A multilevel investigation to reveal the regulatory mechanism of lignin accumulation in juice sac granulation of pomelo.

Granulation of juice sacs is a physiological disorder, which affects pomelo fruit quality. Here, the transcriptome and ubiquitinome of the granulated juice sacs were analyzed in Guanxi pomelo. We found that lignin accumulation in the granulated juice sacs was regulated at transcription and protein modification levels. In transcriptome data, we found that the genes in lignin biosynthesis pathway and antioxidant enzyme system of the granulated juice sacs were significantly upregulated. However, in ubiquitinome data, we found that ubiquitinated antioxidant enzymes increased in abundance but the enzyme activities decreased after the modification, which gave rise to reactive oxygen species (ROS) contents in granulated juice sacs. This finding suggests that ubiquitination level of the antioxidant enzymes is negatively correlated with the enzyme activities. Increased H2O2 is considered to be a signaling molecule to activate the key gene expressions in lignin biosynthesis pathway, which leads to the lignification in granulated juice sacs of pomelo. This regulatory mechanism in juice sac granulation of pomelo was further confirmed through the verification experiment using tissue culture by adding H2O2 or dimethylthiourea (DMTU). Our findings suggest that scavenging H2O2 and other ROS are important for reducing lignin accumulation, alleviating juice sac granulation and improving pomelo fruit quality.

Insight into recent advances in microalgae biogranulation in wastewater treatment.

Microalgae-based technology is widely utilized in wastewater treatment and resource recovery. However, the practical implementation of microalgae-based technology is hampered by the difficulty in separating microalgae from treated water due to the low density of microalgae. This review is designed to find the current status of the development and utilization of microalgae biogranulation technology for better and more cost-effective wastewater treatment. This review reveals that the current trend of research is geared toward developing microalgae-bacterial granules. Most previous works were focused on studying the effect of operating conditions to improve the efficiency of wastewater treatment using microalgae-bacterial granules. Limited studies have been directed toward optimizing operating conditions to induce the secretion of extracellular polymeric substances (EPSs), which promotes the development of denser microalgae granules with enhanced settling ability. Likewise, studies on the understanding of the EPS role and the interaction between microalgae cells in forming granules are scarce. Furthermore, the majority of current research has been on the cultivation of microalgae-bacteria granules, which limits their application only in wastewater treatment. Cultivation of microalgae granules without bacteria has greater potential because it does not require additional purification and can be used for border applications.

The most recent development in microalgae biogranulation research is highlighted.Factors affecting microalgae granule development are discussed for the first time.Duration to develop granules is a crucial aspect that needs further research.Cultivation of single-species microalgae for rapid harvesting needs more attention.

An Evaluation of Wet Granulation Process Selection for API Prone to Polymorphic Form Conversion in the Presence of Moisture and Heat.

PURPOSE: Wet granulation (WG) is one of the most versatile processes to improve blend properties for processing. However, due to its need for moisture and heat, it is often considered not amenable to active pharmaceutical ingredients (APIs) prone to forming hydrates. Despite this claim, little literature exists evaluating the extent to which polymorphic form conversions occur for such API when processed with WG. This work sets out to explore two common WG methods, high-shear (HSG) and fluid-bed (FBG), and two drying processes, tray-drying (TD) and fluid-bed drying (FBD), and evaluate the risk they pose to hydrate form conversion. METHODS: The progression of anhydrous to hydrate form conversion of two model compounds with vastly different solubilities, fexofenadine hydrochloride and carbamazepine, was monitored throughout the various processes using powder X-ray diffraction. The resultant granules were characterized using thermogravimetric analysis, differential scanning calorimetry, BET adsorption, and sieve analysis. RESULTS: FBG and FBD processing resulted in the preservation of the original form of both APIs, while HSG+TD resulted in the complete conversion of the API. The FBD of fexofenadine and carbamazepine granules prepared with HSG resulted in partial and complete re-conversion back to the original anhydrous forms, respectively. CONCLUSION: The drying process is a critical factor in anhydrous form conservation. FBG and FBD yielded better preservation of the initial anhydrous forms. HSG could be an acceptable granulation method for API susceptible to hydrate formation if the API solubility is low. Selecting an FBG+FBD process minimizes API hydrate formation and preserves the original anhydrous form.

Recycled Iron Phosphates: A New Phosphorus Fertilizer for Paddy Rice.

The potential of recycled iron phosphates (FePs), e.g., vivianites (Fe3(PO4)2·8H2O) and Fe(III)-rich phosphorus (P) adsorbent materials, as phosphorus fertilizer is limited by the strong interaction between Fe and P. In this study, the efficiency of FePs as P fertilizer was explored by applying them as granules or powder in flooded strongly P-fixing soils (acid and calcareous), thereby taking advantage of increased P release induced by reductive dissolution of P-bearing Fe(III) minerals. First, no P diffusion from granular FeP fertilizers into flooded soils was detectable by the diffusive gradient in thin films (DGT) technique and microfocused X-ray fluorescence (µ-XRF) analysis of thin soil sections, in contrast to detectable P diffusion away from granules of soluble triple superphosphate (TSP) fertilizer. On the contrary, powdered FePs demonstrated an excellent increase in extractable P (1 mM CaCl2) in a 120-day incubation experiment in flooded soils. Second, a pot experiment was performed with rice (Oryza sativa) grown in flooded acid and calcareous soils. The fertilizer value of FePs was remarkable when dosed as powder, as it was even up to 3-fold higher than TSP in the acid soil and similar to TSP in the calcareous soil. The beneficial effect of FeP over TSP in the acid soil is attributed to the slow release of P from FePs, which allows to partly overcome P fixation. The promising results of FePs as P fertilizer applied as powders in flooded soils debunk the generally accepted idea that FePs are poor sources of P while demonstrating the importance of the timing of FeP fertilizer application.

Deciphering the formation of granules by n-DAMO and Anammox microorganisms.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process is a promising wastewater treatment technology, but the slow microbial growth rate greatly hinders its practical application. Although high-level nitrogen removal and excellent biomass accumulation have been achieved in n-DAMO granule process, the formation mechanism of n-DAMO granules remains unresolved. To elucidate the role of functional microbes in granulation, this study attempted to cultivate granules dominated by n-DAMO microorganisms and granules coupling n-DAMO with anaerobic ammonium oxidation (Anammox). After long-term operation, dense granules were developed in the two systems where both n-DAMO archaea and n-DAMO bacteria were enriched, whereas granulation did not occur in the other system dominated by n-DAMO bacteria. Extracellular polymeric substances (EPS) measurement indicated the critical role of EPS production in the granulation of n-DAMO process. Metagenomic and metatranscriptomic analyses revealed that n-DAMO archaea and Anammox bacteria were active in EPS biosynthesis, while n-DAMO bacteria were inactive. Consequently, more EPS were produced in the systems containing n-DAMO archaea and Anammox bacteria, leading to the successful development of n-DAMO granules. Furthermore, EPS biosynthesis in n-DAMO systems is potentially regulated by acyl-homoserine lactones and c-di-GMP. These findings not only provide new insights into the mechanism of granule formation in n-DAMO systems, but also hint at potential strategies for management of the granule-based n-DAMO process.

Nickel augmented biochar for sustaining produced water treatment to decarbonize oil and gas industrial waste using anaerobic-aerobic granular cylindrical periodic discontinuous batch reactors.

This study assessed the efficacy of granular cylindrical periodic discontinuous batch reactors (GC-PDBRs) for produced water (PW) treatment by employing eggshell and waste activated sludge (WAS) derived Nickel (Ni) augmented biochar. The synthesized biochar was magnetized to further enhance its contribution towards achieving carbon neutrality due to carbon negative nature, Carbon dioxide (CO2) sorption, and negative priming effects. The GC-PDBR1 and GC-PDBR2 process variables were optimized by the application of central composite design (CCD). This is to maximize the decarbonization rate. Results showed that the systems could reduce total phosphorus (TP) and chemical oxygen demand (COD) by 76-80% and 92-99%, respectively. Optimal organic matter and nutrient removals were achieved at 80% volumetric exchange ratio (VER), 5 min settling time and 3000 mg/L mixed liquor suspended solids (MLSS) concentration with desirability values of 0.811 and 0.954 for GC-PDBR1 and GC-PDBR2, respectively. Employing four distinct models, the biokinetic coefficients of the GC-PDBRs treating PW were calculated. The findings indicated that First order (0.0758-0.5365) and Monod models (0.8652-0.9925) have relatively low R2 values. However, the Grau Second-order model and Modified Stover-Kincannon model have high R2 values. This shows that, the Grau Second Order and Modified Stover-Kincannon models under various VER, settling time, and MLSS circumstances, are more suited to explain the removal of pollutants in the GC-PDBRs. Microbiological evaluation demonstrated that a high VER caused notable rises in the quantity of several microorganisms. Under high biological selective pressure, GC-PDBR2 demonstrated a greater percentage of nitrogen removal via autotrophic denitrification and a greater number of nitrifying bacteria. The overgrowth of bacteria such as Actinobacteriota spp. Bacteroidota spp, Gammaproteobacteria, Desulfuromonas Mesotoga in the phylum, class, and genus, has positively impacted on granule formation and stability. Taken together, our study through the introduction of intermittent aeration GC-PDBR systems with added magnetized waste derived biochar, is an innovative approach for simultaneous aerobic sludge granulation and PW treatment, thereby providing valuable contributions in the journey toward achieving decarbonization, carbon neutrality and sustainable development goals (SDGs).

Dynamic contrast-enhanced MR imaging in identifying active anal fistula after surgery.

BACKGROUND: It is challenging to identify residual or recurrent fistulas from the surgical region, while MR imaging is feasible. The aim was to use dynamic contrast-enhanced MR imaging (DCE-MRI) technology to distinguish between active anal fistula and postoperative healing (granulation) tissue. METHODS: Thirty-six patients following idiopathic anal fistula underwent DCE-MRI. Subjects were divided into Group I (active fistula) and Group IV (postoperative healing tissue), with the latter divided into Group II (≤ 75 days) and Group III (> 75 days) according to the 75-day interval from surgery to postoperative MRI reexamination. MRI classification and quantitative analysis were performed. Correlation between postoperative time intervals and parameters was analyzed. The difference of parameters between the four groups was analyzed, and diagnostic efficiency was tested by receiver operating characteristic curve. RESULTS: Wash-in rate (WI) and peak enhancement intensity (PEI) were significantly higher in Group I than in Group II (p = 0.003, p = 0.040), while wash-out rate (WO), time to peak (TTP), and normalized signal intensity (NSI) were opposite (p = 0.031, p = 0.007, p = 0.010). Area under curves for discriminating active fistula from healing tissue within 75 days were 0.810 in WI, 0.708 in PEI, 0.719 in WO, 0.783 in TTP, 0.779 in NSI. All MRI parameters were significantly different between Group I and Group IV, but not between Group II and Group III, and not related to time intervals. CONCLUSION: In early postoperative period, DCE-MRI can be used to identify active anal fistula in the surgical area. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033072.

Impact of ciprofloxacin/dexamethasone on pediatric tracheostomy outcomes.

OBJECTIVE(S): To investigate the effectiveness of ciprofloxacin/dexamethasone in reducing granulation tissue post-tracheostomy in pediatric patients. METHODS: This cohort study examined pediatric patients with a tracheostomy at a single academic institution from 2016 to 2020. Exclusion criteria included: deceased within 1 year (n = 38), >16 years of age (n = 21), decannulated within 1 year (n = 15), lost to follow-up within 1 year (n = 6), and revision tracheostomy (n = 2). Logistic regression or Wilcoxon rank-sum (α = 0.05) were used to compare demographic and clinical characteristics between patients who did and did not receive ciprofloxacin/dexamethasone within 1 year of their tracheostomy. RESULTS: In this cohort, (n = 126, median age 5.2 months, 54.0 % male), 62.7 % received ciprofloxacin/dexamethasone within 1 year, with 27.8 % taking the nebulized form. Granulation tissue occurred in 81.0 % of cases, predominantly peristomal (69.8 %) and suprastomal (34.9 %). Notable complications included accidental decannulation (13.6 %), suprastomal collapse (11.2 %), and bleeding (7.2 %). Although granulation tissue was more common in ciprofloxacin/dexamethasone users (92.4 %) versus non-users (61.7 %) (OR: 7.55, 95 % CI: 2.73-20.9, p < 0.001), patients exhibited less frequent granulation tissue events after initiation (z = 3.88, p < 0.001). No significant differences in antibiotic resistance (p = 1.0) or endocrinology complications (p = 0.1) were found between those with and without ciprofloxacin/dexamethasone. CONCLUSIONS: We found a statistically significant reduction of granulation tissue incidence with ciprofloxacin/dexamethasone use and no significant differences in antibiotic resistance or endocrinology complications were noted. Future investigation is warranted to explore timing of ciprofloxacin/dexamethasone administration for granulation tissue and its role in managing and preventing tracheostomy complications.

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Beyond the surface: exploring contributing factors to bone anchored hearing implant complications.

INTRODUCTION: Bone anchored hearing implants (BAHI) are considered for conductive and mixed hearing loss, relying on osseointegration of a titanium implant. Limitations relate to constant skin contact, with resultant percutaneous infections and granulation. This study investigates whether patient characteristics and implant-specifications contribute to BAHIs' skin complications in a cohort with a uniform surgical approach. METHODS: A 10 year (2014-2024) retrospective cohort study was conducted on BAHI procedures that were undertaken using a tissue-preserving 'punch' technique. Data on patient demographics, co-morbidities, implant type, surgical approach, and complications were collected. Poisson regression analysis was used to identify predictors of complications. RESULTS: A total of 53 patients undergoing 55 BAHI surgeries by three ENT consultants were included. Factors that greatly increased implant-related percutaneous infections included the Cochlear™ BIA400 implant when compared to the Ponto™ BHX implant (twofold, CI 2.03-2.16), abutment sizes ≤ 10 mm (fourfold, CI 3.99-4.12) and male gender (9%, CI 1.07-1.12). Granulation episodes were affected by cardiovascular disease (CVD) status (1.5-fold, CI 0.26-0.78), BIA400 implant (threefold, CI 8.8.-9.2) and abutment sizes ≤ 10 mm (fourfold, CI 3.6-3.73). Revision surgery episodes increased with diabetic status (1.2-fold, CI 0.06-0.37) and abutment sizes ≤ 10 mm (threefold, 3.303-3.304). CONCLUSIONS: Larger cohort studies are required to confirm findings, particularly for implant and abutment size contributions. However, the findings suggest that using a larger abutment size when skin thickness meassuremets are borderline, improved hygiene education in male patients, pre-operative optimisation of CVD and diabetes, and adjusted patient follow-up based on risk stratification of the contributing factors to complication rates could reduce complication rates.

The dragonfly technique for trachea closure in temporary tracheostomies. Surgical steps and clinical results.

PURPOSE: To assess the effectiveness of a new suturing technique called Dragonfly for the closure of temporary tracheotomies. This technique involves placing two sutures during the tracheotomy procedure and leaving them loose and unknotted until the day of skin closure. METHODS: Retrospective case control study. Monocentric study at a department of Otolaryngology and head and neck surgery at a tertiary centre in Italy. A total of 50 patients who underwent temporary tracheotomy between January 2017 and December 2021. Patients were divided into two groups based on the trachea closure method: traditional closure with sutures placed during the skin closure procedure (Group A) and the Dragonfly technique (Group B). The incidence of tracheal stenosis by Computed Tomography (CT), granulation tissue formation, bleeding, procedure duration, patient discomfort were evaluated. RESULTS: The incidence of tracheal complications and tracheal stenosis was reduced in Group B (6%) compared to Group A (24%). Procedure times (3 min vs. 6 min) durations was significantly shorter. No patients had symptoms of tracheal stenosis at the end of the procedures. CONCLUSION: The Dragonfly suturing technique is effective and safe for tracheotomy closure, reducing the incidence of tracheal stenosis and shortening hospitalization duration compared to the traditional method.

Partial (incomplete) removal of granulation tissue using modified minimally invasive surgical technique in treatment of infrabony defects (randomized control clinical trial).

AIM: This study aims to compare the clinical and radiographic outcomes after complete versus incomplete removal of granulation tissue (GT) during modified minimally invasive surgical technique (M-MIST) for management of periodontitis patients with deep pockets associated with infra-bony defects. METHODOLOGY: Ten patients with a total of 14 deep non-resolving pockets (≥ 5 mm) associated with a vertical infra-bony defect were recruited for this study. They were randomized into 2 groups; a test group with incomplete removal of GT and a control group with complete removal of GT. Clinical parameters of clinical attachment level (CAL), residual probing depth (rPD) and buccal recession (Rec.) were recorded every 3 months. Radiographic periapicals were taken at baseline, 6 and 9 months. The significance level was set to 0.05. RESULTS: None of the results showed statistical significance between the 2 groups (p > 0.05). The test group showed less CAL gain (2 ± 0.87 mm, p = 0.062), more reduction in rPD (3.1 ± 0.96 mm, p = 0.017) and more recession (0.857 ± 0.26 mm, p = 0.017) than control group CAL gain (2.4 ± 0.58 mm, p = 0.009), rPD reduction (2.9 ± 0.3 mm, p = 0.001) and recession (0.5 ± 0.34 mm, p = 0.203) respectively. Control group had linear reduction in depth defect (DD) (0.68 ± 0.287, p = 0.064) compared to an increase in DD in test group (-0.59 ± 0.5, p = 0.914). CONCLUSIONS: No statistical significance were observed in healing parameters between complete removal of GT in M-MIST and incomplete (partial) removal of GT of deep pockets with infra-bony defects both clinically and radiographically. Further studies with larger samples are needed to confirm the results.

Correlation between initial serum 25-hydroxyvitamin D and granulation growth in diabetic foot ulcers.

OBJECTIVE: To determine the correlation between initial serum 25-hydroxyvitamin D (25(OH)D) levels with granulation growth in diabetic foot ulcers (DFUs) after 21 days of treatment. METHOD: This cohort study involved patients with type 2 diabetes who had a DFU treated at hospital. Blood samples were taken from patients on admission. The chemiluminescent immunoassay technique was used to measure 25(OH)D levels. Granulation tissue growth was analysed by comparing the photographs from the initial treatment to day 21 of treatment. RESULTS: The median value of 25(OH)D levels at initial treatment was 8 ng/ml. The result showed no correlation between 25(OH)D levels and the granulation growth in DFUs (p=0.86). CONCLUSION: The initial serum 25(OH)D level was not correlated with the growth of granulation tissue in DFUs.

Fingerprinting of physical manufacturing properties of different acids for effervescent systems.

The study aimed to fingerprint the physical manufacturing properties of five commonly used acid sources in effervescent systems for designing the formulation and process of such systems. The hygroscopicity, texture properties, rheological torque, compressibility, tabletability, etc., were investigated to inspect 'powder direct compression (DC)' and 'wet granulation and compression' properties of citric (CA), tartaric (TA), malic (MA), fumaric (FA), and adipic acid (AA). The DC ability was evaluated by the SeDeM expert system. The results indicated that all acid powders failed to meet flowability requirements for DC, and plastic deformation dominated during compression. Furthermore, CA exhibited strong hygroscopicity and punch sticking, while MA demonstrated the best tabletability. TA had a large wet granulation space and was relatively the most suitable for DC. AA was extremely hygroscopic, and its flowability improved significantly as particle size increased. Finally, FA displayed the lowest hygroscopicity and ejection force as well as great compressibility and wet granulation space, and did not exhibit punch sticking, while the granule fragments dissolved slowly during disintegration. Generally speaking, the formulation or granulation affected the tabletability, indicating that pairing with other acids or suitable fillers could potentially improve its disadvantages. These multidimensional assessments effectively reduce the pre-exploration and enhance the efficiency of the development of effervescent systems.

Ten years of the manufacturing classification system: a review of literature applications and an extension of the framework to continuous manufacture.

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications. This article firstly reviews this citing work and considers how the MCS concepts have been received and are being applied. Secondly, we will extend the MCS framework to continuous manufacture. The review structure follows the flow of drug product development focussing first on optimisation of API properties. The exploitation of links between API particle properties and manufacturability using large datasets seems particularly promising. Subsequently, applications of the MCS for formulation design include a detailed look at the impact of percolation threshold, the role of excipients and how other classification systems can be of assistance. The final review section focusses on manufacturing process development, covering the impact of strain rate sensitivity and modelling applications. The second part of the paper focuses on continuous processing proposing a parallel MCS framework alongside the existing batch manufacturing guidance. Specifically, we propose that continuous direct compression can accommodate a wider range of API properties compared to its batch equivalent.

Determining the Impact of Roller Compaction Processing Conditions on Granulate and API Properties: Impact of Formulation API Load.

Previous work demonstrated that roller compaction of a 40%w/w theophylline-loaded formulation resulted in granulate consisting of un-compacted fractions which were shown to constitute between 34 and 48%v/v of the granulate dependent on processing conditions. The active pharmaceutical ingredient (API) primary particle size within the un-compacted fraction was also shown to have undergone notable size reduction. The aim of the current work was to test the hypothesis that the observations may be more indicative of the relative compactability of the API due to the formulation being above the percolation threshold. This was done by assessing the impact of varied API loads in the formulation on the non-granulated fraction of the final granulate and the extent of attrition of API particles within the non-granulated fraction. The influence of processing conditions for all formulations was also investigated. The results verify that the observations, both of this study and the previous work, are not a consequence of exceeding the percolation threshold. The volume of un-compacted material within the granulate samples was observed to range between 34.7 and 65.5% depending on the API load and roll pressure, whilst the API attrition was equivalent across all conditions.

Polymer Characteristics for Drug Layering on Particles Using a Novel Melt Granulation Technology, MALCORE®.

MALCORE®, a novel manufacturing technology for drug-containing particles (DCPs), relies on the melt granulation method to produce spherical particles with high drug content. The crucial aspect of particle preparation through MALCORE® involves utilizing polymers that dissolve in the melt component, thereby enhancing viscosity upon heating. However, only aminoalkyl methacrylate copolymer E (AMCE) has been previously utilized. Therefore, this study aims to discover other polymers and comprehend the essential properties these polymers need to possess. The results showed that polyvinylpyrrolidone (PVP) was soluble in the stearic acid (SA) melt component. FTIR examination revealed no interaction between SA and polymer. The phase diagram was used to analyze the state of the SA and polymer mixture during heating. It revealed the mixing ratio and temperature range where the mixture remained in a liquid state. The viscosity of the mixture depended on the quantity and molecular weight of the polymer dissolved in SA. Furthermore, the DCPs prepared using PVP via MALCORE® exhibited similar pharmaceutical properties to those prepared with AMCE. In conclusion, understanding the properties required for polymers in the melt granulation process of MALCORE® allows for the optimization of manufacturing conditions, such as temperature and mixing ratios, for efficient and consistent drug layering.

An Advanced Twin-Screw Granulation Technology: The use of Non-Volatile Solvents with High Solubilizing Capacity.

PURPOSE: Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders. METHODS: Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®). RESULTS: The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity. CONCLUSIONS: Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.

Comparison of Properties of Acetaminophen Tablets Prepared by Wet Granulation Using Freeze-Dried Versus Phase-Inversion Bacterial Cellulose as Diluent.

Bacterial cellulose (BC) is an interesting material for drug delivery applications due to its high purity. This study aimed to compare the properties of tablets prepared by the wet granulation method using bacterial cellulose prepared by different methods as a diluent, using acetaminophen as a model drug. BC used as diluents were prepared using two different methods: freeze-drying (BC-FD) and phase-inversion (BC-PI), and their characteristics were analyzed and compared with that of commercial microcrystalline cellulose PH 101 (Comprecel® M101). Acetaminophen tablets were prepared by wet granulation using BC-FD, BC-PI, or Comprecel® M101 as diluents, and their tablet properties were examined. The result showed that the morphology, polymorph, and crystallinity of BC-PI and Comprecel® M101 were similar but they were different compared with that of BC-FD. Tablets could be successfully formed using BC-PI and Comprecel® M101 as diluents without any physical defects but the tablet prepared using BC-FD as diluent appeared chipped edge. The characteristics (thickness, weight variation, hardness, friability, disintegration, drug content, and dissolution) of the tablets prepared using BC-PI diluent were also similar to those prepared using Comprecel® M101 diluent, but those of BC-FD diluent were inferior. This indicates that BC prepared in BC-PI can potentially be used as a diluent for tablets prepared by wet granulation.

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation-Where Are We Now?

Hot-melt extrusion (HME) is a globally recognized, robust, effective technology that enhances the bioavailability of poorly soluble active pharmaceutical ingredients and offers an efficient continuous manufacturing process. The twin-screw extruder (TSE) offers an extremely resourceful customizable mixer that is used for continuous compounding and granulation by using different combinations of conveying elements, kneading elements (forward and reverse configuration), and distributive mixing elements. TSE is thus efficiently utilized for dry, wet, or melt granulation not only to manufacture dosage forms such as tablets, capsules, or granule-filled sachets, but also for designing novel formulations such as dry powder inhalers, drying units for granules, nanoextrusion, 3D printing, complexation, and amorphous solid dispersions. Over the past decades, combined academic and pharmaceutical industry collaborations have driven novel innovations for HME technology, which has resulted in a substantial increase in published articles and patents. This article summarizes the challenges and models for executing HME scale-up. Additionally, it covers the benefits of continuous manufacturing, process analytical technology (PAT) considerations, and regulatory requirements. In summary, this well-designed review builds upon our earlier publication, probing deeper into the potential of twin-screw extruders (TSE) for various new applications.