Lactose Monohydrate Research Articles

Preparation and Characterization of Novel Self Nano Emulsifying Drug Delivery System of Allopurinol

The aim of research was to develop self nanoemulsifying drug delivery technology containing low aqueous soluble drug allopurinol for improving solubility, dissolution and bioavaibility. Preliminary screening were carried on the basis of maximum solubility of allopurinol in oil, surfactant, co-surfactant and pseudo-ternary phase diagram was constructed to identify the ratio of surfactant and co-surfactant for nanoemulsion formulation using water titration method. Based on the solubility study, Labrafil M 1944 CS, Cremophor RH 40, Transcutol used as oil, surfactant, and co-surfactant respectively. Pseudo-ternary phase diagram was constructed to identify the ratio of surfactant and co-surfactant for nanoemulsion formation by water titration method. As per the ternary phase diagram ratio of Smix in 2:1 was identified with maximum emulsification area. SNEDDS composed of 35 % Labrafil M 1944 CS, 43.34% Cremophor RH 40, 21.66% Transcutol. Globule size was found to be 25.42 nm, and zeta potential value was -9.26 mV. Prepared SNEDDS were evaluated for globule size, viscosity, emulsification time, cloud point, dilution test and thermodynamic stability study. Prepared liquid SNEDDS then converted into solid SNEDDS via extrusion/spheronization technique using Aerosil 200, lactose monohydrate and Croscarmellose sodium. The pellets containing SNEDDS possessed good flow properties and mechanical strength and other rheological parameters. Self nanoemulsifying pellet exhibited uniform size and shape. Friability, dissolution time and disintegration of pellets formulation shown promising results. Time required for 80% drug release of self nanoemulsifying pellet was found to be 26 min, which was significantly lower than liquid SNEDDS, plain drug containing pellet and marketed preparation of Allopurinol (ZYRIK).

Industrial application of QbD and NIR chemometric models in quality improvement of immediate release tablets

Quality by Design (QbD) and chemometric models are different sides of the same coin. While QbD models utilize experimentally designed settings for optimization of some quality attributes, these settings can also be utilized for chemometric prediction of the same attributes. We aimed to synchronize optimization of comparative dissolution results of carvedilol immediate release tablets with chemometric prediction of dissolution profile and content uniformity of the product. As an industrial application, selection of variables for optimization was done by performing risk assessment utilizing the archived product records at the pharmaceutical site. Experimental tablets were produced with 20 different settings with the variables being contents of sucrose, sodium starch glycolate, lactose monohydrate, and avicel Ph 101. Contents of the excipients were modelled with F1 dissimilarity factor and F2 similarity factor in HCL, acetate, and USP dissolution media to determine the design space. We initiatively utilized Partial Least Square based Structural Equation Modelling (PLS-SEM) to explore how the excipients and their NIR records explained dissolution of the product. Finally, the optimized formula was utilized with varied content of carvedilol for chemometric prediction of the content uniformity.

High-shear granulation: An investigation into granule breakage rates

Granule breakage is an important rate process in wet granulation that promotes product uniformity and controls product size and strength. In this work, a model to predict granule breakage is proposed and experimentally validated. The model assumes exponential of the surviving granules, dependent on a probability of breakage; a function of powder and binder properties, as well as operating parameters. Validation experiments were performed with a breakage-only granulator, filled with cohesive, non-granulating sand. Premade pellets made from lactose monohydrate and silicone oils were granulated at several impeller speeds, and the number of survivors was observed over time. The results revealed that the number of granules did indeed decay exponentially. It was found that the overall probability of breakage was inversely proportional to the capillary number. Moreover, the pore saturation played an important role in determining the probability of breakage, with higher pore saturations reducing breakage overall. A comparison with experimental data from literature revealed that the developed models agrees qualitatively with the experimental data, but is unable to fully capture the effect of powder properties and powder-binder interaction.

Volumetric and 1H NMR spectroscopic studies of saccharides-calcium lactate interactions in aqueous solutions

The solute-solvent interactions governing the hydration behaviour of saccharide [D(+)-glucose, sucrose and D(+)lactose monohydrate) molecules were studied in aqueous solution of calcium salt at temperatures (298.15 K 313.15 K) and at atmospheric pressure. The volumetric properties were evaluated from experimentally measured densities and speed of sound data. The nature of interactions influencing the taste behaviour of saccharides in presence of calcium lactate is evaluated from apparent specific volume and apparent specific isentropic compressibility values. The volumetric transfer parameters (ΔtZ2° = ΔtV2° or ΔtK°s,2) were evaluated and the magnitude of these parameters were analysed on the basis of co-sphere overlap model. Among various interactions occurring in the system, hydrophobic types of interactions were found to be the dominating one. The 1H NMR of the studied system was recorded and from the variation in chemical shift (Δδ) it was further concluded the presence of hydrophobic-ionic types of interactions.

Application of modified SeDeM expert diagram system for selection of direct compression excipient for liquisolid formulation of Neusilin® US2

In the present investigations, the SeDeM expert diagram system, modified to include two important compression properties, i.e. mean yield pressure, Py, and compactibility parameter, σtmax, was used to identify a diluent most suitable for the direct compression of a liquisolid formulation of Neusilin® US2 (50NEU). The mean incidence values of 50NEU demonstrated that it had poor flowability and compactibility, and was highly hygroscopic. Three commonly used directly compressible tablet diluents, viz. lactose monohydrate, microcrystalline cellulose, and dibasic calcium phosphate, selected based on their index of good compressibility (IGC) values were evaluated for their usefulness for direct compression of 50NEU. Mathematical equations based on the linear and power mixing rules were used to calculate the percentage of diluent required for direct compression. The powder blends prepared using lactose monohydrate resulted in fragile tablets, dibasic calcium phosphate exhibited poor compactibility, however, powder blends containing microcrystalline cellulose resulted in tablets with acceptable compactibility. This demonstrated the significance of a rational selection of excipients based on their SeDeM parameters rather than the IGC values. Additionally, the study results showed that the modified SeDeM expert system was superior to the conventional SeDeM system for the selection of diluent for direct compression.

The effect of different types of lactose monohydrate on the stability of acetylcholinesterase immobilized on carriers designed to detect nerve agents

AbstractBACKGROUNDMaintaining the stability of an immobilized enzyme during storage is generally very problematic. However, various substances have been reported to have a positive effect on enzyme stability. These include reducing disaccharide lactose, which is used in carriers in the form of pellets with immobilized cholinesterase. These carriers serve as a filling for detection tubes (biosensor), which are used for detecting nerve agents, wherein the detection itself is based on a colorimetric Ellman's reaction. To date, however, no study has been performed on the effect of different types of lactose monohydrate on the properties of such carriers.RESULTSThe effect of five different types of lactose monohydrate on carrier properties and enzyme stability was examined. The lactose powders used differed in the particle size distribution, shape, compactability and flowability. The carriers were prepared in triplicate and subjected to a 24‐month stability test under three storage conditions, with the results being statistically analyzed by analysis of variance, principal component analysis and t‐test. Samples containing lactose with spherical particles were more resistant to degradation by heat and moisture than samples containing crystalline particles; in addition they had higher hardness and better sensitivity. All samples were also tested with soman after 24 months of storage and were found to retain very good sensitivity.CONCLUSIONSamples containing spherical types of lactose proved to be more stable in some critical parameters compared to the samples with lactose in the form of single crystals, which are currently used in commercially available detection tubes. © 2021 Society of Chemical Industry (SCI).

Particle breakability assessment using an Aero S disperser

Milling is widely used in various industries to tailor the particle size distribution for desired attributes. The ability to predict milling behaviour by testing the breakability of a small quantity of material is of great interest. In this paper, a widely available aerodynamic dispersion method, i.e. the Aero S disperser of Malvern Mastersizer 3000 has been evaluated for this purpose. This device is commonly used for dispersion of fine and cohesive powders, as the particles are accelerated and impacted at a bend, but here its use for assessing particle breakability is explored. The fluid flow field is modelled using one-way coupled Computational Fluid Dynamics approach, as the particle concentration is low, following which the particle impact velocity is calculated by Lagrangian tracking and used in the analysis of particle breakage. Experimental work on the breakability is carried out using aspirin, paracetamol, sucrose and α–lactose monohydrate particles. The relative shift in the specific surface area is determined and together with the calculated particle impact velocity and physical properties, they are used to calculate the breakability index. A good agreement is obtained with the single particle impact testing and aerodynamic dispersion by Scirocco disperser, indicating the breakability could also be inferred from this method.

New Pharmaceutical Salts of Trazodone.

New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.

Classification of polymorphic forms of fluconazole in pharmaceuticals by FT-IR and FT-NIR spectroscopy

The main goal of this work was to test the ability of vibrational spectroscopy techniques to differentiate between different polymorphic forms of fluconazole in pharmaceutical products. These are mostly manufactured with fluconazole as polymorphic form II and form III. These crystalline forms may undergo polymorphic transition during the manufacturing process or storage conditions. Therefore, it is important to have a method to monitor these changes to ensure the stability and efficacy of the drug.Each of FT-IR or FT-NIR spectra were associated to partial least squares-discriminant analysis (PLS-DA) for building classification models to distinguish between form II, form III and monohydrate form. The results has shown that combining either FT-IR or FT-NIR to PLS-DA has a high efficiency to classify various fluconazole polymorphs, with a high sensitivity and specificity. Finally, the selectivity of the PLS-DA models was tested by analyzing separately each of three following samples by FT-IR and FT-NIR: lactose monohydrate, which is an excipient mostly used for manufacturing fluconazole pharmaceutical products, itraconazole and miconazole. These two last compounds mimic potential contaminants and belong to the same class as fluconazole. Based on the plots of Hotelling’s T² vs Q residuals, pure compounds of miconazole and itraconazole, that were analyzed separately, were significantly considered outliers and rejected. Furthermore, binary mixtures consist of fluconazole form-II and monohydrate form with different ratios were used to test the suitability of each technique FT-IR and FT-NIR with PLS-DA to detect minimum contaminant or polymorphic conversion from a polymorphic form to another using also the plots of Hotelling’s T² vs Q residuals.

Application of Aquasolv Lignin in ibuprofen-loaded pharmaceutical formulations obtained via direct compression and wet granulation

AS (Aquasolv) Lignin produced via Liquid Hot Water Pretreatment and Enzymatic Hydrolysis has shown potential as an active pharmaceutical ingredient and/or excipient in solid dosage forms. Moreover, lignin is safe to consume and presents antioxidant and antidiabetic capacity, properties that can add to solid dosage forms in pharmaceuticals. This work aimed to evaluate the performance of tablets produced via direct compression and wet granulation when lignin is used in combination with commercial excipients. In order to find optimal tablet performance, different lignin formulations were assessed, and the concentrations were given by extreme vertices mixture design (13 formulations). The blends were composed of AS Lignin, Microcrystalline Cellulose, and Lactose monohydrate and the optimized blend was found to be 14.53 w/w% of disintegrant, 26.57 w/w% of binder and 58.9 w/w% of AS lignin. This proportion was further used to evaluate the performance of lignin-based tablets in drug release, using Ibuprofen as a drug model (50 w/w% and 70 w/w%) and for comparison of direct compression with wet granulation. Direct compressed tablets resulted in higher drug dissolution rates when compared with wet granulation, nevertheless; both tableting techniques showed promising results for lignin. More than 5 formulations tested in this work are compliant with International Pharmacopoeia regulations for solid dosage pharmaceutical forms, thus AS Lignin shows potential to be used as an excipient in pharmaceutical formulations. Industrial relevanceIndustrially, AS Lignin appears as promising excipient in the pharmaceutical technologies as well as boost in the biorefining technologies in the following years. Lignin produced is free of sulfur, can be labelled as clean and environmentally-friendly and in this study, was proven this non-cytotoxic AS lignin can be used for excipients and drug carriers. The findings in this paper showed the use of product formulation for life science purposes, thus stressing one of possibilities for lignin valorization in biorefineries.

SLOW QUASIKINETIC CHANGES IN WATER-LACTOSE COMPLEXES DURING STORAGE

Objective: To investigate kinetic changes in the spectral characteristics by Fourier Transform Infrared spectroscopy (FTIR) of water-lactose complexes (SMC), derived during the manufacturing process of the drug, containing release-active forms of antibodies.
 Methods: lactose monohydrate substance, saturated with release-active forms of affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma (RA forms of Abs); tablets produced from this substance by direct compression after the addition of excipients (microcrystalline cellulose, magnesium stearate). Powdered and tableted placebo samples saturated with technologically processed water or phosphate-buffered saline, as well as with intact ethanol were used as control. Kinetic changes in SMC were studied using an Agilent Cary 630 FTIR spectrophotometer with a diamond ATR accessory (Agilent Technologies, USA). We used the method of X-ray fluorescence spectroscopy (EDX-7000 Shimadzu energy dispersive X-ray fluorescence spectrometer) to track changes in the fluorescence signal at certain wavelengths. The range of measured elements–11Na-92U.
 Results: Control of some technological characteristics of the obtained active substance (moisture, flowability) and dosage form (mean mass, disintegration rate) was used as indirect indicators of quality, but they did not allow reliably distinguishing intact lactose from the saturated one. Long-period oscillations on FTIR spectra were characteristic for all types of samples; oscillations occur at approximately two-week intervals; S/N indices were more stable for samples of RA forms of Abs than for placebo samples. On some days, the substance saturated with RA forms of Abs significantly differed from the intact lactose powder. The kinetics of the X-ray fluorescence intensity at certain wavelengths indicates the possibility of a periodic cooperative trigger transition of the system. Reversible conformational transitions are observed for powders on the 30th and 130th days (Kα 3.313 keV). For tablets at Kα 3.313 keV and Kα 1.740 keV small changes were visualized on those days (100–110th day) when hysteresis phenomena were recorded in the IR spectra of these samples.
 Conclusion: As a result, the evidence for a long-period dramatic conformational mobility of the water-lactose complex was obtained. Based on the data on the semiannual kinetics of IR spectra, a universal criterion for the identity of lactose powder saturated with RA forms of Abs was obtained. Also, it was confirmed that the lactose conformation state was changed by saturation with RA forms of Abs.

Identification of Maillard Based Lactose Adduct in Roflumilast Generated During Incompatibility Studies and its RP-HPLC Method Development, Validation and Impurity Control

Roflumilast is Prescribe as the first line treatment for COPD (Chronic Obstructive Pulmonary Disease). One of the critical starting materials for the synthesis of Roflumilast API is 3,5-dichloro-4-aminopyridine. It is also generated during the degradation of Roflumilast API and termed as degradant product-1(DP-1). The primary amino group of DP-1 reacts with lactose monohydrate (Maillard reaction) in the formulation to form DP-1Lactose Adduct (DPLA) under relatively harsh conditions. This adduct formed, was isolated and characterized by different spectroscopic methods. In-silico toxicological evaluation of characterized adduct was done using online free access software T.E.S.T toxicity estimation tool, Pro-TOX-II and Pre-ADMET, results advocating that the adduct may have Carcinogenicity, Developmental toxicity or Immuno-toxicity. In addition to this, a selective, robust and precise reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated as per ICH Q2(R1) guideline for the determination of Roflumilast, 3, 5-dichloro-4-aminopyridine in presence of DPLA. The chromatographic separation was performed with Phenomenex Luna C 18 column (250 mm × 4.6 mm, 5 μm) using a mobile phase consisting of Acetonitrile - Ammonium formate (10mM) (pH 8.0). pH was adjusted to 8 with triethylamine, in gradient mode 0 min (75:25, v/v), 3.5min (70:30, v/v) and 5 min (85:15, v/v) keeping the flow rate of 0.6 ml/min. Quantification was achieved using UV detection at 254nm. Linearity, accuracy, and precision were found to be under acceptable criteria for the determination of Roflumilast, 3, 5-dichloro-4-aminopyridine and DPLA in the concentration range of 200-1200 µg ml -1 , 1–6 µg ml -1 and 0.2-1.2 µg ml -1 , respectively. Further for rationalization of formation of DPLA, stability studies of DP-1 spiked in-house and marketed formulation were performed at 25°C ± 2°C and 60% RH ± 5% RH and at 40°C ± 2°C and 75% RH ± 5% RH, which conclude that up to the 180 days there was no evidence of the formation of lactose adduct so far. The DPLA should be controlled ≤ 0.3% during formulation development, calculated concerning the ICH M7 guideline to prevent its genotoxic effect. Overall, this study suggests either replacing the lactose monohydrate as an excipient in tablet or avoidance of high moisture and higher temperature during formulation development to avoid the impurity generation.

Improvement of bioavailability of poorly soluble racecadotril by solid dispersion with surface adsorption method: A case study

Introduction: Biopharmaceutics classification system class II drugs show unpredictable bioavailability based on their solubility. Unfortunately, very few products were manufactured by this technique owing to their poor flowability and stability. The objective of the current investigation was used to improve the flowability by surface solid dispersion (SSD; SD with surface adsorption technology) and improve the absorption of racecadotril (RT) under low pH conditions (i.e., in stomach) to show anti-diarrheal effect by reducing water and electrolyte secretion into the intestine. Materials and Methods: SSDs and physical mixtures (PMs) were prepared using various ratios of hydrophilic carriers (polyethylene glycol 4000, polyethylene glycol 6000, and Gelucire 50/13) and an adsorbent (lactose monohydrate). Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry , and dissolution studies (in vitro) were conducted to characterize SSDs and PMs. Results: Phase solubility curves represent AL type, indicating that the solubility of drug linearly increased with an increase in the concentration of carrier. Characterization studies indicated that no interactions between carrier and drug. Solid-state characterization showed a reduction in crystallinity that further supports increment in solubility and dissolution. The optimized formulation (SDG4) showed 99.84 ± 1.5% drug release in 15 min compared to RT plain drug (11.95 ± 1.72%). In vivo bioavailability studies of SDG4 revealed a significant (P < 0.05) increase in Cmax 65.38 ± 1.34 µg/mL (1.75-fold) with increased relative bioavailability (180.22-fold) against the RT plain drug. Conclusion: Formulation of SD with surface adsorption method could enhance solubility, dissolution, and bioavailability of RT.

FORMULATION AND EVALUATION OF MODIFIED RELEASE TRI-LAYERED TABLET USING A FIXED DOSE COMBINATION OF METFORMIN HCL AND VILDAGLIPTIN

The aim of present investigation is to formulate the tri-layered tablet of an Anti-Hyperglycaemic drug comprising Metformin HCl as sustained release layer and Vildagliptin as an immediate release layer in a fixed dose combination along with a fast dissolving intermediate layer or barrier layer in between the two layers just like a sandwich. Vildagliptin is well-known for its instability in presence of Metformin HCl. Hence, Vildagliptin degrades in formulation of single unit dosage form. The in vitro release layer of Metformin HCl was prepared using combination of sustained release polymer HPMC K100M &amp; HPMC K4M and binder used in formulation is Povidone K90 which was prolonged up to 10 - 12 hours. The In-vitro release of Vildagliptin is rapid from tablet and showed highest drug release of more than 90% in 30 Minutes. Final formulation was tested for accelerated stability study. Intermediate barrier layer was optimised using Lactose Monohydrate and Microcrystalline cellulose as a diluents and Croscarmellose sodium as a disintegrant. The disintegration time of tablet into two halves for final formulation was 51 seconds. Combination of lactose monohydrate and microcrystalline cellulose as well as thickness of the intermediate layer was found important to achieve quick disintegration.

PSV-40 Effects of regrouping and administrations of meloxicam and chromium on plasma cortisol concentrations and behaviors in dairy calves

Abstract This study investigated effects of regrouping and oral meloxicam and chromium administration on growth performance, blood cortisol concentrations, and behaviors in dairy calves. Fifty Holstein calves (average age 196 ± 24.7 days, average body weight 198kg ± 32.7 kg) were equally divided into five groups: no regrouping with lactose monohydrate administration (NL), regrouping with lactose monohydrate administration (GL), regrouping with Cr administration (GC), regrouping with meloxicam administration (GM), and regrouping with both meloxicam and Cr administration (GMC). Blood was collected before regrouping and at 3h, 9h, 24h, 1w, and 2w after regrouping. Behaviors have been monitored from d1 to d7. Regrouping did not affect average daily gain (ADG), and the administrations of both meloxicam and chromium increased (P &amp;lt; 0.02) ADG compared to NL group during 2 weeks. Regrouping increased (P &amp;lt; 0.05) plasma cortisol concentrations in GL group, and both meloxicam and chromium and its combination treatments decreased cortisol concentrations compared to GL group at 24h, but not at other times. Regrouping increased (P &amp;lt; 0.05) fight, duration of eating time, head bunt, drinking time, and standing time behaviors in GL group at d1, d2, d2, d3, and d4 respectively. Regrouping also increased (P &amp;lt; 0.05) displacement at eating place in GL group from d3 to d6, but this effect was not significant (P &amp;lt; 0.05) at d7. In conclusion, regrouping caused elevation of plasma cortisol concentrations and abnormal behaviors. Meloxicam, chromium, and/or its combined administrations improved growth performance and reduced circulating cortisol concentrations in regrouped dairy calves, suggesting a feasible strategy to alleviate regrouping stress.

Predictive evaluation of powder X-ray diffractograms of pharmaceutical formulation powders based on infrared spectroscopy.

To ensure quality and stability, monitoring systems are recommended to analyze pharmaceutical manufacturing processes. This study was performed to predict powder X-ray diffraction (PXRD) patterns of formulation powders through attenuated total reflectance (ATR)-infrared (IR) spectroscopy in a nondestructive manner along with chemometrics. Caffeine anhydrate, acetaminophen, and lactose monohydrate were grinded at six weight ratios. The six sample groups were evaluated using ATR-IR spectroscopy and PXRD analysis. Partial least squares models were constructed to predict the PXRD intensities of the samples from the ATR-IR spectra. The prediction accuracy on the prepared PLS regression models was as high as R2 =0.993. Linear relationships were obtained between the prediction data set and reference PXRD intensity at each degree. 2D PLS regression coefficient analysis enabled the analysis of the correlation between PXRD patterns and IR spectra.

Combining Co-Amorphous-Based Spray Drying with Inert Carriers to Achieve Improved Bioavailability and Excellent Downstream Manufacturability.

It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.

The relevance of granule fragmentation on reduced tabletability of granules from ductile or brittle materials produced by roll compaction/dry granulation.

Roll compaction/dry granulation often results in loss of tabletability. The two main hypotheses for this are granule hardening and granule size enlargement. The aim of this study was to investigate the effect of granule size, roll compaction force, and granule fragmentation upon tableting and its effect on tabletability of granules constituting a ductile or brittle material. Plastically deforming microcrystalline cellulose (MCC) and fragmenting lactose monohydrate (lactose) were roll compacted at five roll compaction forces ranging from 2 to 16 kN/cm. Granule size fractions of 250-355 and 500-710µm were blended with 10% magnesium stearate (MgSt), compressed into tablets and ground to obtain compressed granules. The predominant deformation behaviour of the particles constituting the granules directly impacted granule deformation upon tableting, as lactose granules fractured extensively upon tableting, whereas MCC granules predominantly deformed by plastic deformation. Increased roll compaction force resulted in more granule hardening of both materials and thereby granules less susceptible to fragmentation upon tableting. Granule hardening accounted for the largest loss of tabletability of MCC granules upon roll compaction. Roll compaction force and granule size had no or negligible effect on tabletability of lactose tablets without MgSt, whereas increased roll compaction force and larger granules decreased tensile strength of tablets containing lactose granules blended with MgSt. This was explained by inter-particle and inter-granular bonds contributing equally to the tensile strength of lactose tablets without MgSt. However, after addition of MgSt, the decreased fragmentation tendency of larger granules compacted at higher roll compaction forces resulted in greater MgSt coverage of the granules upon tableting, thereby decreasing tabletability.

Formulation and characterization of catechin‐loaded proniosomes for food fortification

To overcome the problems associated with niosomes, proniosomes - a dry powder - was prepared to nanoencapsulate catechins using Span 60 as surfactant, cholesterol as stabilizer and maltodextrin, lactose monohydrate and pullulan as wall materials. The proniosomes were made by the thin-film hydration technique, and were characterized for fortification in milk beverages. Scanning and atomic force microscopic images showed the varying morphology and ultrastructure of the proniosomes. The mean hydrodynamic diameter of 193.57-262.52 nm, polydispersity index of 0.24-0.25 and zeta potential of -15.8 to -24.73 were suggestive of the size, homogeneity and stability of the catechin-loaded proniosomes. X-ray powder diffractograms and Fourier transform infrared (FTIR) spectra provided insight about the interaction between catechins and wall materials. Entrapment efficiency and in vitro release were calculated to determine the extent of nanoencapsulation of catechins and their bioavailability, respectively. The nanoencapsulates were fortified in milk and yogurt to find their organoleptic acceptability. Moisture content was found to be 20-30 g kg-1 , indicating longer stability of the proniosomes. Scanning electron microscopic and atomic force microscopic images revealed the ultrastructure and spherical-shaped morphology of proniosomes. Entrapment efficiency of catechins using pullulan as wall material was as high as 83.43%. In vitro release studies revealed the sustained release of catechins from the proniosomes. FTIR and X-ray diffraction spectra revealed the absence of chemical interactions between catechins and encapsulants. Food-grade proniosomes are a good vehicle for fortification of milk and yogurt without noticeable adverse changes in their organoleptic and physicochemical properties, thus increasing the potential for bioavailability of catechins in the gastrointestinal tract. © 2020 Society of Chemical Industry.

Lactose monohydrate (C12H22O11 · H2O) mediated synthesis and spectral analysis of nanocrystalline Ni0.5Cu0.5Fe2O4

Abstract Ni0.5Cu0.5Fe2O4 nanocrystalline spinel ferrite was synthesized through a lactose monohydrate (C12H22O11 · H2O) mediated chemical preparation technique (post annealed at 600 °C for 4 h). Va...