A model for the drug release from a polymer matrix tablet—effects of swelling and dissolution (original) (raw)
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Journal of Controlled Release, 1996
The movement of the penetrant and polymer fronts and the drug dissolution in highly loaded swellable matrix tablets were studied with the aim of establishing relationships between front position and drug release kinetics. Three boundaries were identified corresponding to the swelling, diffusion and erosion fronts. The kinetics of drug release depended on the relative movement of the erosion and swelling/diffusion fronts. Under certain conditions of drug solubility and loading in the matrix, the last two could move separately. The data obtained demonstrated that the difference between the diffusion and erosion fronts is decisive for the release kinetics. This leads to a new finding that the distance between diffusion and erosion fronts (dissolved drug gel layer thickness) is the most important parameter for drug release, instead of the distance between swelling and erosion fronts (whole gel layer thickness).
International journal of pharmaceutics, 2011
The time required for the design of a new delivery device can be sensibly reduced if the release mechanism is understood and an appropriate mathematical model is used to characterize the system. Once all the model parameters are obtained, in silico experiments can be performed, to provide estimates of the release from devices with different geometries and compositions. In this review coated and matrix systems are considered. For coated formulations, models describing the diffusional drug release, the osmotic pumping drug release, and the lag phase of pellets undergoing cracking in the coating due to the build-up of a hydrostatic pressure are reviewed. For matrix systems, models describing pure polymer dissolution, diffusion in the polymer and drug release from swelling and eroding polymer matrix formulations are reviewed. Importantly, the experiments used to characterize the processes occurring during the release and to validate the models are presented and discussed.
Analyzing Drug Release Kinetics from Water-Soluble Polymers
Industrial & Engineering Chemistry Research, 2019
The ability to develop predictive mathematical models of therapeutic release from pharmaceutical formulations has enormous potential to enhance our understanding of such systems and improve the controlled release of the payload. The current work describes the development and testing of a onedimensional model of drug transport from amorphous, swelling/dissolving polymers. Model parameters such as the diffusivities of water and drug, the initial loading of the drug, the polymer dissolution rate, drugpolymer interactions, and the tablet thickness were varied, demonstrating the ability to tune the release to be controlled by either drug diffusion or polymer chain disentanglement. In addition, predictions of the concentration profiles of water and drug within the gel layer, the locations of the erosion and swelling boundaries, and gel layer thickness were obtained for diffusion-and disentanglement-controlled release. To highlight the generalizability of this model, multiple parameters were varied, and it was shown that increasing the diffusivities of water and drug and the initial drug loading and decreasing the polymer dissolution rate sufficiently resulted in diffusion-controlled release. The model was fit to experimental data for a model tablet system comprising of sodium diclofenac entrapped in a poly(vinyl pyrrolidone) matrix and yielded physically meaningful values of the model parameters. The work presented here demonstrates the predictive power of the model for rapid and rational design of future pharmaceutical formulations for controlled drug delivery.
Drug diffusion front movement is important in drug release control from swellable matrix tablets
Journal of Pharmaceutical Sciences, 1995
Swellable controlled release devices of buflomedil pyridoxalphosphate in hydroxypropyl methylcellulose were prepared, and their swelling and release behavior was investigated. The drug release as a function of time was investigated for various system parameters. Three distinct fronts were observed during the swelling and release processes, i.e., a swelling, a drug diffusion, and an erosion front. The drug diffusion front could be readily determined due to the drug's yellow color. The relative positions of the fronts and the drug release rate were studied as functions of the initial porosity and the molecular weight of the polymer carrier. It was shown that the drug diffusion front best describes the overall release behavior of the system. The fractional drug release was a strong function of the dissolved drug gel layer thickness, which separates the diffusion front from the erosion front. The effect of drug solubility was also investigated by altering the pH and the ionic strength of the dissolution medium. It was shown that as drug solubility increased, the undissolved drug gel layer thickness decreased, again showing the importance of the movement of the diffusion front in controlling the overall release.
Predicting the Drug Release Kinetics of Matrix Tablets
2008
In this paper we develop two mathematical models to predict the release kinetics of a water soluble drug from a polymer/excipient matrix tablet. The first of our models consists of a random walk on a weighted graph, where the vertices of the graph represent particles of drug, excipient and polymer, respectively. The graph itself is the contact graph of a multidisperse random sphere packing. The second model describes the dissolution and the subsequent diffusion of the active drug out of a porous matrix using a system of partial differential equations. The predictions of both models show good qualitative agreement with experimental release curves. The models will provide tools for designing better controlled release devices.
DEM simulation of drug release from structurally heterogeneous swelling tablets
Powder Technology, 2013
ABSTRACT The Discrete Element Method (DEM) was used to generate an unstructured mesh over which mass transfer equations were solved. This has been applied to model swelling and drug release from pharmaceutical tablets and is useful for studying in vitro-in vivo correlation (IVIVC) and virtual formulation development. Parametric studies were conducted into the effect of tablet shape and aspect ratio, polymer properties and shell thickness, and boundary conditions around the tablet on drug release time (r(90)), the shape of the release curve and tablet evolution. The first study showed that drug release from tablets containing the same mass of polymer and drug but having different shapes and aspect ratios was only dependent on aspect ratio and not tablet shape. Investigations into polymer properties and coating thickness showed that drug release is fastest for moderately swelling polymers and that similar t(90) can be obtained for different combinations of parameters. The final study into different boundary conditions found that for highly soluble drugs, the polymer was the rate limiting step for drug release but in other cases, release was limited by the low permeability of the boundary. The increase in bulk volume also slowed drug release and demonstrated that both permeability and bulk volume couple to influence drug release.
The specific aim of this study was to prepare sustained release matrix tablets containing indapamide as a low dose and low water solubility model drug. The matrix formers were composed of blends of hydroxypropyl methylcellulose as a swellable polymer and methyl cellulose as an erodible polymer. The matrix tablets were prepared by the direct compression technique and they have shown robust and acceptable physical properties with a content uniformity within the acceptable limits. Lactose and microcrystalline cellulose were investigated as additives to these matrices in order to adjust and modulate the release of the drug from the matrices to achieve a release profile similar to that obtained from the reference commercial product, Natrilix ® . All matrix tablets prepared with these two additives have gave a release profile that is close to zero order kinetics, however, the matrix tablets prepared with lactose gave a release profile with closer resemblance to that of the reference product with a similarity factor (F2) of 86. This is attributed to the rapid water solubility of lactose which enhanced higher erosion of the tablets, and thus, higher dissolution and diffusion of the drug. Microcrystalline cellulose is a swellable polymer where it has resulted in delayed release of the drug with time as compared to the reference product. Investigation of the mechanism of release of the drug from the matrices indicated that erosion is the dominant mechanism of drug release from these matrices.
Acta Pharmaceutica, 2009
Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from HPMC based matrix formulations The purpose of the present research work was to observe the effects of drug solubility on their release kinetics of water soluble verpamil hydrochloride and insoluble aceclofenac from hydrophilic polymer based matrix formulations. Matrix formulations were prepared by the direct compression method. The formulations were evaluated for various physical parameters. Along with the dynamics of water uptake and erosion, SEM and in vitro drug release of the tablets were studied. Applying an exponential equation, it was found that the kinetics of soluble drug release followed anomalous non-Fickian diffusion transport whereas insoluble drug showed zero-order release. SEM study showed pore formation on the tablet surface that differed depending on drug solubility. t-Test pointed to a significant difference in amount of both drugs released due to the difference in solubili...
International Communications in Heat and Mass Transfer, 2015
This paper presents a comparative study between the data collected in a drug dissolution experiment and the predictions obtained from simple mathematical approaches of drug diffusion in the delivery device but also with the results achieved from available kinetic models for dissolution processes. The controlled release of timolol maleate from a hydrogel disc, obtained by thermal copolymerization of hydroxyethyl methacrylate and methacrylic acid, was used as the case study. The equilibrium parameter (drug partition coefficient) used to model the mass transfer process dictates the predictions' accuracy. When this parameter is calculated from the drug release experiment, the diffusion equation with a Robin boundary condition type gives good predictions of the dissolution process. Predictions obtained with zero-sink condition in the release medium resulted in an overestimation of data. Several kinetic models available in the literature to describe drug release were used to correlate data. All the models tested describe the data adequately, but the Weibull model was the one that had the best correlation performance.
Pharmaceuticals, 2016
The performance of compressed tablet drug delivery systems made using polymeric materials depend on multiple factors, such as surface properties like contact angle, surface free energy and water absorption rate, besides the release mechanisms driven by the kind of polymer used. Hence, it should be possible to establish a relationship between the surface properties and the drug release kinetics. Compressed tablets with different proportions of poly(maleic acid-alt-octadecene) potassium salt (0%, 10%, 20%, 30% and 40%) were prepared. Blends of a model drug (ampicillin trihydrate) and the polymer material were analyzed by DSC. The surface properties of the tablets were determined by the sessile drop method, while the surface energy was determined using the semi-empirical Young-Dupre, Neumann and OWRK models. The release profiles were determined simulating in vitro conditions (buffer solutions pH 1.2 and pH 7.4 with ionic strength of 1.5 M at 37˝C (310.15 K)). A kinetic analysis of the dissolution profiles using different models (zero order, first order, Higuchi and Korsmeyer-Peppas) was realized. The results showed a significant effect of the proportion of polymer in both the surface properties of the tablets and the dissolution release, indicating a relationship between the kinetic and thermodynamic properties.