Abstracts from the ukpharmsci conference, 13 september 2010

CONCLUSIONS
[2] Cvek B, Dvorak Z, “Can the old drug, disulfi ram, have a bright new future as a novel proteasome inhibitor?” Drug Discovery Today DMSO is a solvent frequently used for preparing disulfi ram solution. The particle size of in situ formed disulfi ram Cu(II) [3] Walker MB, Edwards K, Farmer PJ, “Disulfi ram, metal, and mela- complex in DMSO might infl uence the growth of the cancer noma” J Chem Edu 2009; 86(10): 1224–1226 [4] Ökçelìk B, Atay O, “Quantitative determination of disulfi ram-con- taining pharmaceuticals by IR spectroscopy and high pressure liquid chromatography methods” FABAD J Pharm Sci 2003; 28: 193–200 [5] Sharma VK, Aulakh JS, Malik AK, “Fourth derivative spectrophoto- REFERENCES
metric determination of fungicide thiram tetramethyldithiocarbamate in commercial sample and wheat grains using copper (II) sulphate” [1] Sauna ZE, Shukla S, Ambudkar SV, “Disulfi ram, an old drug with new potential therapeutic uses for human cancers and fungal infec-tions” Molecular BioSystems 2005; 1: 127–134 The infl uence of API isolation and drying methods post crystallisation on API
properties and performance during drug product processing
A. Balasundaram, M. Boukerche, C. Davies, N. Dawson, and P.L. Goggin Pfi zer Global Research & Development, UK E-mail: neil.dawson@pfi zer.com, arulsuthan.balasundaram@pfi zer.com, moussa.boukerche@pfi zer.com INTRODUCTION AND OBJECTIVES
Table 1: API physical propertie
Wet granulation processes can increase the processability Test
Technique
(e.g. fl ow) of active pharmaceutical ingredients (API) which have physical and mechanical properties that mean they cannot be successfully processed into drug product by other manufacturing methods. In addition, APIs that are wet granu- lated often have cohesive properties and hence can adhere to manufacturing equipment and restrict fl ow.
The purpose of this study is to understand how the drying of the API from the crystalliser impacts the physical proper-ties of the API and subsequent downstream drug product 3) Drug product: High shear wet granulation experiments performance following wet granulation. A series of drying were conducted in the Fukae Powtec high speed mixer conditions were investigated to produce variation of API (250 g batch size) using standardised conditions.
The following quality attributes of the drug product were MATERIALS AND METHODS
Total of 8 API lots were dried using either tray or agitated Compact radial tensile strength (RTS) at 0.85 solid fraction 1) Crystallisation and Isolation: The crystallisation process was developed using parallel conditions in 50 ml-scale ᭿ Compact dissolution
crystalliser (MultiMax). Optimised conditions were then
scaled up in a 1 L scale crystalliser (LabMax) to assess
the robustness of the crystallisation process. Thereafter RESULTS AND DISCUSSION
multiple batches were processed at 1 kg scale in a 20 L fi xed rig. These batches were dried using various operat- During the drying process, agglomerates are formed. Increased ing conditions in an AFD to deliver different API particle drying time increased the degree of agglomeration and den- properties. The resultant API was used to investigate the sifi cation of the API. Tray dried batches typically had minimal robustness of the wet granulation process.
agglomeration, a relatively low particle size (D[v,0.9]) and 2) API physical properties: The following particle and bulk low bulk density compared to batches which were agitated powder properties were determined (Table 1).
fi lter dried. Fewer agglomerates of API led to poor blend fl ow and wet granulation processability issues. Controlling the CONCLUSION
agglomeration state through the AFD conditions resulted in improved API bulk powder densifi cation, defi ned by the API Control of agitator fi lter dryer conditions were identifi ed as a particle size distribution and bulk density. These were identi- key step in the drying process of the API improving the proc- fi ed as important quality attributes of the API from a wet essability of a wet granulated drug product.
granulation processing perspective. The drying process did not have any impact on compact RTS, hardness, disintegra-tion and dissolution. The compacts achieved a high RTS and REFERENCE
this in turn formed tablets with high crushing strength. [1] G. Nichols et al “A review of the terms agglomerate and aggregate Targetted compact disintegration time of less than 15 minutes with a recommendation for nomenclature used in powder and particle were met and the dissolution profi les showed 75% release at characterisation” Int. J. Pharm., 91 (2002) 2103–2109.
The Synthesis of New Microgel Particles Based On 2-Hydroxyethyl(meth)acrylates
1School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AD, UK.
Abstract – Microgel particles based on 2-hydroxyethylacr-
ylate (HEA) and 2-hydroxyethylmethacrylate (HEMA)
were synthesised by surfactant-free emulsion copolymeri-
sation. The particles were characterised by dynamic light
scattering and electron microscopy and it is anticipated
that they could have applications in ocular therapeutics.
INTRODUCTION
Random copolymers consisting of varying ratios of 2-hydroxy-ethylmethacrylate (HEMA) and 2-hydroxyethylacrylate (HEA) have previously been synthesised [1]. These polymers have demonstrated promising thermal and biological proper-ties, with polymers with a HEMA content of 0–100% being found to be non-irritating with respect to mucosal tissues, and the temperature response being dependent on the HEMA/HEA concentration. In this research, cross-linked microgel particles have been synthesised as a possible injectable deliv-ery vehicle, a novel application for these copolymers.
Fig. 1. Typical SEM image of HEMA microgel particles cross-linked
MATERIALS AND METHODS
The method of synthesis used was surfactant-free emulsion
polymerisation (SFEP) [2]. In this method the monomer(s) RESULTS AND DISCUSSION
and cross-linker, in this case ethylene glycol dimethacrylate (EGDMA), are added to water at a low weight fraction of Dynamic light scattering was used to measure the mean around 1%. The mixture is heated and continuously stirred. hydrodynamic diameter of the microgel particles. Variations Following the addition of a suitable initiator, such as ammo- in the HEMA/HEA ratio in the reaction mixture were found nium persulphate, a cloudy dispersion of microgel particles to result in signifi cantly different reaction yields and particle is obtained. Unreacted monomer was removed from the par- sizes, with all samples having a signifi cant degree of polydis- ticle dispersion by dialysis. Particles were synthesised with persity (see Fig. 1). The largest particle sizes, around 1 μm, nominal relative HEMA/HEA ratios of 0–100 mol% and were observed at the highest HEMA contents, 90–100%, sug-nominal cross-linker contents of 2 and 5 mol%.
gesting that HEMA is incorporated preferentially into the

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