Underlying Release Mechanisms Research Articles

In-situ forming PLGA implants: Towards less toxic solvents

In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis treatment. The polymer is dissolved in a water-miscible solvent. The drug is dissolved or dispersed in this solution. Upon contact with aqueous body fluids, the solvent diffuses into the surrounding tissue and water penetrates into the formulation. Consequently, PLGA precipitates, trapping the drug. Often, N-methyl-2-pyrrolidine (NMP) is used as a water-miscible solvent. However, parenteral administration of NMP raises toxicity concerns. The aim of this study was to identify less toxic alternative solvent systems for in-situ forming PLGA implants. Various blends of polyethylene glycol 400 (PEG 400), triethyl citrate (TEC) and ethanol were used to prepare liquid formulations containing PLGA, ibuprofen (as an anti-inflammatory drug) and/or chlorhexidine dihydrochloride (as an antiseptic agent). Implant formation and drug release kinetics were monitored upon exposure to phosphate buffer pH 6.8 at 37 °C. Furthermore, the syringeability of the liquids, antimicrobial activity of the implants, and dynamic changes in the latter’s wet mass and pH of the release medium were studied. Importantly, 85:10:5 and 60:30:10 PEG 400:TEC:ethanol blends provided good syringeability and allowed for rapid implant formation. The latter controlled ibuprofen and chlorhexidine release over several weeks and assured efficient antimicrobial activity. Interestingly, fundamental differences were observed concerning the underlying release mechanisms of the two drugs: Ibuprofen was dissolved in the solvent mixtures and partially leached out together with the solvents during implant formation, resulting in relatively pronounced burst effects. In contrast, chlorhexidine dihydrochloride was dispersed in the liquids in the form of tiny particles, which were effectively trapped by precipitating PLGA during implant formation, leading to initial lag-phases for drug release.

The modified boundary layer mechanism for the release between polyimide film and poly(ether ketone ketone) thermoplastics

AbstractSticking between the thermoplastic polymer and metal tool is a crucial issue, as it determines whether the manufactured part can be ejected from the metal mold. Polyimide (PI) release films have been widely used in the processing of fiber‐reinforced thermoplastic polymer composites. Compared with other release mediums such as release agents, PI release film has a higher release efficiency. However, the underlying release mechanism is still not well understood which is essential to improve their performance further and reduce the cost. In this paper, poly(ether ketone ketone) (PEKK) polymer was melted and cooled down between two PI films. The surface morphologies and chemical compositions of the PI film and PEKK were characterized both before and after release using atomic force microscope, x‐ray photoelectron spectroscopy, contact angle measurements, and confocal microscopy. It showed that a thin PI layer was transferred from the PI release film to the PEKK surface during the release process. Based on these experimental results, a modified boundary layer mechanism is proposed as a hypothesis to describe the release mechanism of PI films. Our results give a fundamental understanding of how PI film works for the release of thermoplastics with high processing temperatures and may help to improve the performance and reduce the costs of existing PI films and may give guidance to the design of new release media.

Direct visualization of the drug release process of non-conductive polymeric implants via molecular imaging

Long-acting parenteral (LAP) implant has garnered the attraction as a drug delivery technique in recent years. Understanding the drug release process is critical for the study of underlying release mechanism. In this paper, we present a novel application of matrix-assisted laser desorption/ionization-mass spectrometry imaging (MADLI-MSI) for the direct visualization of the drug release process from non-conductive polymeric based LAP implants at molecular level. Custom-made sample holders were designed for LAP sample introduction in place of traditional conductive glass slides. The main technical obstacles of applying MALDI-MSI to study non-conductive materials are surface conductivity which can lead to charge build-up. In order to obtain homogeneous imaging of non-conductive sample surfaces, we developed a new sample surface treatment procedure, which is a critical control step to ensure the data reliability and accuracy in understanding kinetics of drug release process of LAP. Overall, this is the first comprehensive report of a sample preparation methodology tailored for imaging LAP at molecular level, allowing for the direct chemical identification and 2D mapping of an active pharmaceutical ingredient (API) distribution during LAP release process. Furthermore, this work has established the foundation to apply MALDI-MSI to the understanding of LAP implant formulation homogeneity, chemical composition, and degradation. More importantly, this work enabled the extension of MALDI-MSI technique to study a wide range of non-conductive materials.

Insights into the release mechanisms of antioxidants from nanoemulsion droplets.

The therapeutic effects of antioxidant-loaded nanoemulsion can be often optimized by controlling the release rate in human body. Release kinetic models can be used to predict the release profile of antioxidant compounds and allow identification of key parameters that affect the release rate. It is known that one of the critical aspects in establishing a reliable release kinetic model is to understand the underlying release mechanisms. Presently, the underlying release mechanisms of antioxidants from nanoemulsion droplets are not yet fully understood. In this context, this review scrutinized the current formulation strategies to encapsulate antioxidant compounds and provide an outlook into the future of this research area by elucidating possible release mechanisms of antioxidant compounds from nanoemulsion system.

Polyphenol-Based Microencapsulated Extracts as Novel Green Insecticides for Sustainable Management of Polyphagous Brown Marmorated Stink Bug (Halyomorpha halys Stål, 1855)

The brown marmorated stink bug (Halyomorpha halys Stål, 1855) is an invasive polyphagous species that threatens fruit growing both in the United States and Europe. Many pesticide active ingredients have been studied in H. halys management, but for sustainable fruit growing, which implies the reduction of chemical harm to the environment, new safe insecticides should be implemented into the practice. For this purpose, novel green insecticide based on natural polyphenols of species Stevia rebaudiana (Bertoni) Bertoni and Aronia melanocarpa (Michx.) Elliott 1821 was developed. Stevia leaves (SLE) and Aronia pomace (APE) aqueous extracts were prepared using the ultrasound-assisted extraction method. Optimal extraction conditions for bioactive compounds (total polyphenols, flavonoids, anthocyanins, and flavan-3-ols, respectively) and antioxidant activity were determined using response surface methodology. Bioactive compounds rich SLE and APE were encapsulated in calcium alginate microparticles by the ionic gelation method. Physicochemical characteristics (morphology, size, encapsulation efficiency, loading capacity, and swelling) of microparticles showed very good properties with especially high encapsulation efficiency. Fitting to simple Korsmeyer–Peppa’s empirical model revealed that the underlying release mechanism of polyphenols is Fickian diffusion. SLE loaded microparticles showed very good pesticidal efficiency against Halyomorpha halys, especially on younger larval stages after both contact and digestive treatment. Microparticles loaded with APE did not achieve satisfactory digestive efficiency, but a certain toxic impact has been observed at contact application on all H. halys growth stages. Microparticles loaded with SLS exhibited prolonged insecticidal action against H. halys and could be a potential candidate as a green insecticide whose application could increase fruit growing safety.

Silica particles incorporated into PLGA-based in situ-forming implants exploit the dual advantage of sustained release and particulate delivery

Poly (lactic-co-glycolic acid) (PLGA) in situ-forming implants are well-established drug delivery systems for controlled drug release over weeks up to months. To prevent initial burst release, which is still a major issue associated with PLGA-based implants, drugs attached to particulate carriers have been encapsulated. Unfortunately, former studies only investigated the resulting release of the soluble drugs and hence missed the potential offered by particulate drug release. In this study, we developed a system capable of releasing functional drug-carrying particles over a prolonged time. First, we evaluated the feasibility of our approach by encapsulating silica particles of different sizes (500 nm and 1 μm) and surface properties (OH or NH2 groups) into in situ-forming PLGA implants. In this way, we achieved sustained release of particles over periods ranging from 30 to 70 days. OH-carrying particles were released much more quickly when compared to NH2-modified particles. We demonstrated that the underlying release mechanisms involve size-dependent diffusion and polymer-particle interactions. Second, particles that carried covalently-attached ovalbumin (OVA) on their surfaces were incorporated into the implant. We demonstrated that OVA was released in association with the particles as functional entities over a period of 30 days. The released particle-drug conjugates maintained their colloidal stability and were efficiently taken up by antigen presenting cells. This system consisting of particles incorporated into PLGA-based in situ-forming implants offers the dual advantage of sustained and particulate release of drugs as a functional unit and has potential for future use in many applications, particularly in single-dose vaccines.

Critical insight and indication on particle size effects towards uranium release from uranium mill tailings: Geochemical and mineralogical aspects

Uranium (U) is both chemically toxic and radioactive. Uranium mill tailings (UMTs) are one of the most important sources of U contamination in the environment, wherein the mechanisms that control U release from UMTs with different granularities have not yet been well understood. Herein, the release behaviours and underlying release mechanisms of U from UMTs with five different particle size fractions (<0.45, 0.45–0.9, 0.9–2, 2–6 and 6–10 mm) were studied with a well-defined leaching test (ANS 16.1) combined with geochemical and mineralogical characterizations. The results showed that the most remarkable U release unexpectedly emerged from UMT2–6 mm; in contrast, the smallest particle size UMT<0.45 mm contributed to the least U release. The predominant mechanism of U release from UMT2–6 mm was the oxidative dissolution of U-bearing sulfides, while abundant gypsum present in UMT<0.45 mm inhibited U release. The study highlights the importance of combined geochemical and mineralogical investigation when performing leaching tests of mineral-containing hazardous materials such as UMTs with consideration of particle size effects. The findings also indicate that elevating the content of gypsum and avoiding the oxidation of sulfides can effectively help immobilize and minimize the residual U release from the UMTs.

Mechanism of a long-term controlled drug release system based on simple blended electrospun fibers

BackgroundDrug delivery systems based on electrospun fibers have been under development for many years. However, studies of controllable long-term drug release from electrospun membrane systems and the underlying release mechanisms have seldom been reported. MethodsIn this study, electrospun membrane drug delivery systems consisting of the antibiotic ciprofloxacin hydrochloride and FDA-approved polymers are fabricated. Different second-component polymers are introduced to change the properties of a poly(d,l-lactide-co-glycolide) (PLGA) matrix, thereby altering the drug release behavior. On the basis of observations of morphology, cumulative release profiles, and determinations of release duration, the drug release kinetics and critical characteristics influencing drug release behavior are discussed. ResultsIt is found that the drug release profiles can be divided into three stages according to the rate of drug release. Stage I is controlled by fiber swelling and diffusion according to Fick's second law. Stage II is controlled by diffusion through a fused membrane structure, which results in very slow drug release. Stage III is controlled by polymer degradation and involves release of the remaining drug. ConclusionsThe results of this study of release mechanisms should provide a basis for adjustments of drug release dosage and duration, thereby contributing to the development of drug delivery systems satisfying clinical requirements.

Co-gasification of waste wood with coal: Release of condensable and non-condensable inorganic gas species

This letter deals with the in-situ determination of important inorganic gas phase species in high temperature gasification product gas. The fuels are waste wood and German hard coal which were co-gasified at 1500 °C in lab-scale experiments. The release of the vapour species 34H2S+, 36HCl+, 56KOH+, 58NaCl+, 60COS+, 64SO2+, and 74KCl+ was determined online by a Molecular Beam Mass Spectrometer. The experimentally determined data sets were compared to calculated data sets in order to distinguish the underlying release mechanisms. The release behaviour of the inorganics 34H2S+, 36HCl+, 60COS+, 64SO2+ and 58NaCl+ cannot be attributed to simple mixing and dilution effect only. Further, it is shown that the release of these inorganics is significantly influenced by secondary reactions, e.g. competitive reaction with S and Cl.

Kinetics and Mechanisms of Chemical and Biological Agents Release from Biopolymeric Microcapsules

Kinetics and mechanisms of copper cations and Trichoderma viride spores release from uncoated and chitosan coated alginate microcapsules were investigated. The gelation of a fixed amount of sodium alginate at different concentrations of copper ion solutions resulted in distinct kinetics and release mechanisms. The increase in copper cation concentration promoted, but the presence of the chitosan layer on the microcapsule surface and the increase in microcapsule size reduced the rate of active agent release. Fitting to simple Korsmeyer-Peppas empirical model revealed that the underlying release mechanism (Fickian diffusion or a combination of the diffusion and erosion mechanisms) depends on the copper cation concentration and presence of T. viride spores. The investigation pointed out that the proper selection of formulation variables helps in designing microcapsules with the desirable release of copper ions and T. viride for plant protection and nutrition.

Release kinetics of highly porous floating tablets containing cilostazol

This study focuses on developing a highly porous floating tablet containing cilostazol. The underlying release mechanism of cilostazol from porous and floating tablets in dissolution media containing surfactants was investigated. The tablets were prepared by compressing granules and excipients with a sublimating agent, followed by sublimation under vacuum. The volatile material for the sublimating agent was chosen based on its flow properties using conventional methods as well as the twisted blade method. Resultant tablets could float immediately and had significantly higher tensile strengths than conventional tablets of similar porosities, holding a promising potential for increasing gastroretentive properties. Fitting the release profiles to the Korsmeyer-Peppas equation indicated Super Case II, Case II and non-Fickian kinetics, which implied that the release was affected by both floating behavior and matrix erosion. Abrupt changes in release kinetic parameters and erosional behaviors were found between the tablets containing different amounts of HPMC, indicating the existence of an excipient percolation threshold. Neither the surfactant in the media nor the porosity affected the dominant release mechanism, which was matrix erosion. Understanding the dominant release mechanism and percolation threshold allows for tuning the formulation to obtain various release profiles.

Hemolysis is a primary ATP-release mechanism in human erythrocytes

AbstractThe hypothesis that regulated ATP release from red blood cells (RBCs) contributes to nitric oxide-dependent control of local blood flow has sparked much interest in underlying release mechanisms. Several stimuli, including shear stress and hypoxia, have been found to induce significant RBC ATP release attributed to activation of ATP-conducting channels. In the present study, we first evaluated different experimental approaches investigating stimulated RBC ATP release and quantifying hemolysis. We then measured ATP and free hemoglobin in each and every RBC supernatant sample to directly assess the contribution of hemolysis to ATP release. Hypotonic shock, shear stress, and hypoxia, but not cyclic adenosine monophosphate agonists, significantly enhanced ATP release. It tightly correlated, however, with free hemoglobin in RBC supernatants, indicating that lysis was responsible for most, if not all, ATP release. Luminescence ATP imaging combined with simultaneous infrared cell imaging showed that ATP was released exclusively from lysing cells with no contribution from intact cells. In summary, with all stimuli tested, we found no evidence of regulated ATP release from intact RBCs other than by cell lysis. Such a release mechanism might be physiologically relevant in vivo, eg, during exercise and hypoxia where intravascular hemolysis, predominantly of senescent cells, is augmented.

Release of Inorganic Trace Elements from Dried Distillers Grains with Solubles during Gasification at 600–1400 °C

This work focused on the release of alkali metals (K and Na) and non-metals (S, Cl, and P) during high-temperature gasification of dried distillers grains with solubles. The release experiments were performed at 600–1400 °C in a flow channel reactor. Hot-gas analysis was performed by a molecular beam mass spectrometer. The underlying release mechanisms are discussed with dependence upon the temperature.

Imaging and characterization of stretch‐induced ATP release from alveolar A549 cells

Abstract Mechano-transduction at cellular and tissue levels often involves ATP release and activation of the purinergic signalling cascade. In the lungs, stretch is an important physical stimulus but its impact on ATP release, the underlying release mechanisms and transduction pathways are poorly understood. Here, we investigated the effect of unidirectional stretch on ATP release from human alveolar A549 cells by real-time luciferin-luciferase bioluminescence imaging coupled with simultaneous infrared imaging, to monitor the extent of cell stretch and to identify ATP releasing cells. In subconfluent (<90%) cell cultures, single 1 s stretch (10-40%)-induced transient ATP release from a small fraction (1.5%) of cells that grew in number dose-dependently with increasing extent of stretch. ATP concentration in the proximity (150 μm) of releasing cells often exceeded 10 μm, sufficient for autocrine/paracrine purinoreceptor stimulation of neighbouring cells. ATP release responses were insensitive to the putative ATP channel blockers carbenoxolone and 5-nitro-2-(3-phenylpropyl-amino) benzoic acid, but were inhibited by N-ethylmaleimide and bafilomycin. In confluent cell cultures, the maximal fraction of responding cells dropped to <0.2%, but was enhanced several-fold in the wound/scratch area after it was repopulated by new cells during the healing process. Fluo8 fluorescence experiments revealed two types of stretch-induced intracellular Ca(2+) responses, rapid sustained Ca(2+) elevations in a limited number of cells and delayed secondary responses in neighbouring cells, seen as Ca(2+) waves whose propagation was consistent with extracellular diffusion of released ATP. Our experiments revealed that a single >10% stretch was sufficient to initiate intercellular purinergic signalling in alveolar cells, which may contribute to the regulation of surfactant secretion and wound healing.

Release Behavior of Tanshinone IIA Sustained-Release Pellets Based on Crack Formation Theory

The objective of this study was to investigate the drug release mechanism and in vivo performance of Tanshinone IIA sustained-release pellets, coated with blends of polyvinyl acetate (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A formulation screening study showed that pellets coated with PVAc-PVA-PEG at a ratio of 70:30 (w/w) succeeded in achieving a 24 h sustained release, irrespective of the coating weight (from 2% to 10%). Both the microscopic observation and mathematical model gave further insight into the underlying release mechanism, indicating that diffusion through water-filled cracks was dominant for the control of drug release. In vivo test showed that the maximum plasma concentration of sustained-release pellets was decreased from 82.13 ± 17.05 to 40.50 ± 11.72 ng mL as that of quick-release pellets. The time of maximum concentration, half time, and mean residence time were all prolonged from 3.80 ± 0.40 to 8.02 ± 0.81 h, 4.28 ± 1.21 to 8.18 ± 2.06 h, and 8.60 ± 1.59 to 17.50 ± 2.78 h, compared with uncoated preparations. A good in vitro-in vivo correlation was characterized by a high coefficient of determination (r = 0.9772). In conclusion, pellets coated with PVAc-PVA-PEG could achieve a satisfactory sustained-release behavior based on crack formation theory.

Mass spectrometric investigations on the release of inorganic species during gasification and combustion of German hard coals

Na-, K-, Cl-, and S-species released during thermal conversion of coal can cause several problems such as fouling, slagging and corrosion, especially in gas turbines and heat recovery systems. To reduce this problems an enhanced understanding of the underlying release mechanisms for Na-, K-, Cl-, and S-species is needed. Therefore, basic investigations have been performed in an atmospheric lab-scale tube furnace at 1400 °C under gasification and combustion conditions. Hot gas analysis has been carried out by molecular beam mass spectrometry. The release of H 2S, HCl, K+, NaCl, COS, and SO 2 has been qualitative and quantitative analysed and correlated with the coal composition. The results show a strong dependence of coal composition and reaction atmosphere on the release of Na-, K-, Cl-, and S-species. Additionally, thermodynamic equilibrium calculations with the software package FactSage 5.4.1 have been undertaken for comparison with the experimental results.

Mass spectrometric investigations on the release of inorganic species during gasification and combustion of Rhenish lignite

To reduce problems such as fouling, slagging and corrosion, which can occur during thermal utilisation of lignite, an enhanced understanding of the underlying release mechanisms for the involved Na-, K-, Cl-, and S-species is needed. Therefore basic investigations have been performed in an atmospheric tube furnace at 1400 °C under gasification and combustion like conditions in lab-scale experiments. Molecular beam mass spectrometry has been used for on-line qualitative and semi-quantitative analysis of the hot product gas. 34H 2S + has been formed during gasification experiments, while 64 SO 2 + has been formed during combustion experiments. 36HCl +, 58NaCl +, 39K + (assumed to be partly a fragment of KCl) have been the main alkali and chlorine species and have been released mainly during pyrolysis phase. Linear correlation analysis has been undertaken to investigate the dependence of coal composition on the release of Na-, K-, Cl, and S-species. The correlations have been found to be similar for both gasification and combustion experiments. The release of 34H 2S + and 64 SO 2 + is in high negative correlation with the Ca/S ratio and in high positive correlation with the S-content of the coals. The release of 36HCl + shows a negative correlation with the Na/S ratio and the Na/Si ratio of the lignite under investigation. The release of 58NaCl + depends with negative correlation on the S/Cl ratio and the content of Al + Si of the investigated lignite. The experimental results have been compared with thermodynamic equilibrium calculations. The release of H 2S, SO 2, and NaCl could be predicted with sufficient accuracy, though the release of HCl and K-species could not satisfactorily be predicted.

Release Kinetics of Volatile Organic Compounds from Roasted and Ground Coffee: Online Measurements by PTR-MS and Mathematical Modeling

The present work shows the possibilities and limitations in modeling release kinetics of volatile organic compounds (VOCs) from roasted and ground coffee by applying physical and empirical models such as the diffusion and Weibull models. The release kinetics of VOCs were measured online by proton transfer reaction-mass spectrometry (PTR-MS). Compounds were identified by GC-MS, and the contribution of the individual compounds to different mass fragments was elucidated by GC/PTR-MS. Coffee samples roasted to different roasting degrees and ground to different particle sizes were studied under dry and wet stripping conditions. To investigate the accuracy of modeling the VOC release kinetics recorded using PTR-MS, online kinetics were compared with kinetics reconstituted from purge and trap samplings. Results showed that uncertainties in ion intensities due to the presence of isobaric species may prevent the development of a robust mathematical model. Of the 20 identified compounds, 5 were affected to a lower extent as their contribution to specific m/z intensity varied by <15% over the stripping time. The kinetics of these compounds were fitted using physical and statistical models, respectively, the diffusion and Weibull models, which helped to identify the underlying release mechanisms. For dry stripping, the diffusion model allowed a good representation of the release kinetics, whereas for wet stripping conditions, release patterns were very complex and almost specific for each compound analyzed. In the case of prewetted coffee, varying particle size (approximately 400-1200 microm) had no significant effect on the VOC release rate, whereas for dry coffee, the release was faster for smaller particles. The absence of particle size effect in wet coffee was attributed to the increase of opened porosity and compound diffusivity by solubilization and matrix relaxation. To conclude, the accurate modeling of VOC release kinetics from coffee allowed small variations in compound release to be discriminated. Furthermore, it evidenced the different aroma compositions that may be obtained depending on the time when VOCs are recovered.

Drug release from lipid-based implants: Elucidation of the underlying mass transport mechanisms

The aim of this study was to better understand the mass transport mechanisms involved in the control of drug release from lipid-based implants. Different types of triglyceride-based cylinders were prepared by compression. Glycerol-trilaurate, -trimyristate, -tripalmitate and -tristearate were used as model lipids, lysozyme and pyranine as model drugs. The effects of several formulation and processing parameters on the resulting drug release kinetics in phosphate buffer pH 7.4 were studied and the obtained results analyzed using Fick's second law of diffusion. Interestingly, lysozyme release from implants prepared by compression of a lyophilized emulsion (containing dissolved drug and lipid) was found to be purely diffusion-controlled, irrespective of the type of triglyceride. In contrast, the dominating release mechanism depended on the type of lipid in the case of pyranine-loaded implants prepared by compression of a lyophilized lipid-drug solution: with glycerol-trilaurate and -tristearate the systems were found to be purely diffusion-controlled, whereas also other mass transport phenomena are of importance in glycerol-trimyristate and -tripalmitate-based devices. Similarly, changes in the size of the compressed lipid-drug particles, drug loading and compression force significantly affected the underlying release mechanisms. The addition of a drug-free, poly(lactic-co-glycolic acid) (PLGA)-based coating around the implants delayed the onset of pyranine release for about 20 days. Interestingly, the subsequent drug release was purely diffusion-controlled, irrespective of the type of triglyceride. Also the addition of different amounts (and particle size fractions) of saccharose to pyranine-loaded implants led to purely diffusion-controlled drug release.

Measurement of Protein Diffusion Through Poly(d,l-Lactide-Co-Glycolide)

A novel method was developed for studying the diffusion of proteins through poly(d,l-lactide-co-glycolide) (PLG), using a diffusion cell. To develop improved formulations for the controlled release of encapsulated drugs it is important to understand the underlying release mechanisms. When using low-molecular-weight PLG as the release-controlling polymer, diffusion through the pores is often proposed as the main release mechanism. The experimental set-up and method of determining the diffusion coefficient were thoroughly evaluated with regard to the reliability and the influence of the stirring rate. A procedure for spraying thin films of PLG onto a filter, which could be placed in the diffusion cell, was optimized. The method was then applied to the determination of the diffusion coefficient of human growth hormone (hGH) through a PLG film. The results show that the method enables measurements of the diffusion coefficient through the polymer film. Neither the stirring rate nor the concentration of hGH influenced the diffusion coefficient. The diffusion coefficient of hGH through degraded PLG films was 5.0 · 10− 13 m2/s, which is in the range that could be expected, i.e., several orders of magnitude smaller than its the diffusivity in pure water. The reproducibility was good, considering the dynamic properties of PLG, i.e., the difference in diffusion coefficients, at, for example, different stages of degradation and for different compositions of PLG, is expected to be much higher. The variation is probably also present in PLG films used for controlled-release formulations. Although the PLG film contains a large amount of water, a considerable time elapsed before pores of sufficient size formed and diffusion through the film started. In two-component diffusion experiments, the difference in diffusion rate did not correspond to the difference in molecular weight of the solutes, indicating a size exclusion effect. This method can be used to study the effect of changes in the formulation specification. By studying the change in the diffusion coefficient through the degradation process of PLG, or similar polymers, a better understanding of diffusion and, thus, also release mechanisms can be obtained.