Material-Sparing Approach to Predict Tablet Capping Under Processing Compression Conditions Based on Mechanical and Molecular Properties Derived from Compaction Simulation and Crystal Structural Analysis.

Present study evaluates the usability of compaction simulation-based mechanical models as a material-sparing approach to predict tablet capping under processing compression conditions using Acetaminophen (APAP) and Ibuprofen (IBU). Measured mechanical properties were evaluated using principal component analysis (PCA) and principal component regression (PCR) models. PCR models were then utilized to predict the capping score (CS) from compression pressure (CP). APAP formulations displayed a quadratic correlation between CS and CP, with CS rank order following CP of 200MPa < 300MPa < 100MPa, indicating threshold compression pressure (TCP) limit between 200 and 300 MPa, resulting in higher CS at 300 than 200 MPa regardless of increased CP. IBU formulations displayed a linear correlation between CS and CP, with CS rank order following CP of 100MPa < 200MPa < 300MPa, indicating TCP limit between 100 and 200 MPa, resulting in higher CS at 200 and 300 than 100 MPa regardless of increased CP. Molecular models were developed as validation methods to predict capping from CP. Measured XRPD patterns of compressed tablets were linked with calculated Eatt and d-spacing of slip planes and analyzed using variable component least square methods to predict TCP triggering cleavage in slip planes and leading to capping. In APAP and IBU, TCP values were predicted at 245 and 175 MPa, meaning capped tablets above these TCP limits regardless of increased CP. A similar trend was observed in CS predictions from mechanical assessment, confirming that compaction simulation-based mechanical models can predict capping risk under desired compression conditions rapidly and accurately.

Explainable Machine Learning Models to Predict Gibbs-Donnan Effect During Ultrafiltration and Diafiltration of High-Concentration Monoclonal Antibody Formulations.

Evaluating the Gibbs-Donnan and volume exclusion effects during protein ultrafiltration and diafiltration (UF/DF) is crucial in biopharmaceutical process development to precisely control the concentration of the drug substance in the final formulation. Understanding the interactions between formulation excipients and proteins under these conditions requires a domain-specific knowledge of molecular-level phenomena. This study developed gradient boosted tree models to predict the Gibbs-Donnan and volume exclusion effects for amino acids and therapeutic monoclonal antibodies using simple molecular descriptors. The models' predictions were interpreted by information gain and Shapley additive explanation (SHAP) values to understand the modes of action of the antibodies and excipients and to validate the models. The results translated feature effects in machine learning to real-world molecular interactions, which were cross-referenced with existing scientific literature for verification. The models were validated in pilot-scale manufacturing runs of two antibody products requiring high levels of concentration. By only requiring a molecule's biophysicochemical descriptors and process conditions, the proposed models provide an in silico alternative to conventional UF/DF experiments to accelerate process development and boost process understanding of the underlying molecular mechanisms through rational interpretation of the models.

Advancements in Colon-Targeted Drug Delivery: A Comprehensive Review on Recent Techniques with Emphasis on Hot-Melt Extrusion and 3D Printing Technologies.

This review investigates the progression and effectiveness of colon-targeted drug delivery systems, offering a comprehensive understanding of the colon's anatomy and physiological environment. Recognizing the distinctive features of the colon is crucial for successfully formulating oral dosage forms that precisely target specific areas in the gastrointestinal tract (GIT) while minimizing side effects through mitigating off-target sites. This understanding forms the basis for designing effective targeted drug delivery systems. The article extensively examines diverse approaches to formulating drugs for colonic targeting, highlighting key polymers and excipients in their production. Special emphasis is given to innovative approaches such as hot-melt extrusion (HME) and three-dimensional printing (3D-P), renowned for their accuracy in drug release kinetics and intricate dosage form geometry. However, challenges arise regarding material standardization and the complex network of regulatory clearances required to confirm safety and effectiveness. The review provides insights into each application's advantages and potential challenges. Furthermore, it sheds light on the local diseases that necessitate colon targeting and the available marketed products, providing an overview of the current state of colon-targeted drug delivery systems. Additionally, the review emphasizes the importance of testing drugs in a controlled in vitro environment during the development phase. It also discusses the future directions for successful development in this field. By integrating knowledge across anatomy, formulation techniques, and assessment methodologies, this review is a valuable resource for researchers navigating the dynamic field of colonic drug delivery.

Investigations on the Impacts of Drugs or Excipients with Different Physicochemical and Compaction Properties on the Disintegration Behavior of Kollidon®SR-Based Binary Controlled Release Matrix Tablets.

The objective of this study was to examine the impact of the physicochemical properties of the loaded drug or excipient, the concentration of Kollidon®SR (KSR), and the mechanical characteristics of KSR compacts on their disintegration times. Using disintegration apparatus, a two-hour constraint was chosen as the process's end point. Lactose-KSR compacts subjected to the highest compression pressure and Microcrystalline cellulose-KSR compacts with KSR concentrations exceeding 30% exhibited disintegration times of less than ten minutes. Likewise, compacts containing Diltiazem HCl-KSR demonstrated brief disintegration times across all tested KSR concentrations and compression pressures. Compacts of Modafinil, Metformin HCl, and Ascorbic acid-KSR displayed disintegration times ranging from fast to moderate, contingent upon the levels of KSR and compression pressure applied. Compacts containing KSR with Aspirin, Salicylic acid, or Ibuprofen did not exhibit significant disintegration even at minimal amounts of KSR (0.5%). Theophylline-KSR tablets also showed prolonged dissolution times, even at very low concentrations of KSR. The disintegration times of Dic-KSR tablets were roughly close to an hour and were predominantly unaffected by varying KSR levels and only marginally influenced by compression pressures. It is possible to draw the conclusion that different drugs or excipients have different minimum KSR requirements to resist compacts' disintegration process. Compounds that demonstrate low solubility in water can result in extended disintegration times for KSR compacts. The melting points of these compounds, in conjunction with the Py values of the compacts and their compaction properties, could affect the disintegration process, although a precise evaluation is necessary.

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-term therapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certain shortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7 nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. The solubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

Experimental investigation of dynamic drying in single pharmaceutical granules containing acetaminophen or carbamazepine using synchrotron X-ray micro computed tomography.

Drying time, velocity, and temperature are important aspects of the drying process for pharmaceutical granules observed during tablet manufacturing. However, the drying mechanism of single granules is often limited to modelling and simulation, with the internal and physical changes difficult to quantify at an experimental level. In this study, in-situ synchrotron-based X-ray imaging techniques were used for the first time to investigate the dynamic drying of single pharmaceutical granules, quantifying internal changes occurring over the drying time. Two commonly used excipients (lactose monohydrate (LMH) and microcrystalline cellulose (MCC)) were used as pure components and binary mixtures with one of either two active pharmaceutical ingredients of differing hydrophilicity/hydrophobicity (acetaminophen (APAP) and carbamazepine (CBZ)). Water was used as a liquid binder to generate single granules of 25 % to 30 % moisture content. Results showed that for most samples, the drying time and composition significantly influences the pore volume evolution and the moisture ratio, with the velocity and temperature of the drying air possessing mixed significance on increasing the rate of pore connectivity and moisture removal depending on the sample composition. Effects of active ingredient loading resulted in minimal influence on the drying of CBZ and generated binary mixtures, with APAP and its respective mixtures' drying behaviour dominated by the material's hydrophilic nature.

Polysorbate stability: Effects of packaging materials, buffers, counterions, and pH.

Polysorbates, widely used excipients in drug formulations, present a stability challenge due to complex degradation processes. This study investigates the hydrolysis of polysorbate (PS) under temperature stress (50 °C), focusing on the impact of primary packaging materials (glass vs. plastic vials), buffers (histidine and acetic acid), counterions (chloride vs. malate), and pH (4-7). Our findings reveal that leachables from plastic vials inhibit PS degradation in both histidine and acetic acid buffers. Kinetic parameters derived from sigmoidal fitting suggest distinct degradation mechanisms for each buffer. Furthermore, the malate counterion with histidine displays inhibitory effects on PS hydrolysis. Principal component analysis was employed to identify key factors. These results highlight the critical role of excipients and packaging in PS stability, providing valuable insights for biopharmaceutical formulation development and a deeper understanding of PS degradation complexities.

Encapsulation of astaxanthin in OSA-starch based amorphous solid dispersions with HPMCAS-HF/Soluplus® as effective recrystallization inhibitor.

In this study, the interaction among multifunctional excipients, including polysaccharides, cellulose derivatives, and surfactants, was particularly investigated, together with its impact on the physicochemical properties of astaxanthin amorphous solid dispersions (ASTX ASDs). It was indicated that Span 20 could rapidly form hemimicelles or aggregates in the presence of hypromellose acetate succinate HF (HPMCAS-HF, HF) or Soluplus®, while octenyl succinic anhydride modified starch (OSA-starch) efficiently assisted in the coalescence inhibition of drug-excipients aggregates, which was jointly beneficial to the recrystallization inhibition of amorphous ASTX. ASTX ASDs were further prepared with OSA-starch, HPMCAS-HF/Soluplus®, and Span 20 as the wall materials. DSC, SEM, and XRD confirmed that crystalline ASTX had transformed to amorphous state in the ASDs, while FT-IR spectra provided evidence suggesting the existence of hydrogen bonds and hydrophobic interaction between ASTX and the excipients. The dissolution of ASTX ASDs in different media revealed significant promotion, while the pharmacokinetic results further demonstrated the oral bioavailability of ASTX ASDs enhanced remarkably, exhibiting 2.75-fold (SD1) and 1.87-fold (SD2) increase, respectively, compared to ASTX bulk powder. In summary, the cellulose derivatives-surfactant interaction had great impact on the physicochemical properties of ASTX ASDs, and their combinations exhibited great potential for delivering the hydrophobic bioactive compounds efficiently.

Excipient-free nanotransformation of hydrophilic macromolecules using aqueous counter collision for enhanced bioavailability.

The demand for sustainable, eco-friendly biopolymer transdermal delivery systems has increased owing to growing environmental awareness. In this study, we used aqueous counter collision (ACC), a nontoxic nanotransformation method, to convert high- and ultrahigh-molecular-weight hydrophilic macromolecules into their corresponding nanoparticles (NPs). Hyaluronic acid (HA) and crosslinked HA (CLHA) were chosen as the model compounds. Their NPs exhibited particle sizes in the range of 10-100 nm and negative zeta potentials (-20 to -30 mV). Transmission electron microscopy revealed that the NPs were nearly spherical with smooth surfaces. Fourier-transform infrared and proton nuclear magnetic resonance spectroscopy and agarose gel electrophoresis confirmed that the structures and molecular weights of HA and CLHA remained unaltered after ACC. However, the storage and loss moduli of HANPs and CLHANPs were significantly lower than those of HA and CLHA, respectively. Furthermore, the permeation of HANPs and CLHANPs in reconstructed human skin and human cadaver skin was visualized and quantified. HANPs and CLHANPs penetrated deeper into the skin, whereas HA and CLHA were mainly found in the stratum corneum. The total skin absorption (permeation and deposition) of HANPs and CLHANPs was approximately 2.952 and 5.572 times those of HA and CLHA, respectively. Furthermore, HANPs and CLHANPs exhibited resistance to enzyme and free radical degradation. Our findings reveal ACC as a promising, sustainable hydrophilic macromolecule delivery system compared with the chemical hydrolysis of HA.

Optimization of a Twin screw melt granulation process for fixed dose combination immediate release Tablets: Differential amorphization of one drug and crystalline continuance in the other.

Interest in Twin Screw Melt Granulation (TSMG) processes is rapidly increasing, along with the search for suitable excipients. This study aims to optimize the TSMG process for immediate-release tablets containing two different drugs. The hypothesis is that one poorly water-soluble drug requires amorphous conversion for improved dissolution, while the other water-soluble drug, with a higher melting point (Tm), remains more stable in its crystalline form. Ibuprofen (IBU) and Acetaminophen (APAP) were chosen as the model drug combination to test this hypothesis. Various diluents, binders, and disintegrating agents were assessed for their impact on processability, crystallinity, disintegration, and dissolution during development. The temperatures used during processing were below the Tm of all components, except for IBU. Melted IBU acted as a granulating aid in addition to the binders in the formulation, facilitating granule formation. Physicochemical analyses by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD) confirmed the complete conversion of IBU into an amorphous state and the preserved crystalline nature of APAP. Saturation solubility studies showed an improvement in IBU's solubility by âˆ¼ 32-fold in 0.1 N HCl. Poor tablet disintegration performance led to the addition of disintegrating agents, where osmotic agents (sorbitol and NaCl) were found to significantly enhance disintegration compared to super disintegrants. The optimized formulation showed an enhanced IBU release (∼20 %) compared to the physical mixture (∼12.5) in 0.1 N HCl dissolution studies.

Relaxation tests for the time dependent behavior of pharmaceutical tablets: A revised interpretation.

Relaxation tests are often used in the pharmaceutical field to assess the strain rate sensitivity of pharmaceutical powders and tablets. These tests involve applying a constant strain to the powder in the die and then monitoring the stress evolution over time. Interpreting these tests is complicated because different physical phenomena, mainly viscoelasticity and viscoplasticity, occur simultaneously. These two phenomena cannot be distinguished by observing the evolution of the axial pressure alone, as it decreases in both cases. In this work, it was shown that monitoring the evolution of the die-wall pressure during relaxation can help separate the effects of these phenomena. Theoretical considerations revealed that during viscoplasticity, the die-wall pressure also decreases, whereas an increase in the die-wall pressure during relaxation indicates a viscoelastic relaxation. This was confirmed experimentally using specially designed compaction cycles on four different pharmaceutical excipients. Experimental results indicated that at low pressure, viscoplasticity was predominant, whereas at high pressure, viscoelasticity became more prominent. These results suggest that at low pressures, relaxation tests can be used to assess the viscoplastic properties of different products. However, the use of high pressure should always be avoided as viscoelastic phenomena might become more significant, and the combination of both phenomena might compromise the interpretation.

Comparison of in vitro screening methods for evaluating the effects of pharmaceutical excipients on membrane permeability.

The effects of pharmaceutical excipients on intestinal drug absorption have been highlighted and careful excipient selection is required to develop biologically equivalent formulations. This study aimed to evaluate the effects of excipients on drug permeability and compare the characteristics of in vitro screening methods. Three in vitro models, the commercial precoated parallel artificial membrane permeability assay (PAMPA), PermeaPadTM, and Caco-2 monolayer, were used to evaluate the effects of 14 excipients on the permeability of several drugs with different biopharmaceutical classification system classes. Concentration-dependent effects were analyzed to distinguish non-specific effects. The permeability of low-permeability drugs was increased by excipients such as hydroxypropyl cellulose and povidone K30 in the precoated PAMPA model, whereas PermeaPadTM maintained membrane integrity at higher concentrations. Conversely, croscarmellose sodium and sodium lauryl sulfate (SLS) decreased the permeability of highly permeable drugs in both precoated PAMPA and PermeaPadTM assays in a concentration-dependent manner. In Caco-2 monolayer assays, most excipients showed minimal effects on drug permeability. However, SLS significantly reduces the permeability of highly permeable drugs at concentrations above the critical micelle concentration, thereby compromising the integrity of the cell monolayer. Our results suggested that most of excipients, except SLS, did not affect the membrane permeation of drugs at clinically used concentrations. The pre-coated PAMPA model demonstrated high sensitivity to excipient effects, making it suitable for conservative evaluation. The PermeaPadTM and Caco-2 models allowed assessment at higher excipient concentrations, with PermeaPadTM being particularly useful for excipients that cause toxicity in Caco-2 cells.

The Langmuir-Blodgett trough (Langmuir film balance) can be used to understand the stabilizer concentrations in aqueous nano- and microsuspensions.

Aqueous suspensions of poorly soluble, crystalline drug particles in the sub-micron range hold the ability to regulate the drug release for a defined period of time after e.g., intramuscular, or subcutaneous administration, working as an eminent formulation strategy for the preparation of long-acting injectables. Aqueous suspensions are typically prepared by top-down approaches, e.g., wet bead media milling or high-pressure homogenization, containing the active pharmaceutical compound and surfactants and/or polymers for stabilization purposes. Currently, the screening of proper stabilizers and adequate stabilizer concentration during formulation investigations is based on a trial-and-error approach with variations in combinations, concentrations, and/or ratios. To obtain a more efficient methodology during formulation screening, the present study investigated the correlation between the surface activity of two different surfactants, i.e., poloxamer 188 and polysorbate 20, by drop profile tensiometry and Langmuir trough monolayer, and the obtained sizes of cinnarizine particles as a tool to predict the optimal surfactant concentration to prepare physical stable nano- and microsuspensions. The obtained results demonstrated that the molecular area determined as the area per surfactant molecule measured in the Langmuir trough combined with the specific surface area of the prepared suspensions could be used to predict the suitable concentration of the surfactant based upon short-term stress stability data. The results further showed that higher concentrations of poloxamer 188 were necessary to stabilize the suspensions when compared to the needed concentration of polysorbate 20. In addition, it was observed that there was a need for a slightly higher surfactant concentration when the suspensions were milled with the smallest bead size of 0.5 mm instead of larger sizes of bead (0.8 and 1.0 mm), which could not be accounted for by differences in specific surface area.

Enhancing topical delivery of ISRIB: Optimizing cream formulations with chemical enhancers and pH adjustment.

Chemical warfare agents, particularly vesicants like lewisite, pose a threat due to their ability to cause skin damage through accidental exposure or deliberate attacks. Lewisite rapidly penetrates the skin, causing inflammation and blistering. This study focuses on developing a cream formulation of a therapeutic agent, called integrated stress response inhibitor (ISRIB), to treat lewisite-induced injuries. Moreover, animal studies demonstrate a molecular target engagement (ISR) and significant efficacy of ISRIB against lewisite-induced cutaneous injury. The goal of this formulation is to enhance the delivery of ISRIB directly to affected skin areas using an oil-in-water cream emulsion system. We investigated various excipients, including oils, surfactants, emollients, and permeation enhancers, to optimize ISRIB's solubility and penetration through the skin. The result of this study indicated that the optimal formulation includes 30 % w/w of N-Methyl-2-pyrrolidone, dimethyl sulfoxide and Azone® at a pH of 5. 5. It delivered the highest amount of ISRIB into the skin, demonstrating highest skin absorption with no detectable systemic exposure. Additionally, characterization of the cream, including texture analysis, emulsion type, and content uniformity, confirmed its' suitability for topical application. These findings suggest that ISRIB cream formulation is a promising approach for the localized treatment of skin injuries caused by lewisite.

Fabrication of osmotic pump tablets utilizing semisolid extrusion three-dimensional printing technology.

The utilization of three-dimensional (3D) printing technology is prevalent in the fabrication of oral sustained release preparations; however, there is a lack of research on 3D-printed osmotic pump tablets. A 3D-printed core-shell structure bezafibrate osmotic pump tablet was developed based on the characteristics of rapid absorption and short half-life of bezafibrate, utilizing semisolid extrusion (SSE) 3D printing technology. First, the properties of different shell materials were investigated to define the composition of the shell, and ultimately, the optimal formulation was found to be ethyl cellulose:cellulose acetate:polyethylene glycol = 2:1:2. The formulation of the tablet core was defined based on the printing performance and release behavior. The formulation consisted of bezafibrate, lactis anhydrous, sodium bicarbonate, sodium alginate, polyethylene oxide and sodium dodecyl sulfate at a ratio of 400:400:300:80:50:50. The tablet was capable of achieving zero-order release. The physicochemical properties were also characterized. The pharmacokinetic data analysis indicated that there were no statistically significant differences in the pharmacokinetic parameters between the 3D-printed tablets and the reference listed drugs. There was a strong correlation between the in vitro and in vivo results for the 3D-printed tablets. The results showed that SSE printing is a practical approach for manufacturing osmotic pump tablets.

Evaluation of Different Formulations on the Viability of Phages for Use in Agriculture.

Bacteriophages have been proposed as biological controllers to protect plants against different bacterial pathogens. In this scenario, one of the main challenges is the low viability of phages in plants and under adverse environmental conditions. This work explores the use of 12 compounds and 14 different formulations to increase the viability of a phage mixture that demonstrated biocontrol capacity against Pseudomonas syringae pv. actinidiae (Psa) in kiwi plants. The results showed that the viability of the phage mixture decreases at 44 °C, at a pH lower than 4, and under UV radiation. However, using excipients such as skim milk, casein, and glutamic acid can prevent the viability loss of the phages under these conditions. Likewise, it was demonstrated that the use of these compounds prolongs the presence of phages in kiwi plants from 48 h to at least 96 h. In addition, it was observed that phages remained stable for seven weeks when stored in powder with skim milk, casein, or sucrose after lyophilization and at 4 °C. Finally, the phages with glutamic acid, sucrose, or skim milk maintained their antimicrobial activity against Psa on kiwi leaves and persisted within kiwi plants when added through roots. This study contributes to overcoming the challenges associated with the use of phages as biological controllers in agriculture.

Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients.

The focus of current studies was to fabricate dose flexible printlets of dapsone (DDS) for pediatric patients by selective laser sintering (SLS) 3D printing method, and evaluate its physicochemical, patient in-use stability, and pharmacokinetic attributes. Eight formulations were fabricated using Kollicoat® IR, Eudragit® L-100-55 and StarCap®as excipients and evaluated for hardness, disintegration, dissolution, amorphous phase by differential scanning calorimetry and X-ray powder diffraction, in-use stability at 30 oC/75% RH for a month, and pharmacokinetic study in Sprague Dawley rats. The hardness, and disintegration of the printlets varied from 2.6±1.0 (F4) to 7.7±0.9 (F3) N and 2.0±0.4 (F2) to 7.6±0.6 (F3) sec, respectively. The drug was partially present as an amorphous form in the printlets. The drug was completely (>85%) dissolved in 20 min. No change in drug form or dissolution extent was observed after storage at in use condition. Pharmacokinetic profiles of both formulations (tablets and printlets) were almost superimposable with no statistical difference in pharmacokinetic parameters (Tmax, Cmax, and AUC0-¥)between formulations (p>0.05). Values of EC50 (half maximal effective concentration) and EC90 (maximal concentration inducing 90% maximal response) were 0.50±0.15 and 1.32±0.26 mM, 0.41±0.06 and 1.11±0.21, and 0.42±0.13 and 1.36±0.19 mM for DDS, printlet and tablet formulations, respectively, and differences were statistically insignificant (p>0.05). In conclusion, tablet and printlet formulations are expected to be clinical similar, thus clinically interchangeable.

Preparation and In Vitro Evaluation of Montelukast Sodium-Loaded 3D Printed Orodispersible Films for the Treatment of Asthma.

This research aims to produce orodispersible films (ODFs) and determine their potential use in the oral delivery of montelukast sodium for asthma treatment and allergic rhinitis. ODFs were successfully developed by Three-dimensional (3D) printing using propylene glycol (PG), and hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG). Finally, the amount of montelukast sodium in the ODFs was 5% (w/w). Drug-excipients compatibility with Fourier Transformed Infrared (FTIR) spectroscopy, mass uniformity, thickness, disintegration time, folding endurance, moisture absorption, pH, in vitro drug release (dissolution), drug content, moisture loss, moisture content, mechanical properties, and cytotoxicity studies were performed on the prepared films. All formulations disintegrated in approximately 40 s. Over 98% of drug release from all films within 2 min was confirmed. It was reported that Fm1-4 (8% HPMC and 1% PEG) and Fm2-4 (10% HPMC and 3% PEG) are more suitable for drug content, but Fm2-4 may be the ideal formulation considering its durability and transportability properties. Based on the characterization results and in vitro release values, the montelukast sodium ODF can be an option for other dosage forms. It was concluded that the formulations did not show toxic potential by in vitro cytotoxicity study with 3T3 cells. This new formulation can efficiently treat allergic rhinitis and asthma diseases.

Assessing disintegration effectiveness: A thorough evaluation using the SeDeM-ODT expert system for doxylamine succinate orodispersible formulation.

BACKGROUND: The SeDeM-ODT expert system is designed to assess the suitability of the pharmaceutical ingredients for their conversion into an orodispersible formulation by direct compression. The tool can be utilized to select the most appropriate excipients that improve the compressibility and buccodispersibility of the formulation. OBJECTIVE: This study aimed to utilize the SeDeM-ODT expert system to evaluate the performance of superdisintegrants and select an appropriate superdisntegrant for Doxylamine Succinate orodispersible formulation. METHOD: The SeDeM-ODT expert system scrutinized the excipients to develop an orodispersible Doxylamine Succinate formulation. Among the 15 parameters of the tool, some of them were determined through experimental work, while the remaining were calculated through the experimental values of other parameters. The central composite design approach was used for formulation development. The prepared powder blends were compressed using the direct compression method and evaluated for different parameters (hardness, thickness, diameter, friability, weight variation, water absorption ratio, wetting time, and disintegration time). RESULTS: The results of the SeDeM-ODT expert system were correlated with the values obtained by the post-compression tests. The Crospovidone formulation (F7) was found to be an optimized formulation as it disintegrated quickly compared with the other formulations containing other superdisintegtrants. The results perfectly endorsed the SeDeM-ODT expert system evaluation, as Crospovidone showed the highest IGCB value of 6.396. CONCLUSION: The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The assessment proved Crospovidone to produce quicker disintegration in Doxylamine Succinate orodispersible formulation.

Alternative buffer systems in biopharmaceutical formulations and their effect on protein stability.

The formulation of biopharmaceutical drugs is designed to eliminate chemical instabilities, increase conformational and colloidal stability of proteins, and optimize interfacial stability. Among the various excipients involved, buffer composition plays a pivotal role. However, conventional buffers like histidine and phosphate buffers may not always be the optimal choice for all monoclonal antibodies (mAbs). In this study, we investigated the effects of several alternative buffer systems on seven different mAbs, exploring various combinations of ionic strengths, concentrations of the main buffer component, mAb concentrations, and stress conditions. Protein stability was assessed by analyzing soluble aggregate formation through size exclusion chromatography. At low protein concentrations, protein instability after temperature stress was exclusively observed in the bis-TRIS/ glucuronate buffer. Conversely, freeze-thaw stress led to a significant increase in aggregate formation in tested formulations, highlighting the efficacy of several alternative buffers, particularly arginine/ citrate, in preserving protein stability. Under temperature stress, the introduction of arginine to histidine buffer systems provided additional stabilization, while the addition of lysine resulted in protein destabilization. Similarly, the incorporation of arginine into histi-dine/HCl buffer further enhanced protein stability during freeze--thaw cycles. At high protein concentrations, the histidine/citrate buffer emerged as one of the most optimal choices for addressing temperature and light-induced stress. The efficacy of histidine buffers in combating light stress might be attributed to the light-absorbing properties of histidine molecules. Our findings demonstrate that the development of biopharmaceutical formulations should not be confined to conventional buffer systems, as numerous alternative options exhibit comparable or even superior performance.