Mathematical modeling of drug dissolution

Siepmann, Juergen; Siepmann, Florence

doi:10.1016/j.ijpharm.2013.04.044

Cited by 374 publications

(235 citation statements)

References 49 publications

Supporting

Mentioning

218

Contrasting

Unclassified

Order By: Relevance

“…Several questions remain open as to which is the most suitable procedure to declare BE (38,55,(59)(60)(61)(62) and which other mathematical expressions could model drug release more mechanistically (63,64). If these customized DPC tests are attempted to be used for generic drugs, serious harmonization efforts should be made to share these IVIVC models between agencies and manufacturers.…”

Section: Discussionmentioning

confidence: 99%

Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations

Gómez-Mantilla

Schaefer

Casabó

et al. 2014

AAPS J

View full text Add to dashboard Cite

Abstract. Appropriate setting of dissolution specification of extended release (ER) formulations should include precise definition of a multidimensional space of complex definition and interpretation, including limits in dissolution parameters, lag time (t-lag), variability, and goodness of fit. This study aimed to set dissolution specifications of ER by developing drug-specific dissolution profile comparison tests (DPC tests) that are able to detect differences in release profiles between ER formulations that represent a lack of bioequivalence (BE). Dissolution profiles of test formulations were simulated using the Weibull and Hill models. Differential equations based in vivo-in vitro correlation (IVIVC) models were used to simulate plasma concentrations. BE trial simulations were employed to find the formulations likely to be declared bioequivalent and nonbioequivalent (BE space). Customization of DPC tests was made by adjusting the delta of a recently described tolerated difference test (TDT) or the limits of rejection of f2. Drug k a (especially if k a is small), formulation lag time (t-lag), the number of subjects included in the BE studies, and the number of sampled time points in the DPC test were the factors that affected the most these setups of dissolution specifications. Another recently described DPC test, permutation test (PT), showed excellent statistical power. All the formulations declared as similar with PT were also bioequivalent. Similar case-specific studies may support the biowaiving of ER drug formulations based on customized DPC tests.

show abstract

Section: Discussionmentioning

confidence: 99%

Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations

Gómez-Mantilla

Schaefer

Casabó

et al. 2014

AAPS J

View full text Add to dashboard Cite

show abstract

“…The dissolved drug species subsequently diffuse out of the matrix of the delivery system due to concentration gradient. Additionally, the matrix of the delivery system might also undergo several changes such as swelling and consequent dissolution in the aqueous medium, all contributing to the overall drug release process [2,3]. Considering the complexity of mucosal delivery systems, often containing nanoparticulate carriers included in soluble or insoluble matrices, in vitro drug release seems to be the appropriate term when describing the liberation process of the drug from such formulations.…”

Section: Introductionmentioning

confidence: 99%

In vitro dissolution/release methods for mucosal delivery systems

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Accurate mathematical models can be used to facilitate the development of optimized degradable bone substitutes and other biomaterials by allowing rapid evaluation and validation of experimental parameters and also minimizing the number of required experimental studies (Frenning 2004;Kaunisto et al 2013;Lao et al 2011;Masaro and Zhu 1999;Siepmann et al 1999;Siepmann and Siepmann 2013). In addition, they also allow quantitative understanding of the physical, chemical and biological phenomena involved in the controlled release of ions or molecules (Siepmann and Göpferich 2001;Snorradóttir et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Computational modelling of local calcium ions release from calcium phosphate-based scaffolds

Manhas

Guyot

Kerckhofs

et al. 2016

Biomech Model Mechanobiol

View full text Add to dashboard Cite

A variety of natural or synthetic calcium phosphate (CaP)-based scaffolds are currently produced for dental and orthopaedic applications. These scaffolds have been shown to stimulate bone formation due to their biocompatibility, osteoconductivity and osteoinductivity. The release of the Ca 2+ ions from these scaffolds is of great interest in light of the aforementioned properties. It can depend on a number of biophysicochemical phenomena such as dissolution, diffusion and degradation, which in turn depend on specific scaffold characteristics such as composition and morphology. Achieving an optimal release profile can be challenging when relying on traditional experimental work alone. Mathematical modelling can complement experimentation. In this study, the in vitro dissolution behaviour of four CaP-based scaffold types was investigated experimentally. Subsequently, a mechanistic finite element method model based on biophysicochemical phenomena and specific scaffold characteristics was developed to predict the experimentally observed behaviour. Before the model could be used for local Ca 2+ ions release predictions, certain parameters such as dissolution constant (k dc ) and degradation constant (k sc ) for each type of scaffold were determined by calibrating the model to the in vitro dissolution data. The resulting model showed to yield release characteristics in satisfactory agreement with those observed experimentally. This suggests that the mathematical model can be used to investigate the local Ca 2+ ions release from CaP-based scaffolds.

show abstract

Mathematical modeling of drug dissolution

Cited by 374 publications

References 49 publications

Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations

Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations

In vitro dissolution/release methods for mucosal delivery systems

Computational modelling of local calcium ions release from calcium phosphate-based scaffolds

Contact Info

Product

Resources

About