Magnetic Resonance Imaging (MRI) Study of Swelling and Water Mobility in Micronized Low-Substituted Hydroxypropylcellulose Matri Tablets.

Kojima, M.; Ando, Shuichi; Kataoka, Katsuo; Hirota, Toyohiko; Aoyagi, Kazuharu; Nakagami, Hiroaki

doi:10.1248/cpb.46.324

Cited by 35 publications

(16 citation statements)

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“…As reported previously, 7) it was observed through the images that all tablets were hydrated as shown in Fig. 1b.…”

Section: Resultssupporting

confidence: 79%

“…4,5) Kawashima et al 6) also reported that micronized LH41 works as a controlled release matrix. In our previous research, 7) we reported that the magnetic resonance imaging (MRI) method was a useful tool for evaluating the swelling property and the water mobility in hydrating matrix tablets. It was found that LH41 swelled much less than did HPC and HPMC, and that water mobility is highly restricted in all three tablet formulations.…”

mentioning

confidence: 99%

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Investigation of Water Mobility and Diffusivity in Hydrating Micronized Low-substituted Hydroxypropyl Cellulose, Hydroxypropylmethyl Cellulose, and Hydroxypropyl Cellulose Matrix Tablets by Magnetic Resonance Imaging (MRI).

Kojima

Nakagami

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…As reported previously, 7) it was observed through the images that all tablets were hydrated as shown in Fig. 1b.…”

Section: Resultssupporting

confidence: 79%

mentioning

confidence: 99%

Investigation of Water Mobility and Diffusivity in Hydrating Micronized Low-substituted Hydroxypropyl Cellulose, Hydroxypropylmethyl Cellulose, and Hydroxypropyl Cellulose Matrix Tablets by Magnetic Resonance Imaging (MRI).

Kojima

Nakagami

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The identification of different states of water from the water proton spin-spin (T 2 ) relaxation times is an established method. 13,18,19) When the mobility of water molecules is restricted, shorter T 2 relaxation times are observed. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16] In addition to imaging sample sections, MRI also provides valuable information about the state of water in samples, such as the parameters regarding the water mobility and diffusivity within hydrating tablets. [17][18][19] MR signals and image intensities depend on the dynamic state of the water-polymer matrix, and they can directly visualize the spatial variation of water molecule self-diffusion coefficients in hydrating polymer matrices at a molecular level. 20) We considered that MRI analysis is suitable for investigating the drug release mechanism of the sustained release tablet formulation optimized in our previous study.…”

mentioning

confidence: 99%

Relationship between Diffusivity of Water Molecules Inside Hydrating Tablets and Their Drug Release Behavior Elucidated by Magnetic Resonance Imaging

Kikuchi

Onuki

Kuribayashi

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density-and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.Key words magnetic resonance imaging; sustained release; diffusion; swelling; hydration Directly compressed hydrophilic polymer matrix tablets have been widely used as a controlled-release oral formulation because they are easy to manufacture and inexpensive, with versatile release characteristics.1,2) Various hydrophilic matrix tablets are highly water-soluble, show good gelation performance, and are stable and safe. Numerous polymers have been used that enable the formation of a gel layer around the tablets. In these formulations, the factors affecting in vitro drug release, such as drug/polymer ratio, polymer viscosity, and amount of additives, have been studied from the viewpoint of formulation design. [3][4][5] We have been investigating sustained release tablets comprising hydroxypropyl methylcellulose (HPMC) and dextran derivatives as a gel-forming hydrophilic polymer and polyion complex-forming materials. Dextran sulfate (DS) and [2-(diethylamino)ethyl] dextran (EA) are anionic and cationic dextran derivatives and their resultant polyion complex matrix possesses sustainable drug-releasing properties. In a previous study, we manipulated the composition of a gel-forming and polyion complex matrix in an attempt to develop a sustained release tablet having zero-order drug release without being affected by pH change. Diltiazem hydrochloride (DTZ), a highly water-soluble drug, was used as a model. As a ...

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“…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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Magnetic Resonance Imaging (MRI) Study of Swelling and Water Mobility in Micronized Low-Substituted Hydroxypropylcellulose Matri Tablets.

Cited by 35 publications

References 0 publications

Investigation of Water Mobility and Diffusivity in Hydrating Micronized Low-substituted Hydroxypropyl Cellulose, Hydroxypropylmethyl Cellulose, and Hydroxypropyl Cellulose Matrix Tablets by Magnetic Resonance Imaging (MRI).

Investigation of Water Mobility and Diffusivity in Hydrating Micronized Low-substituted Hydroxypropyl Cellulose, Hydroxypropylmethyl Cellulose, and Hydroxypropyl Cellulose Matrix Tablets by Magnetic Resonance Imaging (MRI).

Relationship between Diffusivity of Water Molecules Inside Hydrating Tablets and Their Drug Release Behavior Elucidated by Magnetic Resonance Imaging

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

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