Diffusion Coefficient Of Drug Research Articles

Quantifying diffusion-controlled drug release from spherical devices using Monte Carlo simulations

We numerically calculate drug release profiles from simple spherical devices using Monte Carlo simulations, when diffusion is the dominant release mechanism. Release curves are accurately described by the stretched exponential function, also known as the Weibull function. The dependence of the two stretched exponential parameters on the size of the spherical device and the drug diffusion coefficient is investigated and simple analytical relations are provided. Release kinetics does not depend on the initial drug concentration. The obtained results are compared with predictions derived from the analytical solution of Fick's second law of diffusion.

β-Cyclodextrin inclusion complex: preparation, characterization, and its aspirin release in vitro

In this work, the optimal clathration condition was investigated for the preparation of aspirin-β-cyclodextrin (Asp-β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box-Behnken design with a total of 17 experimental runs was used. The Asp-β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between -COOH group of Asp and O-H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.

Saccade movements effect on the intravitreal drug delivery in vitreous substitutes: a numerical study

In this study, the distributions of intravitreal injected drugs in post-vitrectomy human eyes, which are subjected to periodic saccade movements, are investigated. The computational model for the vitreous cavity of human eye is a sphere with one side truncated by the eye lens. A dynamic mesh technique was used to model the eye motion and the unsteady 3-D forms of continuity; Navier-Stokes and concentration transport of drug equations were solved numerically. The numerical model was validated earlier for the vitreous liquid flow field. The predicted drug concentration for idealized geometry was compared with the available analytic solution and excellent agreement was observed. The validated computer model was then used to simulate a real vitreous cavity filled with Balanced Salt Solution or aqueous humor as a vitreous substitute in order to obtain distribution of drugs in the post-vitrectomy eyes or liquefied vitreous. Additionally, effects of locations of drug injection, drug diffusion coefficients and saccade amplitude on the drug distribution and its uniformity were investigated. Although the earlier findings in the literature reported a day or a week as a needed time for drug uniform distribution in the vitreous substitutes, the present work depicts that saccade movements augment the transport of the drug in a way that the uniformity of the drug distribution can be achieved in a matter of minutes. Furthermore, in a vitreous cavity subjected to the saccade movements, the diffusion coefficient of drugs does not significantly affect their distribution after a few minutes. Even the injection location does not matter as uniform distribution is achieved after some time.

Influence of Drug Distribution and Solubility on Release from Geopolymer Pellets—A Finite element Method Study

This study investigates the influence of drug solubility and distribution on its release from inert geopolymer pellets of three different sizes (1.5 × 1.5, 3 × 6, and 6 × 6 mm), having the same geopolymer composition and containing highly potent opioid fentanyl, sumatriptan, theophylline, or saccharin. Scanning electron microscopy, nitrogen sorption, drug solubility, permeation, and release experiments were performed, and estimates of the drug diffusion coefficients and solubilities in the geopolymer matrix were derived with the aid of finite element method (FEM). FEM was further employed to investigate the effect of a nonuniform drug distribution on the drug release profile. When inspecting the release profiles for each drug, it was observed that their solubilities in the geopolymer matrix imposed a much greater influence on the drug release rate than their diffusion coefficients. Concentrating the initial drug load in FEM into nonuniformly distributed drug regions inside the matrix created drug release profiles that more closely resembled experimental data than an FEM-simulated uniform drug distribution did. The presented FEM simulations and visualization of drug release from geopolymers under varying initial and dynamic conditions should open up for more systematic studies of additional factors that influence the drug release profile from porous delivery vehicles.

The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.

A novel mathematical model considering change of diffusion coefficient for predicting dissolution behavior of acetaminophen from wax matrix dosage form

From wax matrix dosage forms, drug and water-soluble polymer are released into the external solvent over time. As a consequence, the pore volume inside the wax matrix particles is increased and the diffusion coefficient of the drug is altered. In the present study, we attempted to derive a novel empirical mathematical model, namely, a time-dependent diffusivity (TDD) model, that assumes the change in the drug's diffusion coefficient can be used to predict the drug release from spherical wax matrix particles. Wax matrix particles were prepared by using acetaminophen (APAP), a model drug; glyceryl monostearate (GM), a wax base; and aminoalkyl methacrylate copolymer E (AMCE), a functional polymer that dissolves below pH 5.0 and swells over pH 5.0. A three-factor, three-level (33) Box–Behnken design was used to evaluate the effects of several of the variables in the model formulation, and the release of APAP from wax matrix particles was evaluated by the paddle method at pH 4.0 and pH 6.5. When comparing the goodness of fit to the experimental data between the proposed TDD model and the conventional pure diffusion model, a better correspondence was observed for the TDD model in all cases. Multiple regression analysis revealed that an increase in AMCE loading enhanced the diffusion coefficient with time, and that this increase also had a significant effect on drug release behavior. Furthermore, from the results of the multiple regression analysis, a formulation with desired drug release behavior was found to satisfy the criteria of the bitter taste masking of APAP without lowering the bioavailability. That is to say, the amount of APAP released remains below 15% for 10min at pH 6.5 and exceeds 90% within 30min at pH 4.0. The predicted formulation was 15% APAP loading, 8.25% AMCE loading, and 400μm mean particle diameter. When wax matrix dosage forms were prepared accordingly, the predicted drug release behavior agreed well with experimental values at each pH level. Therefore, the proposed model is feasible as a useful tool for predicting drug release behavior, as well as for designing the formulation of wax matrix dosage forms.

Novel Dual-Control Poly( N -Isopropylacrylamide- Co -Chlorophyllin) Nanogels for Improving Drug Release

How to overcome insufficient drug release is an important issue in the drug-delivery system. Here, a novel temperature and UV dual-control poly(N-isopropylacrylamide [PNIPAM]-co-chlorophyllin) nanogel was prepared via the surfactant-free emulsion polymerization. The introduction of hydrophilic chlorophyllin to the PNIPAM chain backbone led to a narrow size of poly[NIPAM-co-CHLN nanogel (D ∼180 nm) confirmed by atomic force microscopy and transmission electron microscopy. This nanogel had a lower critical solution temperature (∼35°C), observed by dynamic laser light scattering. After the phase transition, the size under UV light (50 nm) was much smaller than that induced by temperature (90 nm). The inhomogeneous collapse was attributed to the temperature-gradient generated from the gel surface to the core with a surrounding dense PNIPAM layer. The obstacles that strongly inhibited 5-fluorouracil release was successfully overcome by light irradiation via a large drug diffusion coefficient. Consequently, the novel dual functional nanogel is potent for improving the drug-release profile.

Effects of crosslinking ratio, model drugs, and electric field strength on electrically controlled release for alginate-based hydrogel

The drug release characteristics of calcium alginate hydrogels, (Ca-Alg), under an electric field assisted transdermal drug delivery system were systematically investigated. The Ca-Alg hydrogels were prepared by the solution-casting using CaCl(2) as a crosslinking agent. The diffusion coefficients and the release mechanism of the anionic model drugs, benzoic acid and tannic acid, and a cationic model drug, folic acid on the Ca-Alg hydrogels were determined and investigated using a modified Franz-Diffusion cell in an MES buffer solution of pH 5.5, at a temperature of 37°C, for 48 h. The influences of the crosslinking ratio, -the mole of the crosslinking agent to the mole of the alginate monomer-mesh size, model drug size, drug charge, electric field strength, and electrode polarity were systematically studied. The drug diffusion coefficient decreased with an increasing crosslinking ratio and drug size for all of the model drugs. The drug diffusion coefficient is precisely controlled by an applied electric field and the electrode polarity depending on the drug charge, suitable for a tailor-made transdermal drug delivery system.

Formulation design space analysis for drug release from swelling polymer tablets

Abstract A model is presented which can be used to simulate polymer swelling and drug release from tablets using a combination of the Discrete Element Method (DEM) and solving mass transfer over an unstructured grid formed by the DEM elements. This work extends a recently developed single-component swelling and dissolution model by incorporating an extra component (drug) that can be either homogeneously or heterogeneously dispersed within the tablet. Parametric studies were conducted on some of the key parameters which affect drug release, namely the drug distribution, maximum swelling ratio of the polymer and the drug–polymer diffusivity dependence. The drug heterogeneity study showed that burst release (i.e. dose-dumping) increased as drug loading increased since the polymer could not form a gel layer to surround the tablet but the time taken for 99% drug release was not significantly different when compared to the homogeneous case. The maximum swelling ratio study showed that drug release could be limited either by its diffusion through the dense polymer network or the thickness of the gel layer. It was shown that a minimum release time exists where the drug diffusivity and gel layer thickness would give fast drug release. The drug–polymer diffusivity study showed that drug release could become closer to zero-order the more dependent it was on polymer concentration (as the drug would diffuse very slowly until the polymer was very dilute) compared to more Fickian release if the drug's diffusion coefficient was not as dependent on polymer concentration. Simulated drug release was compared against experiments where tablets containing 10% or 60% w/w nicotinamide and HPMC k100LV were dissolved and imaged using a combination of Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopic imaging and downstream monochromatic UV/Visible detection. The FTIR images and extracted concentration profiles showed that water ingress and drug release were faster for the 60% nicotinamide tablet and that the model could predict drug release using only pure component parameters and the respective mass fractions of drug.

Evaluation of the Predicted Time–Concentration Profile of Serum Tulobuterol in Human after Transdermal Application

We proposed an in vitro/in vivo/in silico method for evaluating the clinical performance of matrix type transdermal therapeutic systems (TTSs). This method is based on the following four approaches: (1) drug release experiment, (2) in vitro penetration experiment using excised hairless mouse skin, (3) clinical pharmacokinetic study, and (4) mathematical model for evaluating the pharmacokinetic profile. The tulobuterol TTS was used as an example of a matrix type TTS in this study. The drug diffusion coefficient in the matrix device was calculated from the result of the release experiment. The drug diffusion coefficient and the partition coefficient in the skin were calculated from the results of in vitro skin penetration experiments where hairless mice and rats were used. Those parameters were used as substitutes of human. Further, these parameters were used for solving the governing partial differential equation on skin penetration. The time profiles of the serum concentration in human after applying the tulobuterol TTS were predicted and compared with the clinical data. The predicted profiles obtained from the data of hairless mice reproduced the influence of drug depletion adequately and well agreed with the clinical data, while those from the data of rats differed clearly in the initial rise. This method is useful for prediction of pharmacokinetic profiles of TTSs.

Diffusion of drugs in hydrogels based on (meth)acrylates, poly(alkylene glycol) (meth)acrylates and itaconic acid

The aim of this paper is to propose equations for the diffusion of drugs for investigated drug/hydrogel systems using the parameters affecting the transport of drug through poly(2-hydroxyethyl methacrylate/itaconic acid) (P(HEMA/IA)), poly(2-hydroxyethyl acrylate/itaconic acid) (P(HEA/IA)), and poly(2-hydroxyethyl methacrylate/poly(alkylene glycol) (meth)acrylates) (P(HEMA/BIS)) copolymeric hydrogels. Different monomer types, as well as the variable content of some components in hydrogel composition (the amount of ionizable comonomer (IA) and different type of nonionic poly(alkylene glycol) (meth)acrylates), ultimately defined the pore size available for drug diffusion. The hydrogels synthesized ranged from nonporous to microporous, based on the classification in accordance to the pore size, and could be classified as hydrogels that contain ionic groups and hydrogels without ionic groups. The drugs selected for this study are bronchodilators-theophylline (TPH), fenethylline hydrochloride (FE), and antibiotic-cephalexin (CEX). Results of in vitro drug release tests defined the release systems based on the drug type, as well as the type of hydrogel used. The diffusion coefficient of drugs and the restriction coefficient, , defined as the ratio of solute to ?pore? radius (rs/r? ) that describes the ease of drug release from the gels, were used as factors that govern the release process.

Prediction of the mutual diffusion coefficient for controlled drug delivery devices

Diffusion coefficients of drugs in polymers were predicted using models based on modified free volume theory of diffusion. The descriptors used were chosen to uniquely relate the structure with desired properties. Model parameters were obtained using quantitative structure property relationships (QSPRs) developed using multiple linear regression and artificial neural networks with Bayesian regularization. Viability of the approach was established by predicting solvent diffusion coefficient in polymer for four polymer–solvent systems (polystyrene–toluene, polyvinylacetate–toluene, polystyrene–ethylbenzene and polystyrene–tetrahydrofuran) and comparing with the experimental values. The model was subsequently used on three polymer–drug systems (paclitaxel–polycaprolactone, hydrocortisone–polyvinylacetate and procaine–polyvinylacetate). The predicted diffusion coefficient for Paclitaxel–Polycaprolactone was used to study the release of Paclitaxel from Polycaprolactone under perfect sink condition. It is envisaged that the proposed model could be used in a reverse engineering framework to select polymers for designing the optimally controlled drug release devices.

Development of a biodegradable nanoparticle platform for sildenafil: Formulation optimization by factorial design analysis combined with application of charge-modified branched polyesters

Biodegradable nanoparticles have gained tremendous attraction as carriers for controlled drug delivery to the lung. Despite numerous advances in the field, e.g. development of suitable methods for pulmonary administration of polymeric nanoparticles, a sufficient association of the therapeutic agent with the carrier system as well as drug release in a controlled fashion remain considerable challenges. Hence, this study examines the optimization of biodegradable sildenafil-loaded nanoparticle formulations intended for aerosol treatment of pulmonary hypertension.A factorial design analysis was employed to identify the important experimental factors involved in the preparation of nanoparticles by the solvent evaporation technique. The effect of tailored charge-modified branched polyesters on drug loading and in vitro drug release from nanoparticles was also evaluated. Moreover, colloidal stability of obtained nanoparticles was assessed, and stabilization of nanoparticles by lyophilization was accomplished without additional excipients.Essential experimental factors were identified and optimized to allow the preparation of nanoparticles composed of linear polyesters with a sildenafil content of ~5wt.%. The in vitro drug release profile from these nanoparticles demonstrated a sustained release of sildenafil over ~90min. Application of charge-modified branched polyesters enhanced the drug content in nanoparticles and drug release profile, according to the charge-density present in the employed polymer. Accordingly an increase in drug loading by a factor of ~1.4, a prolonged drug release profile from nanoparticles over ~240min was achieved. Sildenafil release from nanoparticles made of linear and charge-modified branched polyesters was governed by a diffusion process. The obtained drug diffusion coefficients were decreased as the charge-density present in the applied polymer was increased, which promotes the strategy to improve drug loading and release rates by electrostatic interactions between polymer and drug. In addition, nanoparticles showed high colloidal stability in different media of importance for pulmonary application and were successfully stabilized by lyophilization.In conclusion, optimization of the nanoparticle preparation process together with the application of tailored polymeric materials facilitated the synthesis of promising drug carriers for sildenafil that permit a novel treatment modality for severe pulmonary hypertension.

Drug diffusion from polymeric delivery devices: a problem with two moving boundaries

An existing model for solvent penetration and drug release from a spherically shaped polymeric drug delivery device is revisited. The model has two moving boundaries, one that describes the interface between the glassy and rubbery states of the polymer, and another that defines the interface between the polymer ball and the pool of solvent. The model is extended so that the nonlinear diffusion coefficient of drug explicitly depends on the concentration of solvent, and the resulting equations are solved numerically using a front fixing transformation together with a finite difference spatial discretisation and the method of lines. We present evidence that our scheme is much more accurate than a previous scheme. Asymptotic results in the small time limit are presented, which show how the use of a kinetic law as a boundary condition on the innermost moving boundary dictates qualitative behaviour, the scalings being very different to the similar moving boundary problem that arises from modelling the melting of an ice ball. The implication is that the model considered here exhibits what is referred to as non-Fickian or Case~II diffusion which, together with the initially constant rate of drug release, has certain appeal from a pharmaceutical perspective. References G. Astarita and G. C. Sarti. A class of mathematical models for sorption of swelling solvents in glassy polymers. Polymer Engineering and Science., 18, 1978, 388--395. doi:10.1002/pen.760180510. D. S. Cohen and T. Erneux. Free boundary problems in controlled release pharmaceuticals. I: Diffusion in glassy polymers. SIAM Journal on Applied Mathematics., 48, 1988, 1451--1465. http://www.jstor.org/stable/2101759. D. S. Cohen and T. Erneux.. Free boundary problems in controlled release pharmaceuticals. II: Swelling-controlled release. SIAM Journal on Applied Mathematics., 48, 1988, 1466--1474. http://www.jstor.org/stable/2101760. T. Higuchi. Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences., 52, 1963, 1145--1149. doi:10.1002/jps.2600521210. J.-S. Lin, C.-C. Hwang, C.-M. Lin, and J.-Y. Lai. Solvent transport in spherical polymer-penetrant systems. Chemical Engineering Science., 56, 2001, 151--156. doi:10.1016/S0009-2509(00)00410-3. J.-S. Lin and Y.-L. Peng. Swelling controlled release of drug in spherical polymer-penetrant systems. International Journal of Heat and Mass Transfer., 48, 2005, 1186--1194. doi:10.1016/j.ijheatmasstransfer.2004.08.031. S. W. McCue, M. Hsieh, T. J. Moroney, and M. I. Nelson. Asymptotic and numerical results for a model of solvent-dependent drug diffusion through polymeric spheres. Submitted. B. Narasimhan and N. A. Peppas. Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier. Journal of Pharmaceutical Sciences., 86, 1997, 297--304. doi:10.1021/js960372z. F. A. Radu, M. Bause, P. Knabner, G. W. Lee, and W. C. Friess. Modeling of drug release from collagen matrices. Journal of Pharmaceutical Sciences, 91, 2002, 964--972. doi:10.1002/jps.10098. J. Siepmann, K. Podual, M. Sriwongjanya, N. A. Peppas and R. Bodmeier. A new model describing the swelling and drug release kinetics from hydroxypropyl methylcellulose tablets. Journal of Pharmaceutical Sciences., 88, 1999, 65--72. doi:10.1021/js9802291. S. Kill and K. Dam-Johansen. Controlled drug delivery from swellable hydroxypropylmethylcellulose matrices: model-based analysis of observed radial front movements. Journal of Controlled Release., 90, 2003, 1--21. doi:10.1016/S0168-3659(03)00122-6. N. Wu, L.-S. Wang, D. C.-W. Tan, S. M. Moochhala, and Y.-Y. Yang. Mathematical modeling and in vitro study of controlled drug release via a highly swellable and dissoluble polymer matrix: polyethylene oxide with high molecular weights. Journal of Controlled Release., 102, 2005, 569--581. doi:10.1016/j.jconrel.2004.11.002.

Barium Ions Crosslinked Alginate and Sterculia Gum-Based Gastroretentive Floating Drug Delivery System for Use in Peptic Ulcers

The gastro-retentive drug delivery system is required to improve the bioavailability and therapeutic efficacy of the drugs used for the diseases associated with the stomach. Both sterculia gum and alginate enhance the repair of mucosal damage in the GI tract and pantoprazole is a therapeutic agent for GI tract ulcers. Ionotropic gelation of these polysaccharides for the release of pantoprazole will develop the double potential drug delivery systems. Therefore, in the present study, an attempt has been made to synthesize a gastro-retentive floating drug delivery system by simultaneous ionotropic gelation of alginate and sterculia gum using BaCl2 as a crosslinker. The beads have been characterized by SEMs, EDAX, and FTIR analysis. The swelling of beads has been carried out as a function of pH of the swelling media. In addition, in vitro release dynamics of an anti-ulcer model drug pantoprazole from drug-loaded beads in different release media have been carried out for the evaluation of the drug release mechanism and diffusion coefficients. Release of drug from beads occurred through a Fickian-type diffusion mechanism. The present drug delivery sytem may have a double potential, first due to the therapeutic importance of the sterculia–alginate-based polymer matrix and second, release of pantoprazole in a controlled and sustained manner.

Aqueous block copolymer–surfactant mixtures—Surface tension, DLS and viscosity measurements and their utility in solubilization of hydrophobic drug and its controlled release

The effects of sodium dodecyl sulfate (SDS) and dodecyl trimethylammonium bromide (DTAB) and polyoxyethylene (10) isooctyl phenyl ether (TX-100) as additives on the association characteristics of an amphiphilic tri-block copolymer P105 (E 37P 56E 37) were monitored by surface tension, dynamic light scattering and viscosity measurements at 303.15 and 313.15 K in water as well as in 200 mM sodium chloride aqueous solutions. The successive addition of surfactants resulted not only in the increase of critical micelle concentration (CMC) of the copolymer and also in CMC/ C 20 values indicating that the adsorption tendency of the copolymer–surfactant complexes at water/air interface is more than the association in the bulk. The experimental CMC data of binary mixtures were analyzed using regular solution theory to calculate the interaction parameter. The mixtures exhibited synergistic interaction behavior. The apparent hydrodynamic radius of copolymer micelles decreased drastically by the addition of surfactants and this destabilization effect has been attributed to the shift of copolymer micelle ↔ unimer equilibrium in favor of latter. Dexamethasone, a drug poorly soluble in aqueous media was solubilized into individual copolymer or copolymer–surfactants solutions followed by their loading onto agar agar hydrogels for its immobilization and dispersion. The drug release profiles were established and drug diffusion coefficients were calculated.

Influence of drug partition coefficient and pH value of sink solution on permeation from porous thick-walled ethyl cellulose microcapsules.

The permeation of barbitone sodium, benzoic acid, and salicylic acid from microcapsules into aqueous medium has been examined at different pH values. The apparent diffusion coefficients of drugs were linearly proportional to the ethyl cellulose/water partition coefficient of drugs, and the straight line parameters were dependent upon volume fractions of water-filled pores (i.e. capsule size), testifying to a previously proposed mechanism of drug permeation. The rate of drug permeation was also a function of the pH-value of the surrounding sink solution; the period of zero order release was longer at low pH because of the change of drug partition or solubility or both.

Methylprednisolone release from agar-Carbomer-based hydrogel: a promising tool for local drug delivery

AbstractA number of studies and works in drug delivery literature are focused on the understanding and modelling of transport phenomena, the pivotal point of a good scaffold design for tissue engineering. Accurate knowledge of the diffusion coefficient of an active drug plays a key role in the analysis, prediction of their kinetics and formulation of efficient drug delivery systems. In this work, the kinetics of the release of methylprednisolone from agar-Carbomer hydrogel were studied taking into consideration the different drug concentrations and clearances typically achieved in in vitro or in vivo tests. Starting from the experiments it is possible to model the transport phenomenon and to calculate the diffusion coefficient through the hydrogel matrix.

Comparison between nuclear magnetic resonance profiling and the source/sink approach for characterizing drug diffusion in hydrogel matrices

In controlled drug delivery, the drug diffusion coefficient in a given matrix is a key factor for predicting its release rate. In this work, we compare 31P nuclear magnetic resonance (NMR) profiling for obtaining the mutual-diffusion coefficient () of a drug in hydrogel with results obtained from conventional source/sink experiments. Despite the fact that NMR profiling is a powerful approach for measuring transport properties, it is rarely used for characterizing drug diffusion in gel matrices in pharmaceutical sciences. This work provides an illustration of the applicability of this technique and highlights its advantages for studying drug release systems. The comparison with results obtained from the source/sink experiment clearly establishes the validity of the NMR profiling approach. Alendronate was used as a model drug while curdlan, a gel-forming bacterial polysaccharide, served as a model biomaterial. The determined value (5.6 ± 0.3 × 10−10 m2/s) agrees with the one obtained from a conventional source/sink experiment (5.4 ± 0.5 × 10−10 m2/s). In addition, the alendronate self-diffusion coefficients in solution () and in the hydrogel () were measured on the same system using pulse-field gradient (PFG) 31P NMR. These supplementary parameters provided a more detailed characterization of the drug transport properties in the gel matrix.

Determination of diffusion coefficients of peptides and prediction of permeability through a porous membrane

The diffusion coefficient (D) of peptide and protein drugs needs to be determined to examine the permeability through biological barriers and to optimize delivery systems. In this study, the D values of fluorescein isothiocyanate (FITC)-labelled dextrans (FDs) and peptides were determined and the permeability through a porous membrane was discussed. The observed D values of FDs and peptides, except in the case of insulin, were similar to those calculated based on a relationship previously reported between the molecular weight and D of lower-molecular-weight compounds, although the molecular weight range was completely different. The observed D value of insulin was between the calculated values for the insulin monomer and hexamer. The permeability of poly-lysine and insulin through the membrane was determined and the observed values were compared with predicted values by using the relationship between molecular weight and D and an equation based on the Renkin function. The observed permeability of insulin through the membrane was between that of the predicted permeability for the insulin monomer and hexamer. For the permeation of insulin, the determination of D was useful for estimating the permeability because of the irregular relationship between molecular weight and D. The methodology used in this study will be useful for a more quantitative evaluation of the absorption of peptide and protein drugs applied to mucous membranes.