Low Solubility Compounds Research Articles

Hispidulin-rich fraction of Clerodendrum fragrans Wild. (Sesewanua) dissolving microneedle as antithrombosis candidate: A proof of concept study

Existing conventional antithrombosis drugs have caused many side effects, opening up opportunities for the development of new thrombotic drugs. There is potential to use the hispidulin-rich fraction of sesewanua (HRFS) as a new antithrombotic. The oral route limitation of hispidulin, as a low water solubility and non-polar compound, can be addressed. This study explores the potential of HRFS in the form of dissolving microneedles (DMN). The formula was created using polymers such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone K-30 (PVP), and non-ionic surfactant. Ex vivo permeation studies found that 184.95 µg/cm2 of hispidulin was released 60 h after the best formulation. After 14 days of applying HRFS-DMN, the anticoagulant and antioxidant activity in male albino rats showed higher Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) values and lower Inter Cellular Adhesion Molecule-1 (ICAM-1) values. No statistically significant differences were found between the effects of two and four HRFS-DMN and the injection of heparin at a dosage of 200 IU per kilogram. However, notable distinctions were observed when comparing HRFS-DMN to negative controls, oral and quercetin as positive controls at anti-ICAM activity. The findings confirmed the feasibility of HRFS-DMN for thrombosis and its effectiveness in delivering Hispidulin (HIS) into the bloodstream. This DMN is non-irritating, safe, and painless, showing promising outcomes in enhancing the efficacy of thrombosis treatment via the transdermal route.

Pharmacokinetics of nano- and microcrystal formulations of low solubility compounds after intramuscular injection to mice.

The aim of this study was to investigate the pharmacokinetics (PK) of poorly soluble compounds when administered intramuscularly (i.m.) as crystalline particles of different sizes. Three uncharged compounds (griseofulvin, AZ'72, and AZ'07) with varying aqueous solubility were dosed to mice at 10 and 50mg/kg as nano- and microparticle formulations. The PK of the compounds was evaluated. The smaller particles of the drugs resulted in higher maximum plasma concentration (Cmax) and area under the plasma concentration-time profile (AUC) at 50mg/kg. There was a dose-proportional increase in AUC but less than dose dose-proportional increase in Cmax. The evaluation at 10mg/kg was more complex as increased exposure for nanoparticles was only observed for griseofulvin which has the highest solubility. In addition, there was an increase in half-life with an increase in dose. This study highlights that general expectations based on in vitro dissolution (i.e. that smaller particles dissolve faster than larger particles when surrounded by liquid) do not always translate to in vivo and demonstrates the importance of understanding the physicochemical properties of the drug, the characteristics of the formulations and the microphysiology at the delivery site.

Enzymatic pre-treatment defines the water-binding and rheological properties of dynamic ultra-high-pressure homogenised pea hull suspensions

Pulse hulls are composed of cell wall polysaccharides and are a concentrated source of dietary fibre. However, the dense microstructure hinders their industrial application, resulting in poor techno-functional properties. To improve their functionality, the cell wall (cellulose, hemicellulose, and pectin) is disrupted by combining enzymatic pre-treatments and microfluidization. This work aims to study the impact of a fixed reduction of the insoluble mass by selective enzymatic pre-treatment of pulse hulls on the composition, microstructure, water binding, and rheological properties of microfluidized suspensions. To that end, enzymatic pre-treatments using cellulase, hemicellulase, pectinase, and their binary and ternary mixtures were conducted to reduce insoluble mass content. The combined treatment improved the water-binding properties, leading to the formation of viscoelastic gels. Microfluidized suspensions enzymatically pre-treated with a binary mixture of cellulase and hemicellulase presented the highest water binding capacity, viscosity, and viscoelasticity. The partial enzymatic degradation of the cellulose-hemicellulose network weakened the interactions between both polysaccharides. It facilitates the disruption of the particles and the release of high molecular weight soluble dietary fibre (HMWSDF), which are gelling substances. On the contrary, an enzymatic pre-treatment using only cellulase increased the content of low molecular weight soluble compounds, resulting in low viscous and viscoelastic suspensions. Thus, the concentration of remaining microfibrillated cellulose and HMWSDF are key parameters controlling the rheological behaviour of the suspensions. This study enhances comprehension regarding pea hulls' molecular and macromolecular modifications, potentially enabling the production of tailor-made pulse hull suspensions.

Halogen-Free Purification of Low-Solubility Compounds in Supersaturated Liquid Chromatography Using Monolithic Silica

Halogen-Free Purification of Low-Solubility Compounds in Supersaturated Liquid Chromatography Using Monolithic Silica

Integrating Dynamic in vitro Systems and Mechanistic Absorption Modeling: Case Study of Pralsetinib

Dynamic in vitro absorption systems and mechanistic absorption modeling via PBPK have both shown promise in predicting human oral absorption, although these efforts have been largely separate; this work aimed to integrate knowledge from these approaches to investigate the oral absorption of a RET inhibitor, pralsetinib, with BCS Class II properties. Tiny-TIM (TIM B.V., Weteringbrug​, The Netherlands) is a dynamic in vitro model with close simulation of the successive physiological conditions of the human stomach and small intestine. Tiny-TIM runs with pralsetinib were performed at doses of 200 mg and 400 mg under fasting conditions. Mechanistic modeling of absorption was performed in Simcyp V21 (Certara, Manchester, UK). Pralsetinib fasted bioaccessibility in the Tiny-TIM system was 63% at 200 mg and 53% at 400 mg; a 16% reduction at 400 mg was observed under elevated gastric pH. Maximum pralsetinib solubility from the small intestinal compartment in Tiny-TIM directly informed the supersaturation/precipitation model parameters. The PBPK model predicted a similar fraction absorbed at 200 mg and 400 mg, consistent with the dose proportional increases in observed pralsetinib exposure. Integrating dynamic in vitro systems with mechanistic absorption modeling provides a promising approach for understanding and predicting human absorption with challenging low solubility compounds.

Drug solubility in biorelevant media in the context of an inhalation-based biopharmaceutics classification system (iBCS)

An inhalation-based Biopharmaceutics Classification System for pulmonary drugs (iBCS) holds the perspective to allow for scientifically sound prediction of differences in the in vivo performance of orally inhaled drug products (OIDPs).A set of nine drug substances were selected, that are administered via both the oral and pulmonary routes. Their solubility was determined in media representative for the oral (Fasted State Simulated Intestinal Fluid (FaSSIF)) and pulmonary (Alveofact medium and Simulated Lung Fluid (SLF)) routes of administration to confirm the need for a novel approach for inhaled drugs. The complexity of these media was then stepwise reduced with the purpose of understanding the contribution of their components to the solubilizing capacity of the media. A second reason for varying the complexity was to identify a medium that would allow robust but accurate dissolution testing. Hence, Hank’s balanced salt solution (HBSS) as a medium used in many in vitro biological tests, non-buffered saline solution, and water were included.For some drug substances (salbutamol sulfate, tobramycin, isoniazid, and tiotropium bromide), no significant differences were observed between the solubility in the media used. For other drugs, however, we observed either just small (rifampicin, budesonide, salmeterol) or unexpectedly large differences (beclomethasone dipropionate).Based on the minimum theoretical solubility required for their common pulmonary dose in 10 ml of lung lining fluid, drug solubility was classified as either high or low. Two high solubility and two low solubility compounds were then selected for refined solubility testing in pulmonary relevant media by varying their content of phospholipids, surfactant proteins and other proteins.The solubility of drug substances in simulated lung lining fluids was found to be dependent on the physicochemical properties of the drug substance and the composition of the media. While a pulmonary dissolution medium that would fit all drugs could not be established, our approach may provide guidance for finding the most suitable dissolution medium for a given drug substance and better designing in vitro tests for predicting the in vivo performance of inhalable drug products.

Development and Evaluation of Microemulsion Formualatons of Valsartan for Solubility Enhancement

Microemulsions have attracted considerable amount of interest as potential drug delivery vehicles largely due to their simple method of preparation, stability and their abilities to incorporate a wide range of drugs of varying solubility. O/W microemulsion is expected to increase the solubility by dissolving low water solubility compounds into its dispersed phase and to enhance the oral bioavailability by protecting the drug increasing the rate of absorption and wettability due to surfactants induced permeability changes and smaller droplet size (< 100 nm) and most importantly able to target lymphatic system. 
 In the present study, the drug delivery system contains Valsartan, a hydrophilic component, a lipophillic component, surfactants and co-surfactants. The objective is to provide an increased release of valsartan and increased bioavailability of valsartan. Prepared microemulsion formulations by phase-titration method were evaluated for viscosity, drug content, thermodynamic stability studies and in-vitro dissolution. Resultant microemulsion optimized formulation (ME5) shows drug release (88.2±0.16%.%). Hence, micro-emulsion of valsartan was successfully developed and evaluated.
 Keywords: Microemulsion, Valsartan, solubility, evaluation.

Understanding of surface fouling of brackish water reverse osmosis spiral wound membrane using an integrated analysis of seawater quality and membrane autopsy

To understand the cause of the scale, an integrated analysis of the saline water quality and discarded reverse osmosis membranes was developed. Damaged areas on the membrane were excised and characterized by the Fujiwara test, infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis. A spatula and sonication were used to remove scale. Thermodynamic modeling (PHREEQC) was used to predict scale formation at 75 bar, resulting in saturation index values for both mixed and pure compounds. Fujiwara's test revealed damage to the polyamide and organic fouling by polysaccharides, silica, and aromatics. Thermo-oxidative decomposition and residual masses of metal oxides and salts were observed. The microscopy detected incrustations in the membrane by analyzing compounds with silicon, oxygen, calcium, magnesium, aluminum, etc. The modeling indicated the low-solubility compounds of scale are aluminum silicates, clays, quartz, etc., identified experimentally. PHREEQC can model desalination to predict scale problems, allowing for early decision-making.

Precellys® Evolution Homogenizer - a versatile instrument for milling, mixing, and amorphization of drugs in preformulation

The aim of this work was the evaluation and introduction of the Bertin Precellys® Evolution homogenizer with Cryolys® as a valuable and versatile tool for the improvement of workflows in the preformulation phase of drug development. The presented pilot experiments indicate that the instrument can be applied for (1) screening of appropriate vehicles for the generation of micro- and nano suspensions, (2) small-scale manufacturing of suspension formulations for preclinical animal studies, (3) drug amorphization and identification of appropriate excipients for amorphous systems, and (4) preparation of homogenous powder blends. The instrument allows the rapid, parallel, and compound-sparing screening of formulation approaches and small-scale formulation manufacturing, in particular for low solubility compounds. For the characterization of generated formulations, miniaturized methods are introduced such as a screening tool for suspension sedimentation and redispersion and a non-sink dissolution model in biorelevant media in microtiter plates. This work summarizes exploratory, proof-of-concept studies and opens up new opportunities for more extended studies with this instrument in various application areas.

Evaluating the Sorption Kinetics of Polychlorinated Biphenyls in Powdered and Granular Activated Carbon

Activated carbon (AC) has been applied widely in water treatment as a strong sorbent for organic contaminants and, more recently, in-situ treatment and capping for remediating legacy contaminants. In some sediment environments, the sorption kinetics onto AC may significantly impact remedial performance, particularly for large, highly hydrophobic contaminants such as PCBs, but there is limited kinetic data on such compounds. In this study, batch experiments were conducted over 52 weeks to measure PCB adsorption kinetics on 2 ACs in granular (1.1 mm diameter) and powdered (0.02 mm) form using polydimethylsiloxane (PDMS) fibers to measure aqueous concentrations over time. The experiment was conducted in glass containers with water at known PCB concentration and containing 10 mg/L natural organic matter (NOM) and activated carbon. Blanks without activated carbon were used to estimate kinetics and equilibrium uptake to PDMS and NOM. The PDMS measured aqueous concentration in AC containing slurries was then used to estimate kinetics and equilibrium uptake of the various PCBs onto the AC. Achieving equilibration of PCBs onto the powdered activated carbon (PAC) was accomplished in days to weeks, but granular activated carbon (GAC) uptake was not complete for some high molecular weight congeners in a year. The data were used to fit linear driving force models with both linear and Freundlich models of equilibrium. The models were then used to predict uptake onto powdered and granular AC during in-situ capping and treatment using the CapSim model. Slow kinetics can significantly limit the performance of granular AC in high upwelling (> 1–10 cm/day) environments. This study demonstrates the usage of polymeric passive samplers to explore sorption kinetics and equilibrium for low solubility compounds as well as the differences in performance of granular and powdered forms of AC for remediation of PCB contaminated sediment.

Investigation and Determination of Electrochemical Reaction Kinetics in Lithium-Sulfur Batteries with Electrolyte LiTFSI in DOL/DME

A major challenge in the simulation of Li-S batteries is that the electrochemical reaction parameters supplied from the fitting of 0-d or 1-d models depend on the cathode and separator microstructure, so these parameters cannot be used in the design and optimization of material microstructure. The present investigation fits the electrochemical reaction kinetics employing a continuum model taking into account the pore size distribution and tortuosity of cathode and separator in the transport of sulfur molecules and ion species (Li+ ion, electrolyte and sulfide anions) in solvated or desolvated form depending on pore size. Hence, the specified reaction kinetics parameters are independent from the material microstructure. The Li-S redox reaction model includes six redox reactions in the cathode and the lithium redox reaction at the anode. Reactions are assumed to take place in the electrolyte solution rather than in the solid phase of sulfur or lithium sulfide precipitates, where dissolution/precipitation kinetics is modeled especially for the low solubility compounds: sulfur, Li2S and Li2S2. The fitting exercise is conducted based on experimental data of a cyclic voltammetry cycle accompanied by in operando UV–vis spectroscopy. The investigated battery has electrolyte LiTFSI in DOL/DME and no electrocatalysts in any part of the cell.

Influence of arbuscular mycorrhizal fungi on low molecular weight soluble compounds in the rhizosphere soil of black locust seedlings grown in cadmium-contaminated soils under elevated CO2 scenarios

Influence of arbuscular mycorrhizal fungi on low molecular weight soluble compounds in the rhizosphere soil of black locust seedlings grown in cadmium-contaminated soils under elevated CO2 scenarios

Machine learning using multi-modal data predicts the production of selective laser sintered 3D printed drug products

Three-dimensional (3D) printing is drastically redefining medicine production, offering digital precision and personalized design opportunities. One emerging 3D printing technology is selective laser sintering (SLS), which is garnering attention for its high precision, and compatibility with a wide range of pharmaceutical materials, including low-solubility compounds. However, the full potential of SLS for medicines is yet to be realized, requiring expertise and considerable time-consuming and resource-intensive trial-and-error research. Machine learning (ML), a subset of artificial intelligence, is an in silico tool that is accomplishing remarkable breakthroughs in several sectors for its ability to make highly accurate predictions. Therefore, the present study harnessed ML to predict the printability of SLS formulations. Using a dataset of 170 formulations from 78 materials, ML models were developed from inputs that included the formulation composition and characterization data retrieved from Fourier-transformed infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Multiple ML models were explored, including supervised and unsupervised approaches. The results revealed that ML can achieve high accuracies, by using the formulation composition leading to a maximum F1 score of 81.9%. Using the FT-IR, XRPD and DSC data as inputs resulted in an F1 score of 84.2%, 81.3%, and 80.1%, respectively. A subsequent ML pipeline was built to combine the predictions from FT-IR, XRPD and DSC into one consensus model, where the F1 score was found to further increase to 88.9%. Therefore, it was determined for the first time that ML predictions of 3D printability benefit from multi-modal data, combining numeric, spectral, thermogram and diffraction data. The study lays the groundwork for leveraging existing characterization data for developing high-performing computational models to accelerate formulation development.

Postbiotics: Current Trends in Food and Pharmaceutical Industry.

Postbiotics are non-viable bacterial products or metabolic byproducts produced by probiotic microorganisms that have biologic activity in the host. Postbiotics are functional bioactive compounds, generated in a matrix during anaerobic fermentation of organic nutrients like prebiotics, for the generation of energy in the form of adenosine triphosphate. The byproducts of this metabolic sequence are called postbiotics, these are low molecular weight soluble compounds either secreted by live microflora or released after microbial cell lysis. A few examples of widely studied postbiotics are short-chain fatty acids, microbial cell fragments, extracellular polysaccharides, cell lysates, teichoic acid, vitamins, etc. Presently, prebiotics and probiotics are the products on the market; however, postbiotics are also gaining a great deal of attention. The numerous health advantages of postbiotic components may soon lead to an increase in consumer demand for postbiotic supplements. The most recent research aspects of postbiotics in the food and pharmaceutical industries are included in this review. The review encompasses a brief introduction, classification, production technologies, characterization, biological activities, and potential applications of postbiotics.

Phosphorus forms by depth in sediments from the Qu’Appelle lakes, Saskatchewan, Canada

Understanding sediment phosphorus (P) compounds is essential to managing P in lake sediments because P speciation will determine bioavailability and reactivity. Little is known about organic P (Po) in hardwater eutrophic lakes in the North American Great Plains, or the role of metals in Po cycling. Sediment cores (0–12 cm deep) collected from four lakes from the Qu’Appelle chain in Saskatchewan, Canada, were sectioned by depth and analyzed by solution P nuclear magnetic resonance spectroscopy to characterize P forms. Concentrations and pools of calcium (Ca), magnesium (Mg), iron (Fe), manganese (Mn), and aluminum (Al) were also determined. A range of P compounds was detected with significant interactions between lakes and depth for orthophosphate, phytate and DNA, and significant differences among lakes or with depth for polyphosphates and phosphonates. The main class of Po compounds identified in all lakes was orthophosphate diesters, including phospholipids and DNA, typical of living biota, suggesting that P immobilized by microbes and algae is an important pool in the sediments of these lakes. There were significant differences in metal concentrations among the lakes. In three lakes, Ca concentrations were high, and P was tightly bound with Ca compounds of low solubility. In the fourth lake with lower Ca concentrations, P appeared to be loosely bound to Al and Fe compounds. Our study indicates that there were significant differences in P compounds and the factors controlling their cycling among these four lakes in the same chain, which has implications for P management and water quality control.

Dose Number as a Tool to Guide Lead Optimization for Orally Bioavailable Compounds in Drug Discovery.

Small molecule developability challenges have been well documented over the last two decades. One of these critical developability parameters is aqueous solubility. In general, more soluble compounds have improved oral absorption. While enabling formulation technologies exist to improve bioperformance for low solubility compounds, these are often more complex, expensive, and challenging to scale up. Therefore, to avoid these development issues, medicinal chemists need tools to rapidly profile and improve the physicochemical properties of molecules during discovery. Dose number (Do) is a simple metric to predict whether a compound will be reasonably absorbed based on solubility at an expected clinical dose and represents a valuable parameter to the medicinal chemist defining a clinical candidate. The goal of this mini-Perspective is to present the background of the Do equation and how it can be effectively used to rapidly predict oral absorption potential for molecules in the discovery space.

Integration of In Silico, In Vitro and In Situ Tools for the Preformulation and Characterization of a Novel Cardio-Neuroprotective Compound during the Early Stages of Drug Development.

The main aim of this work is the biopharmaceutical characterization of a new hybrid benzodiazepine-dihydropyridine derivative, JM-20, derived with potent anti-ischemic and neuroprotective effects. In this study, the pKa and the pH-solubility profile were experimentally determined. Additionally, effective intestinal permeability was measured using three in vitro epithelial cell lines (MDCK, MDCK-MDR1 and Caco-2) and an in situ closed-loop intestinal perfusion technique. The results indicate that JM-20 is more soluble at acidic pH (9.18 ± 0.16); however, the Dose number (Do) was greater than 1, suggesting that it is a low-solubility compound. The permeability values obtained with in vitro cell lines as well as with the in situ perfusion method show that JM-20 is a highly permeable compound (Caco-2 value 3.8 × 10−5). The presence of an absorption carrier-mediated transport mechanism was also demonstrated, as well as the efflux effect of P-glycoprotein on the permeability values. Finally, JM-20 was provisionally classified as class 2 according to the biopharmaceutical classification system (BCS) due to its high intestinal permeability and low solubility. The potential good oral absorption of this compound could be limited by its solubility.

Unraveling the accumulation and localization of selenium and barium in Brazil nuts using spectroanalytical techniques

Brazil nuts are native from the Amazon rainforest and their nuts are consumed worldwide having good sensory acceptability. However, knowledge gaps remain concerning elemental composition, localization, and interactions in Brazil nuts. This study presents a detailed assessment regarding the concentration and localization of relevant elements in Brazil nuts using different and complementary spectroanalytical techniques. Samples were collected from six sites of the Brazilian Amazon (Acre, Rondônia, Amazonas, Roraima, Pará, and Amapá) and showed results for selenium (Se) concentration ranging from 0.46 to 356 μg g−1 and barium (Ba) from 12.5 to 7,177 μg g−1. Then, a linear regression model fitted between Se and Ba concentration in Brazil nuts provided an R2 = 0.30. The spatial distribution of major and trace elements in Brazil nuts varied depending on the site of origin and concentration in the sample. The 2D maps performed via μ-XRF showed that Se accumulates mainly in the outer parenchyma tissue of Brazil nuts seeds forming a “ring” shape while Ba tends to accumulate in the epidermal tissue. The possibility of forming compounds of low solubility in Brazil nuts such as BaSO4 and BaSeO4 tends to increase when Ba and Se are higher respectively in the samples studied.

Formulation Development and Evaluation of New Albendazole Tablets with Integrated Quality by Design (QbD) Approach

Hydatid disease occurs in most areas of the world and currently affects about one million people. Albendazole is an orally administered broad spectrum anthelmintic drug approved by US FDA in 1996. Literature review suggests Albendazole is low solubility compound and most of the studies were performed to improve the solubility with traditional approach of product development. The present study was aimed to apply Design of Experiments (DoE) in the development and optimization of drug release from new Albendazole tablets using three factor two level (23) full factorial designs with integrated Quality be Design (QbD) approach. New Albendazole tablets were formulated using micronized grade of the Albendazole active and excipients were selected inline with market reference product. Quality target product profile (QTPP) and Critical quality attributes (CQAs) were designed. Risk assessment was used to identify the Formulation variables impacting CQA dissolution. The amount of Formulation variables were optimized on the basis of drug release profiles at 15 minutes and 30 minutes of different formulation batches manufactured based on 23 full factorial design. Tablets were prepared by wet granulation technique and evaluated for various physicochemical parameters and in vitro drug release. Formulation trials dissolution results at 15 minutes and 30 minutes were evaluated to derive the concentration of Formulation variables which will achieve the release of more than 80%. Analysis of variance (ANOVA) analysis, Pareto chart and Contour plot were used to predict the values of formulation variables and their effect on dissolution. Updated risk assessment of the Formulation Variables was performed and justification was provided for reduction of risk from medium to low level. Optimized formulation from DOE had comparable dissolution profile with market reference tablet. Stability studies of new Albendazole tablets 200 mg were conducted at ICH accelerated conditions and found to be stable. Thus studies revealed that full factorial experimental design could efficiently be applied for optimization of formulation variables affecting drug release. New Albendazole tablets 200 mg successfully formulated with application of the integrated quality by design (QbD) and design of experiment (DOE) approach and thereby achieved comparable release profile with market reference product.

Differing Phosphorus Crop Availability of Aluminium and Calcium Precipitated Dairy Processing Sludge Potential Recycled Alternatives to Mineral Phosphorus Fertiliser

The European dairy industry generates large volumes of wastewater from milk and dairy food processing. Removal of phosphorus (P) by complexing with metal (e.g., aluminium, calcium) cations in P rich sludge is a potential P source for agricultural reuse and P recycling. However, there is a significant knowledge gap concerning the plant availability of this complexed P in comparison to conventional mineral P fertiliser. The current absence of information on plant P bioavailability of dairy processing sludge (DPS) limits the ability of farmers and nutrient management advisors to incorporate it correctly into fertiliser programmes. The present study examined the most common types of dairy sludge—(1) aluminium-precipitated sludge (“Al-DPS”) and (2) calcium-precipitated lime-stabilised sludge (“Ca-DPS”) at field scale to assess P availability in grassland versus mineral P fertiliser over a growing season. The experimental design was a randomised complete block with five replications. Crop yield and P uptake were assessed for 4 harvests. The initial soil test P was at a low level and the experimental treatments were super phosphate at 15, 30, 40, 50 and 60 kg P ha−1, two dairy sludge applied at 40 kg P ha−1 (comparison was made with mineral P at same application rate) and a zero P control applied in a single application at the beginning of the growing season. Results showed a significant positive slope in the relationship between P uptake response and mineral P application rate indicating the suitability of the experimental site for P availability assessment. The P bioavailability of Al- and Ca-DPS varied greatly between treatments. The P fertiliser replacement value based on the 1st harvest was 50 and 16% increased to 109 and 31% cumulatively over the four harvests for Al- and Ca-DPS, respectively. The Al concentration in Al-DPS did not limit P bioavailability, but low P bioavailability from Ca-DPS can be associated with its high Ca content that can lead to formation of low soluble Ca-P compounds at alkaline pH conditions with a high Ca/P ratio. These findings show that P availability from dairy sludge can be quite different depending on treatment process. Consequently, it is critical to have P availability information as well as total P content available to ensure the application rate meets crop requirements without creating environmental risk by over application.