Release kinetics of coated, donut-shaped tablets for water soluble drugs

Coated, donut-shaped tablets (CDST) were designed to achieve parabolic and linear drug release profiles. When rapidly erodible polymers (HPMC E3, HPC, PEG8000, PEOs (Mw=100000 and 200000)) were used, the release profiles of diltiazem HCl from the tablets becomes parabolic whereas zero-order release was achieved by using slowly erodible polymers (HPMC E5, HPMC E15, PEO (Mw=300000)). Drug release from the rapidly erodible polymers was governed by the pure erosion of the polymer while both polymer erosion and drug diffusion controlled drug release from the slowly erodible polymers. As drug loading was increased from 10% to 39% w/w, the drug release rate from CDST based on HPMC E3 became faster and parabolic whereas that from CDST based on HPMC E5 was linear. The slowly erodible polymer (HPMC E5) provided parabolic release profiles when drug loading was greater than 49% w/w. In this case, drug release mechanisms likely shifted from a combination of polymer erosion and drug diffusion to pure polymer erosion due to the enhancement of polymer erosion by faster influx of water. As drug solubility decreased from 61.6% w/v (diltiazem HCl), 1.0% w/v (theophylline), to 0.5% w/v (nicardipine HCl), the drug release rate from CDST based on HPMC E3 decreased due to polymer erosion mechanism but there was little difference in release rate from CDST based on HPMC E5 due to the greater contribution of drug diffusion to drug release kinetics along with polymer erosion. As expected, the drug release rate of diltiazem HCl from HPMC E3 and E5 was significantly influenced by stirring rate and hole size.     

Drug release from drug-polyanion complex tablets: poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate)

A new erodible, anionic carrier for cationic drugs has been synthesized for oral drug delivery systems. The release properties of tablets prepared from this new material, poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate) (PAMPSNa/MMA), are discussed. Pseudo-linear release profiles were obtained and the hydrophobicities of both the polymeric carrier and the bound drugs were found to be an important controlling factor in determining the slopes of these release profiles. The effect of the tablet geometry on the shape of the release profiles was also investigated and tablet thickness was demonstrated to be another key parameter controlling both the linearity of the release profiles, as well as the duration of drug release. The release kinetics are strongly dependent on the drug solubility rather than on the type of amine in the drug (i.e. secondary and tertiary amines). The release of drugs from tablets of drug-PAMPSNa/MMA complexes were well described by the dissociation/erosion mechanism.     

Ca2+ and the regulation of neurotransmitter secretion

A new binary polymer matrix tablet for oral administration was developed. The system will deliver drug at variable rates according to zero-order kinetics for total drug content and is manufactured by direct compression technology. Highly methoxylated pectin and hydroxypropyl methylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results indicate that by increasing pectin:HPMC ratios, release rates are increased, but zero-order kinetics prevail throughout the dissolution period (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of viscosities that modulates drug release and results in rapid hydration/gelation in both axial and radial directions, as evidenced by photomicrographic pictures. This hydration-gelation contributes to the development of swelling/erosion boundaries and consequently to constant drug release. Combination of these particular polymers facilitates rapid formation of necessary boundaries (i.e., gel layer and solid core boundaries) to control overall mass transfer processes. The drug fraction released (Mt/M infinity), release kinetics, and mechanism of release were analyzed by applying the simple power law expression Mt/M infinity = kt(n), where k is a kinetic constant and the exponent n is indicative of the release mechanism. The calculated n values for pectin:HPMC ratios of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II transport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulated by the gelling characteristics of polymers in the formulation.     

Oral solid controlled release dosage forms: role of GI-mechanical destructive forces and colonic release in drug absorption under fasted and fed conditions in humans

PURPOSE: This study was undertaken to examine the effects of mechanical destructive forces on drug release from controlled release (CR) dosage forms in vitro and in vivo and their colonic release, using two CR tablets of acetaminophen A and B, showing slower and faster erosion rates, respectively. METHODS: In vitro release rates were determined by several official methods. Tablets were administered to healthy volunteers under fasting and fed conditions. RESULTS: Both tablets showed similar release rates under mild destructive conditions (e.g., paddle method at 10 rpm) but CR-B showed faster release under highly destructive conditions (e.g., rotating basket method at 150 rpm), where the tablet was eroded. The in vivo release from CR-B was faster than from CR-A, possibly because of enhanced erosion. The variable in vivo release from CR-B indicated large inter-subject differences in destructive GI forces. The fastest in vivo release from CR-B among individuals was approximated by the in vitro dissolution determined by destructive methods such as the rotating basket at 150 rpm. The slowest in vivo release from tablets A and B was lower than the dissolution by the paddle method at 10 rpm. The release from both tablets was markedly reduced at 3-4 hrs after dosing irrespective of feeding conditions which can be attributed to release inhibition in the colon. CONCLUSIONS: Effects of GI destructive forces on the tablet erosion and the release inhibition in the colon must be considered in the development of CR dosage forms.     

Cross-linked high amylose starch for controlled release of drugs: recent advances

Cross-linked high amylose starches have been developed as excipients for the formulation of controlled-release solid dosage forms for the oral delivery of drugs. Advantages of this new class of excipients include cost-effectiveness, readily accessible industrial manufacturing technology, high active ingredient core loading and the possibility of achieving a quasi zero-order release for most drugs. In addition to the latter, other features distinguish cross-linked high amylose starches from other excipients used to prepare hydrophilic matrices. Among these are the absence of erosion, the limited swelling and the fact that increasing cross-linking degrees results in increased water uptake rate, drug release rate and equilibrium swelling. Thus the goal of the present study was to gain some insights into the mechanism of drug release control by matrices of cross-linked high amylose starch. Water transport kinetics and dimensional changes were studied in matrices placed in water at 37 degrees C by an image analysis technique. The results show that in the first 5 min, a gel layer is formed at the surface of the tablet, after which the gel front seems to halt its progression toward the center of the tablet. Water continues to diffuse through the front and to invade the core. As a consequence, this latter swells, with a predominance for radial swelling. Equilibrium swelling is reached over 3 days, when the water concentration in the tablet becomes homogeneous and the whole tablet gelifies. Solid-state 13C-NMR were acquired on cross-linked high amylose starch powders, tablets and hydrated tablets with varying cross-linking degrees. They show a predominance of the V-type single helix arrangement of amylose in the dry state irrespective of the cross-linking degree. Upon hydration, the homologues with a low cross-linking degrees show a transition from the V to the B-type double helix arrangement. It is therefore hypothesized that the capacity of amylose to undergo the V to B transition is an important factor in controlling water transport and drug release rate. Finally applications to different drugs are reviewed briefly. They illustrate the versatility of this technology as generic versions of zero order OROS drug (Efidac) and Fickian release conventional matrices (Voltaren SR) were developed and successfully tested in pilot clinical studies to be bioequivalent to the references. These studies further showed that cross-linked high amylose starch matrices have the lowest inter-subject variability among the systems tested and show a total absence of food effect.     

The influence of moisture content on the consolidation properties of hydroxypropylmethylcellulose K4M (HPMC 2208)

The effect of moisture content, compression speed and compression force on the compaction properties of HPMC K4M has been evaluated. As the moisture content increased from 0 to 14.9% w/w, the thickness of HPMC K4M compacts increased at constant compression force and speed. This increase in moisture content also resulted in a marked increase in the tensile strength of the tablets. At a speed of 15 mm s-1 and force of 10 kN, as the moisture content increased from 0 to 14.9% w/w, the tensile strengths increased from 1.34 to 8.54 Mpa. Equivalent tensile strengths could be obtained with less compression force as the moisture content in the polymer was increased. Increasing the compression speed generally decreased the tensile strength of HPMC K4M tablets. The dependence of tablet porosity and tensile strength on compression speeds showed that HPMC K4M is consolidated by plastic deformation. At all compression speeds, an increase in moisture content reduced the percentage elastic recovery of HPMC compacts due to greater tablet consolidation. The lowest elastic recovery (1.18%) was found for tablets made at 15 mm s-1 and 5 kN, containing 14.9% w/w moisture content.     

In vivo color stability of resin composite veneers and acrylic resin teeth in removable partial dentures

A new core-in-cup tablet that is manufactured from a novel adjustable punch, has been formulated and evaluated for its ability to release with subsequent absorption of theophylline via a zero-order rate of absorption. The core-in-cup tablets were compared with core only tablets and immediate release capsules. Pharmacokinetic parameters used to test the effectiveness of the formulations included, elimination rate, rate and kinetic order of absorption, relative availability as compared with an immediate release capsule of pure theophylline, and percentage area under the curve fluctuation (%AUCF) at steady state. The correlation coefficient, Akaike's information criterion (AIC) and the F-ratio probability were used to test the applicability of a zero-order, first-order, or square root of time model, for the rate of release of theophylline from the core-in-cup and core only tablets. The zero-order rate model was most applicable to the core-in-cup tablet, whereas the square root of time release model was most applicable to the core only tablet. The average %AUCF for the core-in-cup tablet was 9.26+/-3.15 while that for the core only tablet was 16.19+/-2.37 (p = 0.0545). The results of this study suggest that the core-in-cup tablet is a versatile zero-order release rate dosage form that are simple to produce.     

Relating the phagocytosis of microparticles by alveolar macrophages to surface chemistry: the effect of 1,2-dipalmitoylphosphatidylcholine

This paper describes the preparation of new buccal bilayered devices comprising a drug-containing mucoadhesive layer and a drug-free backing layer, by two different methods. Bilaminated films were produced by a casting/solvent evaporation technique and bilayered tablets were obtained by direct compression. The mucoadhesive layer was composed of a mixture of drug and chitosan, with or without an anionic crosslinking polymer (polycarbophil, sodium alginate, gellan gum), and the backing layer was made of ethylcellulose. The double-layered structure design was expected to provide drug delivery in a unidirectional fashion to the mucosa and avoid loss of drug due to wash-out with saliva. Using nifedipine and propranolol hydrochloride as slightly and highly water-soluble model drugs, respectively, it was demonstrated that these new devices show promising potential for use in controlled delivery of drugs to the oral cavity. The uncrosslinked chitosan-containing devices absorbed a large quantity of water, gelled and then eroded, allowing drug release. The bilaminated films showed a sustained drug release in a phosphate buffer (pH 6.4). Furthermore, tablets that displayed controlled swelling and drug release and adequate adhesivity were produced by in situ crosslinking the chitosan with polycarbophil.     

In vitro/in vivo comparison of drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides--a noninvasive approach by the combined use of electron paramagnetic resonance spectroscopy and nuclear magnetic resonance imaging

PURPOSE: The purpose of this study was to compare drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides in vitro and in vivo in real time and with minimal disturbance of the investigated system. METHODS: P(FAD-SA) 20:80 and P(FAD-SA) 50:50 polymer tablets were loaded with the spin probe 3-carboxy-2,2,5,5-tetramethyl-pyrrollidine-1-oxyl (PCA) and implanted subcutaneously in the neck of rats or placed in 0.1 M phosphate buffer. 1.1 GHz EPR spectroscopy experiments and 7T MRI studies (T1 and T2 weighted) were performed. RESULTS: A front of water penetration was visible by MRI in vitro in the case of P(FAD-SA) 20:80, but not for P(FAD-SA) 50:50. For both polymers, the thickness of the tablets decreased with time and a insoluble, easy deformable residue remained. Important processes such as edema, deformation of the implant, encapsulation and bioresorption were observable by MRI in vivo. P(FAD-SA) 50:50 was almost entirely absorbed by day 44, whereas an encapsulated residue was found for P(FAD-SA) 20:80 after 65 days. The EPR studies gave direct evidence of a water penetration induced changes of the microenvironment inside the tablet. EPR signals were still detectable in P(FAD-SA) 20:80 implants after 65 days, while the nitroxide was released in vitro within 16 days. CONCLUSIONS: Important parameters and processes such as edema, deformation of the tablet, microviscosity inside the tablet and encapsulation can be monitored in real time by the combined use of the noninvasive techniques MRI and EPR leading to better understanding of the differences between the in vitro and in vivo situation.     

Augmented expression of glomerular basement membrane specific type IV collagen isoforms (alpha3-alpha5) in experimental membranous nephropathy

The swelling, erosion and solvent front penetration properties of mini-matrices containing xanthan (X), locust bean (LB) and karaya (K) gums were examined, analysed and related to the overall in vitro release kinetics of diclofenac sodium, used as a model drug. Mini-matrices were produced with drug:gum ratios of 1:1 as well as formulations of drug and X in combinations of 2:1, 2:3 and 1:2. The rank order of decreasing swelling index (SI) in both axial and radial dimensions was X?K?LB and each gum showed almost Fickian swelling behaviour. The solvent front penetration rates were consistent with the rates of swelling. However, the order of decreasing drug release and erosion rates was LB>X>K and all formulations demonstrated anomalous (non-Fickian) drug release kinetics. Therefore Fickian drug diffusion and polymer erosion were both occurring simultaneously. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution time period. There was a loss of matrix integrity in formulations containing a high drug:gum ratio.     

Experimental hypoxemic hypoxia: changes in R2* of brain parenchyma accurately reflect the combined effects of changes in arterial and cerebral venous oxygen saturation

PURPOSE: The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS: The erodible plugs were either prepared by direct compression followed by placing the tablets in the capsule opening or by congealing a meltable plug material directly within the capsule opening. The disintegration/erosion properties of these plugs were determined and optimized for the final delivery system. In order to assure rapid drug release of the capsule content after erosion of the plug, various excipients (fillers, effervescent agents) and drugs with different solubilities were evaluated. The lag time prior to drug release and the subsequent drug release were investigated as function of capsule content, plug composition, plug preparation technique, plug hardness, weight, and thickness. RESULTS: The erosion time of the compressed plugs increased with increasing molecular weight of the hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide), decreasing filler (lactose) content and decreased with congealable lipidic plugs with increasing HLB-value and inclusion on surfactants. For complete and rapid release of the drug from the capsule body, effervescent agents had to be included in the capsule content. The drug delivery system showed typical pulsatile release profiles with a lag time followed by a rapid release phase. The lag time prior to the pulsatile drug release correlated well with the erosion properties of the plugs and, besides the composition of the plug, could be controlled by the thickness (weight) of the plug. CONCLUSIONS: A single-unit, capsular-shaped pulsatile drug delivery system was developed wherein the pulsatile release was controlled by the erosion properties of a compressed or congealed plug placed within the opening of the capsule opening.     

Formation of water-insoluble gel in dry-coated tablets for the controlled release of theophylline

Sodium alginate (ALNa) of a natural polysaccharide is known to form a water-insoluble gel when combined with a bivalent metal. In this study, we prepared tablets containing ALNa and calcium gluconate (GLCa) as a bivalent metal, and studied the application of the water-insoluble gel involving the controlled release of a test drug by permeation of water. Dry-coated tablets containing theophylline (TP) as a model drug, ALNa and GLCa were prepared by the dry power compression method. The controlled release of TP was evaluated by the dissolution test according to JP XIII. The release rate was extremely high for the tablets which contained only TP and GLCa. A zero order or sigmoidal release profile was observed for the tablets that contained only TP and ALNa. On the other hand, the lowest dissolution rate and a sigmoidal release profile were observed for the tablet containing TP and GLCa in its core and ALNa in its outer phase. These results suggest that dry-coated tablets containing ALNa and GLCa and prepared by the direct powder compression method would be useful for the controlled release of drugs.     

Design and evaluation of an osmotic pump tablet (OPT) for prednisolone, a poorly water soluble drug, using (SBE)7m-beta-CD

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) for poorly water soluble drugs using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD or Captisol, which acted as both a solubilizer and as an osmotic agent. METHODS: Prednisolone (PDL) was chosen as a model drug for this study. The release of PDL from osmotic pump devices and tablets was studied. In vivo absorption of PDL from OPT was evaluated in male beagle dogs. RESULTS: PDL release from the osmotic pump tablet with (SBE)7m-beta-CD was complete. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in incomplete release. Although PDL release from the OPT with (SBE)7m-beta-CD and the sugar formulation displayed mainly zero-order release characteristics, the tablet utilizing HP-beta-CD showed apparent first-order release characteristics. An in vivo absorption study in dogs correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: The present results confirm that (SBE)7m-gamma-CD can serve as both the solubilizer and the osmotic agent for OPT of PDL, and modify the input rate of PDL without compromising oral bioavailability.     

In vitro evaluation of a controlled-release site-specific diisovaleryl tert-butalone chemical delivery system for the eye

Cellulosic polymers such as cellulose acetate (CA), cellulose acetate butyrate (CAB), and hydroxypropyl methyl cellulose phthalate (HPMCP) and hydrogels (hydroxyethyl/hydroxypropyl acrylate and hydroxypropyl methacrylate monomers) were used to sustain/control the release of diisovaleryl tert-butalone, a novel site-specific chemical delivery system (CDS) for potential antiglaucoma treatment. Diisovaleryl tert-butalone was incorporated into cellulosic polymers by the method of "solution casting" and into hydrogels by the method of "impregnation." In vitro release-rate kinetics from these systems were studied using a closed sink kinetic model. The release rate of CDS from the polymers chosen followed first-order kinetics and the release was sustained for about 2-6 h. In the case of hydrogels a pronounced "burst release" was observed. Increasing the percentage of cross-linker in the linear monomers of the hydrogel was shown to sustain the release longer. When the diisovaleryl tert-butalone CDS was incorporated into one of the cellulosic polymers, cellulose acetate butyrate, as the CDS-beta-cyclodextrin [heptakis(2,6-di-O-methyl)-beta-cyclodextrin] inclusion complex, the release pattern approximated Higuchi's expression for a monolithic matrix system, where the amount of CDS released from the polymer was proportional to the square-root of time. Further, the stability of the CDS in the polymer was improved when it was dispersed in the polymer as the CDS-beta-cyclodextrin CD complex.     

Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. I. In vitro development and evaluation

In vitro preformulation testing has shown that the solubility and dissolution rate of the model drug compound ucb 11056 are highly pH dependent. Considering this, different sustained-release (SR) oral dosage forms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal (GI) tract. Classical approaches based on the use of SR formulations such as hydrophilic matrix tablets or pellets coated with one film-forming polymer (Eudragit NE30D or L30D-55) did not fulfill all expectations on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution medium. Therefore, taking advantage of the flexibility of release adjustment obtainable from coating of pellets with different kinds of pH-sensitive film layers, a quite satisfactory pH independence of the release characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representation of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.     

Complications in investigations of the swelling of hydrogel matrices due to the presence of trapped gas

In recent studies, NMR imaging has been used to investigate the swelling of hydroxypropylmethylcellulose (HPMC) tablets and to determine polymer concentration distributions in the swollen matrix. The total amount of polymer in the system was computed from these distributions and was up to 35% greater than the known weight of HPMC in the tablet. This deviation was traced to the presence of air bubbles in the swollen matrix which occupied a significant volume previously assumed to be occupied by polymer and water. When the air in the tablet was removed by vacuum, the swollen gel contained no evidence of air bubbles and the calculated total polymer weights from the HPMC distributions were equal to the amount of HPMC in the tablet.     

Tableting of coated particles. I. Small particle size chitosan as an agent protecting coating membrane from mechanical damage of compression force

Formulation of sustained release tablets containing coated particles whose coating membrane is not damaged during compression was studied and several kinds of chitosan of different particle size were evaluated as protective agents for the membrane. Comparison was made with the dissolution rate of the coated particles. Ethylcellulose or ethylcellulose/hydroxypropylcellulose was chosen as a coating agent. When the coated particles were compressed with the small particle size chitosan (Marine Chito), the coating membrane was not ruptured, and the protective effect was not influenced by the compression pressure. Both the Eudragit RS-coated particles and the tablets manufactured by compressing the coated particles with Marine Chito were orally administered to dogs, and the plasma theophylline levels of the two dosage forms were compared to determine the drug release characteristics in the gastrointestinal tract. It was found that the plasma concentration-time curve of the tablets coincided with that of the coated particles, and the compressed tablet would disintegrate instantly and redisperse into many particles in the body after oral administration.     

Typical variability in drug dissolution testing: study with USP and FDA calibrator tablets and a marketed drug (glibenclamide) product

To evaluate variability in drug dissolution testing 28 laboratories analyzed USP calibrators, US FDA prednisone tablets and a marketed glibenclamide tablet product. The experiments were conducted using paddle and basket methods at 50 (calibrators) and 75 (glibenclamide) rpm. The media employed were deaerated by equilibrating at 37 degrees C for 24 h and by the USP recommended method. The 95% CI values for percent drug release for the USP calibrator tablets were similar to the reported tolerances for the USP Acceptance Ranges; however, individual results from 15 of 28 laboratories suggest that the apparatus would not comply with the USP Apparatus Suitability Criteria. For FDA prednisone calibrator tablets, percent drug release using equilibrated medium was different (P=0.003) than by the USP recommended method. For the glibenclamide tablet results, a CV of 14-37% was observed, depending upon the sampling time and the type of apparatus employed. The results indicate that failure to meet the USP Dissolution Apparatus Suitability Test may not truly mean that the apparatus is 'out of compliance'. Due to the high variability in dissolution testing, in many cases the impact of formulation or manufacturing changes on drug release characteristics may not be observed, in particular with multi-point profiles.     

Evaluation of two dextrose-based directly compressible excipients

The objectives of this research were to evaluate the physical properties and compaction behavior of two dextrose-based directly compressed excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and or Maltrin M510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. Direct compression and wet granulation methods were used for preparing the compacts. In general, the wet granulation method reduced the density of the mixture and consequently its flow rate compared to the mixture prepared only by solid-solid mixing. All formulations were compressed at four different compressional forces and at a target weight of 450 mg +/- 5%. Tablets obtained were different in physical properties and mechanical strength based on type of excipient used and methods of tablet preparation (direct compression versus wet granulation). Compacts prepared from Maltrin M510 had a longer disintegration time and slower drug release than compacts of the same composition but prepared with Emdex. Disintegration time and drug dissolution from tablets containing Maltrin M510 as diluent and prepared by wet granulation appeared to be controlled by a "gel" layer formation around the tablets and not by the tablets porosity. This study demonstrates that full characterization of excipients is needed because a different manufacturing process for the same excipients may produce differences in the pharmaceutical products.     

Synergistic neurochemical and behavioral effects of fluoxetine and 5-HT1A receptor antagonists

Nuclear magnetic resonance (NMR) imaging is routinely used to detect the protons of mobile water molecules within samples. In this investigation, this non-destructive, non-invasive technique was used to determine the cause for faster than predicted drug release from a dissolution-based regulated-release tablet. The NMR images of tablets, from two different formulations, taken at various intervals of time while immersed in static USP dissolution medium showed that the tablet with faster than predicted drug release had a porous coating. The porous coat exposed more of the core surface area to the dissolution medium than desired and this caused an increase in the rate of dissolution of the core. The data presented in this paper demonstrate the usefulness of NMR imaging in solid dosage form development.