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In vitro drug release from well-defined particle-size fractions of the mesoporous magnesium carbonate material Upsalite(®) was investigated in detail using ibuprofen, a biopharmaceutics classification system class II drug, as the model compound. The weight of loaded drug corresponded to 30% of the weight of the carrier and the pores were filled to approximately 80%. The incorporated ibuprofen was found to be in an amorphous state and was physisorbed, rather than chemisorbed, to the surfaces of the pore walls. In contrast to ibuprofen in mesoporous silica, there was no detectable drug on the outer surface of the carrier particles. Two ibuprofen doses were loaded into Upsalite(®) particles with size fractions ranging from 25 μm to more than 200 μm. The initial release rate was controlled by the particle size; the dissolution rate of the loaded ibuprofen during this period was more than four times faster than that of the crystalline drug. An extended-release period of about 24 h followed the initial rapid-release period. The features of this extended-release period were dependent on the total drug concentration in the release medium. Detailed analysis of the diffusion of ibuprofen in Upsalite(®) provided the ibuprofen diffusion coefficient (9.8 × 10(-8) cm(2)/s), the constrictivity of the diffusion process (0.47) and the tortuosity of the carrier (15). This relatively high tortuosity value indicates that Upsalite(®) can be used not only to enhance the dissolution rate of poorly soluble drugs but also as a carrier in sustained-release applications by using larger particle sizes or even pellets of the material., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Wiley Periodicals, Inc.)

A unique structure-function relationship investigation of mechanically strong geopolymer drug delivery vehicles for sustained release of potent substances is presented. The effect of in-synthesis water content on geopolymer pore structure and diffusive drug transport is investigated. Scanning electron microscopy, N2 gas adsorption, mercury intrusion porosimetry, compression strength test, drug permeation, and release experiments are performed. Effective diffusion coefficients are measured and compared with corresponding theoretical values as derived from pore size distribution and connectivity via pore-network modeling. By solely varying the in-synthesis water content, mesoporous and mechanically strong geopolymers with porosities of 8%-45% are obtained. Effective diffusion coefficients of the model drugs Saccharin and Zolpidem are observed to span two orders of magnitude (∼1.6-120 × 10(-8) cm(2) /s), comparing very well to theoretical estimations. The ability to predict drug permeation and release from geopolymers, and materials alike, allows future formulations to be tailored on a structural and chemical level for specific applications such as controlled drug delivery of highly potent substances., (Copyright © 2011 Wiley-Liss, Inc.)

Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.

In this interdisciplinary study low-frequency dielectric spectroscopy is used to assess the possibilities of intimate surface contact between a polymer gel and mucous tissue, which is generally considered to be the first step in the mucoadhesion process. The dielectric responses of six different gels, made from Carbopol 934 or Pluronic F-127 and containing 15 mM of a drug compound, either atenolol, alprenolol, or naproxen, were measured together with the responses of freshly excised porcine nasal mucosa and of systems made by combining the two. An analytical procedure is presented, which enables the dielectric response arising from the drug ions to be extracted. The drug ions are used as probes for measuring the ease, in terms of conductivity, with which they can pass the interface between the gel and the mucus layer. The results can be described by a compatibility factor that provides us with an assessment of the likelihood of intimate surface contact. The compatibility factors found in this study were generally higher for the Carbopol 934 gels than for the Pluronic F-127 gels, which is in agreement with the results of a previous study where sodium and chloride ions were used as probes for measuring the compatibility. Naproxen exhibited the largest difference in compatibility factor between the two gels; the highest compatibility factor of all systems was found for the Carbopol 934 gel whereas the gel based on Pluronic F-127 gave a value of approximately zero. This may partly be explained by interactions between the drug ions and the polymers.

Temperature-dependent drug release from disintegrating tablets made of NaCl-containing agglomerated micronized cellulose (AMC) granules has been studied to characterize the release process. Release measurements on tablets compacted at three different compaction pressures; 50, 100, and 200 MPa, were performed at seven different temperatures; 6, 23, 33, 43, 50, 55, and 63 degrees C using the recently developed alternating ionic current method. Tablets compacted at different compaction pressures showed similar release rates. The release process was found to be diffusion-controlled, and the activation energy of the diffusion coefficient was comparable to that obtained for diffusion in pure water. The results show that the AMC granules in contact with water swell to a size and shape that is only slightly affected by their compaction history and the ion diffusion operates mainly within liquid-filled pores within the AMC granules. By using the temperature dependence of the release process, it was possible to reach this conclusion without any assumptions concerning the number and radii of the granules into which the tablets disintegrated. Further, the magnitude of the effective diffusion coefficient was found to be approximately 7.5 x 10(-10) cm(2)/s, which is approximately four orders of magnitude lower than for unhindered diffusion of Na(+) and Cl(-) in water but similar to the diffusion coefficient for protons and OH(-) ions in microcrystalline cellulose., (Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1796-1803, 2004)

This interdisciplinary work demonstrates how low-frequency dielectric spectroscopy, a technique that is frequently used within physics, can be used to assess the possibilities of intimate surface contact between a polymer gel and mucous tissue, which is generally considered to be the first step in the mucoadhesion process. The dielectric responses of five different gels, of freshly excised porcine nasal mucosa and of systems made by combining the two were measured. All spectra were modeled by a Randles electric circuit containing a diffusion element, a barrier resistance in parallel with a capacitance, and a high-frequency resistance. The results were used to create a measure of the compatibility between the gel and the mucus, which we have named the compatibility factor. Thus, the compatibility factor provides us with a measure of the ease with which a charged species passes the interface between a gel and the mucus layer. The compatibility factor is calculated from the high frequency (kHz region) response of the gel, of the mucosa, and of the combined system. The two highest compatibility factors in this study were obtained for gels based on crosslinked poly(acrylic acid) and chitosan, which was in agreement with the results from mucoadhesion measurements that were performed using a tensile strength method., (Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association)

A new method is introduced that allows drug release and liquid absorption to be studied simultaneously. The drug release is measured by the alternating ionic current (AIC) method, and the study of liquid uptake is accomplished with a sensitive microbalance from a processor tensiometer. We show that the method can be employed to study anomalous diffusion in the initial phase of the drug release process of disintegrating systems. We also demonstrate that the diffusion layer thickness and the diffusion coefficient in a dissolving system can be obtained with the new measurement technique., (Copyright 2003 Wiley-Liss, Inc.)

The purpose of this article is to introduce a method capable of determining early drug dissolution in small amounts of liquid. The method is based on the measurement of the alternating ionic current through a cell containing the dissolution medium and the substance to be dissolved. Both the initial and more prolonged absorption of liquid into tablets can also be determined by using the same technique. The method has been tested on two tablet formulations containing agglomerated micronized cellulose and NaCl as a model drug. Release of NaCl was delayed from both formulations; the extent of the delay was strongly formulation-dependent only when the surrounding liquid was in short supply. This finding shows that new drug dissolution phenomena may be encountered in small liquid volumes; these phenomena would not have been seen with the large volume methods normally used in in vitro dissolution tests. Hence, for formulations intended for sublingual, buccal, or rectal administration, i.e., in areas where liquid is scarce, in vitro dissolution tests should be performed in small volumes of dissolution medium., (Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.)