variables. The mini-DoE results indicated that a 5% solid load (w/v %) and 35 mm height atomizing spray gas flow were the most optimized parameters. These predefined values were further verified using different formulation compositions, including various polymers (Eudragit L100-55, HPMCAS-MF, PVAP, and PVP-VA64) and drugs (G-F, GEN-A, Indomethacin, and Griseofulvin), a range of drug loading (10 to 40%), and scale (200 mg to 200 g). Using these predefined parameters, all ASD formulations resulted in good yields as well as consistent particle size distribution. This was despite the differences in the formulations, making this a valuable and rapid approach ideal for early development. This strategy of leveraging the preset spray-drying parameters was able to successfully translate into a reproducible and efficient spray-drying platform while also saving material and reducing developmental timelines in early-stage formulation development., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Microencapsulation is an optimistic method for the delivery of live microbial cells through different food products. In this study, riboflavin-producing probiotic strain Lactiplantibacillus plantarum MTCC 25,432 was encapsulated using a spray drying technique with different wall materials including Inulin, maltodextrin (MD), and MD + Inulin (1:1). The obtained spray dried powder was investigated for probiotic viability, encapsulation efficiency, particle size, water activity, moisture content, hygroscopicity, bulk and tapped densities, storage stabilities, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). Besides this, the viability of the free and encapsulated probiotic cells was tested under simulated gastric and intestinal fluid conditions. In the results, microcapsules produced with the combination of MD + Inulin showed higher dry powder yield (36.5%) and viability of L. plantarum MTCC 25,432 (7.4 log CFU / g) as compared with individual coating materials. Further characterization revealed that MD + Inulin microcapsules are spherical (3.50 ± 1.61 μm in diameter) in shape with concavities, showed the highest encapsulation efficiency (82%), low water activity (0.307), moisture content (3.67%) and good survival ability at low pH (pH 2.0 and 3.0), high bile salt concentrations (1.0% and 2.0%), and long storage conditions. No differences in FTIR spectra were observed among the tested samples. However, TGA showed enhanced thermal stability of probiotic-loaded microcapsules when MD + Inulin was used together. In conclusion, MD + Inulin could be a potential encapsulation material for riboflavin-producing probiotic bacteria L. plantarum MTCC 25,432., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pressurized metered dose inhalers (pMDIs) require optimized formulations to provide stable, consistent lung delivery. This study investigates the feasibility of novel rugose lipid particles (RLPs) as potential drug carriers in pMDI formulations. The physical stability of RLPs was assessed in three different propellants: the established HFA-134a and HFA-227ea and the new low global-warming-potential (GWP) propellant HFO-1234ze. A feedstock containing DSPC and calcium chloride was prepared without pore forming agent to spray dry two RLP batches at inlet temperatures of 55 °C (RLP55) and 75 °C (RLP75). RLPs performance in pMDI formulations was compared to two reference samples that exhibit significantly different performance when suspended in propellants: well-established engineered porous particles and particles containing 80% trehalose and 20% leucine (80T20L). An accelerated stability study at 40 °C and relative humidity of 7% ± 5% was conducted over 3 months. At different time points, a shadowgraphic imaging technique was used to evaluate the colloidal stability of particles in pMDIs. Field emission electron microscopy with energy dispersive X-ray spectroscopy was used to evaluate the morphology and elemental composition of particles extracted from the pMDIs. After 2 weeks, all 80T20L formulations rapidly aggregated upon agitation and exhibited significantly inferior colloidal stability compared to the other samples. In comparison, both the RLP55 and RLP75 formulations, regardless of the propellant used, retained their rugose structure and demonstrated excellent suspension stability comparable with the engineered porous particles. The studied RLPs demonstrate great potential for use in pMDI formulations with HFA propellants and the next-generation low-GWP propellant HFO-1234ze., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Drug delivery to the buccal mucosa is one of the most convenient ways to treat common mouth problems. Here, we propose a spray-dried re-dispersible mucoadhesive controlled release gargle formulation to improve the efficacy of chlorhexidine. The present investigation portrays an approach to get stable and free-flowing spray-dried porous aggregates of chlorhexidine-loaded sodium alginate nanoparticles. The ionic gelation technique aided with the chlorhexidine's positive surface charge-based crosslinking, followed by spray drying of the nanoparticle's dispersion in the presence of lactose- and leucine-yielded nano-aggregates with good flow properties and with a size range of about 120-350 nm. Provided with the high entrapment efficiency (87%), the particles showed sustained drug release behaviors over a duration of 10 h, where 87% of the released drug got permeated within 12 h. The antimicrobial activity of the prepared formulation was tested on S. aureus, provided with a higher zone of growth inhibition than the marketed formulation. Aided with an appropriate mucoadhesive strength, this product exhibited extended retention of nanoparticles in the throat region, as shown by in vivo imaging results. In conclusion, the technology, provided with high drug retention and extended effect, could be a potential candidate for treating several types of throat infections., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Abstract The present study uses maize flour and skimmed milk powder to develop a probiotic dairy-cereal-based food powder by spray drying and using response surface methodology for optimization. The processing parameters and ingredients, including inlet spray drying temperature (140–170 ℃), maize flour (80–120 g), and skim milk powder (60–80 g), were optimized against probiotic survivability count, moisture, sensory score, bulk density, and wettability as responses using response surface methodology. The optimum experimental conditions obtained to manufacture acceptable-quality powder were an inlet temperature of 151 ℃, an amount of maize flour of 102.74 g, and skim milk powder at 69.88 g. The probiotic survivability (8.35 log CFU/g) was observed at more than the recommended level (6.0 log CFU/g) due to the probiotic strain's microencapsulation by skim milk and maize flour components. The optimized powder had good nutritional and functional values and was observed to have acceptable water activity, surface structure, and color values. The shelf life of the product on the basis of probiotic survival (minimum 6.0 log CFU/g) was found to be 49 days at 4 ℃. Gastric and pancreatic survival was also observed at more than 50% in refrigerated conditions for up to 56 days of storage.

This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Probiotics, particularly yeasts from the genus Saccharomyces, are valuable for their health benefits and potential as antibiotic alternatives. To be effective, these microorganisms must withstand harsh environmental conditions, necessitating advanced protective technologies such as encapsulation to maintain probiotic viability during processing, storage, and passage through the digestive system. This review and meta-analysis aims to describe and compare methods and agents used for encapsulating Saccharomyces spp., examining operating conditions, yeast origins, and species. It provides an overview of the literature on the health benefits of nutritional yeast consumption. A bibliographic survey was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The meta-analysis compared encapsulation methods regarding their viability after encapsulation and exposure to the gastrointestinal tract. Nineteen studies were selected after applying inclusion/exclusion criteria. Freeze drying was found to be the most efficient for cell survival, while ionic gelation was best for maintaining viability after exposure to the gastrointestinal tract. Consequently, the combination of freeze drying and ionic gelation proved most effective in maintaining high cell viability during encapsulation, storage, and consumption. Research on probiotics for human food and animal feed indicates that combining freeze drying and ionic gelation effectively protects Saccharomyces spp.; however, industrial scalability must be considered. Reports on yeast encapsulation using agro-industrial residues as encapsulants offer promising strategies for preserving potential probiotic yeasts, contributing to the environmental sustainability of industrial processes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study developed and evaluated chitosan-sodium alginate capsules containing the probiotic Lacticaseibacillus rhamnosus GG using extrusion and emulsification techniques. The encapsulated L. rhamnosus GG cells were also evaluated for technological and probiotic-related physiological functionalities, as well as when incorporated in UHT and powdered milk. Extrusion (86.01 ± 1.26%) and emulsification (74.43 ± 1.41%) encapsulation techniques showed high encapsulation efficiency and high survival rates of L. rhamnosus GG during 28 days of refrigeration and room temperature storage, especially emulsification capsules (> 81%). The encapsulated L. rhamnosus GG cells showed high survival rates during exposure to simulated gastrointestinal conditions (72.65 ± 1.09-114.15 ± 0.44%). L. rhamnosus GG encapsulated by extrusion and emulsification performed satisfactorily in probiotic-related physiological (pH and bile salts tolerance) and technological properties (positive proteolytic activity, diacetyl and exopolysaccharides production, high NaCl tolerance (> 91%), besides having high heat tolerance (> 76%)). L. rhamnosus GG in extrusion and emulsification capsules had high survival rates (> 89%) and did not significantly affect physicochemical parameters in Ultra-High Temperature (UHT) and powdered milk during storage. The results demonstrate that L. rhamnosus GG can be successfully encapsulated with alginate-chitosan as a protective material through extrusion and emulsification techniques. UHT and powdered milk could serve as appropriate delivery systems to increase the intake of this encapsulated probiotic by consumers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dry powder inhalers (DPIs) are state-of-the-art pulmonary drug delivery systems. This article explores the transformative impact of nanotechnology on DPIs, emphasizing the Quality Target Product Profile (QTPP) with a focus on aerodynamic performance and particle characteristics. It navigates global regulatory frameworks, underscoring the need for safety and efficacy standards. Additionally, it highlights the emerging field of nanoparticulate dry powder inhalers, showcasing their potential to enhance targeted drug delivery in respiratory medicine. This concise overview is a valuable resource for researchers, physicians, and pharmaceutical developers, providing insights into the development and commercialization of advanced inhalation systems., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Over the past decades, research on nanomedicines as innovative tools in combating complex pathologies has increased tenfold, spanning fields from infectiology and ophthalmology to oncology. This process has further accelerated since the introduction of SARS-CoV-2 vaccines. When it comes to human health, nano-objects are designed to protect, transport, and improve the solubility of compounds to allow the delivery of active ingredients on their targets. Nanomedicines can be administered by different routes, such as intravenous, oral, intramuscular, or pulmonary routes. In the latter route, nanomedicines can be aerosolized or nebulized to reach the deep lung. This review summarizes existing nanomedicines proposed for inhalation administration, from their synthesis to their potential clinical use. It also outlines the respiratory organs, their structure, and particularities, with a specific emphasis on how these factors impact the administration of nanomedicines. Furthermore, the review addresses the organs accessible through pulmonary administration, along with various pathologies such as infections, genetic diseases, or cancer that can be addressed through inhaled nanotherapeutics. Finally, it examines the existing devices suitable for the aerosolization of nanomedicines and the range of nanomedicines in clinical development., (© 2024. Controlled Release Society.)

To improve the therapeutic activity of inhaled glucocorticoids and reduce potential side effects, we designed a formulation combining the advantages of nanoparticles, which have an enhanced uptake by alveolar cells, allow targeted delivery and sustained drug release, as well as limited drug systemic passage, with those of microparticles, which display good alveolar deposition. Herein, a polymer-drug conjugate, poly(malic acid)-budesonide (PMAB), was first synthesized with either 11, 20, 33, or 43 mol% budesonide (drug:polymer from 1:8 to 3:4), the drug creating hydrophobic domains. The obtained conjugates self-assemble into nanoconjugates in water, yielding excellent drug loading of up to 73 wt%, with 80-100 nm diameters. In vitro assays showed that budesonide could be steadily released from the nanoconjugates, and the anti-inflammatory activity was preserved, as evidenced by reduced cytokine production in LPS-activated RAW 264.7 macrophages. Nanoconjugates were then embedded into microparticles through spray-drying with L-leucine, forming nano-embedded microparticles (NEMs). NEMs were produced with an aerodynamic diameter close to 1 µm and a density below 0.1 g.cm -3 , indicative of a high alveolar deposition. NEMs spray-dried with the less hydrophobic nanoconjugates, PMAB 1:4, were readily dissolved in simulated lung fluid and were chosen for in vivo experiments to study pharmacokinetics in healthy rats. As it was released in vivo from NEMs, sustained distribution of budesonide was obtained for 48 h in lung tissue, cells, and lining fluid. With high loading rates, modulable release kinetics, and low cytotoxicity, these nanoconjugates delivered by NEMs are promising for the more efficient treatment of pulmonary inflammatory diseases., (© 2024. Controlled Release Society.)

The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with β-cyclodextrin (β-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-β-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-β-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development., (© 2024. The Author(s).)

Effective strategies against the spread of respiratory viruses are needed, as tragically demonstrated during the COVID-19 pandemic. Apart from vaccines, other preventive or protective measures are necessary: one promising strategy involves the nasal delivery of preventive or protective agents, targeting the site of initial infection. Harnessing the immune system's ability to produce specific antibodies, a hyperimmune serum, collected from an individual vaccinated against SARS-CoV-2, was formulated as a dry powder for nasal administration. The selection of adequate excipients and process are key to maintaining protein stability and modulating the aerodynamic properties of the powders for reaching the desired respiratory regions. To this end, a hyperimmune serum was formulated with trehalose and mannitol as bulking agents during spray drying, then the ability of the redissolved immunoglobulins to bind Spike protein was verified by ELISA; foetal bovine serum was formulated in the same conditions as a reference. Moreover, a seroneutralization assay against SARS-CoV-2 pseudoviruses generated from different variants of concern was performed. The neutralizing ability of the serum was slightly reduced with respect to the starting serum when trehalose was used as a bulking agent. The powders were loaded in hypromellose capsules and aerosolized employing a nasal insufflator in an in vitro model of the nasal cavity connected to a Next Generation Impactor. The analysis of the powder distribution confirmed that all powders were inhalable and could target, at the same time, the upper and the lower airways. This is a preliminary proof-of-concept that this approach can constitute an effective strategy to provide broad coverage and protection against SARS-CoV-2, and in general against viruses affecting the airway. According to blood availability from donors, pools of hyperimmune sera could be rapidly formulated and administered, providing a simultaneous and timely neutralization of emerging viral variants., (© 2024. The Author(s).)

Postpartum reproductive infections in cows generate significant economic losses. The use of lactic acid bacteria in animal health is an alternative tool to avoid antibiotic therapy in the prevention/treatment of bovine reproductive infections. In previous studies, 6 lactic bacteria from bovine mammary glands and vagina with beneficial, safe and technological characteristics were selected, and included in probiotic/phytobiotic formulas (combined with Malva and Lapacho extracts). In this work, probiotic and phytobiotic formulations were designed and their long-term viability determined. They were administered intravaginally to 30 females pregnant bovine pre and postpartum. The modification of the native microbiota and permanence/colonization of cultivable bacteria was evaluated, and also the safety of the designed products through the application of nutritional, clinical, hematological and biochemical parameters. The microorganisms maintained their viability up to 9 months at refrigeration temperature. The number of cultivable bacteria showed different pattern: total aerobic mesophylls increased slightly in all experimental groups, while Enterobacteriaceae increased after delivery, except in beneficial acid lactic bacteria + vegetable extract cows. Control and vegetable extract females showed the highest numbers of Enterobacteriaceae at the end of the trial (30 days postpartum). The number of lactic acid bacteria increased significantly in all the groups between 15 days pre and postpartum. The different parameters evaluated demonstrate the safety and harmlessness of the designed formulas, without producing local and systemic adverse effects in the cows., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Probiotics are live microorganisms that inhabit the gastrointestinal tract and confer health benefits to consumers. However, a sufficient number of viable probiotic cells must be delivered to the specific site of interest in the gastrointestinal tract to exert these benefits. Enhanced viability and tolerance to sublethal gastrointestinal stress can be achieved using appropriate coating materials and food matrices for orally consumed probiotics. The release mechanism and interaction of probiotic microcapsules with the gastrointestinal tract have been minimally explored in the literature to date. To the authors' knowledge, no review has been published to discuss the nature of release and the challenges in the targeted delivery of probiotics. This review addresses gastrointestinal-related complications in the formulation of targeted delivery and controlled release of probiotic strains. It investigates the impacts of environmental stresses during the transition stage and delivery to the target region in the gastrointestinal tract. The influence of factors such as pH levels, enzymatic degradation, and redox conditions on the release mechanisms of probiotics is presented. Finally, the available methods to evaluate the efficiency of a probiotic delivery system, including in vitro and in vivo, are reviewed and assessed. The paper concludes with a discussion highlighting the emerging technologies in the field and emphasising key areas in need of future study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The fundamental idea underlying the use of amorphous solid dispersions (ASDs) is to make the most of the solubility advantage of the amorphous form of a drug. However, the drug stability becomes compromised due to the higher free energy and disorder of molecular packing in the amorphous phase, leading to crystallization. Polymers are used as a matrix to form a stable homogeneous amorphous system to overcome the stability concern. The present work aims to design ASD-based formulations under the umbrella of quality by design principles for improving oral drug bioavailability, using celecoxib (CXB) as a model drug. ASDs were prepared from selected polymers and tested both individually and in combinations, using various manufacturing techniques: high-shear homogenization, high-pressure homogenization, microfluidics-on-a-chip, and spray drying. The resulting dispersions were further optimized, resorting to a 3 2 full-factorial design, considering the drug:polymers ratio and the total solid content as variables. The formulated products were evaluated regarding analytical centrifugation and the influence of the different polymers on the intrinsic dissolution rate of the CXB-ASDs. Microfluidics-on-a-chip led to the amorphous status of the formulation. The in vitro evaluation demonstrated a remarkable 26-fold enhancement in the intrinsic dissolution rate, and the translation of this formulation into tablets as the final dosage form is consistent with the observed performance enhancement. These findings are supported by ex vivo assays, which exhibited a two-fold increase in permeability compared to pure CXB. This study tackles the bioavailability hurdles encountered with diverse active compounds, offering insights into the development of more effective drug delivery platforms., (© 2024. The Author(s).)

In recent years, more and more scientific community, food producers, and food industry show increased interest in functional foods containing probiotics, which is a big challenge. The consumption of probiotics in the context of a balanced diet through the consumption of functional foods or through the intake of pharmaceutical preparations has proven to contribute to the improvement of human health, even contributing to the prevention of diseases. In order for probiotics to be considered suitable for consumption, they must contain a minimum concentration of viable cells, namely, at least 10 7 colony forming units of beneficial microbes per gram. Ensuring the viability of bacterial cells until the moment of consumption is the overriding priority of functional probiotic food manufacturers. Probiotic bacteria are subject to stress conditions not only during food manufacturing but also during gastrointestinal passage, which limit or even compromise their functionality. This paper first examines all the stressful conditions faced by probiotic cells in their production stages and related to the conditions present in the bioreactor fermentation and drying processes as well as factors related to the food matrix and storage. The stress situations faced by probiotic microorganisms during the gastrointestinal transit especially during stomach and intestinal residence are also analyzed. In order to understand the adaptation mechanisms of probiotic bacteria to gastrointestinal stress, intrinsic and adaptive mechanisms identified in probiotic strains in response to acid stress and to bile and bile acid stress are analyzed. In addition, improvement strategies for multiple stress tolerance of lactic acid bacteria through directions dealing with stress, accumulation of metabolites, use of protectants, and regulation of technological parameters are examined. Finally, the definition of postbiotics, inanimate microorganisms and/or their components conferring health benefits, is also introduced. Postbiotics include cell lysates, enzymes, and cell wall fragments derived from probiotic bacteria and may represent an alternative to the use of probiotics, when they do not tolerate stressful conditions., (© 2024. The Author(s).)

Lyophilization also known as freeze-drying is a technique that has been employed to enhance the long-term durability of nanoparticles (NPs) that are utilized for drug delivery applications. This method is used to prevent their instability in suspension. However, this dehydration process can cause stress to the NPs, which can be alleviated by the incorporation of excipients like cryoprotectants and lyoprotectants. Nevertheless, the freeze-drying of NPs is often based on empirical principles without considering the physical-chemical properties of the formulations and the engineering principles of freeze-drying. For this reason, it is crucial to optimize the formulations and the freeze-drying cycle to obtain a good lyophilizate and ensure the preservation of NPs stability. Moreover, proper characterization of the lyophilizate and NPs is of utmost importance in achieving these goals. This review aims to update the recent advancements, including innovative formulations and novel approaches, contributing to the progress in this field, to obtain the maximum stability of formulations. Additionally, we critically analyze the limitations of lyophilization and discuss potential future directions. It addresses the challenges faced by researchers and suggests avenues for further research to overcome these limitations. In conclusion, this review is a valuable contribution to the understanding of the parameters involved in the freeze-drying of NPs. It will definitely aid future studies in obtaining lyophilized NPs with good quality and enhanced drug delivery and therapeutic benefits., (© 2023. Controlled Release Society.)

SD (solid dispersion) technology is one of the well-recognized solubility enhancement methods; but the use of versatile carriers in ASD (amorphous SD) to achieve the added advantage of modified release along with solubility improvement is an emerging area of exploration. Spray drying is a widely used technology with excellent scalability and product attributes. The SD carriers explored were Soluplus ® , possessing excellent solubilization properties that may enhance bioavailability and is suitable for innovative processing, and Gelucire 43/01, a lipid polymer utilized in a non-effervescent-based floating gastro-retentive DDS for the modified release of API. The CPPs of spray drying were screened during preliminary trials, and the formulation variables were optimized using a 3 2 Full Factorial Design. All nine batches were evaluated for % yield, % drug content, flow properties, floating behavior, saturation solubility, and in-vitro drug release in 0.1 N HCl. The optimized batch characterized based on DSC (differential scanning calorimetry) and PXRD (powder X-ray diffraction) confirmed the amorphous nature of entrapped drug in SDD (spray-dried dispersion). Particle size analysis and SEM (scanning electron microscopy) demonstrated micron size irregular shaped particles. Residual solvent analysis by GCMS-HS confirmed the elimination of organic solvents from SDD. The optimized batch was found stable after 6 months stability study as per ICH guidelines. In-vivo roentgenography study in New Zealand white rabbit showed the residence of SDD in gastric environment for sufficient time. The pharmacokinetic study was performed in male Sprague-Dawley rats to determine the bioavailability of developed SDD based product in fasting and fed conditions, and to compare the data with marketed Noxafil formulation. The current research is focused on the development of a novel ternary SDD (spray-dried dispersion)-based gastro-retentive formulation for an anti-fungal drug Posaconazole., (© 2023. Controlled Release Society.)

The challenge of low water solubility in pharmaceutical science profoundly impacts drug absorption and therapeutic effectiveness. Nanocrystals (NC), consisting of drug molecules and stabilizing agents, offer a promising solution to enhance solubility and control release rates. In the pharmaceutical industry, top-down techniques are favored for their flexibility and cost-effectiveness. However, increased solubility can lead to premature drug dissolution in the stomach, which is problematic due to the acidic pH or enzymes. Researchers are exploring encapsulating agents that facilitate drug release at customized pH levels as a valuable strategy to address this. This study employed wet milling and spray drying techniques to create encapsulated NC for delivering the drug to the intestinal tract using the model drug ivermectin (IVM). Nanosuspensions (NS) were efficiently produced within 2 h using NanoDisp ® , with a particle size of 198.4 ± 0.6 nm and a low polydispersity index (PDI) of 0.184, ensuring uniformity. Stability tests over 100 days at 4 °C and 25 °C demonstrated practical viability, with no precipitation or significant changes observed. Cytotoxicity evaluations indicated less harm to Caco-2 cells compared to the pure drug. Furthermore, the solubility of the NC increased by 47-fold in water and 4.8-fold in simulated intestinal fluid compared to the pure active compound. Finally, dissolution tests showed less than 10% release in acidic conditions and significant improvement in simulated intestinal conditions, promising enhanced drug solubility and bioavailability. This addresses a long-standing pharmaceutical challenge in a cost-effective and scalable manner., (© 2023. Controlled Release Society.)

Cyclodextrins (CDs) have been investigated as potential biopolymeric carriers that can form inclusion complexes with numerous bioactive ingredients. The inclusion of micronutrients (e.g. vitamins or minerals) into cyclodextrins can enhance their solubility and provide oxidative or thermal stability. It also enables the formulation of products with extended shelf-life. The designed delivery systems with CDs and their inclusion complexes including electrospun nanofibers, emulsions, liposomes, and hydrogels, show potential in enhancing the solubility and oxidative stability of micronutrients while enabling their controlled and sustained release in applications including food packaging, fortified foods and dietary supplements. Nano or micrometer-sized delivery systems capable of controlling burst release and permeation, or moderating skin hydration have been reported, which can facilitate the formulation of several personal and skin care products for topical or transdermal delivery of micronutrients. This review highlights recent developments in the application of CDs for the delivery of micronutrients, i.e. vitamins, iron, and iodine, which play key roles in the human body, emphasizing their existing and potential applications in the food, pharmaceuticals, and cosmeceuticals industries., (© 2024. Controlled Release Society.)

Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a common side effect of breast cancer therapy which causes oxidative stress and generation of reactive oxygen species (ROS). Ferulic acid (FA), a natural polyphenol, belongs to BCS class II is confirmed to have nootropic, neuroprotective and antioxidant effects. Here, we have developed FA solid dispersion (SD) in order to enhance its therapeutic potential against chemobrain. An amorphous ferulic acid loaded leucin solid dispersion (FA-Leu SD) was prepared by utilizing amino acid through spray-drying technique. The solid-state characterization was carried out via Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Additionally, in-vitro release studies and antioxidant assay were also performed along with in-vivo locomotor, biochemical and histopathological analysis. The physical properties showed that FA-Leu SD so formed exhibited spherical, irregular surface hollow cavity of along with broad melting endotherm as observed from FE-SEM and DSC results. The XRD spectra demonstrated absence of sharp and intense peaks in FA-Leu SD which evidenced for complete encapsulation of drug into carrier. Moreover, in-vitro drug release studies over a period of 5 h in PBS (pH 7.4) displayed a significant enhanced release in the first hr (68. 49 ± 5.39%) and in-vitro DPPH assay displayed greater antioxidant potential of FA in FA-Leu SD. Furthermore, the in-vivo behavioral findings of FA-Leu SD (equivalent to 150 mg/kg of free FA) exhibited positive results accompanied by in-vivo biochemical and molecular TNF-α showed a significant difference (p < 0.001) vis-à-vis DOX treated group upon DOX + FA-Leu SD. Additionally, histopathological analysis revealed neuroprotective effects of FA-Leu SD together with declined oxidative stress due to antioxidant potential of FA which was induced by anticancer drug doxorubicin (DOX). Overall, the above findings concluded that spray-dried FA-Leu SD could be useful for the treatment of chemotherapy induced cognitive impairment., (© 2024. Controlled Release Society.)

Inflammation, a crucial defense mechanism, must be rigorously regulated to prevent the onset of chronic inflammation and subsequent tissue damage. Specialized pro resolving mediators (SPMs) such as lipoxin A4 (LXA4) have demonstrated their ability to facilitate the resolution of inflammation by orchestrating a transition of M1 pro-inflammatory macrophages towards an anti-inflammatory M2 phenotype. However, the hydrophobic and chemically labile nature of LXA4 necessitates the development of a delivery system capable of preserving its integrity for clinical applications. In this study, two types of emulsion were formulated using different homogenization processes:mechanical overhead stirrer (MEB for blank Emulsion and MELX for LXA4 loaded-Emulsion) or Luer-lock syringes (SEB for blank Emulsion and SELX for LXA4 loaded-Emulsion)). Following characterization, including size and droplet morphology assessment by microscopy, the encapsulation efficiency (EE) was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). To exert control over LXA4 release, these emulsions were embedded within silanized hyaluronic acid hydrogels. A comprehensive evaluation, encompassing gel time, swelling, and degradation profiles under acidic, basic, and neutral conditions, preceded the assessment of LXA4 cumulative release using LC-MS/MS. Physicochemical results indicate that H-MELX (Mechanical overhead stirrer LXA4 Emulsion loaded-Hydrogel) exhibits superior efficiency over H-SELX (Luer-lock syringes LXA4 Emulsion loaded-Hydrogel). While both formulations stimulated pro-inflammatory cytokine secretion and promoted a pro-inflammatory macrophage phenotype, LXA4 emulsion-loaded hydrogels displayed a diminished pro-inflammatory activity compared to blank emulsion-loaded hydrogels. These findings highlight the biological efficacy of LXA4 within both systems, with H-SELX outperforming H-MELX in terms of efficiency. To the best of our knowledge, this is the first successful demonstration of the biological efficacy of LXA4 emulsion-loaded hydrogel systems on macrophage polarization. These versatile H-MELX and H-SELX formulations can be customized to enhance their biological activity making them promising tools to promote the resolution of inflammation in diverse clinical applications., (© 2024. Controlled Release Society.)

The food insecurity due to a vertical increase in the global population urgently demands substantial advancements in the agricultural sector and to identify sustainable affordable sources of nutrition, particularly proteins. Single-cell protein (SCP) has been revealed as the dried biomass of microorganisms such as algae, yeast, and bacteria cultivated in a controlled environment. Production of SCP is a promising alternative to conventional protein sources like soy and meat, due to quicker production, minimal land requirement, and flexibility to various climatic conditions. In addition to protein production, it also contributes to waste management by converting it into food and feed for both human and animal consumption. This article provides an overview of SCP production, including its benefits, safety, acceptability, and cost, as well as limitations that constrains its maximum use. Furthermore, this review criticizes the downstream processing of SCP, encompassing cell wall disruption, removal of nucleic acid, harvesting of biomass, drying, packaging, storage, and transportation. The potential applications of SCP, such as in food and feed as well as in the production of bioplastics, emulsifiers, and as flavoring agents for baked food, soup, and salad, are also discussed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microencapsulation is an alternative to increase the survival capacity of microorganisms, including Yarrowia lipolytica, a widely studied yeast that produces high-value metabolites, such as lipids, aromatic compounds, biomass, lipases, and organic acids. Thus, the present study sought to investigate the effectiveness of different wall materials and the influence of the addition of salts on the microencapsulation of Y. lipolytica, evaluating yield, relationship with cell stability, ability to survive during storage, and in vitro application of ruminant diets. The spray drying process was performed via atomization, testing 11 different compositions using maltodextrin (MD), modified starch (MS) and whey protein concentrate (WPC), Y. lipolytica (Y. lipo) cells, tripolyphosphate (TPP), and sodium erythorbate (SE). The data show a reduction in the water activity value in all treatments. The highest encapsulation yield was found in treatments using MD + TPP + Y. lipo (84.0%) and WPC + TPP + Y. lipo (81.6%). Microencapsulated particles showed a survival rate ranging from 71.61 to 99.83% after 24 h. The treatments WPC + Y. lipo, WPC + SE + Y. lipo, WPC + TPP + Y. lipo, and MD + SE + Y. lipo remained stable for up to 105 days under storage conditions. The treatment WPC + SE + Y. lipo (microencapsulated yeast) was applied in the diet of ruminants due to the greater stability of cell survival. The comparison between the WPC + SE + Y. lipo treatment, wall materials, and the non-microencapsulated yeast showed that the microencapsulated yeast obtained a higher soluble fraction, degradability potential, and release of nutrients., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

A highly porous additive, Neusilin ® , with high adsorption capability is investigated to improve bulk properties, hence processability of spray-dried amorphous solid dispersions (ASDs). Griseofulvin (GF) is applied as a model BCS class 2 drug in ASDs. Two grades of Neusilin ® , US2 (coarser) and UFL2 (finer), were used as additives to produce spray-dried amorphous composite (AC) powders, and their performance was compared with the resulting ASDs without added Neusilin ® . The resulting AC powders that included Neusilin ® had greatly enhanced flowability (flow function coefficient (FFC) > 10) comparable to larger particles (100 μm) yet had finer particle size (< 50 μm), hence retaining the advantage of fast dissolution rate of finer sizes. Dissolution results demonstrated that achieved GF supersaturation for AC powders with Neusilin ® was as high as 3 times that of crystalline GF concentration and was achieved within 30 min. In addition, 80% of drug was released within 4 min. The flowability improvement for AC powders with Neusilin ® was more significant as compared to spray-dried ASDs without Neusilin ® . Thus, the role of Neusilin ® in flowability improvement was evident, considering that spray-dried AC with Neusilin ® UFL2 has higher FFC than ASDs having a similar size. Lastly, the AC powders retained a fully amorphous state of GF after 3-month ambient storage. The overall results conveyed that the improved flowability and dissolution rate could outweigh the loss of drug loading resulted by addition of Neusilin ® ., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Nanocrystals and nanosuspensions have become realistic approaches to overcome the formulation challenges of poorly water-soluble drugs. They also represent a less-known but versatile platform for multiple therapeutic applications. They can be integrated into a broad spectrum of drug delivery systems including tablets, hydrogels, microneedles, microparticles, or even functionalized liposomes. The recent progresses, challenges, and opportunities in this field are gathered originally together with an informative case study concerning an itraconazole nanosuspension-in-hydrogel formulation. The translational aspects, historical and current clinical perspectives are also critically reviewed here to shed light on the incoming generation of nanocrystal formulations., (© 2024. The Author(s).)

Lactic acid bacteria (LAB) hold significant importance in diverse fields, including food technology, industrial biotechnology, and medicine. As basic components of starter cultures, probiotics, immunomodulators, and live vaccines, LAB cells resist a variety of stressors, including temperature fluctuations, osmotic and pH shocks, exposure to oxidants and ultraviolet radiation, substrate deprivation, mechanical damage, and more. To stay alive in these adversities, LAB employ a wide range of stress response strategies supported by various mechanisms, for example rearrangement of metabolism, expression of specialized biomolecules (e.g., chaperones and antioxidants), exopolysaccharide synthesis, and complex repair and regulatory systems. LAB can coordinate responses to various stressors using global regulators. In this review, we summarize current knowledge about stress response strategies used by LAB and consider mechanisms of response to specific stressful factors, supported by illustrative examples. In addition, we discuss technical approaches to increase the stress resistance of LAB, including pre-adaptation, genetic modification of strains, and adjustment of cultivation conditions. A critical analysis of the recent findings in this field augments comprehension of stress tolerance mechanisms in LAB, paving the way for prospective research directions with implications in fundamental and practical areas., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study compares rivaroxaban-loaded polymeric microsphere systems with three types of surface microstructure. Three types of polymeric microspheres loaded with rivaroxaban were fabricated using a spray-drying technique: solvent-evaporated, surface-attached, and solvent-wet microspheres, depending on whether the drug and additives used are soluble in the solvent. The solvent-evaporated and surface-attached microspheres had a rivaroxaban/polyvinylpyrrolidone/sodium lauryl sulfate (SLS) weight ratio of 1/0.25/2.2, and the solvent-wetted microspheres contained rivaroxaban/polyvinyl alcohol/SLS in equal weight ratio (1/0.25/2). The physicochemical properties of the microspheres were evaluated using scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and particle size distribution analysis. The aqueous solubility and dissolution rate of rivaroxaban in the three types of microspheres were compared to those of the drug powder. The solvent-evaporated, surface-attached, and solvent-wetted microspheres were approximately 208, 140, and 172 times as soluble as the drug powder, and the final dissolution rate (120 min) was approximately 5, 2, and 4 times that of the drug powder, respectively. In addition, the oral bioavailability increased by approximately 2, 1.3, and 1.6 times compared to that of the drug powder (area under drug concentration-time curve: 2101.3 ± 314.8, 1325.2 ± 333.3, and 1664.0 ± 102.6 h·ng/mL, respectively). Finally, the solvent-evaporated microspheres showed the greatest improvement (solvent evaporating microspheres > solvent wetted microspheres > surface-attached microspheres ≥ drug powder). Therefore, the solvent-evaporated microspheres may represent a novel oral dosage form that improves the oral bioavailability of rivaroxaban, a poorly soluble drug., (© 2023. Controlled Release Society.)

Vaccines are the cornerstone of world health. The majority of vaccines are formulated as injectable products, facing the drawbacks of cold chain transportation, needle-stick injuries, and primary systemic immunity. Inhalable vaccines exhibited unique advantages due to their small dose, easy to use, quick effect, and simultaneous induction of mucosal and systemic responses. Facing global pandemics, especially the coronavirus disease 2019 (COVID-19), a majority of inhalable vaccines are in preclinical or clinical trials. A better understanding of advanced delivery technologies of inhalable vaccines may provide new scientific insights for developing inhalable vaccines. In this review article, detailed immune mechanisms involving mucosal, cellular, and humoral immunity were described. The preparation methods of inhalable vaccines were then introduced. Advanced nanotechnologies of inhalable vaccines containing inhalable nucleic acid vaccines, inhalable adenovirus vector vaccines, novel adjuvant-assisted inhalable vaccines, and biomaterials for inhalable vaccine delivery were emphatically discussed. Meanwhile, the latest clinical progress in inhalable vaccines for COVID-19 and tuberculosis was discussed., (© 2023. Controlled Release Society.)

Lung cancer is the leading cause of cancer-related deaths worldwide, resulting in the highest mortality rates among both men and women with respect to all other types of cancer. Difficulties in treating lung cancer arise from late-stage diagnoses and tumor heterogeneity and current treatment involves a combination of chemotherapeutics, surgery, and radiation. Chemotherapeutics administered systemically can lead to undesirable side effects and severe off-site toxicity. For example, chronic administration of the chemotherapeutic doxorubicin (DOX) leads to cardiotoxicity, thereby limiting its long-term use. Systemic administration of the highly lipophilic molecule paclitaxel (PTX) is hindered by its water solubility, necessitating the use of solubilizing agents, which can induce side effects. Thus, in this investigation, formulations consisting of spray-dried microparticles (MP) containing DOX and PTX were produced to be administered as dry powder aerosols directly to the lungs. Acetalated dextran (Ac-Dex) was used as the polymer in these formulations, as it is a biocompatible and biodegradable polymer that exhibits pH-responsive degradation. Solid-state characterization revealed that DOX and PTX remained in solubility favoring amorphous states in the MP formulations and that both drugs remained thermally stable throughout the spray drying process. In vitro release studies demonstrated the pH sensitivity of the formulations due to the use of Ac-Dex, as well as the release of both therapeutics over the course of at least 48 h. In vitro aerosol dispersion studies demonstrated that both formulations exhibited suitable aerosol dispersion properties for deep lung delivery., (© 2024. The Author(s).)

This research aimed to explore the possibilities of Eudragit S100 (ES100) and sodium alginate as carriers for tenofovir disoproxil fumarate (TDF) in the female genital tract. Alginate and alginate-ES100 nanoparticles were prepared using the ionic gelation and emulsion/gelation complexation method, respectively. The nanocarriers were tested using morphological, physicochemical, in vitro drug release, and cytotoxicity analyses. In SEM and TEM images, the presence of spherical and uniformly distributed nanoparticles was revealed. The FTIR spectrum showed that alginate and calcium chloride interacted due to ionic bonds linking divalent calcium ions and the -COO- of alginate groups. Alginate and ES100 interacted via the ester C=O amide stretching. The results obtained from XRD and DSC, on the other hand, revealed a favorable interaction between sodium alginate and ES100 polymers, as evidenced by the crystallization peaks observed. Under experimental design analysis and optimization, overall size distribution profiles ranged from 134.9 to 228.0 nm, while zeta potential results showed stable nanoparticles (-17.8 to -38.4 MV). The optimal formulation exhibited a maximum cumulative in vitro release of 72% (pH 4.2) up to 96 h. The cytotoxicity tests revealed the safety of TDF-loaded nanoparticles on vaginal epithelial cells at concentrations of 0.025 mg/mL, 0.5 mg/mL, and 1 mg/mL for 72 h. These results indicated that alginate-ES100 nanoparticles have the potential to preserve and sustain the release of the TDF drug in the FGT. The future goal is to develop a low-dose non-toxic microbicide that can be administered long term in the vagina to cater to both pregnant and non-pregnant HIV patients., (© 2023. The Author(s).)

Amorphous solid dispersions enhance solubility and oral bioavailability of poorly water-soluble drugs. The escalating number of drugs with poor aqueous solubility, poor dissolution, and poor oral bioavailability is an unresolved problem that requires adequate interventions. This review article highlights recent solubility and bioavailability enhancement advances using amorphous solid dispersions (ASDs). The review also highlights the mechanism of enhanced dissolution and the challenges faced by ASD-based products, such as stability and scale-up. The role of process analytical technology (PAT) supporting continuous manufacturing is highlighted. Accurately predicting interactions between the drug and polymeric carrier requires long experimental screening methods, and this is a space where computational tools hold significant potential. Recent advancements in data science, computational tools, and easy access to high-end computation power are set to accelerate ASD-based research. Hence, particular emphasis has been given to molecular modeling techniques that can address some of the unsolved questions related to ASDs. With the advancement in PAT tools and artificial intelligence, there is an increasing interest in the continuous manufacturing of pharmaceuticals. ASDs are a suitable option for continuous manufacturing, as production of a drug product from an ASD by direct compression is a reality, where the addition of multiple excipients is easy to avoid. Significant attention is necessary for ongoing clinical studies based on ASDs, which is paving the way for the approval of many new ASDs and their introduction into the market., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The present study aims to develop carboplatin injectable microspheres using spray-drying technology. The optimized powdered microspheres (MS-19-ST2) were morphologically spherical, with a 1.795 μm particle size and good micromeritic properties. Under normal temperature conditions, the MS-19-ST2 formulation exhibited a sustained release behaviour following first-order drug release kinetics with no compatibility issues with aluminium syringes. Furthermore, MS-19-ST2 formulation outperformed its commercial counterpart in terms of in vivo pharmaco-kinetics and -dynamics (MRT-13.9 ± 0.9 h, T 1/2 -8.2 ± 0.3 h, tumour inhibition-74.5%). Additionally, the MS-19-ST2 formulation was much safer to use than its commercial counterpart, as observed from the results of ex vivo (haemolytic, MTT, and cell apoptosis assays) and in vivo (14-day acute and 28-day sub-acute) toxicity studies. The above results confirm the MS-19-ST2 formulation as a good candidate to commercialize carboplatin in a powdered microsphere form (stable for 24 h after reconstitution) with improved pharmacokinetics, therapeutic, and toxicity profile., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Cannabidiol (CBD), a non-psychoactive constituent of Cannabis, has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within nanoparticles of a highly hydrophobic poly(ethylene glycol)-b-poly(epsilon-caprolactone) block copolymer produced by a simple and reproducible nanoprecipitation method. The encapsulation efficiency is ~ 100% and the CBD loading 11% w/w (high performance liquid chromatography). CBD-loaded nanoparticles show a monomodal size distribution with sizes of up to 100 nm (dynamic light scattering), a spherical morphology, and the absence of CBD crystals (high resolution-scanning electron microscopy and cryogenic-transmission electron microscopy) which is in line with a very efficient nanoencapsulation. Then, the CBD release profile from the nanoparticles is assessed under gastric- and intestine-like conditions. At pH 1.2, only 10% of the payload is released after 1 h. Conversely, at pH 6.8, a release of 80% is recorded after 2 h. Finally, the oral pharmacokinetics is investigated in rats and compared to a free CBD suspension. CBD-loaded nanoparticles lead to a statistically significant ~ 20-fold increase of the maximum drug concentration in plasma (C max ) and a shortening of the time to the C max (t max ) from 4 to 0.3 h, indicating a more complete and faster absorption than in free form. Moreover, the area-under-the-curve (AUC), a measure of oral bioavailability, increased by 14 times. Overall results highlight the promise of this simple, reproducible, and scalable nanotechnology strategy to improve the oral performance of CBD with respect to common oily formulations and/or lipid-based drug delivery systems associated with systemic adverse effects., (© 2023. Controlled Release Society.)

The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's central composite design (CCD), and evaluated for pharmaceutical performance and in vivo anticancer activity against melanoma (B16F10)-bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and high-performance thin layer chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in vitro dissolution study revealed excellent wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in vivo oral bioavailability of SD reflected a significant (p < 0.05) improvement in bioavailability (F rel  = 188.765%) as compared to plain extract. The in vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC., (© 2023. Controlled Release Society.)