Lactose Powder Research Articles

Application of Response Surface Methodology to Estimate the Design Space of Pharmaceutical Diluents for Dispensing Powdered Formulations.

Scientific approaches for dispensation are important for the quality and efficacy of drug treatments. Therefore, for the dispensation of powdered medicines, we have developed a powder blending method using a planetary centrifugal mixer (PCM) to replace the empirical manual method involving a mortar and pestle. The aim of this study was to optimize the formulation of pharmaceutical diluents for dispensing powdered medicines, using PCM. The diluents, composed of powdered lactose, crystalline lactose, and corn starch were assigned to a {3,2}-Simplex Lattice design. Then, the designed diluents were blended with model powders, such as carbazochrome sodium sulfonate powder, rifampicin capsule contents, and crushed sulfasarazine tablets, at ratios of 1 : 4, 1 : 1, and 4 : 1 using PCM at 800 rpm for 60 s at a 20% filling rate. The mixtures were examined for content uniformity relative standard deviation (RSD) and flowability angle of repose (AOR). Response surface methodology was applied to optimize the formulation with the smallest RSD and AOR, and then the design space of desired diluents was estimated. On the basis of the design space, crystalline lactose, the mixture of lactose powder and crystalline lactose at a ratio of 1 : 4, and the mixture of corn starch and crystalline lactose at a ratio of 1 : 4, were suitable diluents for the powdered formulation, the content of the capsules, and the crushed tablets, respectively. The selected diluents were successfully applied to other model medicines showing a sufficient RSD and AOR. This technique could contribute to the development of scientific approaches for dispensation.

Acute effects of caffeine on choroidal thickness and ocular pulse amplitude

Objective: To explore ocular changes in healthy people after caffeine consumption.Methods: This prospective observational study was carried out with students of the Turgut Özal University Medical Faculty from May 15 to 15 December 2014. Enrolled in the study were 17 healthy subjects (n = 17 eyes), with a median age of 24 (IQR 1), ranging between 21 and 26 years. The control group (6 females, 11 males) aged between 23 and 28 (median 25 years [IQR 4.75]). For study, one eye from each participant was randomly selected. To obviate the effect of diurnal variations, tests were performed at the same time of the day (10:00 a.m.–12:00 p.m.). Each subject was given an ophthalmologic examination before the study to exclude those with undiagnosed ocular disease. Version 6.0 Cirrus high-definition optical coherence tomography (HD-OCT) (Carl Zeiss Meditec, Dublin, CA) was used to measure CT at the fovea, and 1500 μm nasal and 1500 μm temporal to the fovea. After baseline OCT measurements, participants were asked to have 200 mg oral caffeine intake or a placebo capsule (200 mg lactose powder). Two further OCT measurements were applied at the first and fourth hours of caffeine intake. All participants also had intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements recorded before, first and fourth hours of caffeine intake. IOP and OPA were measured using the dynamic contour tonometry (DCT) (Swiss Micro Technology AG, Port, Switzerland).Results: The groups showed no significant difference by means of age, gender, spherical refraction and axial length (p > 0.05). Baseline choroidal thickness measurements of the study and control group showed no significant difference. Oral caffeine intake caused a significant reduction in choroidal thickness compared with baseline, at all three measurement points, (p < 0.05). There were no significant changes in IOP and OPA measurements compared with the baseline values (p > 0.05). The choroidal thickness still continued to decrease for at least 4 h following caffeine intake; whereas, the difference between 1 and 4 h was not statistically significant (p > 0.05). However, choroidal thicknesses, IOP and OPA values of the control group revealed no significant difference at all points when comparing measurements at baseline with 1 and 4 h after placebo intake (p > 0.05).Conclusions: We found no significant change in IOP and OPA following oral 200 mg caffeine intake, while CT significantly decreased, for at least 4 h.

Dry Powder Coating using Planetary Centrifugal Mixer.

Extemporaneous compounding is an important part of pharmacy practice, and should be standardized and sophisticated to ensure the quality of the compounded preparations. Recently, we applied a planetary centrifugal mixer (PCM) to powder blending, which has attracted interest for its small scale and lack of contamination. In this study, we aimed to reveal the feasibility of dry powder coating through ordered mixing of fine particles using PCM. Cohesive lactose powders (Pharmatose450M) were dry coated with magnesium stearate (MgSt) using from 0.1 to 5%(w/w) content. The operational variables tested were operation time (1-30 min), operation speed (400-1000 rpm), vessel size (24-100 mL), and charging rate in the vessel (20-40%). The processed powders were evaluated for their surface morphology, flowability, and wettability. Furthermore, fine ibuprofen particles were coated with various lubricants, and then the dissolution profiles were examined. The crystallinity of ibuprofen was assessed using FT-IR and PXRD. Lactose powders were successfully coated with MgSt using PCM. When the level of MgSt was over 1%, the surface of the lactose powders was thoroughly covered. Angles of repose were 51° and 41° for unprocessed and processed powders with 1% MgSt, respectively. The contact angle of the water drop on the 1% MgSt sample leached to be 132°, changing to a hydrophobic surface. Investigations under various operational conditions revealed that higher improvement was observed upon higher speed and longer time, and a smaller charging rate in the vessel. Vessel size had no impact. Moreover, improved dissolution of ibuprofen coated with both hydrophilic and hydrophobic lubricants was observed owing to good dispersing behavior. Besides, no alteration of crystallinity was detected. PCM is an effective tool for dry powder coating with low impact stress. The presented method will contribute a great deal to making crushed tablets a functional powder.

Lactose in dairy ingredients: Effect on processing and storage stability

Lactose is the main carbohydrate in the milk of most species. It is present in virtually all dry dairy ingredients, with levels ranging from <2% (e.g., caseinates, milk protein isolates) to 100% in lactose powders. The presence of lactose has a strong effect on ingredient processing and stability. Lactose can negatively influence powder properties and lead to undesirable effects, such as the stickiness of powder resulting in fouling during drying, or caking and related phenomena during storage. In addition, being a reducing carbohydrate, lactose can also participate in the Maillard reaction with free amino groups of proteins, peptides, and free AA. In this review, the influence of the presence (or absence) of lactose on physiochemical properties of dairy ingredients is reviewed, with particular emphasis on behavior during processing and storage. Particularly important features in this respect are whether lactose is in the (glassy) amorphous phase or in the crystalline phase, which is strongly affected by precrystallization conditions (e.g., in lactose, permeate, and whey powders) and by drying conditions. Furthermore, the moisture content and water activity of the ingredients are important parameters to consider, as they determine both mobility and reactivity, influencing Maillard reactions and concomitant browning, the crystallization of amorphous lactose during storage of dairy ingredients, glass transitions temperatures, and associated stickiness and caking phenomena. For the stickiness and caking, a crucial aspect to take into account is powder particle surface composition in relation to the bulk powder. Lactose is typically underrepresented at the powder surface, as a result of which deviations between observed lactose-induced caking and stickiness temperatures, and determined glass transition temperatures arise. By considering lactose as an integral part of ingredient composition along with all other compositional and environmental properties, lactose behavior in dairy ingredients can be understood, controlled, and optimized. Routes to achieve this are outlined in this review paper.

FT-Raman and chemometric tools for rapid determination of quality parameters in milk powder: Classification of samples for the presence of lactose and fraud detection by addition of maltodextrin

FT-Raman spectroscopy has been explored as a quick screening method to evaluate the presence of lactose and identify milk powder samples adulterated with maltodextrin (2.5–50% w/w). Raman measurements can easily differentiate samples of milk powder, without the need for sample preparation, while traditional quality control methods, including high performance liquid chromatography, are cumbersome and slow. FT-Raman spectra were obtained from samples of whole lactose and low-lactose milk powder, both without and with addition of maltodextrin. Differences were observed between the spectra involved in identifying samples with low lactose content, as well as adulterated samples. Exploratory data analysis using Raman spectroscopy and multivariate analysis was also developed to classify samples with PCA and PLS-DA. The PLS-DA models obtained allowed to correctly classify all samples. These results demonstrate the utility of FT-Raman spectroscopy in combination with chemometrics to infer about the quality of milk powder.

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.

Linking flowability and granulometry of lactose powders

The flowing properties of 10 lactose powders commonly used in pharmaceutical industries have been analyzed with three recently improved measurement methods. The first method is based on the heap shape measurement. This straightforward measurement method provides two physical parameters (angle of repose αr and static cohesive index σr) allowing to make a first screening of the powder properties. The second method allows to estimate the rheological properties of a powder by analyzing the powder flow in a rotating drum. This more advanced method gives a large set of physical parameters (flowing angle αf, dynamic cohesive index σf, angle of first avalanche αa and powder aeration %ae) leading to deeper interpretations. The third method is an improvement of the classical bulk and tapped density measurements. In addition to the improvement of the measurement precision, the densification dynamics of the powder bulk submitted to taps is analyzed. The link between the macroscopic physical parameters obtained with these methods and the powder granulometry is analyzed. Moreover, the correlations between the different flowability indexes are discussed. Finally, the link between grain shape and flowability is discussed qualitatively.

Assessing Powder Flow: An Analysis of Starch and Lactose Powders Under Static and Dynamic Conditions

Assessing Powder Flow: An Analysis of Starch and Lactose Powders Under Static and Dynamic Conditions

Measuring the flow properties of small powder samples using an avalanche tester

ABSTRACTThe feasibility of using a small-scale avalanche tester to measure the flow properties of pharmaceutical lactose powders was examined. The modes of behavior observed in larger systems were displayed and showed a clear distinction between angular, free-flowing particles and more spherical particles of similar flow characteristics. Angular Lactohale LH100 particles showed slumping behavior at a rotational frequency of 0.33 Hz that disappeared at higher frequencies. Spherical lactose powder with a similar flow function to LH100 only showed rolling behavior under the same conditions, as did more cohesive powders LH200 and LH300. Further investigation of the LH100 data using fast Fourier analysis showed that the slumping frequency was one tenth of the rotational frequency.

High shear mixing of lactose and salmeterol xinafoate dry powder blends: Biopharmaceutic and aerodynamic performances

This work aimed to investigate the effect of a high shear mixer on the biopharmaceutics and aerodynamic performances of salmeterol xinafoate/lactose blends for inhalation. The influence of mixing energy during blending on powder bulk properties, aerosolisation and in vitro dissolution rate of drug was studied. There was a clear dependence of the blends bulk characteristics on the mixing rate and time that affected the emitted dose. The fine particle dose or respirable fraction of salmeterol xinafoate was favored by the mixing intensity leading to the disaggregation of the drug particles. An important dependence of the extra-fine drug particles on the mixing conditions was determined. The effective dispersion on the carrier particles of the salmeterol xinafoate improved the dissolution rate of the drug from the blend. This was due to the drug particle size distribution in the blend. When the fine particle dose of different blends was dissolved, no differences among the dissolution rates were observed.

Identification of inter-particular forces by atomic force microscopy and how they relate to powder rheological properties measured in shearing tests

In this study, we used atomic force microscopy (AFM) to measure and identify the nature of the forces acting between single pharmaceutical powder particles, namely a crystalline and a semi-crystalline form of lactose. The experiments done at different moisture level, namely from 20% to 60% of relative humidity, identified capillarity as the main source of adhesion between single particles. A strong correlation was observed between the AFM adhesion results and cohesion measurements taken with a FT4 torsional type powder shear tester. This correlation between adhesion and cohesion allows the identification of capillary forces as the main source of the cohesion measured in shearing experiments in ambient moisture conditions. In the case of the semi-crystalline lactose powder, a sharp decrease in both the adhesion and cohesion at 50% RH was linked to absorption of water accumulated at the particle surfaces to fuel a phase transition of the non-crystalline domains to crystalline lactose, hence limiting the capillary action between particles at this specific moisture condition.

Roller compaction: Effect of morphology and amorphous content of lactose powder on product quality

The effect of morphology and amorphous content, of three types of lactose, on the properties of ribbon produced using roller compaction was investigated. The three types of lactose powders were; anhydrous SuperTab21AN, α-lactose monohydrate 200M, and spray dried lactose SuperTab11SD. The morphology of the primary particles was identified using scanning electron microscopy (SEM) and the powder amorphous content was quantified using NIR technique. SEM images showed that 21AN and SD are agglomerated type of lactose whereas the 200M is a non-agglomerated type. During ribbon production, an online thermal imaging technique was used to monitor the surface temperature of the ribbon. It was found that the morphology and the amorphous content of lactose powders have significant effects on the roller compaction behaviour and on ribbon properties. The agglomerated types of lactose produced ribbon with higher surface temperature and tensile strength, larger fragment size, lower porosity and lesser fines percentages than the non-agglomerated type of lactose. The lactose powder with the highest amorphous content showed to result in a better binding ability between the primary particles. This type of lactose produced ribbons with the highest temperature and tensile strength, and the lowest porosity and amount of fines in the product. It also produced ribbon with more smooth surfaces in comparison to the other two types of lactose. It was noticed that there is a relationship between the surface temperature of the ribbon during production and the tensile strength of the ribbon; the higher the temperature of the ribbon during production the higher the tensile strength of the ribbon.

Accuracy of micro powder dosing via a vibratory sieve–chute system

This paper describes a powder dosing system with a vibratory sieve mounted on a chute that doses particles into a capsule. Vertical vibration occurred with a broad range of frequencies and amplitudes. During dosing events, the fill weight was accurately recorded via a capacitance sensor, covering the capsules and making it possible to analyze filling characteristics, that is, the fill rates and their robustness. The range of frequencies and amplitudes was screened for settings that facilitated reasonable (no blocking, no spilling) fill rates for three lactose powders. The filling characteristics were studied within this operating space. The results reveal similar operating spaces for all investigated powders. The fill rate robustness varied distinctly in the operating space, which is of prime importance for selecting the settings for continuous feeding applications. In addition, we present accurate dosing studies utilizing the knowledge about the filling characteristics of each powder.

Integrated production of whey protein concentrate and lactose derivatives: What is the best combination?

In order to model and analyze the techno-economic feasibility of a whey processing unit for the production of whey protein concentrate (WPC) integrated with processing of lactose, the present study utilized the software SuperPro Designer® for modeling of the processes, including risk analysis and study of reduced pollution impacts. Six models were constructed for the production of WPC and processing of lactose, which were (1) WPC 34, (2) WPC 34 and lactose powder, (3) WPC 34 and hydrous ethanol fuel, (4) WPC 80, (5) WPC 80 and lactose powder, and (6) WPC 80 and hydrous ethanol fuel. The economic evaluation was performed by analysis of the Payback Period (PP), Net Present Value (NPV), Breakeven Point (BP) and Internal Rate of Return (IRR). Probability distributions obtained by fitting of historical data for whey prices and the final products were used to perform the risk analysis, submitted to a Monte Carlo simulation using the @Risk software. The project showed to be feasible due to the elevated IRR and NPV values, coupled with low BP and PP. When evaluating the individual production of ethanol, it was verified that the production cost of this product was superior to the sale price, making independent production of ethanol from lactose present in the whey uneconomical. Plants with production of lactose powder were more economically attractive and also presented greater reduction of Biochemical Oxygen Demand (BOD) and Chemical Oxygen Demand (COD). The financial indices suggested greater feasibility of WPC 80 compared to WPC 34.

Crystallinity and quality of spray-dried lactose powder improved by soluble soybean polysaccharide

The crystallinity of lactose is significant to the quality and shelf-life of spray-dried dairy products. In this study, the properties of spray-dried lactose powder were studied after co-spray drying with soluble soybean polysaccharide (SSPS) at mass ratios of 1:0, 19:1 and 9:1. Spray-dried samples with SSPS had the significantly increased crystallinity based on polarized light microscopy, differential scanning calorimetry, and X-ray diffraction spectroscopy (XRD). Increasing the feed rate also increased the crystallinity and moisture content of lactose powder. The XRD data indicated the presence of both α- and β-lactose crystals in the spray-dried powder with 10 g/100 g SSPS. Moisture sorption tests at 65% relative humidity and 25 °C indicated that SSPS delayed the crystallization of amorphous lactose in the powder, which agreed with the reduced caking and clumping. Findings from this study may be valuable in extending the shelf-life and improving the transportation property of spray-dried powder containing lactose.

Surface Free Energy Data to Predict the Surface Modification Ability of Force Control Agents = استخدام طاقة السطوح الحرة كأداة للتنبؤ بقدرة عوامل التحكم بالقوة على تعديل السطح

In this study, the efficiency of using force control agents (FCAs) namely Polyethylenglycol 6000 (PEG) and polyvinylpyrrolidone (povidone k-30) (PVP) and Sodium lauryl sulfate (SLS) in modifying the surface of lactose were invisitigated. Lactose surface was modified by sinking within aqueous solution containing one of each mentioned FCAs. The surface free energies of FCAs unprocessed lactose and processed lactose powders were measured using contact angle measurements. Results showed high negative spreading cofficient ( ) of SLS over lactose which expalins the disability of SLS to adhere to the surfaces of lactose. On other hand, a positive value of PVP enabled its adherence to lactose surfaces and so to modify the surface energy to a significant extent. These changes were furthermore observed in case of PEG which had the highest compared to others. It is concluded that the more positive the spreading coefficient of a FCA over lactose, the higher the ability of the FCA to modify the surface of lactose is. Also the cohesion works of the powders were directly correlated to the Carr’s index and Hausner ratio which are used as indictors of the flow ability. It was also found that all the modified surface lactose powders had surface free energy and cohesion work less than the original lactose. Therefore, surface free energy data can be used as a predict tool to screen for the suitable FCA for each carrier. DSC and FT-IR confirmed the absence of any significant interaction between FCAs and lactose.

Lactose Caking: Influence of the Particle Size Distribution and the Water Content

Industrially, after the crystallisation of lactose from mother liquor, the crystals are separated by centrifugation and then dried in a flash drier followed by a fluid bed drier. It is known that if the moisture content and/or particle size is not correct then lumping and caking of the lactose can occur in the flash drier causing operational problems.The aim of this study was to characterize the influence of water content and particle size distribution on the caking of lactose powders.Powders with different d50's and different water contents had their caking/clumping characteristics analyzed with a texture analyzer, a sticky plate and a blow tester to determine their cohesion. A theoretical approach looking at the capillary interactions of the liquid bridges between lactose crystals was taken from the literature to explain the results obtained.The results showed that lactose powder with a low d50 can cake easily as soon as the water content is higher than 3%. This cohesion between lactose crystals is due to liquid bridges linking them together. The number of bridges formed affects the level of cohesion: the more numerous they are, the more cohesive the lactose crystals are. Therefore, small particles cake more easily because the number of bridges in a given volume is higher than for bigger particles.It was predicted that the capillary force cannot hold together particles with d50 bigger than 400μm and that was confirmed by experiment.Finally, in order to prevent the caking of lactose powders obtained by processes such as a decanter centrifuge, the lactose crystallization step should be controlled to obtain large crystal (with d50>300μm) and/or the final water content should not be higher than 3%.

Correlation between Powder Flow Properties Measured by Shear Testing and Hausner Ratio

Shear testing provides rigorous estimates of flow properties relevant to the characterization, handling, and processing of powders, and is a necessary test procedure in the formal design of powder storage facilities. However, despite the automation of modern test equipment, it can be time consuming and expensive. In contrast, measurement of bulk density is straightforward and less laborious, and tapping devices are cheaper. Here we explore the relationship between Hausner ratio and cohesion and also examine correlation between Hausner ratio, σc/σy, and σpre for a suite of 13 milled and 2 spray-dried lactose powders, 3 sand samples and 3 samples of refractory dust; Hausner ratio is the ratio of tapped bulk density to loose bulk density, σc is major consolidation stress, σy is unconfined yield stress and σpre is preconsolidation stress. Cohesion and flow function were measured with an annular shear cell at values of σpre up to 5kPa. Loose poured bulk density was measured following a modified New Zealand standard and tapped density measurement was based on a method for dry dairy products and the European Pharmacopoeia; Hausner ratio at 1250 taps was used. Our results show that cohesion at σpre of 0.31kPa, 0.61kPa, 1.20kPa, 2.41kPa, and 4.85kPa correlates linearly with Hausner ratio; the slope and intercept of the correlation are functions of σpre. A plot of σc/σy against Hausner ratio shows an exponential decay trend and regression yields two fitting parameters that correlate well with σpre. These correlations are potentially useful for assessing flow characteristics when shear testing cannot be performed.

Developing a new production process for high-porosity lactose particles with high degrees of crystallinity

Highly porous lactose with a high degree of crystallinity has been prepared by a new production process. A solution containing lactose, whey protein isolate, and citric acid as a template has been dried using a Buchi-B290 mini spray dryer with an inlet temperature of 180°C. Samples have been treated with ethanol to dissolve the citric acid and simultaneously increase the crystallinity of the spray-dried lactose. The resulting powder structure is a lactose network with significant porosity and a high surface area of 28.9±0.7m2/g, while maintaining the strong stability of a highly crystalline powder. It has been demonstrated that textural properties, such as surface area and pore volume of the resultant lactose, can be tuned by varying the concentration of citric acid. Increasing the citric acid content decreases the surface area of the ethanol-washed powders beyond a citric acid concentration of 2%, which may be connected with the decrease in the amount of incorporated citric acid molecules due to the increase in the degree of crystallinity for the spray-dried lactose powders. The scanning electron microscope micrographs were consistent with the results of BET surface area measurements. It has been also found that adding citric acid to the lactose and to the lactose/WPI solutions decreases the yield of the spray-drying process due to stickiness. The results allow excipients to be produced with significant concentrations of surface asperities and large specific surface areas for use in direct compression tableting techniques.

Characterisation of lactose powder and granules for multivariate wet granulation modelling

Granulation and size enlargement of particulate materials is a complex process with broad application in industry. For better understanding of the governing mechanisms, we aim to develop a multivariate population balance model to describe granulation. For meaningful model design we require physical characteristics of real materials undergoing granulation. In this work, α-lactose monohydrate powder was investigated as a representative substance due to its broad use in the pharmaceutical industry for tablets. Powder and granules resulting from a high-shear granulation process are characterized with respect to size, shape, porosity and strength using various analytical methods. Particle size distributions are obtained by static image analysis, laser scattering and sieving. Granule porosities are determined using μCT and mercury intrusion porosimetry. Lactose granules show absolute porosities increasing from 30% to 40% along the size classes. The μCT derived visual information of larger granules shows internal pore structures with denser cores and porous shell parts. AFM, SEM and μCT are used for surface characterisation, yielding a maximum value for model particle roughness up to 0.7μm. The strength of the product granules measured via uniaxial compression testing follows a logarithmic decrease with size from 1.2 to 0.2MPa. The multivariate data set was then used for model performance analysis and parameter fitting. The size and porosity prediction performance of the computer model could be improved using the newly available data. The rate of coagulation was found to be the most dominant simulation parameter. Comparison with the experiment revealed limitations, for example in PSD shape predictions.