Reginald B. H. Tan

Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy.

There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2μm. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L(18) orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460±10nm, axial ratio: 1.03±0.00, span 1.03±0.03, yield: 72±4%) was achieved using the 4μm spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150L/min and inlet temperature of 120°C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications.

Food waste conversion options in Singapore: environmental impacts based on an LCA perspective.

Proper management and recycling of huge volumes of food waste is one of the challenges faced by Singapore. Semakau island - the only offshore landfill of the nation - only accepts inert, inorganic solid waste and therefore a large bulk of food waste is directed to incinerators. A remaining small percent is sent for recycling via anaerobic digestion (AD), followed by composting of the digestate material. This article investigates the environmental performance of four food waste conversion scenarios - based on a life cycle assessment perspective - taking into account air emissions, useful energy from the incinerators and AD process, as well as carbon dioxide mitigation from the compost products derived from the digestate material and a proposed aerobic composting system. The life cycle impact results were generated for global warming, acidification, eutrophication, photochemical oxidation and energy use. The total normalized results showed that a small-scale proposed aerobic composting system is more environmentally favorable than incinerators, but less ideal compared to the AD process. By making full use of the ADs Recycling Phase II process alone, the Singapore Green Plans 2012 aim to increase the recycling of food waste to 30% can easily be achieved, along with reduced global warming impacts.

Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: Effects of process variables

This study aimed to prepare solid lipid nanoparticles (SLNs) of a hydrophobic drug, tretinoin, by emulsification-ultrasonication method. Solubility of tretinoin in the solid lipids was examined. Effects of process variables were investigated on particle size, polydispersity index (PI), zeta potential (ZP), drug encapsulation efficiency (EE), and drug loading (L) of the SLNs. Shape and surface morphology of the SLNs were investigated by cryogenic field emission scanning electron microscopy (cryo-FESEM). Complete encapsulation of drug in the nanoparticles was checked by cross-polarized light microscopy and differential scanning calorimetry (DSC). Crystallinity of the formulation was analyzed by DSC and powder X-ray diffraction (PXRD). In addition, drug release and stability studies were also performed. The results indicated that 10mg tretinoin was soluble in 0.45±0.07 g Precirol® ATO5 and 0.36±0.06 g Compritol® 888ATO, respectively. Process variables exhibited significant influence in producing SLNs. SLNs with <120 nm size, <0.2 PI, >I30I mV ZP, >75% EE, and ∼0.8% L can be produced following the appropriate formulation conditions. Cryo-FESEM study showed spherical particles with smooth surface. Cross-polarized light microscopy study revealed that drug crystals in the external aqueous phase were absent when the SLNs were prepared at ≤0.05% drug concentration. DSC and PXRD studies indicated complete drug encapsulation within the nanoparticle matrix as amorphous form. The drug release study demonstrated sustained/prolonged drug release from the SLNs. Furthermore, tretinoin-loaded SLNs were stable for 3 months at 4°C. Hence, the developed SLNs can be used as drug carrier for sustained/prolonged drug release and/or to improve oral absorption/bioavailability.

Stabilized Amorphous State of Ibuprofen by Co-Spray Drying With Mesoporous SBA-15 to Enhance Dissolution Properties

A novel formulation process via co-spray drying ibuprofen (IBU) with mesoporous SBA-15 submicron particles exhibited excellence in production of stable amorphous IBU with significantly enhanced dissolution rate. With drug loading of IBU/SBA-15 ratio being 50:50 (w/w) or below, most drug molecules were entrapped inside the straight mesoporous channels via the co-spray drying and the morphology of SBA-15 submicron particles remained unchanged. IBU confined inside the mesoporous structure was in the amorphous state shown by PXRD and DSC measurements. The amorphous state of IBU in the solid dispersion showed remarkable stability when subject to stress test condition of 40 degrees C/75% RH in open pans for 12 months. The uniform pore walls were believed to prevent the re-crystallization of the homogeneously dispersed drug molecules inside the mesoporous channels with confined nanospace. The dissolution rate of IBU from the co-spray-dried solid dispersion was significantly enhanced to achieve a rapid release. Even after the accelerated stability test, the rapid drug release property was well preserved.

Preparation and characterization of spironolactone nanoparticles by antisolvent precipitation

Due to low aqueous solubility and slow dissolution rate, spironolactone, a synthetic steroid diuretic, has a low and variable oral bioavailability. Nanoparticles were thus prepared by antisolvent precipitation in this work for accelerating dissolution of this kind of poorly water-soluble drugs. Effects of surfactant type/concentration and feed drug concentration on the precipitated particle size were evaluated. It was found that introduction of spironolactone solution in N-methyl-2-pyrrolidone (NMP) to the antisolvent water can produce the particles in the submicron range with hydroxypropyl methylcellulose (HPMC) as the stabilizer. The particle size decreased with the increase of HPMC concentration from 0 to 0.125% (w/v), further increase of which did not affect the size significantly. Increasing feed drug concentration from 10 to 100 mg/ml resulted in the particle size decrease. In comparison with raw drug, the chemical structure of nanosized spironolactone was not changed but the crystallinity was reduced. Dissolution of spironolactone nanoparticles in 0.1M HCl was 2.59 times faster than raw drugs in 60 min.

Trimorphs of a pharmaceutical cocrystal involving two active pharmaceutical ingredients: potential relevance to combination drugs

The first example of a trimorphic cocrystal involving two active pharmaceutical ingredients (APIs), ethenzamide and gentisic acid, is reported; metastable polymorphs convert to the stable form upon solid-state grinding; pharmaceutical cocrystals involving two or more APIs have potential relevance to combination drugs.

Physical state and dissolution of ibuprofen formulated by co-spray drying with mesoporous silica: Effect of pore and particle size

A model poorly aqueous-soluble drug, ibuprofen (IBU), was co-spray dried with mesoporous silica materials having different pore sizes and particle sizes for dissolution enhancement. Drug molecules were entrapped inside the mesoporous channels at a high drug loading of 50:50 (w/w). The pore sizes were found to affect the physical state and particle size of IBU in mesoporous structures, which influenced the dissolution profiles. When IBU was co-spray dried with MCM-41 and SBA-15 with pore size smaller than 10 nm, amorphous state of IBU was obtained due to nano space confinement. In contrast, nanocrystals were obtained when ibuprofen was co-spray dried with large pore SBA-15-LP with pore size above 20 nm. The physical state of ibuprofen played a key role in affecting the dissolution of IBU from the solid dispersion. IBU in the amorphous state exhibited a higher dissolution rate than nanocrystalline IBU, even though the larger pore size could facilitate diffusion from the host matrix. The particle size of mesoporous silica showed a less pronounced effect on the dissolution of IBU. Thus, the amorphous/nanocrystalline state of ibuprofen was the most important influence on drug dissolution followed by the diffusion kinetics, particle size of IBU and path length from host matrix to dissolution medium.

Evaluation of Life Cycle Cost Analysis Methodologies

After the emergence of Life Cycle Engineering as an effective tool for analyzing the various environmental impacts of a product in the stages of designydevelopment, manufacturing, service and disposal, a necessity arises to analyze the cost information pertaining to these impacts. There are possibly many approaches to analyze and evaluate the cost criteria involved in the different life cycle stages of any product or investment. This paper attempts to review many of those approaches methodologically, and specifically outline a practical framework that provides a new tool for evaluating all the eco-costs and developing a cost

Polymorphism in cocrystals: a review and assessment of its significance

Cocrystals have gained much interest in recent years owing to their potential to improve the physicochemical properties of the parent compounds. It was once thought that cocrystals could be a means to prevent polymorphism but many recent examples of cocrystal polymorphism have been discovered and reported. Similar to single component crystals, polymorphs of cocrystals can display significantly different properties. In this contribution, we present a survey of polymorphic cocrystals. The different types of polymorphs, namely synthon, conformational, packing, and tautomeric, are identified and discussed with representative examples. In addition, polymorphs of cocrystals that showed distinct physicochemical properties are highlighted.

Environmental life cycle cost analysis of products

The objective of this life cycle environmental cost analysis (LCECA) model is to include eco‐costs into the total cost of the products. Eco‐costs are both the direct and indirect costs of the environmental impacts caused by the product in its entire life cycle. Subsequently, this LCECA model identifies the feasible alternatives for cost‐effective, eco‐friendly parts/products. This attempts to incorporate costing into the life cycle assessment (LCA) practice. Ultimately, it aims to reduce the total cost with the help of green or eco‐friendly alternatives in all the stages of the life cycle of any product. The new category of eco‐costs of the cost breakdown structure includes eight eco‐costs, namely cost of effluent/waste treatment, cost of effluent/waste control, cost of waste disposal, cost of implementation of environmental management systems, costs of eco‐taxes, costs of rehabilitation (in case of environmental accidents), cost savings of renewable energy utilization, and cost savings of recycling and reuse strategies. Development of a suitable cost model and the identification of the feasible alternatives are performed simultaneously. Various checklists based on multiple environmental criteria will be used to ensure the eco‐friendly nature of the alternatives. On the basis of the calculated environmental impact indices (EII), priorities will be made for the selection of suitable alternatives. The mathematical model of LCECA aims to define the relationships between the total cost of products and the various eco‐costs concerned with the life cycle of the products, and determine quantitative expressions between the above‐said costs. A computational LCECA model has been developed to compare the eco‐costs of the alternatives. This model will include a break‐even analysis to evaluate the alternatives, and sensitivity analysis and risk analysis modules. This model aims at a cost‐effective, eco‐friendly product as an end result. This LCECA model will be compatible with the existing LCA software tools.