'I don't chase drugs as much anymore, and I'm not dead': Client reported outcomes associated with safer opioid supply programs in Ontario, Canada.

INTRODUCTION: The ongoing opioid overdose crisis, which has killed over 30,000 people in Canada since 2016, is driven by the volatility of an unregulated opioid drug supply comprised primarily of fentanyl. The Canadian government has recently funded safer opioid supply (SOS) programs, which include off-label prescriptions of pharmaceutical-grade opioids to high risk individuals with the goal of reducing overdose deaths. METHODS: In 2021, we examined the implementation and adaption of four SOS programs in Ontario. These programs use a primary care model and serve communities experiencing marginalisation. We conducted semi-structured interviews with program clients. We present the results of a thematic analysis with the aim of describing clients' self-reported impact of these programs on their health and well-being. RESULTS: We interviewed 52 clients between June and October 2021 (mean age 47 years, 56% men, 17% self-identified Indigenous, 14% living with HIV). Our results indicate multifaceted pathways to improved self-reported health and well-being among clients including changes to drug use practices, fewer overdoses, reduced criminalised activity, improved trust and engagement in health care, and increased social stability (e.g., housing). DISCUSSION AND CONCLUSION: Most clients reported that the intervention saved their life because of the reduced frequency of overdoses. Findings suggest that SOS programs improved clients' health outcomes and increase opportunities for engagement in health services. Our results provide insight into the mechanisms behind some of the emergent evidence on the impact of safer supply prescribing.

Evolution of nanomaterial Electrochemiluminescence luminophores towards biocompatible materials.

Electrochemiluminescence (ECL) is a powerful electrochemical technique for the detection and quantification of molecules, both synthetic and biological in origin. Traditional ECL luminophores are based on organic or organometallic compounds, however nanoparticle-based materials offer the benefits of tuneable wavelengths and narrow emission profiles. Materials based on cadmium have been the most extensively studied for ECL nanoparticles to date. Cadmium based nanoparticles exhibit high levels of toxicity thereby impacting their suitability for mass produced sensing applications. As such, alternative materials with reduced toxicities are required. This review focuses on the innovations and applications of low toxicity semi-conductor quantum dots (SCQDs) utilised as ECL luminophores within biosensors. These materials include silver, copper, zinc, tin, silicon and germanium. This contribution presents an evaluative overview of these materials for use as ECL luminophores in terms of toxicity, tunability of emission, potential for amplification, and water dispersibility. Capacity for functionalisation and multiplexing potential are also explored.

Cadmium selenide sulfide quantum dots with tuneable emission profiles: An electrochemiluminescence platform for the determination of TIMP-1 protein.

The development of electrochemiluminescent (ECL) luminophores with tuneable emission profiles is a key requirement in the development of multi-analyte ECL sensing platforms. This study presents the first reported use of cadmium selenide sulfide (CdSeS) quantum dots (QDs) as ECL emitters in which both the ECL emission profile and cathodic potential can be tailored by alteration of the Se/S ratio. CdSeS QDs were synthesised using an aqueous synthetic route thereby avoiding the use of organic reagents, high temperatures and inert gasses. The suitability of the CdSeS QDs to ECL sensing applications is demonstrated via the quantitative determination of TIMP-1 protein at clinically relevant concentrations. The developed cathodic ECL immunosensor exhibited a detectable linear range of 6-60 ng/mL and a limit of detection (LOD) of 1.54 ng/mL. TIMP-1 protein plays a crucial role in pregnancy, wound healing, and cancer prognosis.

Stabilizing vaccines via drying: Quality by design considerations.

Pandemics and epidemics are continually challenging human beings' health and imposing major stresses on the societies particularly over the last few decades, when their frequency has increased significantly. Protecting humans from multiple diseases is best achieved through vaccination. However, vaccines thermal instability has always been a hurdle in their widespread application, especially in less developed countries. Furthermore, insufficient vaccine processing capacity is also a major challenge for global vaccination programs. Continuous drying of vaccine formulations is one of the potential solutions to these challenges. This review highlights the challenges on implementing the continuous drying techniques for drying vaccines. The conventional drying methods, emerging technologies and their adaptation by biopharmaceutical industry are investigated considering the patented technologies for drying of vaccines. Moreover, the current progress in applying Quality by Design (QbD) in each of the drying techniques considering the critical quality attributes (CQAs), critical process parameters (CPPs) are comprehensively reviewed. An expert advice is presented on the required actions to be taken within the biopharmaceutical industry to move towards continuous stabilization of vaccines in the realm of QbD.

Synthesis of Poly(acrylic acid)-Cysteine-Based Hydrogels with Highly Customizable Mechanical Properties for Advanced Cell Culture Applications.

The fabrication of highly customizable scaffolds is a key enabling technology in the development of predictive in vitro cell models for applications in drug discovery, cancer research, and regenerative medicine. Naturally derived and synthetic hydrogels are good candidates for in vitro cell growth studies, owing to their soft and biocompatible nature; however, they are often hindered by limited ranges of stiffness and the requirement to modify the gel with additional extracellular matrix (ECM) proteins for cell adherence. Here, we report on the synthesis of a printable synthetic hydrogel based on cysteine-modified poly(acrylic acid) (PAA-Cys) with tuneable mechanical and swelling properties by incorporating acrylic acid into the PAA-Cys network and subsequent photoinitiated thiol-acrylate cross-linking. Control of the acrylic acid concentration and UV curing time produces a series of hydrogels with swelling ratios in excess of 100% and Young's modulus values ranging from ∼2 to ∼35 kPa, of which most soft tissues fall within. Biocompatibility studies with RPE1 cells showed excellent cell adhesion and cell viability without the need for further modification with ECM proteins, but still can be modified as needed. The versatility of the hydrogel tuneable properties is demonstrated by culturing with RPE1 cells, which in vivo perform an important function in the visual process and the dysfunction of which may lead to various retinal abnormalities, such as glaucoma.

Formation of Ciprofloxacin-Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes-An Investigation into Critical Process Parameters.

The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to explore the feasibility of cocrystallization. Ciprofloxacin (CIP) and isonicotinic acid (INCA) were selected as the model API and coformer. CIP-INCA cocrystal was produced in all techniques. It was revealed that higher cocrystal content could be achieved at longer durations of grinding and ball milling. However, milling for more than 10 min led to increased co-amorphous content instead of cocrystal. A design of experiment (DoE) approach was used for deciphering the complex correlation of screw configuration, screw speed, and temperature as HME process parameters and their respective effect on final relative cocrystal yield. Statistical analysis showed that screw configuration, temperature, and their interaction were the most critical factors affecting cocrystallization. Interestingly, screw speed had minimal impact on the relative cocrystallization yield. Cocrystallization led to increased dissolution rate of CIP in phosphate buffer up to 2.5-fold. Overall, this study shed a light on the potential of mechanochemical synthesis techniques with special focus on HME as a continuous process for producing cocrystals.

Synthesis of Silica-Supported Hydroxamic Ligand for Removal of Metals Ions from Water.

Mesoporous silica supported adsorbents have been used towards metal ion removal from water due to their thermally stability and good sorption capacity. Thus, mesoporous silica-based methyl acrylate monomer (Silica-APTES-DPNO) was converted into hydroxamic acid (SBHA) by using oximation reaction and all products are analyzed by by FT-IR. The SBHA showed satisfactory binding properties with copper, cobalt, nickel and lead are 242, 206, 195 and 516 mg g-1, respectively, with the batch adsorption system was set to pH 6. The kinetics of metal ions binding obeyed the pseudo-1st-order process up to 60 min. In this study also consider the Langmuir and Freundlich isotherm to find out the sorption behavior. The isotherm study demonstrated the well fit with Freundlich isotherm (R² > 0.99). Thus, adsorption take place as a multilayer system, therefore, SBHA material is useful for the metal ions removal from water.

An Investigative Study on the Effect of Pre-Coating Polymer Solutions on the Fabrication of Low Cost Anti-Adhesive Release Paper.

This work describes a novel approach to produce high quality release paper at lower cost than traditional methods. The anti-adhesive properties of release paper require the use of expensive machine glazed kraft or "Glassine" paper as the paper base. A series of polymer coatings including polyvinyl alcohol, carboxymethyl cellulose, polyethylene vinyl acetate, and polystyrene were chemically synthesized and coated onto a low cost pulp paper base. Surface roughness (Sa) and smoothness coefficients (k) were determined by atomic force microscopy (AFM), and the interactions between the polymer coating and base paper were investigated by Raman spectroscopy. Studies show the use of polyethylene vinyl acetate (PEVA) as a pre-coating layer on low cost pulp paper exhibits similar anti-adhesive properties as higher cost paper bases. In low margin markets such as the production of release paper, decreases in cost are critical to industry survival.

Poly(amidoxime) ligand derived from waste palm fiber for the removal of heavy metals from electroplating wastewater.

A waste material known as palm oil empty fruit bunch (EFB) is used as a source of cellulose for the development of polymeric materials for the removal of metal ions from industrial wastewater. A poly(acrylonitrile)-grafted palm cellulose copolymer was synthesized by a conventional free radical initiating process followed by synthesis of a poly(amidoxime) ligand by oximation reaction. The resulting products were characterized by FT-IR, FE-SEM, EDX, TGA, DSC, and XPS. The poly(amidoxime) ligand was used to coordinate with and extract a series of transition metal ions from water samples. The binding capacity (qe) of the ligand with the metal ions such as copper, iron, cobalt, nickel, and lead were 260, 210, 168, 172, and 272 mg g-1, respectively at pH 6. The adsorption process followed the pseudo-first-order kinetic model (R2 > 0.99) and as well as the Freundlich isotherm model (R2 > 0.99) indicating the occurrence of a multi-layer adsorption process in the amidoxime ligand adsorbent. Results from reusability studies show that the ligand can be recycled for at least 10 cycles without any significant losses to its initial adsorption capacity. The synthesized polymeric ligand was shown to absorb heavy metals from electroplating wastewater with up to 95% efficiency.

Amorphous solid dispersion of ibuprofen: A comparative study on the effect of solution based techniques.

Amorphous solid dispersion (ASD) is one of the most promising strategies for improving the solubility of active pharmaceutical ingredients (APIs) with low aqueous solubility. Solvent-based techniques such as electrospinning (ES), spray-drying (SD) and rotary evaporation (RE), have all previously been shown to be effective techniques for formulating ASDs. To date however, the effect of these processing techniques on the physicochemical properties and ASD homogeneity or "quality of ASD" produced remains largely unexplored. This work uses ibuprofen (IBU) as a model BCS class II API with two cellulosic excipients, HPMCAS and HPMCP-HP55 to produce ASDs by employing ES, SD and RE processing techniques. The physicochemical, morphological and dissolution properties of each sample were evaluated and the ASD forming strengths of each of the polymers were assessed using Differential Scanning Calorimetry (DSC). Principal |Component Analysis (PCA) of Raman spectra of crystalline and amorphous IBU was employed for qualitative analysis of ASD homogeneity and subsequent ASD stability during long-term storage. Results show that while ASD formation is predominantly dependent on API:excipient ratio, the ASD homogeneity is highly dependent on processing technique. Dissolution studies show that electrospun samples had the highest API release rate due to their fibrous morphology and higher specific surface area. However, these samples were the least homogenous of all ASDs produced thereby potentially influencing sample stability during long term storage. In addition, the higher melting point depression, higher Tg, and increased abundance of functional groups suitable for hydrogen bonding, show HPMCAS to be a significantly better ASD co-former when compared with HPMCP-HP55.

Impact of polymeric excipient on cocrystal formation via hot-melt extrusion and subsequent downstream processing.

Pharmaceutical cocrystals have gained increasing interest due to their potential to modify the physicochemical properties of drugs. Herein, a 1:1 cocrystal of ibuprofen (IBU) as a BCS class II active pharmaceutical ingredient (API) and nicotinamide as coformer was produced using a hot-melt extrusion (HME) process. The effect of process parameters such as barrel temperature and screw speed were studied. It was shown that the addition of polymeric excipient such as soluplus (Sol) decreases the cocrystallization temperature by enhancing the interaction between API and coformer. In order to study the effect of cocrystallization on the tableting properties of IBU-NIC cocrystal, 5 different formulations of pure IBU, IBU-NIC cocrystal, IBU-NIC physical mixture, IBU-NIC-Sol physical mixture and IBU-NIC-Sol cocrystal were tableted by a compaction simulator. Tabletability, compactibility and compressibility were investigated. The sample with IBU-NIC-Sol cocrystal formulation outperformed all the other formulations in terms of tabletability, compactibility and compressibility. Interestingly, this sample was even superior to the IBU-NIC cocrystal sample which verified the advantageous effect of the presence of an excipient. Moreover, dissolution test confirmed a noticeable increase in the dissolution of not only the cocrystal samples but even the physical mixtures of IBU and NIC compared with pure IBU.

Particle engineering of excipients: A mechanistic investigation into the compaction properties of lignin and [co]-spray dried lignin.

In this work, lignin was spray dried with sodium lauryl sulphate (SLS) in order to improve the compaction properties of lignin. Bulk level and physicochemical properties of spray dried formulations were measured and compared to as-received lignin and lactose which was used as a reference excipient. Single component tablets from individual powders were prepared and the mechanical properties of these powders were investigated by analysing force-displacement curves recorded during tableting, using a series of compaction equations. Moreover, the performance of these excipients in binary blends containing an active pharmaceutical ingredient (API) was investigated. A positive effect of SLS on the mechanical properties and bulk level properties of the spray dried formulations was observed. Spray dried formulations containing SLS showed superior flow properties to pure spray dried lignin while retaining similar particle size distributions. Spray dried formulations containing up to 10 w/w% SLS also showed superior compactibility in binary blends to as-received materials at porosity levels relevant for immediate release tablets. This study highlights the importance of understanding the compaction mechanics of single component powders as a means of predicting their behaviour in multi-component blends.

Spray drying of pharmaceuticals and biopharmaceuticals: Critical parameters and experimental process optimization approaches.

Spray drying is increasingly becoming recognized as an efficient drying and formulation technique for pharmaceutical and biopharmaceutical processing. It offers significant economic and processing advantages compared to lyophilisation/freeze-drying techniques even though the optimisation of process parameters is often a costly and time-consuming procedure. Spray Drying has primarily been used in formulating small molecule drugs with low solubility however it is increasingly being applied to the processing of large biomolecules and biopharmaceuticals. This review examines the basics of spray drying process, current technology and various components used in spray drying process. Moreover, it is focused on introducing critical formulation and processing factors in spray drying of small molecule drugs and large biomolecules, their similarities and differences. Finally, it provides an overview of the experimental optimisation strategies designed to achieve optimum spray drying results in the shortest possible timeframe while utilising minimum product.

Cellulose Supported Pd(II) Complex Catalyzed Carbon-Carbon Bonds Formation.

Corn-cobs are an agro-industrial waste and composed of cellulose mostly. In this study cellulose was isolated from the waste corn-cobs and modified to polymeric hydroxamic acid palladium complex 1 and characterized by using a variety of spectroscopic methods such as field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The complex 1 exhibited high catalytic activity towards Suzuki and Heck coupling reactions of activated and deactivated aryl halides to give the respective coupling products with high yield. Moreover, the complex 1 was recovered and recycled five times with no considerable loss of catalytic overall performance.

Spray drying ternary amorphous solid dispersions of ibuprofen - An investigation into critical formulation and processing parameters.

A design of experiment (DoE) approach was used to investigate the critical formulation and processing parameters in spray drying ternary amorphous solid dispersions (ASDs) of ibuprofen. A range of 16 formulations of ibuprofen, HPMCP-HP55 and Kollidon VA 64 were spray dried. Statistical analysis revealed the interrelation of various spray drying process conditions and formulation factors, namely solution feed rate, inlet temperature, Active Pharmaceutical Ingredient (API)/excipients ratio and dichloromethane (DCM)/methanol (MeOH) ratio. Powder X-ray diffraction analysis (PXRD) showed that all the samples with the lowest API/excipient ratio (1:4) were amorphous, while others were crystalline. Moreover, differential scanning calorimetry (DSC) analysis was employed to investigate ASD formulation more in-depth. The glass transition temperatures (Tg) of all ASDs were in the range 70-79°C, while crystalline formulations displayed an endothermic peak of melting of crystalline ibuprofen in the range of 50-80°C. The high Tg of ASDs was an indication of highly stable ASD formulations as verified via PXRD at zero day and afterward at 1, 1.5, 3 and 6month intervals. The intermolecular interactions between ibuprofen molecule and excipients were studied by Fourier transform infrared spectroscopy (FTIR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. FTIR and Carbon-13 ssNMR analysis indicated that hydrogen bond formation involving the carboxyl group in ibuprofen within the ASDs is likely. More importantly, the solubility of ibuprofen in ASD formulations is improved compared to pure ibuprofen. This was due to both the amorphous structure of ibuprofen and of the existence of amphiphilic excipient, Kollidon VA 64, in the formulation.

Insights into electrochemiluminescent enhancement through electrode surface modification.

The electrochemiluminescent (ECL) properties of a luminescent metal centre, [Ru(bpy)(3)](2+), can be significantly modulated through its electronic interaction with neighbouring centres and the polymer backbone used to confine it on an electrode surface. From the perspective of ECL based sensing devices, an increase in the ECL efficiency of a metallopolymer film can result in enhanced sensor sensitivity and selectivity. This work probes the ECL properties of both conjugated, [Ru(bpy)(2)(PPyBBIM)(10)](2+), and non-conjugated, [Ru(bpy)(2)(PVP)(10)](2+), ruthenium based metallopolymer films based on a well documented reaction with sodium oxalate, where bpy is 2,2'-bipyridyl, PPYBBIM is poly[2-(2-pyridyl)-bibenzimidazole] and PVP is poly(4-vinylpyridine). Through a combination of ground state electrochemical studies and ECL measurements, the ECL efficiency for each film is determined. This study reveals that despite a dramatic influence in charge transfer rates between metal centres, as observed for the conducting polymer, mediated through the conducting polymer backbone, a corresponding increase in ECL efficiency is not always observed. The degree of communication between the adjacent excited state metal centres are an important consideration for ECL enhancement however self quenching, luminophore distribution and film porosity must also be considered.

Chronocoulometric determination of urea in human serum using an inkjet printed biosensor.

A biosensor for the determination of urea in human serum was fabricated using a combination of inkjet printed polyaniline nanoparticles and inkjet printed urease enzyme deposited sequentially onto screen-printed carbon paste electrodes. Chronocoulometry was used to measure the decomposition of urea via the doping of ammonium at the polyaniline-modified electrode surface at -0.3 V vs. Ag/AgCl. Ammonium could be measured in the range from 0.1 to 100 mM. Urea could be measured by the sensor in the range of 2-12 mM (r(2)=0.98). The enzyme biosensor was correlated against a spectrophotometric assay for urea in 15 normal human serum samples which yielded a correlation coefficient of 0.85. Bland-Altman plots showed that in the range of 5.8-6.6 mM urea, the developed sensor had an average positive experimental bias of 0.12 mM (<2% RSD) over the reference method.

Ground and excited state communication within a ruthenium containing benzimidazole metallopolymer.

Emission spectroscopy and electrochemistry has been used to probe the electronic communication between adjacent metal centres and the conjugated backbone within a family of imidazole based metallopolymers, [Ru(bpy)(2)(PPyBBIM)(n)](2+), in the ground and excited states, bpy is 2,2'-bipyridyl, PPyBBIM is poly[2-(2-pyridyl)-bibenzimidazole] and n = 3, 10 or 20. Electronic communication in the excited state is not efficient and upon optical excitation dual emission is observed, i.e., both the polymer backbone and the metal centres emit. Coupling the ruthenium moiety to the imidazole backbone results in a red shift of approximately 50 nm in the emission spectrum. Luminescent lifetimes of up to 120 ns were also recorded. Cyclic voltammetry was also utilized to illustrate the distance dependence of the electron hopping rates between adjacent metal centres with ground state communication reduced by up to an order of magnitude compared to previously reported results when the metal to backbone ratio was not altered. D(CT) and D(e) values of up to 3.96 × 10(-10) and 5.32 × 10(-10) cm(2) S(-1) were observed with corresponding conductivity values of up to 2.34 × 10(-8) S cm(-1).

Solid state photochemistry of novel composites containing luminescent metal centers and poly(2-methoxyaniline-5-sulfonic acid).

Steady state luminescence and measurements of the luminescent lifetime as well as cyclic voltammetry have been used to elucidate the mechanism and dynamics of interaction between a luminescent ruthenium metal center and two different fractions of poly(2-methoxyaniline-5-sulfonic acid) (PMAS). The two fractions, high molecular weight (HMWT) PMAS and low molecular weight (LMWT) PMAS oligomer, showed significantly distinctive influences on the luminophore. The HMWT PMAS, confirmed to be an emeraldine salt by its characteristic redox chemistry, greatly impacted the diffusion coefficient of the Ru2+/3+ within the composite film, increasing the diffusion coefficient, DCT, by 2 orders of magnitude. The HMWT PMAS also resulted in quenching of the ruthenium-based emission. Significantly, these results indicate that quenching involves both static and dynamic processes, with the static quenching being the dominant process, suggesting that the metal center and polymer backbone were strongly associated. In stark contrast, the LMWT PMAS did not influence the electrochemical properties of the ruthenium metal center; however, it did double the emission observed from the ruthenium metal center. The insensitivity of the luminescence lifetime does suggest that, as with the HMWT PMAS, LWMT PMAS is strongly associated with the ruthenium metal center. The enhanced luminescence may allow for many potential sensor developments based on the luminescent ruthenium metal center, while the HMWT PMAS quenching could be utilized within quenching-based strategies or electrochemical devices.