Commercial Lactose Research Articles

Study of lactose crystallization in vibrated bed using high and specific seeding

Lactose crystallization is an operation addressed in several scientific studies and used in dairy industries to obtain a final product with high purity, even from impure solutions. Vibration agitation becomes a relevant factor in promoting mass transfer solution-crystalline surface and minimizing breakages and ruptures in the latter. The crystallization step can be triggered by the seeding of particles (fines) of the same substance to be crystallized, promoting greater control and uniform particle size. The objective of this work was to study the operation of crystallization of lactose in a vibrated bed, using high seeding with controlled structure and size (specific). A central composite design with subsequent optimization was used as a statistical tool. Optimum operating levels were obtained, which returned responses of average productivity of 119.0 ± 2.1% and average diameter of 8.06 ± 0.22×10-6 m, also promoting an increase in the average size of crystallization products (growth of 43.6%), which was not observed in the previous study such as seeding with milled commercial lactose.

Crystallization induced flower-like lactose as potential carriers for dry powder inhaler application

The study documents the flower-like lactose particles as potential carriers to improve Dry Powder Inhaler (DPI) efficiency. The lactose particles (LMx, LMf) are prepared by anti-solvent crystallization and compared with commercial lactose carriers (Inhalac 251; LMc). Formulations of 1.48% w/w drug loading are prepared using salbutamol sulfate (model drug) and different lactose carriers. The carrier properties are correlated with %FPF using principal component analysis. The analytical results confirm LMx is α-lactose monohydrate, LMf comprises α and β-lactose. Time-resolved crystal growth shows that the LMx particle is agglomerated structure while, LMf particle appear as flower-like structure of size (~45.37–63.92 μm) with high surface and aerodynamic properties compared to LMc. The in-vitro aerosolization studies resulted in higher fine particle fraction (%FPF) for formulations with LMx (~33.23%) and LMf (~44.85%) compared to LMc (~23.40%). The high %FPF is mainly attributed to the higher surface roughness, amorphicity, surface energy of engineered lactose carriers.

Rapid, Sensitive and Reliable Ricin Identification in Serum Samples Using LC-MS/MS.

Ricin, a protein derived from the seeds of the castor bean plant (Ricinus communis), is a highly lethal toxin that inhibits protein synthesis, resulting in cell death. The widespread availability of ricin, its ease of extraction and its extreme toxicity make it an ideal agent for bioterrorism and self-poisoning. Thus, a rapid, sensitive and reliable method for ricin identification in clinical samples is required for applying appropriate and timely medical intervention. However, this goal is challenging due to the low predicted toxin concentrations in bio-fluids, accompanied by significantly high matrix interferences. Here we report the applicability of a sensitive, selective, rapid, simple and antibody-independent assay for the identification of ricin in body fluids using mass spectrometry (MS). The assay involves lectin affinity capturing of ricin by easy-to-use commercial lactose–agarose (LA) beads, following by tryptic digestion and selected marker identification using targeted LC–MS/MS (Multiple Reaction Monitoring) analysis. This enables ricin identification down to 5 ng/mL in serum samples in 2.5 h. To validate the assay, twenty-four diverse naive- or ricin-spiked serum samples were evaluated, and both precision and accuracy were determined. A real-life test of the assay was successfully executed in a challenging clinical scenario, where the toxin was identified in an abdominal fluid sample taken 72 h post self-injection of castor beans extraction in an eventual suicide case. This demonstrates both the high sensitivity of this assay and the extended identification time window, compared to similar events that were previously documented. This method developed for ricin identification in clinical samples has the potential to be applied to the identification of other lectin toxins.

Biochemical characterization of two cellobiose 2-epimerases and application for efficient production of lactulose and epilactose

Lactose is the most abundant by-product of the dairy industry and is increasingly recognized as an important feedstock to produce value-added compounds. Lactulose and epilactose are valuable prebiotics that can be generated from lactose with cellobiose 2-epimerases (CEases). Here we describe the characterization of the two CEases CbCEP and RfCEP, originated from the thermophilic microorganism Caldicellulosiruptor bescii and the mesophilic microorganism Roseburia faecis, respectively. CbCEP showed exceptional pH and temperature stability, with maximal activity at pH 7.5 and 70 °C. RfCEP exhibited maximum activity at 50 °C and pH 8. Under optimal conditions in small-scale experiments with commercial lactose, CbCEP produced both lactulose and epilactose with yields of 29.8% and 21.6%, respectively, while RfCEP produced only epilactose with a yield of 19.3%. Furthermore, we evaluated the application of CbCEP for lactulose and epilactose production in stirred fermenters at two different temperatures (70 and 30 °C) at a scale of 5 L volume and a concentration of cheese-whey permeate of 50 g/L. At 70 °C, lactulose was the predominant product of CbCEP-mediated lactose conversion, with a final yield of 30% (12.8 g/L) lactulose and 24.7% (10.6 g/L) epilactose. At 30 °C, lactose was mainly converted into epilactose, with a final yield of 35% (14.9 g/L), and a minor amount of lactulose (final yield of 4.3%, 1.8 g/L). The findings presented here may guide the design of an industrial strategy, based on the temperature-tunable activity of CbCEP, for production of valuable lactose derivatives at high yields directly from whey permeate.

A Single Meal of Milk Containing A2 Β-Casein Causes Fewer Symptoms and Lower Gas Production than Milk Containing Both A1 and A2 Β-Casein Among Lactose Intolerant Individuals

Abstract Objectives We evaluated tolerance to single meals of milks containing different levels of a1 and a2 β-casein as compared to lactose-free milk. We also determined if lactose digestion was affected by a2, high a2 (Jersey) and high a1 (commercial) β-casein milks, as measured by breath hydrogen. Methods A double-blinded, randomized crossover trial was conducted in 21 verified lactose intolerant subjects, feeding four milks (commercial, Jersey, a2 and commercial lactose free) after an overnight fast. Breath hydrogen was measured, and intolerance symptoms were recorded for 6 hours following treatment. Results Mean hydrogen production and total symptoms were significantly lower following consumption of a2 milk as compared to commercial milk (P = 0.03 for both). Similarly, high a2 Jersey milk produced significantly lower hydrogen than commercial milk (P = 0.01). However, symptoms due to Jersey were not significantly different from commercial milk (P = 0.47). Conclusions A2 milk caused fewer symptoms and lower gas production in verified lactose intolerant subjects. Funding Sources Gift funds from the a2 Milk Company.

Continuously monitored lactose crystallization in a vibrated bed

Abstract The aim of this work was to evaluate the crystal size distribution (CSD) and microscopy of the crystalline phase in isothermal lactose crystallization, using a high seeding concentration (dense phase). In-line monitoring was carried out using Focused Beam Reflectance Measurement (FBRM) and Particle Vision Measurement (PVM) probes in a stainless steel trunk-conical shaped jacketed crystallizer. The vibratory shaking system consisted of two perforated discs coupled to a movable axle. A conventional crystallization unit, with a three-blade propeller attached to a stainless steel shaft, was used for comparison. Concentrated cheese whey, purified with an organic coagulant, and commercial lactose solutions were used. Crystallization was improved in the high-purity solutions. Microparticles and/or aggregates appeared before seeding, mainly in the purified cheese whey solution, in which there are impurities. Secondary nucleation was present in both the vibratory agitation and conventional rotary agitation systems, being intensified by increases in agitation. Crystallization in a vibratory system should be carried out with a vibration frequency of 250 rpm, since an increase to 400 rpm reduced the amount of larger crystals.

Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery

Context: Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs.Objective: The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated.Materials and methods: Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr’s index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose® (SV003, Goch, Germany)] used in DPI formulations.Results and discussion: EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose® (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose® (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology.Conclusion: Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.

Preparation of slab-shaped lactose carrier particles for dry powder inhalers by air jet milling

Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e., classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm. The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.

Production and characterization of poly(3-hydroxybutyrate) generated by Alcaligenes latus using lactose and whey after acid protein precipitation process

Whey after acid protein precipitation was used as substrate for PHB production in orbital shaker using Alcaligenes latus. Statistical analysis determined the most appropriate hydroxide for pH neutralization of whey after protein precipitation among NH4OH, KOH and NaOH 10%w/v. The results were compared to those of commercial lactose. A scale-up test in a 4L bioreactor was done at 35°C, 750rpm, 7L/min air flow, and 6.5 pH. The PHB was characterized through Fourier Transform Infrared Spectroscopy, thermogravimetry and differential scanning calorimetry. NH4OH provided the best results for productivity (p), 0.11g/L.h, and for polymer yield, (YP/S), 1.08g/g. The bioreactor experiment resulted in lower p and YP/S. PHB showed maximum degradation temperature (291°C), melting temperature (169°C), and chemical properties similar to those of standard PHB. The use of whey as a substrate for PHB production did not affect significantly the final product quality.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

The use of freeze-dried mannitol to enhance the in vitro aerosolization behaviour of budesonide from the Aerolizer®

The efficiency of drug delivery from drug-carrier dry powder inhaler (DPI) systems is typically low. The purpose of this study was to examine the aerosolization performance of a hydrophobic drug, budesonide (BUD), from DPI formulations containing a promising carrier, freeze-dried mannitol (FDM), and to compare the results to those obtained previously with a hydrophilic drug, salbutamol sulphate (SS).The results showed that, in comparison to the formulation containing commercial BUD and commercial lactose, a total of 3.8-fold increase in the fine particle fraction (FPF) was obtained from the formulation containing FDM (FPF: 7.5% versus 29%) whereas a total of 4.6-fold increase in the FPF was obtained from the formulation containing FDM and leucine additive (FPF: 35%). Regression analysis showed DPI formulations containing carrier particles with a more elongated/less spherical shape, a higher content of fine particulates (<5μm) and a higher porosity to produce higher FPFs of BUD.FDM promoted the aerosolization of budesonide intended for pulmonary delivery. The addition of leucine (by 4.8%, w/w) has further improved the flow and the aerosolization properties of FDM. FDM produced higher aerodynamic diameters and smaller FPFs of BUD as compared to SS, attributable to BUD having a higher electrostatic charge density and a higher agglomeration tendency than SS.

Galactooligosaccharide and Sialyllactose Content in Commercial Lactose Powders from Goat and Cow Milk.

The most commonly used infant formulas contain lactose originating from cow milk. Goat milk has recently been claimed to be nutritionally more effective for infants than other milks. In baby foods, much emphasis is placed on the concentrations of intestinal microflora-promoting oligosaccharides, which are generally transferred into lactose from milk during crystallization process. Here we show that higher level of free sialic acid is present in goat lactose powder compared to cow lactose powder. Without proteinase K treatment, the amount of 3-sialyllactose and 6-sialyllactose were similar in goat and cow lactose powders. However, after proteolysis, 6-sialyllactose was present at higher levels in goat than in cow lactose powder. Galactooligosaccharides, a group of prebiotics, are present in milk in the form of glycoproteins. Galactooligosaccharide content was also higher in goat lactose powder than in cow lactose powder.

Technical note: Optimization of lactose quantification based on coupled enzymatic reactions

A colorimetric microplate-adapted lactose assay was developed to quantify lactose in dairy products. The assay was based on the coupled enzymatic reaction of β-galactosidase-glucose oxidase-horseradish peroxidase using Amplex red as detection probe. The assay showed good linearity in the range of 0.1 to 0.5mmol of lactose/L, with a limit of detection of 0.0433mmol/L and a limit of quantification of 0.1313mmol/L. The lactose assay at optimized conditions (5 U of β-galactosidase/mL, 5 U of glucose oxidase/mL, 1 U of horseradish peroxidase/mL, and 100μmol of Amplex red/L for 1h at 37°C in the dark) showed good correlation with a commercial lactose enzymatic kit with intraassay variation below 10% and interassay variations below 7.6%. The developed lactose microplate assay can be adopted as routine analysis for lactose determination in dairy products due to its relatively low cost compared with a commercial kit, relatively short reaction time, and high sensitivity and reproducibility.

Antisolvent crystallisation is a potential technique to prepare engineered lactose with promising aerosolisation properties: Effect of saturation degree

Engineered lactose particles were prepared by anti-solvent crystallisation technique using lactose solutions with different saturation degrees. In comparison to commercial lactose, engineered lactose particles exhibited less elongated and more irregular shape (large aggregates composed of smaller sub-units), rougher surface texture, higher specific surface area, and different anomer form. Engineered lactose powders demonstrated smaller bulk density, smaller tap density, and higher porosity than commercial lactose powder. Dry powder inhaler (DPI) formulations containing engineered lactose and salbutamol sulphate as a model drug demonstrated improved drug content homogeneity and higher amounts of drug delivered to lower airway regions. Higher fine particle fraction of drug was obtained in the case of lactose powders with higher porosity, higher specific surface area and higher fine particle content (<5 μm). The results indicated that the higher the saturation degree of lactose solution used during crystallisation the smaller the specific surface area, the higher the amorphous lactose content, and the higher the β-lactose content of engineered lactose particles. Also, lactose powders obtained from lactose solution with higher degree of saturation showed higher bulk and tap densities and smaller porosity. Engineered lactose powders crystallized from lower saturation degree (20% and 30% w/v) deposited higher amounts of drug on lower airway regions. In conclusion, this study demonstrated that it is possible to prepare engineered lactose particles with favourable properties (e.g. higher fine particle fraction and better drug content homogeneity) for DPI formulations by using lactose solutions with lower degree of saturation during crystallisation process.

Letter to the Editor regarding “Lactose does not interfere with the analysis of sialic acids as their 1,2-diamino-4,5-methylenedioxybenzene derivatives”

Dear Sir,Recently, Spichtig et al. [1] published in this journal aTechnical Note regarding the analysis of sialic acids frominfant formulas using 1,2-diamino-4,5-methylenedioxyben-zene derivatives, a method previously proposed by us in2007 [2]. In this Technical Note, Spichtig et al. stated thatlactose does not interfere with the analysis, conversely towhat we hypothesized in our article. Although in the workreported in their Technical Note they did not include infantformulas or milk, in workpublished in 2010 [3]they appliedthe proposed method to several dairy products, includinginfant formulas. In the most recent work, they used com-mercial lactose and quantified fetuin sialic acids when thisprotein was in lactose solution (no concentration reported)and in aqueous solution. They reported an increase of30 μg/100 mg in the former solution when comparedwith the latter, which they attributed to a certain amountof sialyllactose present in the commercial lactose be-cause of its dairy origin. This residual sialic acid in lactosewas quantified (6.5-24.7 μg/100 mg), and the concentrationdiffered withthe supplierand was consideredverylow bytheauthors.Regarding this controversial topic, and in response to theaforementioned article, we would like to clarify our previousreport.First,weobservedaproblemintheaccuratequantitationof sialic acids from infant formulas and proposed a way toeffectively resolve this via an additional purification step. Wesuggested that lactose could be a possible reason for the ob-served phenomenon. In fact, in a series of recent tests in ourlaboratory, when commercial lactose (from Sigma) was spikedwith different amounts of N-acetylneuraminic acid (Neu5Ac)and quantified using the method reported the recovery in-creased as the amount of Neu5Ac added increased: 5.15 μgwas recovered when 5 μg was added, but 19.55 μg wasrecoveredwhen15μg was added. This represents a matrixeffect caused by lactose that produces a systematic error pro-portional to the concentration of Neu5Ac. So, we do not agreewith the statement in the abstract of the technical note thatlactose does not interfere with the analysis and we stronglyrecommend the purification step if accurate quantitation ofsialic acids in infant formulas is required.References

The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance

To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. Mannitol and lactose individually and the two sugars with three different ratios were crystallised/co-crystallised using anti-solvent precipitation technique. Obtained crystals were sieved to separate 63-90 μm size fractions and then characterised by size, shape, density and in vitro aerosolisation performance. Solid state of crystallized samples was studied using FT-IR, XRPD and DSC. At unequal ratios of mannitol to lactose, the elongated shape dominated in the crystallisation process. However, lactose exerted an opposite effect to that of mannitol by reducing elongation ratio and increasing the crystals' width and thickness. Crystallised β-lactose showed different anomers compared to commercial lactose (α-lactose monohydrate). Crystallised α-mannitol showed different polymorphic form compared to commercial mannitol (β-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to α-mannitol, α-lactose monohydrate, β-lactose, 5α-/3β-lactose and 4α-/1β-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate compared to formulations containing commercial grade carriers. The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations.

Effect of carrier particle shape on dry powder inhaler performance

The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer® inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER=1.62±0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER=4.83±0.18, ECM: ER=5.89±0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (Db), smaller tap density (Dt), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a “limit” as increasing carrier ER from 4.83±0.18 (ACM) to 5.89±0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in inhaler device (drug loss) and deposited on throat. Linear relationship was established (r2=0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for carrier products with higher ER is disadvantageous in terms of DPI formulation dose metering and processing on handling scale. In conclusion, despite that using carrier particles with higher ER can considerably increase the amounts of drug delivered to lower airway regions; this enhancement is restricted to certain point. Also, other limitations should be taken into account including higher drug loss and poorer flowability.

The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers

The aim of this work was to investigate the mechanistic evaluation of physicochemical properties of new engineered lactose on aerosolisation performance of salbutamol sulphate (SS) delivered from dry powder inhaler (DPI). Different crystallised lactose particles were obtained from binary mixtures of butanol:acetone. The sieved fractions (63–90μm) of crystallised lactose were characterised in terms of size, shape, flowability, true density and aerosolisation performance (using multiple twin stage impinger (MSLI), Aerolizer® inhaler device, and salbutamol sulphate as a model drug). Compared to commercial lactose, crystallised lactose particles were less elongated, covered with fine lactose particles, and had a rougher surface morphology. The crystallised lactose powders had a considerably lower bulk and tap density and poorer flow when compared to commercial lactose. Engineered carrier with better flow showed improved drug content homogeneity, reduced amounts of drug “deposited” on the inhaler device and throat, and a smaller drug aerodynamic diameter upon inhalation. Aerodynamic diameter of salbutamol sulphate increased as lactose aerodynamic diameter decreased (linear, R2=0.9191) and/or as fine particle lactose content increased (linear, R2=0.8653). Improved drug aerosolisation performance in the case of crystallised lactose particles was attributed to lower drug–carrier adhesion forces due to a rougher surface and higher fine particle content. In conclusion, this work proved that using binary combinations of solvents in crystallisation medium is vital in modification of the physicochemical and micromeritic properties of carriers to achieve a desirable aerosolisation performance from DPI formulations. Among all lactose samples, lactose particles crystallised from pure butanol generated the highest overall DPI formulations desirability.

Improved Aerosolization Performance of Salbutamol Sulfate Formulated with Lactose Crystallized from Binary Mixtures of Ethanol—Acetone

It has been shown that dry powder inhaler (DPI) formulations typically achieve low fine particle fractions (poor performance). A commonly held theory is that this is due, at least in part, to low levels of detachment of drug from lactose during aerosolization as a result of strong adhesion of drug particles to the carrier surfaces. Therefore, the purpose of the present study is to overcome poor aerosolization performance of DPI formulation by modification of lactose particles. Lactose particles were crystallized by adding solution in water to different ratios of binary mixtures of ethanol-acetone. The results showed that modified lactose particles had exceptional aerosolization performance that makes them superior to commercial lactose particles. Morphology assessment showed that crystallized lactose particles were less elongated, more irregular in shape, and composed of smaller primary lactose particles compared with commercial lactose. Solid-state characterization showed that commercial lactose particles were α-lactose monohydrate, whereas crystallized lactose particles were a mixture of α-lactose monohydrate and β-lactose according to the ratio of ethanol-acetone used during crystallization process. The enhanced performance could be mainly due to rougher surface and/or higher amounts of fines compared with the lactose crystallized from pure ethanol or commercial lactose.

Formulation and evaluation and terbutaline sulphate and beclomethasone dipropionate inhalation mixtures in the rotahaler device

We report the use of low rugosity lactose, product of controlled crystallization of this carrier, in the formulation of terbutaline sulphate and beclomethasone dipropionate dry powder inhalers. The deposition patterns obtained with inhalation mixtures consisting of the modified lactose and each of the micronised drugs terbutaline sulphate and beclomethasone dipropionate have been used to assess the effect of the surface smoothing technique on aerosolised drug delivery. The ROTAHALER device and the Twin Impinger BP were used in the assessment. Drug deposited in the throat, stage 1 and stage 2 of the Twin Impinger BP was determined and used to assess the difference between commercial lactose and the modified lactose prepared. The respirable fraction obtained with inhalation mixtures containing the recrystallized lactose samples was higher compared with inhalation mixtures containing regular lactose BP.Keywords: Rotahaler device, terbutaline sulphate, beclomethasone dipropionate, inhalation mixtures, twin impinger BP, respirable fraction