A new approach in the prediction of the dissolution behavior of suspended particles by means of their particle size distribution

Tinke, A.P.; Vanhoutte, Koen; Maesschalck, Roy De; Verheyen, Steven; Winter, Hans De

doi:10.1016/j.jpba.2005.05.014

Cited by 53 publications

(39 citation statements)

References 16 publications

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“…Various attempts have been made to simulate the effect of mean particle size on dissolution [10][11][12][13][14][15][16][17][18] ; however, at this time there is no universal approach for the specification of drug particle size due to insufficient understanding of the complex relationship between mean particle diameter and the dissolution rate of polydispersed particles. As an alternative to using representative particle diameters, dissolution from polydispersed particles can be modeled by dividing the particle sizes into 16 discrete fractions.…”

Section: Discussionmentioning

confidence: 99%

A Theoretical-Empirical Analysis on the Initial Dissolution Rate of Drugs from Polydispersed Particles

Takano

Takata

Shiraki

et al. 2009

Biological & Pharmaceutical Bulletin

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The number of poorly water-soluble drug candidates in drug discovery has recently increased.1) Their limited solubility often causes not only poor but also variable oral absorption because the dissolution rate is insufficient to completely dissolve the drug in the gastrointestinal (GI) tract. Thus, control of the dissolution rate of drug is significant in obtaining sufficient oral absorption. One of the important factors in determining the dissolution rate of an active pharmaceutical ingredient (API) is particle size. Thus, understanding the dissolution of an API will benefit from clarification of the relationship between particle size and dissolution.The dissolution rate can be calculated from particle diameter under the assumption that the particles are spheres of relatively the same size because the dissolution rate of a drug is proportional to the solid surface area, as expressed by the Noyes-Whitney Equation.2) APIs normally include various or polydispersed particle sizes and, to specify the particle diameter for these polydispersed particles, representative diameters such as mean particle diameter or a statistical descriptor of cumulative undersize particles, such as D 50 or D 90 to designate diameters below which 50% or 90% of the drug is contained, are used. However, knowledge of the relationship between representative particle diameters and the dissolution rate is insufficient, and there is no validated method for determining the appropriate particle diameter in order to calculate the dissolution rate. In the present study, we attempt to identify the mean particle diameter of a drug with polydispersed particles that would best determine the dissolution rate of the drug. Our approach includes an investigation into the theory of the relationship between mean particle diameters and dissolution under sink conditions, simulation profiles of the dissolution of different particle sizes of a hypothetically generated drug, experimental dissolution profiles of different particle sizes of aprepitant as the model of a poorly water-soluble drug, the use of the dissolution profiles to predict dissolution in the human GI tracts, and lastly, discussion of particle size requirements for APIs. THEORETICAL BACKGROUNDDissolution Rate Equations for Mono-Dispersed Particles The Noyes-Whitney equation was used to determine the dissolution of a single particle.2) The Noyes-Whitney model of dissolution is based on the assumption that the particles have the same diameter a(t) and the ratio of D/h, where D is the diffusion coefficient and h is the diffusion layer thickness, is constant during the dissolution process. The dissolution rate is given by the following equation: (1) where X s (t) is the mass of undissolved drug at time t, C s is the saturated solubility of drug, C is the dissolved drug concentration at time t and a(t) is a function of t.Solving with the volume of the particle and density, r, results in:Equating Eq. 1 with Eq. 3 gives: (4) To simplify, dissolution under sink conditions is assumed to clarify the relation...

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Section: Discussionmentioning

confidence: 99%

A Theoretical-Empirical Analysis on the Initial Dissolution Rate of Drugs from Polydispersed Particles

Takano

Takata

Shiraki

et al. 2009

Biological & Pharmaceutical Bulletin

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“…If the drug particles with different d are present, a new correlation model between particle size distribution and dissolution rate was proposed. In this model, the volumeweighted contribution of each particle size fraction to the overall rate of dissolution is calculated [117] . Felodipine particles of various sizes were studied with higher dissolution rates found for smaller particles compared to larger particles.…”

Section: Figurementioning

confidence: 99%

Why is the nanoscale special (or not)? Fundamental properties and how it relates to the design of nano-enabled drug delivery systems

Otto

Villiers

2013

Nanotechnology Reviews

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Why is the nanoscale special (or not) ?Fundamental properties and how it relates to the design of nano-enabled drug delivery systems Abstract: Nanoscience studies describe natural phenomena at the submicron scale. Below a critical nanoscale limit, the physical, chemical, and biological properties of materials show a marked departure in their behavior compared to the bulk. At the nanoscale, energy conversion is dominated by phonons, whereas at larger scales, electrons determine the process. The surface-to-volume ratio at the nanoscale is immense, and interfacial interactions are markedly more important than at the macroscopic level, where the majority of the material is shielded from the surface. These properties render the nanoparticles to be significantly different from their larger counterparts. Nano-enabled drug delivery systems have resulted from multidisciplinary cooperation aimed at improving drug delivery. Significant improvements in the thermodynamic and delivery properties are seen due to nanotechnology. Hybrid nanodelivery systems, i.e., membranes with nanopores that can gate stimuli-responsive drug release could be a future development. Nanotechnology will improve current drug delivery and create novel future delivery systems. The fundamental properties and challenges of nanodelivery systems are discussed in this review.

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“…So the question arises as to how does a smaller particle size affect this parameter? It has been experimentally proved in a number of studies that the smaller the particle size, the smaller the diffusion layer thickness and the higher the dissolution rate (Bisrat and Nystrom 1988;Hintz and Johnson 1989;Wang and Flanagan 2002;Tinke et al 2005). The relationship between the boundary layer thickness and the particle size can be best understood using the Prandtl equation:…”

Section: Increased Saturation Solubility and Dissolution Ratementioning

confidence: 99%

Solid Nanosuspensions: The Emerging Technology and Pharmaceutical Applications as Nanomedicine

Verma

Burgess

2009

Pharmaceutical Suspensions

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One of the foremost reasons for such a widespread interest in nanosuspensions as drug delivery systems is their ability to provide formulations of poorly soluble drugs with increased saturation solubility and higher dissolution rates. Nanosuspensions manifest these properties because of their small size and high surface area. The unique properties of the nanosuspensions along with their fast development times, low production costs, ease of manufacture and scale-up as well as their ability to extend the lifecycle of off-patent drugs have resulted in rapid commercialization. Nanosuspensions provide us with a useful tool for formulating an ever-increasing number of poorly water soluble drugs in pharmaceutical development programs.

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A new approach in the prediction of the dissolution behavior of suspended particles by means of their particle size distribution

Cited by 53 publications

References 16 publications

A Theoretical-Empirical Analysis on the Initial Dissolution Rate of Drugs from Polydispersed Particles

A Theoretical-Empirical Analysis on the Initial Dissolution Rate of Drugs from Polydispersed Particles

Why is the nanoscale special (or not)? Fundamental properties and how it relates to the design of nano-enabled drug delivery systems

Solid Nanosuspensions: The Emerging Technology and Pharmaceutical Applications as Nanomedicine

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