Numerical methods for the estimation of effective diffusion coefficients of 2D controlled drug delivery systems

We present a numerical approach to the estimation of effective diffusion coefficients and other unknown parameters determining the diffusion process of a drug delivery device, based on experimental data. This approach is to formulate the estimation problem as a nonlinear least-squares problem subject to some constraints including a partial differential equation (PDE) system. Numerical algorithms are developed for both of the solution of the optimization problem and the discretization of the PDE system. To show the usefulness of the methods, numerical experiments are performed using some laboratory observed data. The numerical results show that the methods are accurate and reliable.     

A probability-based method for calculating effective diffusion coefficients of composite media

A probability-based method is proposed for calculating the concentration of chloride at specified points of deterministic and random heterogeneous microstructures. The method, referred to as local method, is used to calculate effective diffusion coefficients of composite media. The effective diffusion coefficient of a heterogeneous material specimen is defined as the diffusion coefficient of a fictitious homogeneous specimen with the same global properties as those of the original specimen. The local method is based on properties of diffusion processes and Itô’s formula; it is simple to code, always stable, accurate and suitable for parallel computing. We use the method to calculate effective diffusion coefficients of a material specimen with a deterministic diffusivity field and a random heterogeneous mortar specimen calibrated to an experiment reported in Ref. Caré (2003) [11].     

Interactive mixture as a rapid drug delivery system

The effectiveness of an interactive mixture as a rapid drug delivery system is compared with that of a solid dispersion. The influences of drug load, particle size, and crystallinity of these test systems are investigated. The interactive mixtures and solid dispersions were prepared from polyethylene glycol (PEG) 3350 and hydrophobic nifedipine drug by means of physical mixing and melting methods, respectively. The formed products were subjected to drug particle size and crystallinity analyses, and dissolution tests. In comparison with the interactive mixtures, the solid dispersions with low drug load were more effective as a rapid drug delivery system, as the size of a given batch of drug particles was markedly reduced by the molten PEG 3350. The rate and extent of drug dissolution were mainly promoted by decreasing effective drug particle size. However, these were lower in the solid dispersions than in the interactive mixtures when a high load of fine drug particles was used as the starting material. This was attributed to drug coarsening during the preparation of the solid dispersion. Unlike solid dispersions, the interactive mixtures could accommodate a high load of fine drug particles without compromising its capacity to enhance the rate and extent of drug dissolution. The interactive mixture is appropriate for use to deliver a fine hydrophobic drug in a formulation requiring a high drug load.     

Estimation of diffusion coefficients and a plausible identification of species from one-dimensional Liesegang-ring formations in multicomponent systems

Liesegang-ring phenomenon has been explained for two-component systems by many workers. In this paper an attempt has been made to extend the theory to three-component systems. It is observed that two types of rings are formed consisting of two types of species. The experimental observations verify the validity of the proposed theory. This theory can also be extended to multicomponent systems.     

Physical characterization of polymer electrolytes as novel iontophoretic drug delivery devices

Polymer electrolytes are solidlike materials formed by dispersing a salt at the molecular level in a high molecular weight polymer such as poly(ethylene oxide) (PEO). They have been extensively studied for use in electrochemical applications such as batteries and display devices. This paper considers a novel application of polymer electrolytes as the basis of iontophoretic drug delivery systems. Polymer electrolyte films were cast from solutions of PEO and various drug salts using either water or an acetonitrile/ethanol mixture as the solvent. These films were characterized by variable-temperature polarizing microscopy (VTPM), differential scanning calorimetry (DSC), and alternating current (AC) impedance analysis. The films were around 100-μm thick and mechanically strong; the optical and thermal methods provided evidence that the polymer electrolytes had crystalline and amorphous phases, although some drugs may exist in films as nanodispersions. The amorphous phase is important as ions have greater mobility in this phase and therefore allow a current to be passed when the material is incorporated into a device such as one suitable for drug delivery by iontophoresis. The AC impedance analysis showed that the conductivity of the films varied between 10^-6 and 10^-3 S cm^-1, depending on the salt, casting solvent, and temperature. Two drugs in particular were shown to be promising candidates in these systems: lidocaine hydrochloride and lithium chloride.     

石墨烯基药物传输系统结合强度和药物扩散的分子动力学研究

通过在石墨烯片层上分别搭载抗癌药物分子CE6、DOX、MTX、SN38,构建多种石墨烯-药物分子复合体系。然后通过分子动力学模拟考察石墨烯片层大小、药物分子的种类、数目以及搭载方式对复合体系结合强度和药物分子扩散的影响。计算表明,石墨烯片的形变对石墨烯和药物分子的结合有决定作用。石墨烯片的边界对药物分子的扩散有限制作用;相比单面搭载药物分子,双面搭载通常会延缓药物分子的扩散。     

Novel drug delivery system for captopril

Abstract

It is known that drug substances showing no difference in absorbance along the whole gastro-intestinal (GI) tract are suitable for SR-formulations with an extended release characteristic. However, a decrease in bioavailability from proximal to distal parts of the gut may be suited for a limited retard effect. In this investigation, attempts have been made to design a suitable delivery system for captopril which is poorly bio-available from the alkaline regions of the GI-tract. The principles of ‘Bioadhesion’ as well as ‘Gastric Floating Systems’ are utilized in this study.     

Novel drug delivery system for captopril

It is known that drug substances showing no difference in absorbance along the whole gastro-intestinal (GI) tract are suitable for SR-formulations with an extended release characteristic. However, a decrease in bioavailability from proximal to distal parts of the gut may be suited for a limited retard effect. In this investigation, attempts have been made to design a suitable delivery system for captopril which is poorly bio-available from the alkaline regions of the GI-tract. The principles of 'Bioadhesion' as well as 'Gastric Floating Systems' are utilized in this study.     

Porous pellets as drug delivery system

Background: Multiparticulate drug delivery systems, such as pellets, are frequently used as they offer therapeutic advantages over single-unit dosage forms. Aim: Development of porous pellets followed by evaluation of potential drug loading techniques. Method: Porous microcrystalline pellets were manufactured and evaluated as drug delivery system. Pellets consisting of Avicel PH 101 and NaCl (70%, w/w) were prepared by extrusion/spheronization. The NaCl fraction was extracted with water and after drying porous pellets were obtained (33.2% porosity). Immersion of the porous pellets in a 15% and 30% (w/v) metoprolol tartrate solution, ibuprofen impregnation via supercritical fluids and paracetamol layering via fluidized bed coating were evaluated as drug loading techniques. Results: Raman spectroscopy revealed that immersion of the pellets in a drug solution and supercritical fluid impregnation allowed the drug to penetrate into the porous structure of the pellets. The amount of drug incorporated depended on the solubility of the drug in the solvent (water or supercritical CO₂). Drug release from the porous pellets was immediate and primarily controlled by pure diffusion. Conclusion: The technique described in this research work is suitable for the production of porous pellets. Drug loading via immersion the pellets in a drug solution and supercritical fluid impregnation resulted in a drug deposition in the entire pellet in contrast to fluid bed layering where drugs were only deposed on the pellet surface.     

Solid self-microemulsifying drug delivery system of ritonavir

Context: Ritonavir (RTV) is a human immunodeficiency virus (HIV) protease inhibitor (PI) with activity against HIV, practically insoluble in water and recommended to co-administer as a booster along with other HIV-PI to enhance their bioavailability. The present study is aimed to enhance the dissolution and oral bioavailability of water-insoluble RTV using the Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS).

Objective: To enhance the dissolution and oral bioavailability of water-insoluble RTV using the S-SMEDDS.

Material and methods: Liquid SMEDDS (L-SMEDDS) of RTV was formulated by the optimizing ratio of Imwitor 988 (Oil), Cremophor EL and Cremophor RH 40 (1:1) (surfactant) and Capmul GMS K-50 (cosurfactant). Optimized L-SMEDDS showed improved dissolution rate of RTV compared to pure RTV powder. Optimized L-SMEDDS of RTV was adsorbed on Neusilin US-2 using a simple wet granulation technique with selected excipients to convert it into S-SMEDDS.

Results and discussion: Optimized L-SMEDDS showed an improved dissolution rate of RTV compared to pure RTV powder. Droplet size of resultant microemulsion of L-SMEDDS of RTV was observed between 16 and 22 nm and independent of pH (i.e. 0.1 N HCl and water). Conversion of the crystalline form of RTV to amorphous form was observed when RTV formulated into SMEDDS form as per X-ray diffraction study. In vitro dissolution study, stability study of optimized S-SMEDDS confirmed the formulation of stable and improved dissolution of RTV. Relative bioavailability of RTV was determined in male Wistar rats and pharmacokinetic parameters were calculated by the comparison of optimized S-SMEDDS versus aqueous suspension of RTV. S-SMEDDS improved the plasma profile in terms of maximum plasma concentration (C_max), and area under curve (AUC_0–24h), which is almost twofolds higher than the aqueous suspension of RTV.

Conclusion: S-SMEDDS tablet of RTV was formulated successfully by adsorbing optimized L-SMEDDS of RTV on Neusilin-US2® as a potential carrier with enhanced solubility and relative oral bioavailability compared to pure RTV by twofolds.     

Polymers for mucoadhesive drug delivery system: a current status

To overcome the relatively short gastrointestinal (GI) time and improve localization for oral controlled or sustained release drug delivery systems, bioadhesive polymers that adhere to the mucin/epithelial surface are effective and lead to significant improvement in oral drug delivery. Improvements are also expected for other mucus-covered sites of drug administration. Bioadhesive polymers find application in the eye, nose, and vaginal cavity as well as in the GI tract, including the buccal cavity and rectum. This article lays emphasis mainly on mucoadhesive polymers, their properties, and their applications in buccal, ocular, nasal, and vaginal drug delivery systems with its evaluation methods.     

The intra-vascular stent as a site-specific local drug delivery system

The current review focuses on utilization of a tubular structure (coated or uncoated, balloon expandable or self expanding) known as a “stent” for localized intravascular drug delivery. Emphasis of the review is on technologies currently employed for immobilization and coating for drug onto the stent prior to its placement in various lumen of the body. A brief discussion on stent design, comparison of angioplasty and coronary stenting, and market status complements the review for researchers new to this area.     

Hydroxybutyl chitosan thermo-sensitive hydrogel: a potential drug delivery system

Drug delivery mediated by hydrogel has shown great promise in controlled drug release field. We report here the development of a hydroxybutyl chitosan (HBC) thermo-sensitive gel to deliver doxorubicine hydrochloride (DOX·HCl) for cancer treatment. Concentrated HBC aqueous solution could transform into hydrogel within 30 s after injection under physiological temperature in non-chemical fashion. The properties of the HBC gels including chemical structure, surface morphology, and rheologic properties were studied. Gelation temperature and gelation time of HBC could be adjusted by HBC concentrations. The gel erosion rate in vivo was faster than solubilization rate in vitro. The mild inflammatory response caused by implantation of the hydrogel was acceptable. The DOX·HCl (1 mg/ml) loaded HBC gels displayed slow release rates that were independent of the HBC concentration, and significantly reduced viability of 4T-1 cells compared with the HBC gels after 1 day incubation. These results indicate that thermo-sensitive HBC hydrogels have promising potential as an injectable drug carrier for pharmaceutical applications.     

Design and evaluation of a self-microemulsifying drug delivery system for apigenin

Objective of this study was to prepare, characterize and evaluate a self-microemulsifying drug delivery system (SMEDDS) with the aim to improve the solubility and dissolution of apigenin. Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of apigenin loaded SMEDDS was optimized by a simplex lattice experiment design. The optimal formulation of SMEDDS obtained was comprised of 60% Cremophor^®EL, 30% Transcutol^®HP and 10% Capryol? 90. The equilibrium solubility of apigenin in SMEDDS was about 15 mg/g, and it could increase the solubility of apigenin in water for about 7500 folds. Apigenin loaded SMEDDS could turn into microemulsion when diluted with distilled water and the droplets were spherical under transmission electron microscope (TEM), the average particle size was 17.1 nm and zeta potential ?5.18 mV. In vitro dissolution studies showed about 95% of apigenin was released within 10 min. All of the results showed that SMEDDS could enhance the solubility and dissolution of apigenin, and would be a potential carrier to improve the oral absorption of apigenin, a poorly water soluble drug.     

Estimation of Fourier coefficients

It is shown that the maximum-likelihood estimation or robust estimation of the Fourier coefficients may be preferable to Fourier transformation if the noise contains outliers or is otherwise not normally distributed. The reason is that, in that case, these estimators produce Fourier coefficient estimates and, therefore, system parameter estimates having a smaller variance     

In vitro and in vivo performance of a multiparticulate pulsatile drug delivery system

The objective of this study was to investigate the in vitro and in vivo drug release performance of a rupturable multiparticulate pulsatile system, coated with aqueous polymer dispersion Aquacoat® ECD. Acetaminophen was used as a model drug, because in vivo performance can be monitored by measuring its concentration in saliva. Drug release was typical pulsatile, characterized by lag time, followed by fast drug release. Increasing the coating level of outer membrane lag time was clearly delayed. In vitro the lag time in 0.1 N HCl was longer, compared to phosphate buffer pH 7.4 because of ionisable ingredients present in the formulation (crosscarmelose sodium and sodium dodecyl sulphate). In vitro release was also longer in medium with higher ion concentration (0.9% NaCl solution compared to purified water); but independent of paddle rotation speed (50 vs.100 rpm). Macroscopically observation of the pellets during release experiment confirms that the rupturing of outer membrane was the main trigger for the onset of release. At the end of release outer membrane of all pellets was destructed and the content completely released.

However, pellets with higher coating level and correspondingly longer lag time showed decreased bioavailability of acetaminophen. This phenomenon was described previously and explained by decreased liquid flow in the lower part of intestine. This disadvantage can be considered as a limitation for drugs (like acetaminophen) with high dose and moderate solubility; however, it should not diminish performance of the investigated system in principle.     

Thermodynamic analysis of diffusion coefficients

An analysis is presented of the process of diffusion of a multicomponent fluid through a solid porous medium. It is shown that there are conditions in which the diffusion fluxes vanish, and for which the multicomponent system may be replaced by a one-component system in aerodynamic problems.