LacdiNAc to LacNAc: remodelling of bovine α-lactalbumin N-glycosylation during the transition from colostrum to mature milk.

α -Lactalbumin, an abundant protein present in the milk of most mammals, is associated with biological, nutritional and technological functionality. Its sequence presents N-glycosylation motifs, the occupancy of which is species-specific, ranging from no to full occupancy. Here, we investigated the N-glycosylation of bovine α-lactalbumin in colostrum and milk sampled from four individual cows, each at 9 time points starting from the day of calving up to 28.0 d post-partum. Using a glycopeptide-centric mass spectrometry-based glycoproteomics approach, we identified N-glycosylation at both Asn residues found in the canonical Asn-Xxx-Ser/Thr motif, i.e. Asn45 and Asn74 of the secreted protein. We found similar glycan profiles in all four cows, with partial site occupancies, averaging at 35% and 4% for Asn45 and Asn74, respectively. No substantial changes in occupancy occurred over lactation at either site. Fucosylation, sialylation, primarily with N-acetylneuraminic acid (Neu5Ac), and a high ratio of N,N'-diacetyllactosamine (LacdiNAc)/N-acetyllactosamine (LacNAc) motifs were characteristic features of the identified N-glycans. While no substantial changes occurred in site occupancy at either site during lactation, the glycoproteoform (i.e. glycosylated form of the protein) profile revealed dynamic changes; the maturation of the α-lactalbumin glycoproteoform repertoire from colostrum to mature milk was marked by substantial increases in neutral glycans and the number of LacNAc motifs per glycan, at the expense of LacdiNAc motifs. While the implications of α-lactalbumin N-glycosylation on functionality are still unclear, we speculate that N-glycosylation at Asn74 results in a structurally and functionally different protein, due to competition with the formation of its two intra-molecular disulphide bridges.

Cysteine Oxidation in Human Galectin-1 Occurs Sequentially via a Folded Intermediate to a Fully Oxidized Unfolded Form.

Galectins are multifunctional effectors in cellular homeostasis and dysregulation. Oxidation of human galectin-1 (Gal-1) with its six sulfhydryls produces a disulfide-bridged oxidized form that lacks normal lectin activity yet gains new glycan-independent functionality. Nevertheless, the mechanistic details as to how Gal-1 oxidation occurs remain unclear. Here, we used 15N and 13C HSQC NMR spectroscopy to gain structural insight into the CuSO4-mediated path of Gal-1 oxidation and identified a minimum two-stage conversion process. During the first phase, disulfide bridges form slowly between C16-C88 and/or C42-C66 to produce a partially oxidized, conformationally flexible intermediate that retains the ability to bind lactose. Site-directed mutagenesis of C16 to S16 impedes the onset of this overall slow process. During the second phase, increased motional dynamics of the intermediate enable the relatively distant C2 and C130 residues to form the third and final disulfide bond, leading to an unfolded state and consequent dimer dissociation. This fully oxidized end state loses the ability to bind lactose, as shown by the hemagglutination assay. Consistent with this model, we observed that the Gal-1 C2S mutant maintains intermediate-state structural features with a free sulfhydryl group at C130. Incubation with dithiothreitol reduces all disulfide bonds and allows the lectin to revert to its native state. Thus, the sequential, non-random formation of three disulfide bridges in Gal-1 in an oxidative environment acts as a molecular switch for fundamental changes to its functionality. These data inspire detailed bioactivity analysis of the structurally defined oxidized intermediate in, e.g., acute and chronic inflammation.

Risks of dairy derived excipients in medications for lactose intolerant and cow milk protein allergic patients.

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.

Development and Validation of Novel Z-360-Based Macromolecules for the Active Targeting of CCK2-R.

The cholecystokinin type 2 receptor (CCK2-R) represents an ideal target for cancer therapy since it is overexpressed in several tumors and is associated with poor prognosis. Nastorazepide (Z-360), a selective CCK2-R antagonist, has been widely investigated as a CCK2-R ligand for targeted therapy; however, its high hydrophobicity may represent a limit to cell selectivity and optimal in vivo biodistribution. Here, we present three new fluorescent Z-360 derivatives (IP-002G-Rho, IP-002L-Rho, and IP-002M-Rho) in which nastorazepide was linked, through spacers bearing different saccharides (glucose (G), lactose (L), and maltotriose (M)), to sulforhodamine B. A fourth compound (IP-002H-Rho) with no pendant sugar was also synthesized as a control. Through two-dimensional (2D) and three-dimensional (3D) in vitro studies, we evaluated the compound association with and selectivity for CCK2-R-overexpressing cells (A431-CCK2-R+) vs CCK2-R-underexpressing cells (A431 WT). 2D in vitro studies highlighted a progressive increase of IP-002x-Rho association with A431-CCK2-R+ cells according to the linker hydrophilicity, that is, maltotriose > lactose > glucose > hydrogen, with IP-002M-Rho showing a 2.4- and a 1.36-fold higher uptake than IP-002G-Rho and IP-002L-Rho, respectively. Unexpectedly, IP-002H-Rho showed a similar cell association to that of IP-002L-Rho but with no difference between the two tested cell lines. On the contrary, association with A431-CCK2-R+ cells as compared to the A431 WT was found to be 1.08-, 1.14-, and 1.37-fold higher for IP-002G-Rho, IP-002L-Rho, and IP-002M-Rho, respectively, proving IP-002M-Rho to be the best-performing compound, as also confirmed by competition studies. Trafficking studies on A431-CCK2-R+ cells incubated with IP-002M-Rho suggested the coexistence of receptor-mediated endocytosis and simple diffusion. On the contrary, a high and selective uptake of IP-002M-Rho by A431-CCK2-R+ cells only was observed on 3D scaffolds embedded with cells, underlining the importance of 3D models in in vitro preliminary evaluation.

Co-immobilization of a bi-enzymatic cascade into hierarchically porous MIL-53 for efficient 6'-sialyllactose production.

6'-Sialyllactose (6'-SL), the most abundant sialylated human milk oligosaccharide, has attracted attention for its potential application in supplementary infant formulas. Herein, we report a facile strategy to construct a cascade bioreactor for the enzymatic synthesis of 6'-SL by co-immobilizing an enzymatic module consisting of CMP-sialic acid synthase and α-2,6-sialyltransferase into hierarchically porous MIL-53 (HP-MIL-53). The as-prepared HP-MIL-53 showed high enzyme immobilization capacity, reaching 226 mg g-1. Furthermore, the co-immobilized enzymes exhibited higher initial catalytic efficiency, and thermal, pH and storage stability than the free ones. Finally, the 6'-SL yield remained >80% after 13 cycles of use. We expect that HP-MIL-53 would have potential industrial applications in the enzymatic modular synthesis of 6'-SL and other glycans.

Glycopolymer with Sulfated Fucose and 6'-Sialyllactose as a Dual-Targeted Inhibitor on Resistant Influenza A Virus Strains.

The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6'-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.

Stabilization of ß-D-galactosidase in solution containing chitosan-based membrane: Central composite rotatable design.

ß-D-galactosidase is a hydrolase enzyme capable of hydrolyzing lactose in milk-based foods. Its free form can be inactivated in solution during the production of low-dosage lactose foods. Then, it is important to study strategies for avoiding the free enzyme inactivation with the aim of circumventing this problem. The stabilization of ß-D-galactosidase in aqueous solution after interactions with chitosan/eucalyptus sawdust composite membrane proved to be a potential strategy when optimized by central composite rotatable (CCR) design. In this case, the best experimental conditions for ß-D-galactosidase partitioning and stability in an aqueous medium containing the chitosan-based composite membrane reinforced with eucalyptus sawdust were i) enzyme/buffer solution ratio of 0.0057, ii) pH 5.6, iii) membrane mass of 50 mg, and iv) temperature lower than 37 °C. Significance was found for the linear enzyme/buffer solution ratio, linear temperature, and quadratic pH (p < 0.05) in the interval between 0 and 60 min of study. In the interval between 60 and 120 min, there was significance (p < 0.12) for linear temperature, the temperature-enzyme/buffer solution ratio interaction and the interaction between linear pH and linear enzyme/buffer solution ratio. The Pareto charts and response surfaces clearly showed all the effects of the experimental variables on the stabilization of ß-D-galactosidase in solution after interactions with the chitosan composite membrane. In this case, industrial food reactors covered with chitosan/eucalyptus sawdust composite membrane could be a strategy for the hydrolysis of lactose during milk-producing processes.

Enzymatically Oxidized Carbohydrates As Dicarbonyl Biobased Cross-Linkers for Polyamines.

Carbonyl cross-linkers are used to modify textiles and form resins, and are produced annually in megatonne volumes. Due to their toxicity toward the environment and human health, however, less harmful biobased alternatives are needed. This study introduces carbonyl groups to lactose and galactose using galactose oxidase from Fusarium graminearum (FgrGalOx) and pyranose dehydrogenase from Agaricus bisporus (AbPDH1) to produce four cross-linkers. Differential scanning calorimetry was used to compare cross-linker reactivity, most notably resulting in a 34 °C decrease in reaction peak temperature (72 °C) for FgrGalOx-oxidized galactose compared to unmodified galactose. Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and proton nuclear magnetic resonance (1H NMR) spectroscopy were used to verify imine formation and amine and aldehyde depletion. Cross-linkers were shown to form gels when mixed with polyallylamine, with FgrGalOx-oxidized lactose forming gels more effectively than all other cross-linkers, including glutaraldehyde. Further development of carbohydrate cross-linker technologies could lead to their adoption in various applications, including in adhesives, resins, and textiles.

Calorimetric investigation on heat release during the disintegration process of pharmaceutical tablets.

The compendial USP〈701〉 disintegration test method offers a crucial pass/fail assessment for immediate release tablet disintegration. However, its single end-point approach provides limited insight into underlying mechanisms. This study introduces a novel calorimetric approach, aimed at providing comprehensive process profiles beyond binary outcomes. We developed a novel disintegration reaction calorimeter to monitor the heat release throughout the disintegration process and successfully obtained enthalpy change profiles of placebo tablets with various porosities. The formulation comprised microcrystalline cellulose (MCC), anhydrous lactose, croscarmellose sodium (CCS), and magnesium stearate (MgSt). An abrupt temperature rise was observed after introducing the disintegration medium to tablets, and the relationship between the heat rise time and the tablet's porosity was investigated. The calorimeter's sensitivity was sufficient to discern distinct heat changes among individual tablets, and the analysis revealed a direct correlation between the two. Higher porosity corresponded to shorter heat rise time, indicating faster disintegration rates. Additionally, the analysis identified a concurrent endothermic process alongside the anticipated exothermic phenomenon, potentially associated with the dissolution of anhydrous lactose. Since lactose is the only soluble excipient within the blend composition, the endothermic process can be attributed to the absorption of heat as lactose molecules dissolve in water. The findings from this study underscore the potential of utilising calorimetric methods to quantify the wettability of complex compounds and, ultimately, optimise tablet formulations.

Use of dairy industry side-stream lactose for tablet manufacturing - proof of concept study.

During recent years there have been shortages of certain drugs due to problems in raw material supply. These are often related to active ingredients but could also affect excipients. Lactose is one of the most used excipients in tableting and comes in two anomeric and several solid-state forms. The aim of this study was to utilize lactose from a dairy side-stream and compare it against a commercial reference in direct compression. This would be a sustainable option and would secure domestic availability during crises. Two types of lactose, spray-dried and freeze-dried, were evaluated. Lactose was mixed with microcrystalline cellulose in different ratios together with lubricant and glidant, and flowability and tabletability of the formulations was characterized. The fully amorphous and small particle-sized spray-dried lactose flowed inadequately but exhibited good tabletability. The larger particle-sized, freeze-dried lactose exhibited sufficient flow and better tabletability than the commercial reference. However, disintegration and drug release were slower when using the investigational lactose formulations. This was most likely due to remaining milk proteins, especially caseins, in the lactose. Overall, the investigational lactose provides promise for the use of such a side-stream product during crisis situations but enhancing their properties and/or purity would be needed.

A modified mechanistic approach for predicting ribbon solid fraction at different roller compaction speeds.

This research investigates the modeling of the pharmaceutical roller compaction process, focusing on the application of the Johanson model and the impact of varying roll speeds from 1 to 15 RPM on predictive accuracy of ribbon solid fraction. The classical Johanson's model was integrated with a dwell time parameter leading to an expression of a floating correction factor as a function of roll speed. Through systematic analysis of the effect of different roll speeds on the solid fraction of ribbons composed of microcrystalline cellulose, lactose, and their blends, corrective adjustment to the Johanson model was found to depend on both roll speed and formulation composition. Interestingly, the correction factor demonstrated excellent correlation with the blend's mechanical properties, namely yield stress (Py) and elastic modulus (E0), representative of the deformability of the powder. Validated by a multicomponent drug formulation with ±0.4-1.3 % differences, the findings underscore the utility of this modified mechanistic approach for precise prediction of ribbon solid fraction when Py or E0 is known for a given blend. Hence, this work advances the field by offering early insights for more accurate and controllable roller compaction operations during late-stage pharmaceutical manufacturing.

Effects of Three Kinds of Carbohydrate Pharmaceutical Excipients-Fructose, Lactose and Arabic Gum on Intestinal Absorption of Gastrodin through Glucose Transport Pathway in Rats.

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.

Promotion of lactose isomerization to fructose and lactulose in one batch by immobilized enzymes on bacterial cellulose membranes.

The production of the sugars fructose and lactulose from lactose using the enzymes ß-galactosidase and glucose isomerase immobilized on bacterial cellulose (BC) membranes has been investigated. Lactose is hydrolyzed by ß-galactosidase at 30 °C to glucose and galactose at a high conversion rate, while at the same temperature, glucose isomerase is not effective in converting the produced glucose to fructose. The rate of the isomerization reaction of glucose to fructose at 70 °C has been studied. Two types of enzyme immobilization were investigated: immobilization in one stage and immobilization in two stages. The results showed that BC membrane increased three-fold the yield and the reaction rate of fructose and lactulose production from lactose. The noteworthy enhancement of BC membranes' impact on the isomerization reaction by immobilized enzymes grants permission for a novel research avenue within the context of white biotechnology development. Additionally, this effect amplifies the role of BC in sustainability and the circular economy.

The archaeal highly thermostable GH35 family ß-galactosidase DaßGal has a unique seven domain protein fold.

The most extensively studied ß-d-galactosidases (EC3.2.1.23) belonging to four glycoside hydrolase (GH) families 1, 2, 35, and 42 are widely distributed among Bacteria, Archaea and Eukaryotes. Here, we report a novel GH35 family ß-galactosidase from the hyperthermophilic Thermoprotei archaeon Desulfurococcus amylolyticus (DaßGal). Unlike fungal monomeric six-domain ß-galactosidases, the DaßGal enzyme is a dimer; it has an extra jelly roll domain D7 and three composite domains (D4, D5, and D6) that are formed by the distantly located polypeptide chain regions. The enzyme possesses a high specificity for ß-d-galactopyranosides, and its distinguishing feature is the ability to cleave pNP-ß-d-fucopyranoside. DaßGal efficiently catalyzes the hydrolysis of lactose at high temperatures, remains stable and active at 65 °Ð¡, and retains activity at 95 °Ð¡ with a half-life time value equal to 73 min. These properties make archaeal DaßGal a more attractive candidate for biotechnology than the widely used fungal ß-galactosidases.

Rational Design of Highly Selective Sialyllactose-Imprinted Nanogels.

We describe a facile method to prepare water-compatible molecularly imprinted polymer nanogels (MIP NGs) as synthetic antibodies against target glycans. Three different phenylboronic acid (PBA) derivatives were explored as monomers for the synthesis of MIP NGs targeting either α2,6- or α2,3-sialyllactose, taken as oversimplified models of cancer-related sT and sTn antigens. Starting from commercially available 3-acrylamidophenylboronic acid, also its 2-substituted isomer and the 5-acrylamido-2-hydroxymethyl cyclic PBA monoester derivative were initially evaluated by NMR studies. Then, a small library of MIP NGs imprinted with the α2,6-linked template was synthesized and tested by mobility shift Affinity Capillary Electrophoresis (msACE), to rapidly assess an affinity ranking. Finally, the best monomer 2-acrylamido PBA was selected for the synthesis of polymers targeting both sialyllactoses. The resulting MIP NGs display an affinity constant≈106 M-1 and selectivity towards imprinted glycans. This general procedure could be applied to any non-modified carbohydrate template possessing a reducing end.

Potential of Powder Rheology for Detecting Unforeseen Cross-Contamination of Foreign Active Pharmaceutical Ingredients.

Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.

Croscarmellose Sodium as Pelletization Aid in Extrusion-Spheronization.

Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was investigated. Furthermore, the impact of cations on extrusion-spheronization (ES) of CCS was studied and different grades of CCS were tested. The influence of different cations on the swelling of CCS was investigated by laser diffraction. Mixtures of CCS with lactose monohydrate as filler with or without the inclusion of different cations were produced. The mixtures were investigated by mixer torque rheometry and consequently extruded and spheronized. Resulting pellets were analyzed by dynamic image analysis. In addition, mixtures of different CCS grades with dibasic calcium phosphate anhydrous (DP) and a mixture with praziquantel (PZQ) as filler were investigated. Calcium and magnesium cations caused a decrease of the swelling of CCS and influenced the use of CCS as pelletization aid since they needed to be included for successful ES. Aluminum, however, led to an aggregation of the CCS particles and to failure of extrusion. The inclusion of cations decreased the uptake of water by the mixtures which also reduced the liquid-to-solid-ratio (L/S) for successful ES. This was shown to be dependent on the amount of divalent cations in the mixture. With DP or PZQ as filler, no addition of cations was necessary for a successful production of pellets, however the optimal L/S for ES was dependent on the CCS grade used. In conclusion, CCS can be used as a pelletization aid.

Reduction of maillard browning in spray dried low-lactose milk powders due to protein polysaccharide interactions.

Lactose hydrolysed concentrated milk was prepared using ß-galactosidase enzyme (4.76U/mL) with a reaction period of 12 h at 4 °C. Addition of polysaccharides (5 % maltodextrin/ß-cyclodextrin) to concentrated milk either before or after lactose hydrolysis did not result in significant differences (p > 0.05) in degree of hydrolysis (% DH) of lactose and residual lactose content (%). Three different inlet temperatures (165 °C, 175 °C and 185 °C) were used for the preparation of powders which were later characterised based on physico-chemical and maillard browning characteristics. Moisture content, solubility and available lysine content of the powders decreased significantly, whereas, browning parameters i.e., browning index, 5-hydroxymethylfurfural, furosine content increased significantly (p < 0.05) with an increase in inlet air temperature. The powder was finally prepared with 5 % polysaccharide and an inlet air temperature of 185 °C which reduced maillard browning. Protein-polysaccharide interactions were identified using Fourier Transform infrared spectroscopy, fluorescence spectroscopy and determination of free amino groups in the powder samples. Maltodextrin and ß-cyclodextrin containing powder samples exhibited lower free amino groups and higher degree of graft value as compared to control sample which indicated protein-polysaccharide interactions. Results obtained from Fourier Transform infrared spectroscopy also confirmed strong protein-polysaccharide interactions, moreover a significant decrease in fluorescence intensity was also observed in the powder samples. These interactions between the proteins and polysaccharides reduced the maillard browning in powders.

Selection of lubricant type and concentration for orodispersible tablets.

Lubricants are essential for most tablet formulations as they assist powder flow, prevent adhesion to tableting tools and facilitate tablet ejection. Magnesium stearate (MgSt) is an effective lubricant but may compromise tablet strength and disintegratability. In the design of orodispersible tablets, tablet strength and disintegratability are critical attributes of the dosage form. Hence, this study aimed to conduct an in-depth comparative study of MgSt with alternative lubricants, namely sodium lauryl sulphate (SLS), stearic acid (SA) and hydrogenated castor oil (HCO), for their effects on the tableting process as well as tablet properties. Powder blends were prepared with lactose, sodium starch glycolate or crospovidone as the disintegrant, and a lubricant at different concentrations. Angle of repose was determined for the mixtures. Comparative evaluation was carried out based on the ejection force, tensile strength, liquid penetration and disintegratability of the tablets produced. As the lubricant concentration increased, powder flow and tablet ejection improved. The lubrication efficiency generally decreased as follows: MgSt > HCO > SA > SLS. Despite its superior lubrication efficacy, MgSt is the only lubricant of four evaluated that reduced tablet tensile strength. Tablet disintegration time was strongly determined by tensile strength and liquid penetration, which were in turn affected by the lubricant type and concentration. All the above factors should be taken into consideration when deciding the type and concentration of lubricant for an orodispersible tablet formulation.

Evaluation of binders in twin-screw wet granulation - Optimization of tabletability.

The influence of hydroxypropyl cellulose type (HPC-SSL SFP, HPC-SSL), concentration (2 %, 3.5 %, 5 %) and filler (lactose, calcium hydrogen phosphate (DCP)/microcrystalline cellulose (MCC)) on twin-screw wet granulation and subsequent tableting was studied. The aim was to identify the formulation of the highest tabletability which still fulfills the requirements of the disintegration. Lactose combined with 5 % binder enabled a higher tabletability and a faster disintegration than DCP/MCC. It was found that tabletability of lactose formulations can be increased by higher binder concentration and higher compression pressure while tabletability of DCP/MCC formulations can be only increased by higher compression pressure. It was observed that batches containing DCP/MCC failed the disintegration test, if the highest binder concentration and the highest compression pressure were used. To ensure a fast disintegration, the compression pressure or at least the binder concentration had to be low. Changing the disintegrant and its localization improved the DCP/MCC formulation, resulting in faster disintegration than lactose tablets. However, it also resulted in a lower tabletability. In this study best tablets were achieved with 3.5 % or 5 % binder and lactose as filler. These tablets presented the highest tabletability but still disintegrated in less than 500 s.