The role of C18 fatty acids in improving the digestion and retrogradation properties of highland barley starch.

In this study, five C18 fatty acids (FA) with different numbers of double bonds and configurations including stearic acid (SA), oleic acid (OA), elaidic acid (EA), linoleic acid (LA), and α-linolenic acid (ALA), were selected to prepare highland barely starch (HBS)-FA complexes to modulate digestibility and elaborate the underlying mechanism. The results showed that HBS-SA had the highest complex index (34.18 %), relative crystallinity (17.62 %) and single helix content (25.78 %). Furthermore, the HBS-C18 FA complexes were formed by EA (C18 FA with monounsaturated bonds) that had the highest R1047/1022 (1.0509) and lowest full width at half-maximum (FWHM, 20.85), suggesting good short-range ordered structure. Moreover, all C18 FAs could form two kinds of V-type complexes with HBS, which can be confirmed by the results of CLSM and DSC measurements, and all of them showed significantly lower digestibility. HBS-EA possessed the highest resistant starch content (20.17 %), while HBS-SA had the highest slowly digestible starch content (26.61 %). In addition, the inhibition of HBS retrogradation by fatty acid addition was further proven, where HBS-SA gel firmness (37.80 g) and aging enthalpy value were the lowest, indicating the most effective. Overall, compounding with fatty acids, especially SA, could be used as a novel way to make functional foods based on HBS.

Oral In-Situ Nanoplatform with Balanced Hydrophobic-Hydrophilic Property for Transport Across Gastrointestinal Mucosa.

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez™ AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur (Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE). Cur-Lipo size and EE was optimized by Box-Behnken Design. Cur-Lipomers of varying hydrophobic-hydrophilic property obtained by varying the stearic acid: Gantrez ratio exhibited size in the range 200-400 nm, EE > 95% and spherical morphology as seen in the TEM. A decrease in contact angle and in mucus interaction, evident with increase in Gantrez concentration, indicated an inverse corelation with hydrophilicity, while a linear corelation was observed for mucopenetration and hydrophilicity. Cur-SLN (solid lipid nanoparticles) which served as the hydrophobic reference revealed contact angle > 90°, maximum interaction with mucus and minimal mucopenetration. The ex-vivo permeation study through chicken ileum, revealed maximum permeation with Cur-Lipo1 and comparable and significantly lower permeation of Cur-Lipo1-D and Cur-SLN proposing the importance of balancing the hydrophobic-hydrophilic property of the nanoparticles. A 1.78-fold enhancement in flux of hydrophobic Cur-SLN, with no significant change in permeation of the hydrophilic Cur-Lipomers (p > 0.05) following stripping off the mucosal layer was observed. This reiterated the significance of hydrophobic-hydrophilic balance as a promising strategy to design nanoformulations with superior permeation across the GI barrier.

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.

Metal-organic complex coating for enhanced corrosion control and biocompatibility on biodegradable magnesium alloy for orthopaedic implants.

Magnesium alloy is currently regarded as the most favourable biodegradable metal; however, obstacles remain to be overcome in terms of managing its corrosion and ensuring its biocompatibility. In this study, a metal-organic complex comprising Ca ions incorporated in tannic acid (TA) was prepared and used to coat magnesium alloy by chemical conversion and dipping processes, followed by modification with stearic acid (SA). This metal-organic complex coating was demonstrated to be homogeneous and compact, and it significantly improved the electrochemical corrosion resistance and long-term degradation behaviour of the coated samples. Consequently, the well-controlled release of Mg and Ca ions, as well as the osteo-compatible TA and SA molecules, promoted the proliferation of osteoblast cells. This metal-organic complex coating offers a promising modifying strategy for magnesium-based orthopaedic implants.

Investigating the impact of common migration substances found in milk packaging on proteases: A multispectral and molecular docking approach.

The effects of common migration substances in milk packaging on digestive protease were studied. We choose the common migrants found in eight types of multi-layer composite milk packaging. Enzyme activity experiments revealed that pepsin activity decreased by approximately 18 % at 500 µg/mL of stearic acid and stearamide treatment, while trypsin activity decreased by approximately 18 % only by stearic acid treatment (500 µg/mL). Subsequently, fluorescence spectroscopy, circular dichroism spectroscopy, and molecular docking technology were employed to investigate the inhibition mechanism of protease activity by migrating substances in three systems: stearic acid-trypsin, stearic acid-pepsin, and stearamide-pepsin. Results showed that the inhibitory effect of stearic acid on trypsin is a reversible mixed inhibition, whereas the inhibitory effects of stearic acid and stearamide on pepsin are non-competitive. In all three systems, ΔH < 0, ΔS < 0, and ΔG < 0, indicating the binding process between the migrant and the protease is a spontaneous exothermic process primarily driven by hydrogen bonding and van der Waals forces. In addition, their binding constants are all around 104 L/moL, indicating that there are moderate binding affinities exist between migrants and proteases. The binding process results in the quenching of the protease's endogenous fluorescence and induces alterations in the enzyme's secondary structure. Synchronized fluorescence spectroscopy showed that stearic acid enhanced the hydrophobicity near the Tyr residue of trypsin. The molecular docking results indicated that the binding affinity of stearic acid-trypsin, stearic acid-pepsin, and stearamide-pepsin was -22.51 kJ/mol, -12.35 kJ/mol, -19.28 kJ/mol respectively, which consistent with the trend in the enzyme activity results. This study can provide references for the selection of milk packaging materials and the use of processing additives, ensuring food health and safety.

Time-Dependent and Coating Modulation of Tomato Response upon Sulfur Nanoparticle Internalization and Assimilation: An Orthogonal Mechanistic Investigation.

Nanoenabled strategies have recently attracted attention as a sustainable platform for agricultural applications. Here, we present a mechanistic understanding of nanobiointeraction through an orthogonal investigation. Pristine (nS) and stearic acid surface-modified (cS) sulfur nanoparticles (NPs) as a multifunctional nanofertilizer were applied to tomato (Solanum lycopersicumL.) through soil. Both nS and cS increased root mass by 73% and 81% and increased shoot weight by 35% and 50%, respectively, compared to the untreated controls. Bulk sulfur (bS) and ionic sulfate (iS) had no such stimulatory effect. Notably, surface modification of S NPs had a positive impact, as cS yielded 38% and 51% greater shoot weight compared to nS at 100 and 200 mg/L, respectively. Moreover, nS and cS significantly improved leaf photosynthesis by promoting the linear electron flow, quantum yield of photosystem II, and relative chlorophyll content. The time-dependent gene expression related to two S bioassimilation and signaling pathways showed a specific role of NP surface physicochemical properties. Additionally, a time-dependent Global Test and machine learning strategy applied to understand the NP surface modification domain metabolomic profiling showed that cS increased the contents of IA, tryptophan, tomatidine, and scopoletin in plant leaves compared to the other treatments. These findings provide critical mechanistic insights into the use of nanoscale sulfur as a multifunctional soil amendment to enhance plant performance as part of nanoenabled agriculture.

Preparation, Optimization and In Vitro Characterization of Fluticasoneloaded Mixed Micelles Based on Stearic Acid-g-chitosan as a Pulmonary Delivery System.

PURPOSE: The primary objective of this study was to optimize formulation variables and investigate the in vitro characteristics of fluticasone propionate (FP)-loaded mixed polymeric micelles, which were composed of depolymerized chitosan-stearic acid copolymer (DC-SA) in combination with either tocopheryl polyethylene glycol succinate or dipalmitoylphosphatidylcholine for pulmonary drug delivery. METHODS: A D-optimal design was employed for the optimization procedure, considering lipid/ polymer ratio, polymer concentration, drug/ polymer ratio, and lipid type as independent variables. Dependent variables included particle size, polydispersion index, zeta potential, drug encapsulation efficiency, and loading efficiency of the polymeric micelles. Additionally, the nebulization efficacy and cell viability of the optimal FP-loaded DC-SA micellar formulations were evaluated. RESULTS: The mixed polymeric micelles were successfully prepared with properties falling within the desired ranges, resulting in four optimized formulations. The release of FP from the optimal systems exhibited a sustained release profile over 72 hours, with 70% of the drug still retained within the core of the micelles. The nebulization efficiency of these optimal formulations reached up to 63%, and the fine particle fraction (FPF) ranged from 41% to 48%. Cellular viability assays demonstrated that FP-loaded DC-SA polymeric micelles exhibited lower cytotoxicity than the free drug but were slightly more cytotoxic than empty mixed micelles. CONCLUSION: In conclusion, this study suggests that DC-SA/ lipid mixed micelles have the potential to serve as effective carriers for nebulizing poorly soluble FP.

Effect of particle size on the dispersion behavior of magnesium stearate blended with microcrystalline cellulose.

The majority of tablets manufactured contain lubricants to reduce friction during ejection. However, especially for plastically deforming materials, e.g., microcrystalline cellulose (MCC), the internal addition of lubricants is known to reduce tablet tensile strength. This reduction is caused by the surface coverage by lubricant particles, the extent of which depends on both process and formulation parameters. Previously published models to predict the lubrication effect on mechanical strength do not account for changes in the excipient particle size. In this study, the impact of both lubricant concentration and mixing time on the tensile strength of tablets consisting of three different grades of MCC and four grades of magnesium stearate (MgSt) was evaluated. By taking into account the particle size of the applied excipients, a unifying relationship between the theoretically estimated surface coverage and compactibility reduction was identified. Evaluating the dispersion kinetics of MgSt as a function of time reveals a substantial impact of the initial surface coverage on the dispersion rate, while the minimal tensile strength was found to be comparable for the majority of formulations. In summary, the presented work extends the knowledge of lubricant dispersion and facilitates the reduction of necessary experiments during the development of new tablet formulations.

Effect of magnesium stearate solid lipid nanoparticles as a lubricant on the properties of tablets by direct compression.

This study discusses the lubricant properties of magnesium stearate solid lipid nanoparticles (MgSt-SLN) and their effect on the tabletability, mechanical properties, disintegration, and acetaminophen-model dissolution time of microcrystalline cellulose (MCC) tablets prepared by direct compression. The behavior of MgSt-SLN was compared to reference material (RM) to identify advantages and drawbacks. The nanoprecipitation/ion exchange method was employed to prepare the MgSt-SLN. Particle size, zeta potential, specific surface area, morphology, and true density were measured to characterize the nanosystem. The MgSt-SLN particle sizes obtained were 240 ± 5 nm with a specific surface area of 12.2 m2/g. The MCC tablets with MgSt-SLN presented a reduction greater than 20 % in their ejection force, good tabletability, higher tensile strength, lower disintegration delay, and marked differences in acetaminophen dissolution when compared to the RM. The reduced particle size of the magnesium stearate seems to offer a promising technological advantage as an efficient lubricant process that does not affect the properties of tablets.

Effects of tableting process parameters and powder lubrication levels on tablet surface temperature and moisture content.

Punch sticking is a recurrent problem during the pharmaceutical tableting process. Powder moisture content plays a key role in the buildup of sticking; it evaporates due to increased tablet temperature, accumulates at the punch-tablet interface, and causes sticking through capillary force. This study investigated the effects of compaction pressure (CP), compaction speed (CS), and lubrication level (magnesium stearate (MgSt) ratio) on tablet surface temperature (TST) and tablet surface moisture content (TSMC). TST and TSMC were measured with an infrared thermal camera and near-infrared sensor, respectively. Microcrystalline cellulose was used as the tableting powder and MgSt as the lubricant. The low range of CS values (16-32 mm/s) considered in this study did not have significant effects on TST and TSMC. MgSt ratio had a significant positive effect on TST; this may be explained by the increase in powder blend effusivity with the addition of MgSt. However, MgSt ratio did not have a significant effect on TSMC. CP had a significant positive effect on both TST and TSMC. Increased CP induced higher heat generation through particle deformation and friction during the compaction phase, leading to increased TST. Furthermore, the water vapor diffusion rate through the powder bed might have increased due to the rise in thermal energy and led to further moisture accumulation at the tablet-punch interface, causing the significant positive effect of CP on TSMC. This result may explain the occurrence of sticking regardless of the CP applied during the tableting process.

Development and Characterization of Coconut Oil Oleogel with Lycopene and Stearic Acid.

Lycopene is a natural bioactive compound possessing higher antioxidant and anti-inflammatory properties, which are known to efficiently eliminate the risk of cancer, cardiac complications, and oxidative stress. Food manufacturers are keen on producing lycopene-fortified food products owing to their numerous health benefits and higher nutritional value. The incorporation of lycopene is limited to food products due to its hydrophobic nature and low chemical stability. This study aims to understand the incorporation of lycopene in Oleogel as a new delivery system. Briefly, lycopene and stearic acid (gelator) were combined at ratios of 0, 25, 50, 75, and 100% (w/w) and added to coconut oil (20 g (w/w) ) for the preparation of edible oleogel combinations. These combinations were characterized for oil binding capacity, swelling capacity, color analysis, and texture profile analysis. Further, the formulations were characterized by FTIR (Fourier Transform Infrared Spectroscopy) and DSC (Differential scanning calorimetry). It was observed that samples prepared with a combination of 50% lycopene and stearic acid were found to possess a firm texture and good stability. Conversely, samples with no gelator produced oleogels with less stability. Further, the FTIR spectra helped determine the network formation in the oleogels, which was stabilized by the hydrogen bond. Furthermore, the results of DSC exhibited that the oleogel combinations with gelator and lycopene were not in the crystalline state, and the oleogels held superior internal structure till 45°C. Overall, oleogel-based carrier systems can be used as an alternative method to encapsulate various bioactive compounds having possible potential applications in the bakery and confectionery industries.

Sodium lauryl sulfate as lubricant in tablets formulations: Is it worth?

Lubricants are excipients used in tablet formulations to reduce friction and adhesion forces within the die or on the punches surface during the manufacturing process. Despite these excipients are always required for the tablets production, their amount must be carefully evaluated since lubricants can negatively impact on mechanical strength, disintegration and dissolution behavior of solid dosage forms. Alternative compounds have been suggested to overcome the issues of conventional lubricants and sodium lauryl sulfate (SDS) is one of the most promising one. Despite SDS has been object of several investigations, a definitive conclusion on its effectiveness cannot still be drawn. Particularly, its efficacy on tablets disaggregation and API dissolution is still unclear. Here, the effect of SDS on all the relevant features of tablets and tableting process has been evaluated on immediate release hydrophobic tablets formulations in comparison with conventional lubricants. The results of this investigation are quite outspoken: SDS has a low lubricant power while it determines only a limited improvement on tablets hardness. It greatly improves the tablets wettability but only on model formulations, the presence of superdisintegrants resets its effectiveness and any possible effect on tablets disaggregation. None of the tested formulations showed improvement on the API dissolution rate.

Aqueous Binary Mixtures of Stearic Acid and Its Hydroxylated Counterpart 12-Hydroxystearic Acid: Cascade of Morphological Transitions at Room Temperature.

Here, we describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature as a function of the 12-HSA/SA mole ratio R. The morphologies of the self-assembled aggregates are obtained through a multi-structural approach that combines confocal and cryo-TEM microscopies with small-angle neutron scattering (SANS) and wide-angle X-ray scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multilamellar tubes are formed. The doping via a low amount of SA molecules slightly modifies the dimensions of the tubes and decreases the bilayer rigidity. The solutions have a gel-like behavior. At intermediate R, tubes coexist in solution with helical ribbons. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems: they are faceted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus. The solutions remain, however, viscous fluids in this regime.

Magnesium stearate surface coverage on tablets and drug crystals: Insights from SEM-EDS elemental mapping.

Scanning electron microscopy-based energy dispersive X-ray spectroscopy (SEM-EDS) is proposed as a versatile tool for quantifying surface area coverage (SAC) by magnesium stearate (MgSt) on pharmaceutical tablets and particles. Our approach involved fast elemental mapping and subsequent SAC quantitation by image analysis. The study was conducted using a multi-component system, but the particle-level mapping was limited to active pharmaceutical ingredient (API) crystals. For both tablets and API particles, the calculated SAC against MgSt loading afforded a positive linear correlation over the range of MgSt levels examined in this work. On the tablet surface, MgSt was found to be preferentially concentrated at or in the close vicinity of grain boundaries, supporting the idea of compression-driven migration and relocation of MgSt within the tablet. On the particle surface, only discrete aggregates of MgSt were observed, as opposed to the widely accepted phenomenon of the formation of a thin lubricant film around host particles. The selection of proper SEM-EDS operating conditions and the challenges confronted in particle surface mapping are discussed in detail.

Microscopic insight into the interactions between pea protein and fatty acids during high-moisture extrusion processing.

To provide a theoretical basis for the quality improvement of plant protein-based meat substitutes with lipids, the interactions between pea protein and fatty acids (stearic, oleic and linoleic acids) and the effect on protein conformational changes during high-moisture extrusion (HME) processing were investigated using a dead-stop operation. The surface hydrophobicity analysis and Fourier transform infrared spectroscopy results revealed that the fatty acids induced the exposure of hydrophobic groups in the pea proteins, weakened hydrogen bonds, affected the aggregation of legumin subunits and promoted the conversion of α-helix and ß-sheet structures to ß-turn and random coil during HME processing. In the die, unsaturated fatty acids limited the refolding of protein chains and covalent interactions between proteins. Micromorphology analysis indicated that the coalescence of oleic and linoleic acids in the cooling zone hindered the formation of anisotropic structures while stearic acid promoted the formation of fibrous structures by enhanced disulfide bonds.

Synthesis of a new hydrophobic coating film from stearic acid of buffalo fat.

This experiment involved the chemical conversion of pure stearic acid from buffalo adipose tissue to a waxy stearyl stearate, which was subsequently applied as a coating film to extend the shelf life of recently harvested fruits. Fat was extracted from minced adipose tissue using the dry rendering procedure, and it was then characterized. The extracted fat was hydrolyzed into a mixture of free fatty acids and glycerol. The supercritical CO2 extractor was used for stearic acid individual extraction in pure form from the free fatty acid mixture, and it was confirmed according to its melting point (69.2-70.0 °C), elemental analysis, GC-MS for esterified fatty acids. The isolated stearic acid was used for the synthesis of a new hydrophobic wax named stearyl stearate. The chemical structure of the prepared compound was established according to its elemental analysis and spectral data. The new hydrophobic wax was used as a coating film to enhance the shelf life of freshly harvested tomato fruits. Therefore, stearyl stearate solution (2.00% w/v diethyl ether) was used for tomato coating and compared to chitosan-coated tomatoes, where weight loss, pH, fruit firmness, ascorbic acid concentration, and total soluble solids were studied for a period of 15 days at 23 ± 1.0 °C and 65 ± 2.0% relative humidity. The results revealed that coating with stearyl stearate solution (2.00% w/v diethyl ether) could delay tomatoes' ripening during the experiment condition. A sensory evaluation of the coated tomatoes was carried out and showed acceptable taste for the tomatoes that were coated with stearyl stearate. On the other hand, the acute oral toxicity of stearyl stearate using albino mice showed complete safety up to 25 g/kg mice weight.

A compactibility-based lubricant dispersion model describing the effect of formulation and paddle speed.

In rotary tablet presses, the powder flow into the dies is typically facilitated by paddle feeder. For internally lubricated formulations, the shear forces exerted by the paddle rotation can result in a considerable decrease in tablet strength due to the dispersion of lubricant agglomerates. Available models to describe the lubricant dispersion in paddle feeder allow only a limited quantitative description and transferability of the process. This study introduces an empirical dispersion kinetic which is able to precisely describe the reduction of compactibility due to the shear stresses inside the paddle feeder, even for inhomogeneously flowing material. Additionally, by blending different grades of magnesium stearate at three levels of lubricant concentration with two different grades of microcrystalline cellulose, the impact of bulk properties on the lubrication dispersion in the feed frame was investigated. It was shown, that for a given formulation, the kinetics of compactibility reduction are comparable for different magnesium stearate concentrations. Additionally, the bulk properties of the applied magnesium stearate grade critically affect the dispersion kinetics as well as the maximum compactibility reduction inside the feed frame. In summary, the developed model represents a meaningful extension of the currently available process models for pharmaceutical tablet lubrication.

Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation.

Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also negatively affect the critical quality attributes of pharmaceutical products. Therefore, we provided a rather comprehensive evaluation of another two FDA-approved metallic stearates, sodium stearate (NaSt) and calcium stearate (CaSt), as alternative tablet lubricants. The primary objective of the present study is to comparatively evaluate the physicochemical properties and lubrication efficiency of the three metallic stearates. In addition, it was also aimed to specify the most influential factor for ranking and differentiating the lubricity of various lubricants using principal component analysis. Unit ejection force could be used herein as a simple and the most powerful parameter to evaluate the lubrication performance instead of the friction coefficient. The results suggested that CaSt, MgSt, and NaSt had similar impacts on the mechanical strength of tablets. However, CaSt exhibited insufficient lubrication effects as the formulations containing CaSt showed low pressure transmission ratios, high unit ejection forces, and high friction coefficients. In contrast, both MgSt and NaSt displayed satisfactory lubrication efficiency without negatively impacting tabletability. Notably, the lubrication performance of the formulation containing 0.5 wt% NaSt was almost identical to that of the formulation with 1 wt% MgSt, indicating that NaSt had a remarkable lubrication capability probably due to its high specific surface area. In summary, the findings of this investigation should provide practical information and feasible methodologies to readily determine the lubricity and to sensibly select alternative lubricants for pharmaceutical tablet formulations.

Impact of alternative lubricants on process and tablet quality for direct compression.

Internal lubrication with magnesium stearate (MgSt) is associated with a reduced tensile strength and prolonged disintegration and dissolution times. In the current study, alternative lubricants to MgSt were compared with regard to lubrication efficacy and their impact on tablet properties. The lubricants were combined in different concentrations (0.5-5% w/w) with three fillers (lactose, mannitol and microcrystalline cellulose (MCC)). The high lubrication efficiency of MgSt was associated with the highest reduction of tensile strength. The micronized stearic acid (SA) grades proved good alternatives as they showed a good lubrication efficiency in combination with a limited negative effect on tensile strength. The hydrophobic lubricants (e.g., MgSt and SA) did not prolong disintegration. In contrast, delayed disintegration was observed for sucrose monopalmitate combined with all three fillers and for several other hydrophilic lubricants (sodium lauryl sulfate, poloxamers 188 and P407) combined with MCC. These unexpected findings were explained by the competition-for-water hypothesis. The potential of alternative lubricants to MgSt was demonstrated in this study. Nevertheless, the impact of lubricant addition on process and tablet quality depended on lubricant (type and concentration) and formulation (lubrication need, deformation mechanism and disintegration behavior) properties. Therefore, lubricant selection should be carefully considered in formulation development.

Effect of feed frame on lubricant sensitivity during upscaling from a compaction simulator to a rotary tablet press.

Internal lubrication can be associated with reduced tabletability. Deformation mechanism, lubricant type, lubricant blending time and paddle speed (PS) of the forced feeder are known to be influenceable factors. This study investigated the effect of lubricant blending time and PS of forced feeders on the tensile strength of lubricated microcrystalline cellulose (MCC) and lactose tablets. Magnesium stearate (MgSt), sodium stearyl fumarate (SSF) and stearic acid (SA) were used as lubricants. Tablets were produced on a compaction simulator and a rotary tablet press to investigate lubricant sensitivity during upscaling. Lubricant sensitivity was found higher for MCC compared to lactose which was attributed to the higher plasticity of MCC. The reduction in tensile strength upon lubricant addition followed the order: MgSt > SSF > SA; which could be linked to particle size, specific surface area and particle shape of the lubricants. Although differences in tensile strength were observed between the lubricant types, comparable ejection forces were obtained. The impact of PS on tensile strength was higher compared to lubricant blending time for both tableting machines. A good correlation of tensile strength and lubricant sensitivity between the compaction simulator and rotary tablet press was observed based on the calculation of paddle passes (NPP).