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.

Effervescent and standard formulations of ranitidine--a comparison of their pharmacokinetics and pharmacology

An effervescent formulation of ranitidine may be absorbed faster and achieve a faster onset of action than conventional tablet form. The aim of this study was to compare the effects of effervescent formulations of ranitidine with equivalent dose standard tablets, in terms of intragastric pH and plasma pharmacokinetics in the initial 6 h following dosing.

Parameter estimation and equation formulation in Business Dynamics

System Dynamics enables modelling and simulation of highly non-linear feedback systems to predict future system behaviour. Parameter estimation and equation formulation are techniques in System Dynamics, used to retrieve the values of parameters or the equations for ?ows and/or variables. These techniques are crucial for the annotations and thereafter the simulation. This paper critically examines existing and well established approaches in parameter estimation and equation formulation along with their limitations, identifying performance gaps as well as providing directions for potential future research.

Development of an objective structured clinical examination (OSCE) to assess formulation and extemporaneous dispensing skills in MPharm undergraduates

Background: The use of Objective Structured Clinical Examination (OSCE) in Pharmacy has been explored; however this is the first attempt in Queen’s University School of Pharmacy, Belfast to assess students via this method in a module where chemistry is the main discipline.

Aims: To devise an OSCE to assess undergraduate ability to check extemporaneously dispensed products for clinical and formulation errors. This activity also aims to consider whether it is a viable method of assessment in such a science-based class, from a staff and student perspective.

Method: Students rotated around a number of stations, performing a check of the product, corresponding prescription and formulation record sheet detailing the theory behind the formulation. They were assessed on their ability to spot intentional mistakes at each one.

Results: Of the 79 students questioned, 95% indicated that OSCE made them aware of the importance of the clinical check carried out by the pharmacist. Nearly all of the undergraduates (72 out of 79) felt that OSCE made them aware of the type of mistakes that students make in class. Most (5 out of 7) of the academic team members strongly agreed that it made students aware of ‘point of dispensing’ checks carried out by pharmacists, in addition to helping them to prepare for their exam.

Conclusion: OSCE assesses both scientific and formulation skills, and has increased the diversity of assessment of this module, bringing with it many additional benefits for the undergraduates since it measures their ability to exercise professional judgement in a time- constrained environment and, in this way, mirrors the conditions many pharmacists work within.

Influence of fill factor variation in high shear granulation on the post granulation processes: Compression and tablet properties

This paper describes an investigation of the effect of fill factor; on the compaction behaviour of the granules during tableting and hence mechanical properties of tablets formed. The fill factor; which is the ratio of volume of wet powder material to vessel volume of the granulator, was used as an indicator of batch size. It has been established previously that in high shear granulation the batch size influences the size distribution and granule mechanical properties [1]. The work reported in this paper is an extension to the work presented in [1], hence granules from the same batches were used in production of tablets. The same tabletting conditions were employed during tabletting to allow a comparison of their properties. The compaction properties of the granules are inferred from the data generated during the tabletting process. The tablet strength and dissolution properties of the tablets were also measured. The results obtained show that the granule batch size affects the strength and dissolution of the tablets formed. The tablets produced from large batches were found to be weaker and had a faster dissolution rate. The fill factor was also found to affect the tablet to tablet variation of a non-functional active pharmaceutical ingredient included in the feed powder. Tablets produced from larger batches show greater variation compared to those from smaller batches.

Synergistic effects on gene delivery - co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000 (TM)

This paper describes the application of gene delivery vectors based on connecting together two well-defined low-generation poly(L-lysine) (PLL) dendrons using a disulfide-containing linker unit. We report that the transfection ability of these vectors in their own right is relatively low, because the low-generation number limits the endosomal buffering capacity. Importantly, however, we demonstrate that when applied in combination with Lipofectamine 2000 (TM), a vector from the cationic lipid family, these small cationic additives significantly enhance the levels of gene delivery (up to four-fold). Notably, the cationic additives have no effect on the levels of transfection observed with a cationic polymer, such as DEAE dextran. We therefore argue that the synergistic effects observed with Lipofectamine 2000 (TM) arise as a result of combining the delivery advantages of two different classes of vector within a single formulation, with our dendritic additives providing a degree of pH buffering within the endosome. As such, the data we present indicate that small dendritic structures, although previously largely overlooked for gene delivery owing to their inability to transfect in their own right, may actually be useful well-defined additives to well-established vector systems in order to enhance the gene delivery payload.