Lag Time in Diffusion-Controlled Release Formulations Containing a Drug-Free Outer Layer

Kalosakas, G.; Panagopoulou, Eleni

doi:10.3390/pr10122592

Cited by 6 publications

(3 citation statements)

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“…As expected, this result coincides with that of a thin slab with a thickness H, see Equation (16). It can be easily seen that, in the limit where the aspect ratio A tends to zero, the fractional release profile of Equation ( 20) reduces to the corresponding fractional release from a slab, i.e.…”

Section: Very Short Cylinders (H R)supporting

confidence: 85%

“…Depending on the physical mechanism that dominates the release process in a particular case, various analytical methods or numerical simulations have been proposed in order to investigate the release characteristics. Therefore, different models have been developed which describe situations ranging from pure diffusion [8][9][10][11][12][13][14][15][16][17] to reaction-diffusion systems [18][19][20][21][22][23][24], to hydrogel swelling [25][26][27], or to kinetically limited release [28,29].…”

Section: Introductionmentioning

confidence: 99%

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Exact Analytical Relations for the Average Release Time in Diffusional Drug Release

Kalosakas

2023

Processes

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Although analytical solutions for the problem of diffusion-controlled drug release from uniform formulations of simple geometries, like slabs, spheres, or cylinders, are well known, corresponding exact expressions for the average release times are not widely used. However, such exact analytical formulae are very simple and useful. When the drug is initially distributed homogeneously within the matrix, the average time of release from a sphere of radius R is tav=(1/15)R2/D and from a slab of thickness L is tav=(1/12)L2/D, where D is the corresponding drug diffusion coefficient. Regarding cylindrical tablets of height H and radius R, simple analytical expressions are obtained in the two opposite limits of either very long (H≫R) or very short (H≪R) cylinders. In the former case, of practically radial release, the average release time is tav=(1/8)R2/D, while in the latter case the same result as that of a slab with thickness H is recovered, tav=(1/12)H2/D, as expected. These simple and exact relations are useful not only for an estimate of the average release time from a drug carrier device when diffusion is the dominant mechanism of drug delivery, but also for the experimental determination of the drug diffusion coefficient in a release system of interest through the measured release profile, given the mean squared size of the formulation.

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Section: Very Short Cylinders (H R)supporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Exact Analytical Relations for the Average Release Time in Diffusional Drug Release

Kalosakas

2023

Processes

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“…There exist many Monte Carlo calculations applied in various drug delivery devices for different situations. However, in the majority of these cases, the release is determined mainly by diffusion and/or matrix bulk degradation or erosion [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Corresponding applications in conjugated polymer–drug systems containing labile bonds and the subsequent diffusion of the detached drug particles are rare [ 60 ].…”

Section: Introductionmentioning

confidence: 99%

Interplay between Diffusion and Bond Cleavage Reaction for Determining Release in Polymer–Drug Conjugates

Kalosakas

2023

Materials

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In conjugated polymeric drug delivery systems, both the covalent bond degradation rate and the diffusion of the freely moving drug particles affect the release profile of the formulation. Using Monte Carlo simulations in spherical matrices, the release kinetics resulting from the competition between the reaction and diffusion processes is discussed. For different values of the relative bond cleavage rate, varied over four orders of magnitude, the evolution of (i) the number of bonded drug molecules, (ii) the fraction of the freely moved detached drug within the polymer matrix, and (iii) the resulting fractional release of the drug is presented. The characteristic release time scale is found to increase by several orders of magnitude as the cleavage reaction rate constant decreases. The two extreme rate-limiting cases where either the diffusion or the reaction dominates the release are clearly distinguishable. The crossover between the diffusion-controlled and reaction-controlled regimes is also examined and a simple analytical formula is presented that can describe the full dependence of the release time on the bond cleavage rate constant. This simple relation is provided simply by the sum of the characteristic time for purely diffusional release and the bond cleavage decay time, which equals the inverse of the reaction rate constant.

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Controlled release of vancomycin from PEGylated fibrinogen polyethylene glycol diacrylate hydrogel

Nguyen,

Yuan,

Kukumberg

et al. 2024

Biomaterials Advances

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Lag Time in Diffusion-Controlled Release Formulations Containing a Drug-Free Outer Layer

Cited by 6 publications

References 50 publications

Exact Analytical Relations for the Average Release Time in Diffusional Drug Release

Exact Analytical Relations for the Average Release Time in Diffusional Drug Release

Interplay between Diffusion and Bond Cleavage Reaction for Determining Release in Polymer–Drug Conjugates

Controlled release of vancomycin from PEGylated fibrinogen polyethylene glycol diacrylate hydrogel

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