Critical parameters involved in producing microspheres by prilling of molten lipids: From theoretical prediction of particle size to practice

Séquier, F.; Faivre, Vincent; Daste, Georges; Renouard, M.; Lesieur, Sylviane

doi:10.1016/j.ejpb.2014.03.005

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…The difference in cooling rate between the point of origin and the top of the sphere, led to an inhomogeneous shrinking process resulting in a stress field that created a cavity upon full solidification. These observations are in agreement with the characteristic shrinking properties of lipids during their crystallization [10,[32][33]. In contrast, the visualisation of droplet solidification of a transparent 30% MPT in BA solution revealed the creation of the expulsion at the surface of the final prills.…”

Section: Size and Shape Of The Prillssupporting

confidence: 85%

“…Initial screening experiments revealed that sieved (150 µm) PAR in BA suspensions were processable up to a drug load of 20%, while sieved (50 µm) MET in BA suspensions were processable up to a drug load of at least 40%. Since viscosity is a critical process parameter during droplet formation at the nozzle, this difference in maximum processable drug load could be attributed to the higher viscosity of PAR in BA suspensions in comparison with MET in BA suspensions at equal drug loads [10,23]. Rheological experiments confirmed this hypothesis and revealed an almost Newtonian behaviour for MET suspensions while distinct shear thinning was observed for PAR suspensions (Fig.…”

Section: Processabilitymentioning

confidence: 67%

“…Moreover, on an industrial scale droplets will be formed by the laminar jet break-up of a continuous flow by a vibrating nozzle system and subsequently being cooled during their falling motion in a cooling tower. Consequently, this will result in an even more homogeneous particle size distribution and droplet cooling [10,[36][37].…”

Section: In Vitro Drug Releasementioning

confidence: 99%

“…As Vervaeck et al focused on API/FA solutions (e.g. metoprolol tartrate (MPT) in BA), no information is available on the feasibility of prilling API/FA suspensions as indicated by Séquier et al [7,10]. Therefore the aim of current study was to evaluate the potential of prilling for APIs suspended in molten FA.…”

mentioning

confidence: 99%

“…Via spray congealing perfectly spherical microspheres consisting of a drug imbedded in a lipid matrix can be produced [8][9]. A specific type of spray congealing, called prilling, yields larger spherical particles (>500µm) resulting in a slower controlled release system and excellent flow properties for volumetric capsule filling [2,5,[10][11].…”

mentioning

confidence: 99%

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Prilling of API/fatty acid suspensions: Processability and characterisation

Coninck

Vanhoorne

Elmahdy

et al. 2019

International Journal of Pharmaceutics

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Current study evaluated the processability and characteristics of prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension instead of previously studied API/FA solutions to enlarge the application field of prilling. Metformin hydrochloride (MET) and paracetamol (PAR) were used as model APIs while both the effect of drug load (10% to 40%) and FA chain length (C14 to C22) were evaluated.Prevention of nozzle obstruction due to large or agglomerated API particles in the molten FA was achieved via API sieving while sedimentation during processing was avoid via equipment modifications. Finally, the API/FA suspensions were processable on lab-scale prilling equipment without thermal degradation, nozzle obstruction or sedimentation in function of processing time. The processability of API/FA suspensions was only limited by the viscosity of the molten mixture which was mainly affected by the size and shape of the API particles but independent of the FA chain length. A lower API particle size and aspect ratio, resulted in a higher amount of particle-particle interactions and consequently a higher viscosity at equal drug load. Current study also gained more insight in the solidification behavior of API/FA based formulations in liquid nitrogen via high speed camera analysis and rapid heat calorimetry. The collected prills were spherical (AR ≥ 0.898) with a smooth surface (sphericity ≥ 0.914) and a stable particle size of ± 2.3mm and 2.4mm for MET and PAR prills respectively, independent of the drug load and/or FA chain length. In vitro drug release evaluation revealed a faster drug release at higher drug load, higher API water solubility and shorter FA chain length. Except for a 10% MET in behenic acid (C22) formulation since the low viscosity of the mixture resulted in an inhomogeneous API distribution in the prill, while stearic acid (C18) based formulations had an increased drug release due to their high porosity. Solid state characterization via XRD and Raman spectroscopy proved the preservation of API and FA crystallinity after thermal processing via prilling and during storage. Evaluation of the similarity factor proved a stable drug release (f2 >50) of both MET and PAR prills after storage at 25°C or 40°C for 6 months.

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Section: Size and Shape Of The Prillssupporting

confidence: 85%

Section: Processabilitymentioning

confidence: 67%