Percolation theory: application to the study of the release behaviour from inert matrix systems

Caraballo, Isidoro; Fernández‐Arévalo, M.; Holgado, M.A.; Rabasco, A. M.

doi:10.1016/0378-5173(93)90225-5

Cited by 73 publications

(27 citation statements)

References 4 publications

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“…Binary mixtures were prepared with different excipient contents (10,15,20,30,40, 50, 60, 70, 80% w/w) keeping constant the dose of the drug (150 mg of LBD) (see Table 1). Both components were mixed for 3 min (optimal mixing time) using a Turbula mixer.…”

Section: Methodsmentioning

confidence: 99%

“…[15][16][17][18][19] Our research group is employing the percolation theory in order to describe solid forms, in concrete controlled release inert matrix systems. 15,16,[20][21][22][23][24][25][26] One of the most important parameters of percolation theory is the percolation threshold, where there is a maximum probability of appearance of an infinite or percolating cluster of a substance and some properties of the system change suddenly. A cluster is defined as a group of neighboring occupied sites in the lattice and is considered infinite or percolating when it extends from one side to the rest of the sides of the lattice, i.e.…”

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confidence: 99%

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Study of the Critical Points in Lobenzarit Disodium Hydrophilic Matrices for Controlled Drug Delivery

Miranda

Millán

Caraballo

2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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The hydrophilic matrices are one of the most used types of Controlled Release Systems in the world. In comparison with other Controlled Release Devices, they have the advantage of their low cost and simple technology, that facilitates their application to an important sector of the population, as well as their safety against the dose dumping (accidental fast release of the whole drug dose).1) Another advantage of these matrices concerns the drug release kinetics. Using these systems, it is possible to obtain a variety of release kinetics, including in some cases zero-order release kinetics.2)The study of hydrophilic matrices is a difficult task due to its complex and disordered structure. A number of publications have reported studies about the mechanisms of drug release from hydrophilic matrices. [3][4][5][6][7][8][9][10][11] In recent works, our research group has applied the percolation theory to study the release and hydration rate of hydrophilic matrices, in order to contribute to the rationalization of the design of these controlled release systems and to obtain a better knowledge of the processes that occur during the release of the drug. [12][13][14] Percolation Theory is a statistical theory that studies disordered or chaotic systems where the components are randomly distributed in a lattice. This theory has wide application in many scientific disciplines and was introduced by Leuenberger et al. in the pharmaceutical field in 1987 to improve the characterization of solid dosage forms. [15][16][17][18][19] Our research group is employing the percolation theory in order to describe solid forms, in concrete controlled release inert matrix systems. 15,16,[20][21][22][23][24][25][26] One of the most important parameters of percolation theory is the percolation threshold, where there is a maximum probability of appearance of an infinite or percolating cluster of a substance and some properties of the system change suddenly. A cluster is defined as a group of neighboring occupied sites in the lattice and is considered infinite or percolating when it extends from one side to the rest of the sides of the lattice, i.e. percolates the whole system. 27)The application of this theory to study the release and hydration rate of hydrophilic matrices allowed for first time to explain the changes in release and hydration kinetic of swellable matrices type controlled delivery systems. [12][13][14] According to this theory, the critical points observed in dissolution and water uptake studies can be attributed to the existence of excipient percolation thresholds. The knowledge of these thresholds is very important to optimize the design of swellable matrix tablets. Above the excipient percolation threshold an infinite cluster of this component is formed, controlling the hydration and release rate. Below this threshold the excipient does not percolate the system and, as a consequence, the drug release can not be controlled. It has to be emphasized that the infinite cluster of excipient responsible for the drug release contro...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Study of the Critical Points in Lobenzarit Disodium Hydrophilic Matrices for Controlled Drug Delivery

Miranda

Millán

Caraballo

2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The relationship derived for transport near and above the percolation threshold was given in Eq. (12). Using Ø c = 0.09 and a = 3.8 Â 10 j6 , Eq.…”

Section: Estimation Of the Model Parametersmentioning

confidence: 98%

“…Equation 12 states that for a system where transport can occur through the polymer as well as through pores, the bulk diffusion coefficient is composed of a continuous pore structure transport component and a heterogeneous transport component (comprised of polymer, dead end and isolated pore clusters). The porous component is the value c(ØjØ c ) 2.0 derived directly from the volume fraction effective percolation scaling laws as described previously and the heterogeneous transport…”

Section: Drug Release Model Developmentmentioning

confidence: 99%

Percolative Transport and Cluster Diffusion Near and Below the Percolation Threshold of a Porous Polymeric Matrix

Hastedt¹,

Wright

2006

Pharm Res

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A model describing transport near and below the percolation threshold in matrices composed of two phases, polymer and drug, was developed. The percolation model developed accounts for diffusion within the porous structure and through the inert, insoluble polymeric amorphous regions of the matrix. The low percolation threshold and subsequently high coordination was concluded to be due to the biphasic classical porous and nonclassical polymeric diffusional transport mechanisms associated with the system studied.

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“…Since then, concepts of the percolation theory have been applied to the study and design of different types of sustained release matrix systems, starting with inert matrices (3,(11)(12). According to the percolation theory, an inert matrix must be formulated above the drug percolation threshold (the sum of the initial porosity of the system plus the volumetric fraction of the drug must percolate through the system, since in inert matrices the pores allow water uptake and drug release).…”

mentioning

confidence: 99%

Critical points in ethylcellulose matrices: Influence of the polymer, drug and filler properties

Cifuentes¹,

Aguilar-de-Leyva²,

Rajabi‐Siahboomi³

et al. 2013

Acta Pharmaceutica

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Due to their simple and low-cost manufacturing process, matrix tablets are pharmaceutical dosage forms most widely used for the formulation of oral controlled release of drugs (1). These systems involve dispersion of one or more drugs in a support structure, which in the majority of the cases is of polymeric nature.Inert matrices are systems that consist of a polymeric porous solid network, which is insoluble and indigestible in the gastrointestinal tract (2). Drug release from these dosage forms occurs by drug diffusion through the pores of the matrices, including the initial pores and the pores that appear when the drug or soluble excipients have been dissolved (3).Ethylcellulose is a water insoluble polymer that has been used in the manufacturing of different solid oral dosage forms. It is used in the preparation of microcapsules and microspheres, as a barrier membrane in reservoirs, and as inert matrix-former for oral Percolation theory has been applied to study the drug release behaviour in multicomponent inert matrices containing ethylcellulose as a matrix forming polymer. Global influence of major formulation factors such as polymer viscosity, polymer particle size, drug and filler solubility and porosity of the tablets in drug release kinetics has been studied for the first time. Batches containing three viscosity grades of Ethocel™, microcrystalline cellulose (MCC) and lactose as fillers, a lubricant and flow aid mixture and three drugs with different solubility have been manufactured. For some batches, compression pressure was varied in order to obtain matrices with five levels of initial porosity. The behaviour of inert matrices was explained based on the percolation ranges of the main components of the formulation. The effect of the porosity percolation threshold was observed and the existence of a tricoherent drug-polymer-filler system is hypothesized.

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Percolation theory: application to the study of the release behaviour from inert matrix systems

Cited by 73 publications

References 4 publications

Study of the Critical Points in Lobenzarit Disodium Hydrophilic Matrices for Controlled Drug Delivery

Study of the Critical Points in Lobenzarit Disodium Hydrophilic Matrices for Controlled Drug Delivery

Percolative Transport and Cluster Diffusion Near and Below the Percolation Threshold of a Porous Polymeric Matrix

Critical points in ethylcellulose matrices: Influence of the polymer, drug and filler properties

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