The development of an eco-friendly cold mix asphalt using wastewater sludge ash.

The aim of this research was to develop a sustainable and ecologically sound, non-traditional cold mix asphalt (CMA) that can be used in the construction industry. This new type of CMA incorporates wastewater sludge fly ash (UFA) and bottom ash (UBA) as a replacement filler for ordinary Portland cement and limestone. Silica fume (SF) was also used as an additional filler. The mechanical and durability characteristics of the new CMAs were examined in terms of indirect tensile stiffness modulus (ITSM), and rutting, fatigue, water and fuel resistance. The results showed that CMA with 2.1% OPC +3.9% UFA at 3 days of age, had ITSM values 11 times that of traditional CMA, while CMA with 2.1% OPC+ 3.3% UFA +0.6% UBA, had ITSM values 5 times that of traditional CMA at 28 days of age. SF activated hydration for both mixes, significantly increasing ITSM. These results indicate that CMA has a comparable mechanical performance to standard Hot Mix Asphalt (HMA) mixtures for use as surface pavement layers. This study offers a novel CMA with improved mechanical performance. It is economically effective and ecologically beneficial, compared to HMA, due to its ability to accommodate wastewater sludge ashes that are often disposed of in landfill sites.

Film-coated matrix mini-tablets for the extended release of a water-soluble drug.

Extended release (ER) of water-soluble drugs from hydroxypropylmethylcellulose (HPMC) matrix mini-tablets (mini-matrices) is difficult to achieve due to the large surface area to volume ratio of the mini matrices. Therefore, the aims of this study were to control the release of a water-soluble drug (theophylline) from mini-matrices by applying ER ethylcellulose film coating (Surelease®), and to assess the effects of Surelease®:pore former (Opadry®) ratio and coating load on release rates. Mini-matrices containing 40%w/w HPMC K100M CR were coated with 100:0, 85:15, 80:20, 75:25 or 70:30 Surelease®:Opadry® to different coating weight gains (6-20%). Non-matrix mini-tablets were also produced and coated with 80:20 Surelease®:Opadry® to different coating weight gains. At low coating weight gains, nonmatrix mini-tablets released the entire drug within 0.5 h, while at high coating weight gains only a very small amount (<5%) of drug was released after 12 h. The gel formation of HPMC prevented disintegration of mini-matrices at low coating weight gains but contributed to rupture of the film even at high coating weight gains. As a result, drug release from mini-matrices was slower than that from nonmatrix mini-tablets at low coating weight gains, yet faster at high coating weight gains. An increase in the lag time of drug release from mini-matrices was observed as the concentration of Opadry® reduced or the coating weight gain increased. This study has demonstrated the possibility of extending the release of a water-soluble drug from HPMC mini-matrices by applying ER film coating with appropriate levels of pore former and coating weight gains to tailor the release rate.

The effect of HPMC particle size on the drug release rate and the percolation threshold in extended-release mini-tablets.

The particle size of HPMC is a critical factor that can influence drug release rate from hydrophilic matrix systems. Percolation theory is a statistical tool which is used to study the disorder of particles in a lattice of a sample. The percolation threshold is the point at which a component is dominant in a cluster resulting in significant changes in drug release rates. Mini-tablets are compact dosage forms of 1.5-4 mm diameter, which have potential benefits in the delivery of drug to some patient groups such as pediatrics. In this study, the effect of HPMC particle size on hydrocortisone release and its associated percolation threshold for mini-tablets and tablets was assessed. For both mini-tablets and tablets, large polymer particles reduced tensile strength, but increased the drug release rate and the percolation threshold. Upon hydration, compacts with 45-125 µm HPMC particles formed a strong gel layer with low porosity, reducing hydrocortisone release rates. In comparison, faster drug release rates were obtained when 125-355 µm HPMC particles were used, due to the greater pore sizes that resulted in the formation of a weaker gel. Using 125-355 µm HPMC particles increased the percolation threshold for tablets and to a greater extent for mini-tablets. This work has demonstrated the importance of HPMC particle size in ER matrices, the effects of which are even more obvious for mini-tablets.

The crystal engineering of salbutamol sulphate via simulated pulmonary surfactant monolayers.

PURPOSE: This study aims to crystallise salbutamol sulphate beneath simulated pulmonary surfactant monolayers. Such ensembles serve as heterogeneous nucleating sites to direct crystallisation. This contribution builds upon previous work to confirm the suitability of Langmuir monolayers in supporting the rational generation of respirable therapeutic material. METHODS: Langmuir monolayers (i.e. DPPC or a 'mixed' system) were supported on a subphase containing the extremely water soluble model drug (2.5 g/ml) and compressed to 5 mN m(-1) or 35 mN m(-1) whilst experiencing a temperature reduction and positioned within a humid environment. Control samples were produced via batch crystallisation. Analysis involved scanning electron microscopy (SEM), atomic force microscopy (AFM), powder X-ray diffraction (PXRD) and inverse gas chromatography (IGC). RESULTS: Expanded Langmuir isotherms confirmed drug-surfactant interaction; crystal growth was inhibited at high surface pressure. Resultant crystals exhibited a range of morphologies, dependent upon the crystallisation route. AFM analysis highlighted nanoscale surface undulations. IGC data confirmed sample surface energy profiles were variable and influenced by crystallisation route. CONCLUSIONS: Principal modes of drug-surfactant interaction are proposed as hydrogen bond and ion-dipole associations. A range of pharmaceutical approaches have been applied to understand drug-surfactant complementarity. The results strengthen the argument for the use of Langmuir monolayers in drug particle engineering.

The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets.

CONTEXT: Mini-tablets are compact dosage forms, typically 2-3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices. OBJECTIVE: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate. METHODS: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL™ K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied. RESULTS AND DISCUSSION: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements. CONCLUSION: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.

Production of extended release mini-tablets using directly compressible grades of HPMC.

CONTEXT: Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company. OBJECTIVE: To compare the properties of HPMC DC (METHOCEL™ K4M and K100M) with regular (REG) HPMC grades. METHOD: Particle size distribution and flowability of HPMC REG and DC were evaluated. 3 mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2-4 kN and speeds of 5, 10, 15 or 20 rpm. Mini-tablets containing HPMC REG were produced manually. RESULTS AND DISCUSSION: The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79-4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles. CONCLUSIONS: Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.

Polymorphs of anhydrous theophylline: stable form IV consists of dimer pairs and metastable form I consists of hydrogen-bonded chains.

The structure of a previously unreported polymorph of anhydrous theophylline (1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione), C(7)H(8)N(4)O(2), has been determined at 100 K and shown to have monoclinic symmetry with Z' = 2. The structure is named form IV and experimental observation indicates that this is the stable form of the material. The molecular packing consists of discrete hydrogen-bonded dimers similar to that observed in the monohydrate structure. The structure of form I has also been determined and consists of hydrogen-bonded chains.

Towards crystal engineering via simulated pulmonary surfactant monolayers to optimise inhaled drug delivery.

PURPOSE: To generate theophylline monohydrate crystals underneath Langmuir monolayers composed of material expressed at the alveolar air-liquid interface. Such monolayers can act as nucleation sites to direct crystallisation. The approach offers a novel route to rationally engineer therapeutic crystals and thereby optimise inhaled drug delivery. METHODS: Langmuir monolayers consisting of either dipalmitoylphosphatidylcholine (DPPC) or a surfactant mix reflecting pulmonary surfactant were supported on an aqueous theophylline (5.7 mg/ml) subphase. The monolayers were compressed to surface pressures reflecting inhalation and exhalation (i.e. 5 mNm(-1) or 55 mNm(-1)) with a period of 16 h to allow crystallisation. Analysis involved scanning electron microscopy (SEM), atomic force microscopy (AFM) and powder X-ray diffraction (PXRD). RESULTS: Condensed isotherms were acquired, which signified surfactant-theophylline interaction. Theophylline monohydrate crystals were obtained and exhibited needle-like morphology. SEM and AFM data highlighted regions of roughened growth along with smooth, stepwise growth on the same crystal face. The surfactant monolayers appeared to influence crystal morphology over time. CONCLUSIONS: The data indicate a favourable interaction between each species. The principal mechanism of interaction is thought to be an ion-dipole association. This approach may be applied to generate material with improved complementarity with pulmonary surfactant thus enhancing the interaction between inhaled drug particles and internal lung surfaces.

Using a liquid emulsion membrane system for the encapsulation of organic and inorganic substrates within inorganic microcapsules.

We report the development of a novel technique for the encapsulation of molecular and condensed organic and inorganic substrates within hollow calcium carbonate microspheres; the process utilises precipitation at the oil-water interface of a pseudovesicular water-in-oil-in-water emulsion liquid membrane (ELM) system in order to create an inorganic shell around the pre-dispersed media.