MRI as a tool for evaluation of oral controlled release dosage forms

Dorożyński, Przemysław; Kulinowski, Piotr; Młynarczyk, Anna; Stanisz, Greg J.

doi:10.1016/j.drudis.2011.10.026

Cited by 28 publications

(25 citation statements)

References 77 publications

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“…Magnetic Resonance Imaging (MRI) is a method ideally suited for the visualization of water ingress into the polymer matrix and is widely used for controlled release applications (10,11). In most of the MRI studies so far, the gel layer and core (unhydrated part of the matrix) were distinguishable (12–17).…”

Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethyl Cellulose Matrix Tablets In Situ

et al. 2012

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PurposeTo resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified.MethodsMultiparametric, spatially and temporally resolved T2 MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences—one of them designed to specifically study short T2 signals—were used.ResultsTwo components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion.ConclusionsThe MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.

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Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethyl Cellulose Matrix Tablets In Situ

et al. 2012

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“…Therefore, there is a need to combine dissolution methods with other techniques to improve their specificity and to further elucidate the mechanisms of drug dissolution. In the recent decades, the application of combined methods that integrate drug dissolution and imaging techniques has increased noticeably (3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Microstructural properties of controlled-release dosage forms as observed by MRI correspond to molecular properties/behavior of water and its interaction with matrix components. During matrix hydration, water concentration within the matrix as well as its interaction with polymer molecules can result in the formation of specific zones or layers (9,(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets

et al. 2015

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Abstract. In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

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“…This design feature enables optimal signal-to-noise ratios during MRI analysis, as good images require the tablet to be positioned at the most homogeneous part of the magnetic field within the instrument and remain there during the time course of each experiment. 5 To validate and demonstrate the utility of our novel holder for MRI tablet dissolution studies, MRI images of an MR tablet were obtained during field testing using the final product.…”

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confidence: 99%

“…This technique is well known for in vivo imaging, which differentiates types of tissues as a function of signal from hydrogen atoms (e.g., in water or fat). [2][3][4][5] We used MRI to study water diffusion into modified-release (MR) tablets. The key element of the type of MR tablet we chose to test is the formation of an outer hydrogel layer when exposed to dissolution medium.…”

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confidence: 99%

Fused Deposition Modeling Provides Solution for Magnetic Resonance Imaging of Solid Dosage Form by Advancing Design Quickly from Prototype to Final Product

et al. 2013

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The release profile of active pharmaceutical ingredient (API) from its solid dosage form is an important aspect of drug development as it is often used to predict potential drug release characteristics of a product in vivo. In recent years, magnetic resonance imaging has emerged as a nondestructive technique that captures the physical changes of solid dosage forms during dissolution. An example that highlights this application is in the dissolution of modified-release tablet studies. As the tablet dissolves, API disperses in a hydrogel matrix within the tablet, and swelling of the hydrogel layer eventually leads to release of API over time. To achieve optimum signal-to-noise ratios, the tablet should be placed in the most homogeneous region of the magnet and remain there throughout the dissolution experiment. Moreover, the tablet holder must maintain the tablet position without interfering with the natural dissolution process, such as by crushing the softened tablet. This can be difficult because the size, shape, and rigidity of the tablet change during dissolution. This article describes the process, material, and manufacture of a novel device that meets these challenges, with emphasis on how additive manufacturing on a 3D printer enabled an efficient and inexpensive process of design improvements.

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MRI as a tool for evaluation of oral controlled release dosage forms

Cited by 28 publications

References 77 publications

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethyl Cellulose Matrix Tablets In Situ

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethyl Cellulose Matrix Tablets In Situ

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets

Fused Deposition Modeling Provides Solution for Magnetic Resonance Imaging of Solid Dosage Form by Advancing Design Quickly from Prototype to Final Product

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