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The main objective of the development of drug delivery devices is to successfully deliver the drug to the desired sites of therapeutic action while reducing adverse side effects. In this paper, mathematical models have been developed for controlled drug delivery from cylindrical shaped devices consisting of disks, which is covered by erodible polymer and membrane. The use of polymers is necessary to provide controlled long term delivery of drugs. These implants need not be removed after drug delivery from the body because these are erodible. A model is presented for delivered of the drug from the device to the body. This model provides design of drug delivery device for eroding tumour or chemotherapy to cancerous regions and many such diseases. The results have been obtained for steady state release time and life time of the device. It has been observed that life time increases by adjusting some parameters.
Provides solutions for two- and three-dimensional linear models of controlled-release systems Real-world applications are taken from used to help illustrate the methods in Cartesian, cylindrical and spherical coordinate systems Covers the modeling of drug-delivery systems and provides mathematical tools to evaluate and build controlled-release devices Includes classical and analytical techniques to solve boundary-value problems involving two- and three-dimensional partial differential equations Provides detailed examples, case studies and step-by-step analytical solutions to relevant problems using popular computational software
Exploring how to apply in vitro/in vivo correlations for controlled release dosage forms, Bioavailability of Drug Delivery Systems: Mathematical Modeling clearly elucidates this complex phenomena and provides a guide for the respective mathematical modeling. The book introduces mathematical modeling methods for calculating the profiles of plasma le
Numerical analysis of matter transfer is an area that pharmacists find difficult, but which is a technique frequently used in preparing controlled drug release and oral dosage forms. A practical guide which explains how to carry out the numerical analysis of matter transfer - a vital process when examining the formulation of oral dosage forms with controlled drug release. The author models the process of drug delivery using numerical analysis and computerization.
Since the earliest dosage forms to modern drug delivery systems, came a great development and growth of knowledge with respect to drug delivery. Strategies to Modify the Drug Release from Pharmaceutical Systems will address principles, systems, applications and advances in the field.It will be principally a textbook and a reference source of strategies to modify the drug release. Moreover, the characterization, mathematical and physicochemical models, applications and the systems will be discussed. Addresses the principles, systems, applications and advances in the field of drug delivery Highlights the mathematical and physicochemical principles related to strategies Discusses drug release and its possible modifications
Development of new galenic devices needs series experiments with variation of number parameters. For industrial, it's a lost in time and money. Food and Drug Administration initiated since several years, Process Analytical Technology (PAT) as a tool to analyze and control pharmaceutical process. These tools can be helpful to determine drug release mechanism and allow application of mathematical model to predict drug release kinetics. One objective of this work is to develop a mechanistically realistic mathematical model allowing for the quantification of vitamin release from Compritol 888 (glyceryl dibehenate NF)-based matrix tablets, prepared either by direct compression or via hot-melt extrusion/grinding/compression. Nicotinic acid has been used as highly soluble drug in surrounding medium. Dissolution studies show vitamin release rates increased with increasing initial niacin content, due to the increased matrix porosity upon vitamin depletion. In all cases, niacin release from tablets prepared via hot-melt extrusion was slower than from tablets prepared by direct compression, due to more intense embedding of the vitamin within the lipid. Importantly, a numerical model based on Fick's law of diffusion and considering the co-existence of dissolved and non-dissolved vitamin could successfully be used to quantify vitamin release from both types of tablets, irrespective of the initial niacin loading and tablet size. In-silico simulations can be very helpful to accelerate product optimization of Compritol 888-based matrices, saving development time and costs. For multiparticulates systems, and more again for coated forms, mathematical models are more complexes. In this goal, development of new tools to characterize devices is primordial. Technology Terahertz offers an interesting potential. This technique can be used to detect difference in size and uniformity for polymeric film from multilayer pellets of 1 mm diameter. Pellets consisting of a sugar starter core and a metoprolol succinate layer were coated with a Kollicoat® SR: Kollicoat® IR polymer blend. Pellets with several coating thickness are studied. No drug layer thickness difference between batches was observed, and the average coating thicknesses were 46 μm, 71 μm and 114 μm, for the different batches. Terahertz results compared with experimental data from dissolution methods, allow predicting coating thickness results correlated with the subsequent drug release behavior. Multiparticulates systems have important interest: they allow avoiding "dose dumping". Dose dumping is described as an unintended, rapid drug release in a short period of time of the entire amount or a significant fraction of the drug contained in a modified release dosage form (Meyer, 2005). This phenomenon can be observed in the case of ethylcellulose-based devices in presence with ethanol rich-media. Recently, ethylcellulose:guar gum blend have been reported to provide ethanol-resistant drug release kinetics from coated dosage forms. Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. These granules show no change in drug release profiles upon contact with medium containing 40% of ethanol (v/v). This is because the ethanol insoluble guar gum effectively avoids undesired ethylcellulose dissolution in ethanol-rich bulk fluids. However, so far the importance of crucial formulation parameters, including the minimum amount of guar gum to be incorporated and the minimum required guar gum viscosity, remains unclear. It was found that more than 5% guar gum (referred to the total polymer content) must be incorporated in the film coating and that the apparent viscosity of a 1% aqueous guar gum solution must be greater than 150 cPs to provide ethanol-resistance. [...].
Demand for better reliability from drug delivery systems has caused designers and researchers to move away from trial-and-error approaches and toward model-based methods of product development. Developing such models requires cross-disciplinary physical, mathematical, and physiological knowledge. Combining these areas under a single cover, Understanding Drug Release and Absorption Mechanisms builds a firm understanding ofall elements needed to conceive, build, and implement successful models of drug release. Written by experts with broad industrial and academic experience, this book discusses the underlying physical principles, shows how to build mathematical models based on these principles, and finally compares the resulting models with experimental results. The authors begin by introducing the basics of modeling, physiological details of gastrointestinal and dermal absorption pathways, rheology, mass transport and thermodynamics, dissolution and partitioning, as well as size effects on the dissolution of crystallites. From this baseline, the authors explore applications in drug release from various delivery systems, specifically matrix systems, microemulsions, and permeability through membranes. Working systematically from theory to working models, Understanding Drug Release and Absorption Mechanisms: A Physical and Mathematical Approach demonstrates the steps involved in designing, building, and implementing realistic and reliable models of drug release without unrealistically simplifying the theoretical parameters.
This will be a substantial revision of a good selling text for upper division/first graduate courses in biomedical transport phenomena, offered in many departments of biomedical and chemical engineering. Each chapter will be updated accordingly, with new problems and examples incorporated where appropriate. A particular emphasis will be on new information related to tissue engineering and organ regeneration. A key new feature will be the inclusion of complete solutions within the body of the text, rather than in a separate solutions manual. Also, Matlab will be incorporated for the first time with this Fourth Edition.
[Truncated abstract] In this thesis we develop various numerical tools for estimating unknown parameters that characterise the diffusion property of a polymeric drug device in controlled drug delivery. Two types of fluid systems are considered in this work: the rotating fluid system and the flow-through fluid system. Based on the consideration of effects from the initial burst and boundary layer phenomena, three mathematical models are developed for the parameter estimation problem. They are the basic model (BM), initial burst model (IB) and boundary layer model (BL). The latter two models can also be combined to form the initial burst and boundary layer model (IB+BL). In these models, up to four unknown parameters need to be determined. These are the diffusion coefficient in the initial burst phase, diffusion coefficient after the initial burst, width of the boundary layer and the time of the initial burst. We first develop analytical solutions for the diffusion process of a drug from a spherical device to a finite external volume. In these solutions, we assume that the container of the system is spherical and concentric with the spherical device. The formula for the ratio of the mass released in a given time interval and the total mass released in infinite time is also derived for both BM and IB models. We then propose an optimisation approach to the estimation of the parameters based on a nonlinear least-squares method and the developed analytical solutions. A new observer approach method is developed for the parameter estimation problems. In this approach, we construct estimators for the unknown effective diffusion coefficients characterising the diffusion process of a drug release device using a combination of state observers from the area of adaptive control and the developed drug diffusion models. We show that the constructed systems are asymptotically stable and the estimators converge to the exact diffusion coefficients. An algorithm is proposed to recursively compute the estimators using a given time series of a release profile of a device. The numerical results show that this approach is much faster than the conventional least squares method when applied to the test problems. We then present a full numerical approach to the estimation of effective diffusion coefficients of drug diffusion from a device into a container in a flow-through fluid system. Compared to the rotating fluid system considered earlier, this system has a source and a sink condition due to a fluid flowing through the system at a constant rate. In this approach we first formulate the drug delivery problem as an initial boundary value problem containing the diffusion equation. We then propose a continuous nonlinear least-squares problem containing the system as a constraint to estimate the unknown parameters. The nonlinear optimisation problem is discretised by applying a finite volume scheme in space and an implicit time stepping scheme to the equation system, yielding a finite-dimensional nonlinear least-squares problem. Finally, we extend the full numerical technique to three dimensions for estimating effective diffusion coefficients of drug release devices in both rotating and flow-through fluid systems. The 3-dimensional full numerical technique is crucial for solving the parameter estimation problems in their real 3D geometries...