Exploring conventional and emerging dehydration technologies for slurry/liquid food matrices and their impact on porosity of powders: A comprehensive review.

The contribution of dehydration to the growing market of food powders from slurry/liquid matrices is inevitable. To overcome the challenges posed by conventional drying technologies, several innovative approaches have emerged. However, industrial implementation is limited due to insufficient information on the best-suited drying technologies for targeted products. Therefore, this review aimed to compare various conventional and emerging dehydration technologies (such as active freeze, supercritical, agitated thin-film, and vortex chamber drying) based on their fundamental principles, potential applications, and limitations. Additionally, this article reviewed the effects of drying technologies on porosity, which greatly influence the solubility, rehydration, and stability of powder. The comparison between different drying technologies enables informed decision-making in selecting the appropriate one. It was found that active freeze drying is effective in producing free-flowing powders, unlike conventional freeze drying. Vortex chamber drying could be considered a viable alternative to spray drying, requiring a compact chamber than the large tower needed for spray drying. Freeze-dried, spray freeze-dried, and foam mat-dried powders exhibit higher porosity than spray-dried ones, whereas supercritical drying produces nano-porous interconnected powders. Notably, several factors like glass transition temperature, drying technologies, particle aggregation, agglomeration, and sintering impact powder porosity. However, some binders, such as maltodextrin, sucrose, and lactose, could be applied in controlled agglomeration to enhance powder porosity. Further investigation on the effect of emerging technologies on powder properties and their commercial feasibility is required to discover their potential in liquid drying. Moreover, utilizing clean-label drying ingredients like dietary fibers, derived from agricultural waste, presents promising opportunities.

General aspects of powder rheology applied to pharmaceutical formulations.

Powder flowability is crucial in the pharmaceutical industry, strongly affecting solid dosage processing. Classical experimental techniques offer straightforward results for the rapid screening of formulations during development. However, they fail to describe powder properties under consolidation. Complex techniques, such as shear cell, accurately assess fundamental properties of particulate samples under realistic conditions, enabling prediction of their flow. Ideally, a combination of experimental methods should be used to comprehensively assess powder flowability, ensuring consistent product performance. Moreover, researchers and analytical scientists must have a solid understanding of powder rheology to effectively interpret acquired data. In this review, common techniques, experimental protocols, and typical results observed in a pharmaceutical context are described.

The Fast Quantification of Vitamin B12 in Milk Powder by High-Performance Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry.

This study presents a new technique for determining vitamin B12 in milk powder using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). We used ultrasonics with potassium ferrocyanide and zinc acetate solutions to extract the samples. 59Co was employed as the analytical target for cyanocobalamin. It was separated using a Phenomenex Luna 5 µm C18 (250 × 4.6 mm) chromatographic column with a mobile phase consisting of 1.6 mmol/L EDTA and 0.4 mmol/L KH2PO4 in a 60% v/v methanol solution (pH = 4.0). The sample has an excellent separating degree for free cobalt and cyanocobalamin, and isocratic elution can be finished within 4.0 min. To eliminate the matrix interference due to the presence of milk powder, we applied collision mode (KED). The linear range of cyanocobalamine ranged from 1.0 µg/L to 20 µg/L, with correlation coefficients (r2) of 0.9994. The limit of detection (LOD) was 0.63 µg/kg, and the limit of quantitation (LOQ) was 2.11 µg/kg. The mean recoveries were in the range of 87.4-103.6%. The accuracy and precision of the developed method are well suited for the fast quantification of the trace vitamin B12 in milk powder.

Detection and quantification of cocoa powder adulteration using Vis-NIR spectroscopy with chemometrics approach.

The rising demand for cocoa powder has resulted in an upsurge in market prices, leading to the emergence of adulteration practices aimed at achieving economic benefits. This study aimed to detect and quantify cocoa powder adulteration using visible and near-infrared spectroscopy (Vis-NIRS). The adulterants used in this study were powdered carob, cocoa shell, foxtail millet, soybean, and whole wheat. The NIRS data could not be resolved using Savitzky-Golay smoothing. Nevertheless, the application of a random forest and support vector machine successfully classified the samples with 100% accuracy. Quantification of adulteration using partial least squares (PLS), Lasso, Ridge, elastic Net, and RF regressions provided R2 higher than 0.96 and root mean square error <2.6. Coupling PLS with the Boruta algorithm produced the most reliable regression model (R2 = 1, RMSE = 0.0000). Finally, an online application was prepared to facilitate the determination of adulterants in the cocoa powder.

Effect of (multi pin) atmospheric cold plasma treatment on curcumin extraction and investigating phytochemicals, antioxidants, physical and morphological properties of turmeric (Curcuma longa L.) powder.

This investigation was focused on the impact of cold plasma (CP) on the extraction of curcumin and bioactive compounds of turmeric powder (TP). TP was treated with CP at different applied voltages (10, 20, and 30 kV), with various exposure times (10, 20, and 30 min). The curcumin content was highest at 30 kV for 10 min with a yield of 46.49 mg/g of TP. Total phenols significantly (p < 0.05) enhanced from 163.91 to 360.78 mg GAE/g DW accompanied by a remarkable 16% increment in total flavonoids, paralleled by a 26% increment in antioxidants as of control. Nuclear magnetic resonance spectra justified the extraction of curcuminoids. Moreover, micrographs displayed cell lysis in the treated powder. CP has exhibited a positive effect on surface colour parameters and thermal properties of TP. Overall, CP technology can be tailored for better curcumin extraction and the enhancement of phytochemicals.

Conformation-Activity Mechanism of Alcalase Hydrolysis for Reducing In Vitro Allergenicity of Instant Soy Milk Powder.

Effective reduction of the allergenicity of instant soy milk powder (ISMP) is practically valuable for expanding its applications. This study optimized the enzymolysis technology of ISMP using single-factor experiments and response surface methodology, combined serological analysis, cellular immunological models, bioinformatics tools, and multiple spectroscopy techniques to investigate the effects of alcalase hydrolysis on allergenicity, spatial conformation, and linear epitopes of ISMP. Under the optimal process, special IgE and IgG1 binding abilities and allergenic activity to induce cell degranulation of alcalase-hydrolyzed ISMP were reduced by (64.72 ± 1.76)%, (56.79 ± 3.72)%, and (73.3 ± 1.19)%, respectively (P < 0.05). Moreover, the spatial conformation of instant soy milk powder hydrolysates (ISMPH) changed, including decreased surface hydrophobicity, a weaker peak of amide II band, lower contents of α-helix and ß-sheet, and an enhanced content of random coil. Furthermore, the linear epitopes of major soy allergens, 9 from glycinin and 13 from ß-conglycinin, could be directionally disrupted by alcalase hydrolysis. Overall, the structure-activity mechanism of alcalase hydrolysis to reduce ISMP allergenicity in vitro was preliminarily clarified. It provided a new research direction for the breakthrough in the desensitization of ISMP and a theoretical basis for revealing the potential mechanism of alcalase enzymolysis to reduce the allergenicity of ISMP.

Manufacturing process transfer to a 30 kg/h continuous direct compression line with real-time composition monitoring.

Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes. The present work reports a successful transfer of an existing drug product from batch to continuous manufacturing process without changing the formulation. A key step was continuous powder blending, whose design and operating parameters including weir type, agitation rate, dynamic hold-up and residence time were systematically investigated with respect to process repeatability. A NIR-based multivariate data model for in-line composition monitoring has been developed and validated against an existing quality control method for measuring tablet content uniformity. A continuous manufacturing long-run with a throughput of 30 kg/h (approx. 128,000 tablets per hour), uninterrupted for 320 min, has been performed to test and validate the multivariate data model as well as the batch to continuous process transfer. The final disintegration and dissolution properties of tablets manufactured by the continuous process were found to be equivalent to those manufactured by the original batch process.

Critical attributes of fine excipient materials in carrier-based dry powder inhalation formulations: The particle shape and surface properties.

The potential of fine excipient materials to improve the aerodynamic performance of carrier-based dry powder inhalation (DPI) formulations is well acknowledged but not fully elucidated. To improve the understanding of this potential, we studied two fine excipient materials: micronized lactose particles and silica microspheres. Inhalation formulations, each composed of a coarse lactose carrier, one of the two fine excipient materials (0.0-15.0 % w/w), and a spray-dried drug (fluticasone propionate) material (1.5 % w/w) were prepared. The physical structure, the flow behavior, the aerosolization behavior, and the aerodynamic performance of the formulations were studied. The two fine excipient materials similarly occupied carrier surface macropores. However, only the micronized lactose particles formed agglomerates and appeared to increase the tensile strength of the formulations. At 2.5 % w/w, the two fine excipient materials similarly improved drug dispersibility, whereas at higher concentrations, the micronized lactose material was more beneficial than the silica microspheres. The findings suggest that fine excipient materials improve drug dispersibility from carrier-based DPI formulations at low concentrations by filling carrier surface macropores and at high concentrations by forming agglomerates and/or enforcing fluidization. The study emphasizes critical attributes of fine excipient materials in carrier-based DPI formulations.

UV-VIS imaging-based investigation of API concentration fluctuation caused by the sticking behaviour of pharmaceutical powder blends.

Surface powder sticking in pharmaceutical mixing vessels poses a risk to the uniformity and quality of drug formulations. This study explores methods for evaluating the amount of pharmaceutical powder mixtures adhering to the metallic surfaces. Binary powder blends consisting of amlodipine and microcrystalline cellulose (MCC) were used to investigate the effect of the mixing order on the adherence to the vessel wall. Elevated API concentrations were measured on the wall and within the dislodged material from the surface, regardless of the mixing order of the components. UV imaging was used to determine the particle size and the distribution of the API on the metallic surface. The results were compared to chemical maps obtained by Raman chemical imaging. The combination of UV and VIS imaging enabled the rapid acquisition of chemical maps, covering a substantially large area representative of the analysed sample. UV imaging was also applied in tablet inspection to detect tablets that fail to meet the content uniformity criteria. The results present powder adherence as a possible source of poor content uniformity, highlighting the need for 100% inspection of pharmaceutical products to ensure product quality and safety.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part II: Exploring each protein stabilizer effect.

Despite extensive research in spray drying of biopharmaceuticals, identifying the optimal formulation composition and process conditions to minimize the various stresses a biopharmaceutical undergoes during this drying process. The current study extends previous research on investigating how spray drying processing and solution composition can affect the stability of monoclonal antibodies (mAbs) in reconstituted solutions for subcutaneous injections. The decoupling process stresses on a model mAb (mAb-A) compared to the effect of coupled spray-drying stresses revealed that excipients and protein concentration had a more pronounced effect on stabilizing mAb-A against shear and thermal/dehydration stresses than spray drying operating conditions. These results prompted the continuation of the study, with the aim to investigate in greater depth the effect of mAb-A concentration in the formulation designated to spray-drying and then the effect of type and the concentration of individual excipients (sugars, amino acids and surfactants). The outcomes of this investigation suggest that a general increase in the concentration of excipients, particularly surfactants, correlates with a reduction in aggregation and turbidity observed in the reconstituted spray-dried mAb-A powders. These results, contribute to the identification of a suitable composition for a spray-dried mAb-A powder that ensures robust stability of the protein in reconstituted solutions intended for subcutaneous injection. This valuable insight has important implications for advancing the development of pharmaceutical formulations with enhanced stability and efficacy.

Metabolomic analysis reveals the effect of ultrasonic-microwave pretreatment on flavonoids in tribute Citrus powder.

In this study, the ultrasonic-microwave pretreatment was defined as a processing technology in the production of tribute citrus powder, and it could increase the flavonoid compounds in the processing fruit powder. A total of 183 upregulated metabolites and 280 downregulated metabolites were obtained by non-targeted metabolomics, and the differential metabolites was mainly involved in the pathways of flavonoid biosynthesis, flavone and flavonol biosynthesis. A total of 8 flavonoid differential metabolites were obtained including 5 upregulated metabolites (6"-O-acetylglycitin, scutellarin, isosakuranin, rutin, and robinin), and 3 downregulated metabolites (astragalin, luteolin, and (-)-catechin gallate) by flavonoids-targeted metabolomics. The 8 flavonoid differential metabolites participated in the flavonoid biosynthesis pathways, flavone and flavonol biosynthesis pathways, and isoflavonoid biosynthesis pathways. The results provide a reference for further understanding the relationship between food processing and food components, and also lay a basis for the development of food targeted-processing technologies.

Tableting behavior of freeze and spray-dried excipients in pharmaceutical formulations.

Most of biopharmaceuticals, in their liquid form, are prone to instabilities during storage. In order to improve their stability, lyophilization is the most commonly used drying technique in the pharmaceutical industry. In addition, certain applications of biopharmaceutical products can be considered by oral administration and tablets are the most frequent solid pharmaceutical dosage form used for oral route. Thus, the tableting properties of freeze-dried products used as cryo and lyoprotectant could be a key element for future pharmaceutical developments and applications. In this study, we investigated the properties that might play a particular role in the specific compaction behavior of freeze-dried excipients. The tableting properties of freeze-dried trehalose, lactose and mannitol were investigated and compared to other forms of these excipients (spray-dried, commercial crystalline and commercial crystalline milled powders). The obtained results showed a specific behavior in terms of compressibility, tabletability and brittleness for the amorphous powders obtained after freeze-drying. The comparison with the other powders showed that this specific tableting behavior is linked to both the specific texture and the physical state (amorphization) of these freeze-dried powders.

A new insight into the mechanism of the tabletability flip phenomenon.

Tabletability is an outcome of interparticulate bonding area (BA) - bonding strength (BS) interplay, influenced by the mechanical properties, size and shape, surface energetics of the constituent particles, and compaction parameters. Typically, a more plastic active pharmaceutical ingredient (API) exhibits a better tabletability than less plastic APIs due to the formation of a larger BA during tablet compression. Thus, solid forms of an API with greater plasticity are traditionally preferred if other critical pharmaceutical properties are comparable. However, the tabletability flip phenomenon (TFP) suggests that a solid form of an API with poorer tabletability may exhibit better tabletability when formulated with plastic excipients. In this study, we propose another possible mechanism of TFP, wherein softer excipient particles conform to the shape of harder API particles during compaction, leading to a larger BA under certain pressures and, hence, better tabletability. In this scenario, the BA-BS interplay is dominated by BA. Accordingly, TFP should tend to occur when API solid forms are formulated with a soft excipient. We tested this hypothesis by visualizing the deformation of particles in a model compressed tablet by nondestructive micro-computed tomography and by optical microscopy when the particles were separated from the tablet. The results confirmed that soft particles wrapped around hard particles at their interfaces, while an approximately flat contact was formed between two adjacent soft particles. In addition to the direct visual evidence, the BA-dominating mechanism was also supported by the observation that TFP occurred in the p-aminobenzoic acid polymorph system only when mixed with a soft excipient.

Synergistic combination of antimicrobial peptide and isoniazid as inhalable dry powder formulation against multi-drug resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has posed a serious threat to global public health, and antimicrobial peptides (AMPs) have emerged to be promising candidates to tackle this deadly infectious disease. Previous study has suggested that two AMPs, namely D-LAK120-A and D-LAK120-HP13, can potentiate the effect of isoniazid (INH) against mycobacteria. In this study, the strategy of combining INH and D-LAK peptide as a dry powder formulation for inhalation was explored. The antibacterial effect of INH and D-LAK combination was first evaluated on three MDR clinical isolates of Mycobacteria tuberculosis (Mtb). The minimum inhibitory concentrations (MICs) and fractional inhibitory concentration indexes (FICIs) were determined. The combination was synergistic against Mtb with FICIs ranged from 0.25 to 0.38. The INH and D-LAK peptide at 2:1 mole ratio (equivalent to 1: 10 mass ratio) was identified to be optimal. This ratio was adopted for the preparation of dry powder formulation for pulmonary delivery, with mannitol used as bulking excipient. Spherical particles with mass median aerodynamic diameter (MMAD) of around 5 µm were produced by spray drying. The aerosol performance of the spray dried powder was moderate, as evaluated by the Next Generation Impactor (NGI), with emitted fraction and fine particle fraction of above 70 % and 45 %, respectively. The circular dichroism spectra revealed that both D-LAK peptides retained their secondary structure after spray drying, and the antibacterial effect of the combination against the MDR Mtb clinical isolates was successfully preserved. The combination was found to be effective against MDR Mtb isolates with KatG or InhA mutations. Overall, the synergistic combination of INH with D-LAK peptide formulated as inhaled dry powder offers a new therapeutic approach against MDR-TB.

Triple combination dry powder formulation of pretomanid, moxifloxacin, and pyrazinamide for treatment of multidrug-resistant tuberculosis.

Both latent and multidrug-resistant tuberculosis (TB) have been causing significant concern worldwide. A novel drug, pretomanid (PA-824), has shown a potent bactericidal effect against both active and latent forms of Mycobacterium tuberculosis (MTb) and a synergistic effect when combined with pyrazinamide and moxifloxacin. This study aimed to develop triple combination spray dried inhalable formulations composed of antitubercular drugs, pretomanid, moxifloxacin, and pyrazinamide (1:2:8 w/w/w), alone (PaMP) and in combination with an aerosolization enhancer, L-leucine (20 % w/w, PaMPL). The formulation PaMPL consisted of hollow, spherical, dimpled particles (<5 µm) and showed good aerosolization behaviour with a fine particle fraction of 70 %. Solid-state characterization of formulations with and without L-leucine confirmed the amorphous nature of moxifloxacin and pretomanid and the crystalline nature of pyrazinamide with polymorphic transformation after the spray drying process. Further, the X-ray photoelectron spectroscopic analysis revealed the predominant surface composition of L-leucine on PaMPL dry powder particles. The dose-response cytotoxicity results showed pyrazinamide and moxifloxacin were non-toxic in both A549 and Calu-3 cell lines up to 150 µg/mL. However, the cell viability gradually decreased to 50 % when the pretomanid concentration increased to 150 µg/mL. The in vitro efficacy studies demonstrated that the triple combination formulation had more prominent antibacterial activity with a minimum inhibitory concentration (MIC) of 1 µg/mL against the MTb H37Rv strain as compared to individual drugs. In conclusion, the triple combination of pretomanid, moxifloxacin, and pyrazinamide as an inhalable dry powder formulation will potentially improve treatment efficacy with fewer systemic side effects in patients suffering from latent and multidrug-resistant TB.

Effect of cinnamon powder on quality attributes and off-flavor in fried chicken drumsticks made from long-term thawed Korean native chicken.

The effect of cinnamon powder on the quality and mitigation of off-flavor in fried chicken drumsticks made from long-term thawed Korean native chicken (Woorimatdag No. 1, WRMD1) was investigated. The WRMD1 drumsticks were categorized into 5 groups: conventional thawing (16 h, CT), long-term thawing (48 h, LT), cinnamon powder added into 'LT' as marinade (0.03%, CM) or incorporated into the batter (1.35%, CB), and long-term thawing with cinnamon powder incorporated both in the marinade and batter (0.03% + 1.35%, CMB). The crude fat content was significantly higher in the CT and CMB than that of the CB. The CM, CB, and CMB showed significantly lower levels of 2-thiobarbituric acid reactive substance compared with the CT and LT. The predominant fatty acids in all treatments were C18:1n9, C18:2n6, and C16:0. The LT displayed lower total unsaturated fatty acid content than the CT (P < 0.05). The CM effectively decreased lipid oxidative volatiles, such as 1-octanol, 1-octen-3-ol, and 2-octen-1-ol, (E), in the LT (P < 0.05). Both the CM and CB showed an inclination to increase specific pyrazines associated with pleasant notes compared with the LT, and showed higher levels of pyrazines, such as pyrazine, 2-ethyl-6-methyl-, and pyrazine, 3-ethyl-2,5-dimethyl-, than those of the CMB (P < 0.05). The CM contained higher levels of 2,3-butanedione when compared with the other groups (P < 0.05). Multivariate analysis demonstrated that cinnamon had an effect in discriminating the treatment groups with cinnamon addition from both the CT and LT, whereas the CM, CB, and CMB formed distinct clusters. The CM and CMB received significantly higher aroma scores from panelists in comparison to the other groups. These findings suggest that the CM (0.03% cinnamon powder) can be used to enhance the aroma in fried WRMD1 drumsticks by reducing or masking the off-flavor volatiles associated with long-term thawing.

Fermented bamboo powder activates gut odorant receptors, and promotes intestinal health and growth performance of dwarf yellow-feathered broiler chickens.

The present study investigated the effects of fermented bamboo powder (FPB) on gut odorant receptors (OR), intestinal health, and growth performance of dwarf yellow-feathered broiler chickens. Six hundred (600) healthy 1-day-old chicks were randomly assigned into 2 groups, with 10 replicates consisting of 30 chicks each. The control group was fed a basal diet. In contrast, the experimental group was fed the basal diet supplemented with 1.0, 2.0, 4.0, and 6.0 g/kg FBP for 4 different phases, namely phase I (1-22 d), phase II (23-45 d), phase III (46-60 d), and phase IV (61-77 d), respectively. The first 2 phases were considered pretreatment (0-45 d), and the remaining were experimental (46-77 d) periods. The tissue samples were collected from phase IV. The chickens in the FBP supplementation group exhibited a significant increment in body weight gain, evisceration yield, breast, thigh, and liver weight, while also experiencing a decrease in the FCR (P < 0.05). Furthermore, the villus height, crypt depth, and villus area exhibited significant increases in the FBP group (P < 0.01). Additionally, the secretion levels of gut hormones such as glucagon-like peptide-1, peptide YY, cholecystokinin, and 5-hydroxytryptamine were significantly elevated in the serum, duodenum, jejunum, and ileum tissues in the FBP group (P < 0.05). The results of qRT-PCR indicated that ORs had responsive expression in the gizzard, proventriculus, and small intestine of chickens when fed with the FBP diet (P < 0.05). Notably, the expression of the COR1, COR2, COR4, COR6, COR8, COR9, OR52R1, OR51M1, OR1F2P, OR5AP2, and OR14J1L112 genes was stronger in the small intestines compared to the gizzard and proventriculus. In conclusion, these results suggest that the FPB plays a crucial role in growth performance, activation of ORs, and gut health and development.

Effectiveness of cork and pine bark powders as biosorbents for potentially toxic elements present in aqueous solution.

Cork oak and pine bark, two of the most prolific byproducts of the European forestry sector, were assessed as biosorbents for eliminating potentially toxic elements (PTEs) from water-based solutions. Our research suggests that bioadsorption stands out as a viable and environmental eco-friendly technology, presenting a sustainable method for the extraction of PTEs from polluted water sources. This study aimed to evaluate and compare the efficiency of cork powder and pine bark powder as biosorbents. Specifically, the adsorption of Fe, Cu, Zn, Cd, Ni, Pb and Sn at equilibrium were studied through batch experiments by varying PTEs concentrations, pH, and ionic strength. Results from adsorption-desorption experiments demonstrate the remarkable capacity of both materials to retain the studied PTE. Cork powder and pine bark powder exhibited the maximum retention capacity for Fe and Cd, while they performed poorly for Pb and Sn, respectively. Nevertheless, pine bark showed a slightly lower retention capacity than cork. Increasing the pH resulted in cork showing the highest adsorption for Zn and the lowest for Sn, while for pine bark, Cd was the most adsorbed, and Sn was the least adsorbed, respectively. The highest adsorption of both materials occurred at pH 3.5-5, depending on the PTE tested. The ionic strength also influenced the adsorption of the various PTEs for both materials, with decreased adsorption as ionic strength increased. The findings suggest that both materials could be effective for capturing and eliminating the examined PTEs, albeit with different efficiencies. Remarkably, pine bark demonstrated superior adsorption capabilities, which were observed to vary based on the specific element and the experimental conditions. These findings contribute to elucidating the bio-adsorption potential of these natural materials, specifically their suitability in mitigating PTEs pollution, and favoring the recycling and revalorization of byproducts that might otherwise be considered residue.

Trace polymer coated clarithromycin spherulites: Formation mechanism, improvement in pharmaceutical properties and development of high-drug-loading direct compression tablets.

Clarithromycin (CLA) is a high dose antibiotic drug exhibiting poor flowability and tabletability, making the tablet development challenging. This study aims to develop spherulitic CLA by introducing trace amount of polymer in crystallization solution. Its formation mechanism, physicochemical properties and potential for the direct compression (DC) tablets development were also investigated. Morphological analyses and the in situ observation on crystallization process revealed that the CLA spherulites are formed by fractal branching growth from both sides of the threadlike precursor fibers. 1H NMR analysis and nucleation time monitoring indicated that the existence of hydroxypropyl cellulose in solution slowed down the crystal nucleation and growth rate by forming hydrogen bonding interactions with CLA molecules, making the system maintain high supersaturation, providing high driving forces for CLA spherulitic growth. In comparison to commercial CLA, the CLA spherulites exhibit profoundly improved flowability, tabletability and dissolution behaviors. XPS, contact angle and Raman mapping analysis confirmed the presence of a thin HPC layer on the surfaces and interior of CLA spherulitic particles, resulting in increasing powder plasticity, interparticulate bonding strength and powder wettability, thus better tabletability and dissolution performances. The improved flowability and tabletability of CLA spherulites also enabled the successful development of DC tablet formulation with a high CLA loading (82.8 wt%) and similar dissolution profiles to reference listed drug. This study provides a novel solid form of CLA with superior manufacturability for further development.

Co-spray dried inhalable composite powders of ciprofloxacin and alginate oligosaccharide as anti-biofilm therapy.

The treatment of chronic respiratory infections caused by biofilm formation are extremely challenging owing to poor drug penetration into the complex biofilm structure and high drug resistance. Local delivery of an antibiotic together with a non-antibiotic adjuvant to the lungs could often enhance the therapeutic responses by targeting different bacterial growth pathways and minimizing drug resistance. In this study, we designed new inhalable dry powders containing ciprofloxacin (CIP) and OligoG (Oli, a low-molecular-weight alginate oligosaccharide impairing the mucoid biofilms by interacting with their cationic ions) to combat respiratory bacterial biofilm infections. The resulting powders were characterized with respect to their morphology, solid-state property, surface chemistry, moisture sorption behavior, and dissolution rate. The aerosol performance and storage stability of the dry powders were also evaluated. The results showed that inhalable dry powders composed of CIP and Oli could be readily accomplished via the wet milling and spray drying process. Upon the storage under 20 ± 2 °C/20 ± 2 % relative humidity (RH) for one month, there was no significant change in the in vitro aerosol performances of the dry powders. In contrast, the dry powders became non-inhalable following the storage at 20 ± 2 °C/53 ± 2 % RH for one month due to the hygroscopic nature of Oli, which could be largely prevented by incorporation of leucine. Collectively, this study suggests that the newly developed co-spray-dried powders composed of CIP and Oli might represent a promising and alternative treatment strategy against respiratory bacterial biofilm infections.