An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties. © 2012 Elsevier B.V. All rights reserved.

Gastroretentive Extended-Release Floating Granules Prepared Using a Novel Fluidized Hot Melt Granulation (FHMG) Technique

The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.

Novel temperature-activated, humidity-sensitive optical sensor

A novel, colorimetric, temperature-activated humidity indicator is presented, with a colour change based on the semi-reversible aggregation of thiazine dyes (esp. methylene blue, MB) encapsulated within the polymer, hydroxypropyl cellulose (HPC). The initially purple MB/HPC film is activated by heat treatment at 370 °C for 4 s, at which point the film (with a colour associated with a highly aggregated form of MB; λmax = 530 nm) becomes blue (indicating the presence of monomeric and dimeric MB; i.e. with λmax = 665; 605 nm respectively). The blue, heat-treated MB/HPC films respond to an ambient environment with a relative humidity (RH) exceeding 70% at 21 °C within seconds, returning to their initial purple colour. This colour change is irreversible until the film is heat-treated once more. When exposed to a lower RH of up to ca. 47%, the film is stable in its blue form. In contrast, a MB/HPC film treated only at 220 °C for 15 s also turns a blue colour and responds in the same way to a RH value of ca. 70%, but it is unstable at moderate RH 37-50% values, so that it gradually returns to its purple form over a period of approximately 6 hours. The possible use of the high heat-treated MB/HPC humidity indicator in the packaging of goods that cannot tolerate high RH, such as dry foods and electronics, is discussed.

Dilute acid hydrolysis of cellulose and cellulosic bio-waste using a microwave reactor system

The dilute acid hydrolysis of grass and cellulose with phosphoric acid was undertaken in a microwave reactor system. The experimental data and reaction kinetic analysis indicate that this is a potential process for cellulose and hemi-cellulose hydrolysis, due to a rapid hydrolysis reaction at moderate temperatures. The optimum conditions for grass hydrolysis were found to be 2.5% phosphoric acid at a temperature of 175 degrees C. It was found that sugar degradation occurred at acid concentrations greater than 2.5% (v/v) and temperatures greater than 175 degrees C. In a further series of experiments, the kinetics of dilute acid hydrolysis of cellulose was investigated varying phosphoric acid concentration and reaction temperatures. The experimental data indicate that the use of microwave technology can successfully facilitate dilute acid hydrolysis of cellulose allowing high yields of glucose in short reaction times. The optimum conditions gave a yield of 90% glucose. A pseudo-homogeneous consecutive first order reaction was assumed and the reaction rate constants were calculated as: k(1) = 0.0813 s(-1); k(2) = 0.0075 s(-1), which compare favourably with reaction rate constants found in conventional non-microwave reaction systems. The kinetic analysis would indicate that the primary advantages of employing microwave heating were to: achieve a high rate constant at moderate temperatures: and to prevent 'hot spot' formation within the reactor, which would have cause localised degradation of glucose.

Sensor technologies based on a cellulose supported platform

A simple approach to sensor development based on encapsulating a probe molecule in a cellulose support followed by regeneration from an ionic liquid solution is demonstrated here by the codissolution of cellulose and 1-(2-pyridylazo)-2-naphthol in 1-butyl-3-methylimidazolium chloride followed by regeneration with water to form strips which exhibit a proportionate (1 : 1) response to Hg(II) in aqueous solution.

Preparation of magnetic cellulose composites using ionic liquids

Cellulose-magnetite composites have been prepared by suspension and dispersion of magnetite particles in a homogenous ionic liquid solution of cellulose, followed by regeneration into water, enabling the preparation of magnetically responsive films, flocs, fibers, or beads. The materials prepared were ferromagnetic, with a small superparamagnetic response, characteristic of the initial magnetite added. X-ray diffraction data indicated that the magnetite particles were chemically unaltered after encapsulation with an average particle size of approximately 25 nm.

Ionic liquid-reconstituted cellulose composites as solid support matrices for biocatalyst immobilization

Preparation of cellulose-polyamine composite films and beads, which provide high loading of primary amines on the surface allowing direct one-step bioconjugation of active species, is reported using an ionic liquid (IL) dissolution and regeneration process. Films and bead architectures were prepared and used as immobilization supports for laccase as a model system demonstrating the applicability of this approach. Performance of these materials, compared to commercially available products, has been assessed using millimeter-sized beads of the composites and the lipase-catalyzed transesterification of ethyl butyrate.

Production of bioactive cellulose films reconstituted from ionic liquids

A new method for introducing enzymes into cellulosic matrixes which can be formed into membranes, films, or beads has been developed using a cellulose-in-ionic-liquid dissolution and regeneration process. Initial results on the formation of thin cellulose films incorporating dispersed laccase indicate that active enzyme-encapsulated films can be prepared using this methodology and that precoating the enzyme with a second. hydrophobic ionic liquid prior to dispersion in the cellulose/ionic liquid solution can provide an increase in enzyme activity relative to that of untreated films, presumably by providing a stabilizing microenvironment for the enzyme.