Characterization of chitin–metal silicates as binding superdisintegrants

When chitin is used in pharmaceutical formulations, processing of chitin with metal silicates is advantageous, from both an industrial and pharmaceutical perspective, compared to processing using silicon dioxide. Unlike the use of acidic and basic reagents for the industrial preparation of chitin-silica particles, coprecipitation of metal silicates is dependent upon a simple replacement reaction between sodium silicate and metal chlorides. When coprecipitated onto chitin particles, aluminum, magnesium, or calcium silicates result in nonhygroscopic, highly compactable/disintegrable compacts. Disintegration and hardness parameters for coprocessed chitin compacts were investigated and found to be independent of the particle size. Capillary action appears to be the major contributor to both water uptake and the driving force for disintegration of compacts. The good compaction and compression properties shown by the chitin-metal silicates were found to be strongly dependent upon the type of metal silicate coprecipitated onto chitin. In addition, the inherent binding and disintegration abilities of chitin-metal silicates are useful in pharmaceutical applications when poorly compressible and/or highly nonpolar drugs need to be formulated. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4887-4901, 2009.

Investigation of the permeation of model formulations and a commercial ibuprofen formulation in Carbosil® and human skin using ATR-FTIR and multivariate spectral analysis

The purpose of the present study was to use attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and target factor analysis (TFA) to investigate the permeation of model drugs and formulation components through Carbosil® membrane and human skin. Diffusion studies of saturated solutions in 50:50 water/ethanol of methyl paraben (MP), ibuprofen (IBU) and caffeine (CF) were performed on Carbosil® membrane. The spectroscopic data were analysed by target factor analysis, and evolution profiles of the signal for each component (i.e. the drug, water, ethanol and membrane) over time were obtained. Results showed that the data were successfully deconvoluted as correlations between factors from the data and reference spectra of the components, were above 0.8 in all cases. Good reproducibility over three runs for the evolution profiles was obtained. From the evolution profiles it was observed that water diffused better through the Carbosil® membrane than ethanol, confirming the hydrophilic properties of the Carbosil® membrane used. IBU diffused slower compared with MP and CF. The evolution profile of CF was very similar to that of water, probably because of the high solubility of CF in water, indicating that both compounds are diffusing concurrently. The second part of the work involved a study of the evolution profiles of the components of a commercial topical gel containing 5% (w/w) of ibuprofen as it permeated through human skin. Although the system was much more complex, data were still successfully deconvoluted and the different components of the formulation identified except for benzyl alcohol which might be attributed to the low concentrations of benzyl alcohol used in topical formulations. (C) 2009 Elsevier B.V. All rights reserved.

Raman spectroscopy in pharmaceutical analysis

A wide and versatile range of analytical techniques are routinely used, indeed are necessary, in pharmaceutical analysis. Over the past decade Raman spectroscopy has increasingly come to the fore as a valuable member of the arsenal of methods used, from both a fundamental and applied perspective, for the interrogation of solid, liquid and solution phase samples. Advances have occurred not only in instrumentation but also in fundamental techniques and applications. The method holds substantial potential for the investigation of, what are normally considered, problematic or challenging areas of analysis. The aforementioned areas include – but are, definitely not limited too reaction kinetics, pharmaceutical drug discovery, detection of counterfeit/adulterated/illegal drugs, trace analysis and uses for on-line pharmaceutical process manufacturing. This, the first of several articles on the use of Raman spectroscopic techniques in pharmaceutical analysis, provides an introductory overview of the theory of the technique.

Using a modified shepards method for optimization of a nanoparticulate cyclosporine a formulation prepared by a static mixer technique

An innovative methodology has been used for the formulation development of Cyclosporine A (CyA) nanoparticles. In the present study the static mixer technique, which is a novel method for producing nanoparticles, was employed. The formulation optimum was calculated by the modified Shepard's method (MSM), an advanced data analysis technique not adopted so far in pharmaceutical applications. Controlled precipitation was achieved injecting the organic CyA solution rapidly into an aqueous protective solution by means of a static mixer. Furthermore the computer based MSM was implemented for data analysis, visualization, and application development. For the optimization studies, the gelatin/lipoid S75 amounts and the organic/aqueous phase were selected as independent variables while the obtained particle size as a dependent variable. The optimum predicted formulation was characterized by cryo-TEM microscopy, particle size measurements, stability, and in vitro release. The produced nanoparticles contain drug in amorphous state and decreased amounts of stabilizing agents. The dissolution rate of the lyophilized powder was significantly enhanced in the first 2 h. MSM was proved capable to interpret in detail and to predict with high accuracy the optimum formulation. The mixer technique was proved capable to develop CyA nanoparticulate formulations.

Practical solvent system selection for counter-current separation of pharmaceutical compounds

Counter-current chromatography (CCC) is a technique that shows a lot of potential for large scale purification. Its usefulness in a "research and development" pharmaceutical environment has been investigated, and the conclusions are shown in this article. The use of CCC requires the development of an appropriate solvent system (a parameter of critical importance), a process which can be tedious. This article presents a novel strategy, combining a statistical approach and fast HPLC to generate a three-dimensional partition coefficient map and rapidly predict an optimal solvent system. This screen is performed in half a day and involves 9 experiments per solvent mixture. Test separations were performed using that screen to ensure the validity of the method.

Wound healing dressings and drug delivery systems: a review

The variety of wound types has resulted in a wide range of wound dressings with new products frequently introduced to target different aspects of the wound healing process. The ideal dressing should achieve rapid healing at reasonable cost with minimal inconvenience to the patient. This article offers a review of the common wound management dressings and emerging technologies for achieving improved wound healing. It also reviews many of the dressings and novel polymers used for the delivery of drugs to acute, chronic and other types of wound. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. There is also a brief section on the use of biological polymers as tissue engineered scaffolds and skin grafts. Pharmacological agents such as antibiotics, vitamins, minerals, growth factors and other wound healing accelerators that take active part in the healing process are discussed. Direct delivery of these agents to the wound site is desirable, particularly when systemic delivery could cause organ damage due to toxicological concerns associated with the preferred agents. This review concerns the requirement for formulations with improved properties for effective and accurate delivery of the required therapeutic agents. General formulation approaches towards achieving optimum physical properties and controlled delivery characteristics for an active wound healing dosage form are also considered briefly.

The implementation of FT-Raman spectroscopy to study solid state moisture induced changes in the crystallographic nature of pharmaceutical excipients - a lesson in humidity

An aqueous solution of sucrose was lyophilised, producing amorphous sucrose. This wasthen stored under different humidity at 25ºC for 1 week, allowing some samples tocrystallise. FT-Raman spectroscopy and PXRD have been successfully shown toqualitatively distinguish between amorphous and crystalline samples of sucrose. The datafrom the two techniques is complementary.

Modelling dosator filling and discharge of powder

Dosators and other dosing mechanisms operating on generally similar principles are very widely used in the pharmaceutical industry for capsule filling, and for dosing products that are delivered to the customer in powder form such as inhalers. This is a trend that is set to increase. However a significant problem for this technology is being able to predict how accurately and reliably, new drug formulations will be dosed from these machines prior to manufacture. This paper presents a review of the literature relating to powder dosators which considers mathematical models for predicting dosator performance, the effects of the dosator geometry and machine settings on the accuracy of the dose weight. An overview of a model based on classical powder mechanics theory that has been developed at The University of Greenwich is presented. The model uses inputs from a range of powder characterisation tests including, wall friction, bulk density, stress ratio and permeability. To validate the model it is anticipated that it will be trialled for a range of powders alongside a single shot dosator test rig.

A methodology for characterising new lead-free solder paste formulations used for flip-chip assembly applications

The paper reports on the investigation of the rheological behaviour new lead-free solder pastes formulations for use in flip-chip assembly applications. The study is made up of three parts; namely the evaluation of the effect of plate geometry, the effect of temperature and processing environment and the effect of torsional frequencies on the rheological measurements. Different plate geometries and rheological tests were used to evaluate new formulations in terms of wall slip characteristics, linear viscoelastic region and shear thinning behaviour. A technique which combines the use of the creep-recovery and dynamic frequency sweep tests was used to further characterise the paste structure, rheological behaviour and the processing performance of the new paste formulations. The technique demonstrated in this study has wide utility for R & D personnel involved in new paste formulation, for implementing quality control procedures used in paste manufacture and packaging and for qualifying new flip-chip assembly lines

A conceptual framework for designing pharmaceutical reverse logistics networks in China

Over latest decade, Reverse Logistics (RL) has gained more and more attention from both industry and academia. In the past, most research on RL has been focused on automobile, electronic waste, computer, paper, package and package material. There is very little research and practice on drug recycling. Nevertheless, it is vital important to properly dispose expired drug because of hazardous contain which may harm to people and environment. In China, public awareness of the harmfulness of expired drugs is still very low and very few efforts have been made to recycle drugs. Therefore, this research aims to build up a conceptual framework to indentify factors of influencing drug recycling in China, from scratch borrowing from existing literature and industry practices in other recycling areas. This framework helps in designing reverse logistic (RL) network and also can provide a useful reference tool for policymakers at the local and national level. Furthermore, a primary research is planed to validate the framework and RL network.