Melt Granulation in A Laboratory Scale High Shear Mixer

Schæfer, Torben; Holm, Per; Kristensen, H. G.

doi:10.3109/03639049009115960

Cited by 115 publications

(46 citation statements)

References 5 publications

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“…Various particle size enlargement techniques, which offer freedom from solvents include, melt granulation, melt extrusion, melt dispersion, and pastillation. [1][2][3][4][5] Development of new lipophilic excipients has provided impetus to the research in the area of processing techniques involving molten state. 6 Melt dispersion technique involves emulsification of molten drug or drug-excipient mixture in an aqueous system, followed by cooling.…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of flurbiprofen beads by melt solidification technique

et al. 2003

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KEYWORDS: flurbiprofen, melt solidification technique, factorial design, cetyl alcohol, response surface methodology, zero order kinetics A melt solidification technique has been developed to obtain sustained-release waxy beads of flurbiprofen. Low glass transition temperature (t g ) and shear-induced crystallization of flurbiprofen made it a suitable candidate for melt solidification technique. The process involved emulsification and solidification of flurbiprofen-cetyl alcohol melt at significantly low temperature (5°C). The effect of variables, namely, the amount of cetyl alcohol and the speed of agitation, was studied using 3 2 factorial design. The technique and the beads were evaluated on the basis of process and desired yield, surface topography, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), particle size distribution, crushing strength, and drug release. Average values for process and desired yields were 97% wt/wt and 26% wt/wt, respectively. No interaction was observed between drug and excipient. Multiple regression analysis was carried out, and response surfaces were obtained. A curvilinear relationship was observed between percentage of desired yield and the amount of cetyl alcohol. Linear decrease in crushing strength was observed with increase in the amount of cetyl alcohol. Drug released from the beads followed zero order kinetics. Burst release was shown to a greater extent in beads containing a lower amount of cetyl alcohol. Response surfaces of time required for certain percentage of drug (t D %) showed that after critical concentration of about 20% of cetyl alcohol (400 mg/batch), no significant release retardant effect was observed.

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Section: Introductionmentioning

confidence: 99%

Preparation and characterization of flurbiprofen beads by melt solidification technique

et al. 2003

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“…Following the steps that were summarized in Figure 8, the impeller speed and the granulation time are utilized in addition to the error vector that results from the integrated network to develop the error model for the binder content. The selection of these parameters by the optimisation process was expected, since the effects of these parameters appear to be incompatible as reported by previous research [39][40]. This may perhaps relate to the interaction among the parameters which may result in the unpredictable behaviour of the granulation process.…”

Section: Error Modelling Using Gaussian Mixture Model: Results and DImentioning

confidence: 89%

Predictive modelling of the granulation process using a systems-engineering approach

2016

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“…Finally, the granule growth can be slower. 3,4,14) It is the balance of the counteracting effects of the viscosity that determines the different growth rates. 3 2 -Design for HCO It was possible to prepare pellets in the most 3 2 factorial design points.…”

Section: Resultsmentioning

confidence: 99%

“…3,4) The granulation cannot be achieved if the binder amount is too low. In contrary, an excess and/or high binder amount results in an uncontrollable granule growth.…”

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confidence: 99%

Melt Pelletization of a Hygroscopic Drug in a High Shear Mixer. Part 3.<SUP>1)</SUP> Effects of Binder Variation

Thies¹,

Kleinebudde

2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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Melt pelletization in a high shear mixer is a process used to produce pellets by agitation of a mixture of particulate solids and a meltable binder at a certain temperature, which enables the liquefying or softening of the binder. The equipment used, the process parameters, and the chosen formulation influence this process.2)The amount of binder was found to be important to control the granule growth.3,4) The granulation cannot be achieved if the binder amount is too low. In contrary, an excess and/or high binder amount results in an uncontrollable granule growth. Generally, only little variation is tolerable, if the other variables are kept constant.2) Also, changing the type of binder liquid requires adjustment of the amount of binder.The physicochemical properties of the binder (e.g. viscosity or polarity) and substrate-binder interactions were found to influence the granule growth and the strength of the agglomerates. This was examined in wet granulation 5,6) as well as in melt granulation. 7,8) Binder viscosity strongly depends on the product temperature, which is in turn influenced by process variables such as jacket temperature and impeller speed. The effect of viscosity on granule growth is complex, as demonstrated by Ennis et al. 9) Experiments with extremely viscous binders showed an increased potential for agglomeration growth by coalescence. This was related to the increased force of dynamic pendular bridges due to the viscous contribution.10) Consequently, the growth promoting effect of increasing viscosity dominates beyond an upper critical limit. Below that limit, decreasing binder viscosity leads to a faster granule growth.In a previous work, it has been shown that the pelletization of sodium valproate (SV) with glycerol monostearate was successful using 1.1 to 14.1% glycerol monostearate (GMS) as a binder and by adjusting the impeller speed and massing time.11) As seen, the appropriate binder concentration for successful pelletization was very low. It was assumed that the high solubility of SV is associated with the low amount of binder.In the present study, melt pelletization with three different types of binder was investigated. The binders differed in polarity and in the ability to dissolve SV. The aim was to examine the effect of the binder type on the pelletization process and to elucidate the critical binder properties in determining the granule growth. Moreover, in aiming to obtain a better understanding of how the viscosity of the binder liquid influences the process, some experiments were carried out separately. ExperimentalMaterials The model drug, SV (Katwijk, NL), is a hygroscopic and freely water soluble substance, which takes up water at relative humidity (rh) higher than 40% at 20°C. 12) At higher humidity it liquefies quickly. The water content of untreated SV was 0.10% measured by Karl-Fischer-titration (nϭ3).Fine powders of GMS (Myvaplex 600P, Eastman Kodak, U.S.A.), hydrated castor oil (HCO) (Cutina HR, Henkel, Germany), and polyethylene glycol (PEG) (Lutrol E 1500, BASF AG,...

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Melt Granulation in A Laboratory Scale High Shear Mixer

Cited by 115 publications

References 5 publications

Preparation and characterization of flurbiprofen beads by melt solidification technique

Preparation and characterization of flurbiprofen beads by melt solidification technique

Predictive modelling of the granulation process using a systems-engineering approach

Melt Pelletization of a Hygroscopic Drug in a High Shear Mixer. Part 3.<SUP>1)</SUP> Effects of Binder Variation

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