Aqueous Hydroxypropyl Methylcellulose Research Articles

Rheology of nano ZnO - Hydroxypropyl Methylcellulose (HPMC) based suspensions and structural properties of resulting films

Effect of polyethylene glycol (PEG) and ZnO nanoparticles concentration on rheological properties of the hydroxypropyl methylcellulose (HPMC) based film forming suspensions (FFS) and, on the structural properties of the resulting films were characterized. Rheological properties of FFS were not significantly affected by PEG concentration and ZnO NPs incorporation. Intrinsic viscosity [η] of aqueous HPMC solution obtained from extrapolation of Huggins and Kraemer plot was 0.115–0.118 (L/g). Coating thickness calculated as a function of coating solution viscosity, concentration and draining time for strawberry coating was 1.26–1.49 μm. Tensile strength (TS) of HPMC film decreased while water vapour permeability (WVP) increased with increasing PEG concentration. Elongation at break (%E) increased up to 25% PEG concentration and decreased afterward. Incorporation of ZnO NPs improved the tensile strength and barrier properties of HPMC film. Relaxation percentage and stress decay rate increased with increasing plasticizer concentration while decreased with incorporation of ZnO NPs. • Rheological behaviour of aqueous HPMC solution (4% w/v) was Newtonian. • Calculated Intrinsic viscosity [η] of aqueous HPMC solution was 0.115–0.118 (L/g). • Relaxation % and stress decay rate showed positive correlation with PEG concentration. • Added ZnO nanoparticles improves the HPMC film properties.

Gelation, Phase Separation, and Fibril Formation in Aqueous Hydroxypropylmethylcellulose Solutions.

The thermoresponsive behavior of a hydroxypropylmethylcellulose (HPMC) sample in aqueous solutions has been studied by a powerful combination of characterization tools, including rheology, turbidimetry, cryogenic transmission electron microscopy (cryoTEM), light scattering, small-angle neutron scattering (SANS), and small-angle X-ray scattering (SAXS). Consistent with prior literature, solutions with concentrations ranging from 0.3 to 3 wt % exhibit a sharp drop in the dynamic viscoelastic moduli G' and G″ upon heating near 57 °C. The drop in moduli is accompanied by an abrupt increase in turbidity. All the evidence is consistent with this corresponding to liquid-liquid phase separation, leading to polymer-rich droplets in a polymer-depleted matrix. Upon further heating, the moduli increase, and G' exceeds G″, corresponding to gelation. CryoTEM in dilute solutions reveals that HPMC forms fibrils at the same temperature range where the moduli increase. SANS and SAXS confirm the appearance of fibrils over a range of concentration, and that their average diameter is ca. 18 nm; thus gelation is attributable to formation of a sample-spanning network of fibrils. These results are compared in detail with the closely related and well-studied methylcellulose (MC). The HPMC fibrils are generally shorter, more flexible, and contain more water than with MC, and the resulting gel at high temperatures has a much lower modulus. In addition to the differences in fibril structure, the key distinction between HPMC and MC is that the former undergoes liquid-liquid phase separation prior to forming fibrils and associated gelation, whereas the latter forms fibrils first. These results and their interpretation are compared with the prior literature, in light of the relatively recent discovery of the propensity of MC and HPMC to self-assemble into fibrils on heating.

Incorporation of surface-modified dry micronized poorly water-soluble drug powders into polymer strip films

Recent work has established polymer strip films as a robust platform for delivery of poorly water-soluble drugs via slurry casting, in particular using stable drug nanosuspensions. Here, a simpler, robust method to directly incorporate dry micronized poorly water-soluble drug, fenofibrate (FNB), is introduced. As a major novelty, simultaneous surface modification using hydrophilic silica along with micronization was done using fluid energy mill (FEM) in order to reduce FNB hydrophobicity and powder agglomeration. It is hypothesized that silica coating promotes easy, uniform dispersion of micronized and coated FNB (MC-FNB) during direct mixing with aqueous hydroxypropyl methylcellulose (HPMC-E15LV) and glycerin solutions. Uniform dispersion leads to improved film critical quality attributes (CQAs) such as appearance, drug content uniformity and drug dissolution. The impact of polymer solution viscosity (low and high), mixer type (low versus high shear), and FNB surface modification on film CQAs were also assessed. Films with as-received FNB (AR-FNB) and micronized uncoated FNB (MU-FNB) were prepared as control. When MC-FNB powders were used, films exhibited improved appearance (thickness uniformity, visible lumps/agglomerates), better drug content uniformity (expressed as relative standard deviation), fast and immediate drug release, and enhanced mechanical properties (tensile strength, elongation percentage), regardless of the polymer solution viscosity or mixer type. These results compare favorably with those reported using nanosuspensions of FNB, establishing the feasibility of directly incorporating surface modified-micronized poorly water-soluble drug powders in film manufacturing.

Suberin fatty acids isolated from outer birch bark improve moisture barrier properties of cellulose ether films intended for tablet coatings

We showed that the addition of suberin fatty acids (SFAs) even at small concentrations significantly improves the water vapor barrier properties of hydroxypropyl methylcellulose (HPMC) films. SFAs were isolated from the outer birch bark using extractive hydrolysis. The effects of SFAs on the film formation of aqueous HPMC were investigated with free films plasticized with polyethylene glycol (PEG 400). Special attention was paid on the physical solid-state, moisture barrier and mechanical stress-strain properties of films intended for tablet film coatings. Topography and surface morphology, glass transition temperature (Tg), tensile strength, Young’s modulus, and water vapor permeation (WVP) of films were studied. The addition of SFAs lowered the Tg of films suggesting partial enhancement in film plasticization. The WVP of films decreased with increasing SFAs concentration up to 15% (calculated as a % w/w from a polymer weight). The WVP value for a non-suberized reference film and suberized film plasticized with PEG 400 was 2.13×10−6 and 0.69[×10−6g/(mm2×h)×mm/Pa], respectively. The addition of SFAs impaired the mechanical stress-strain properties of HPMC films by reducing the deformation capacity of film. In conclusion, the film properties and performance of aqueous HPMC can be modified by including SFAs in the films.

Thermal gelation of aqueous hydroxypropylmethylcellulose solutions with SDS and hydrophobic drug particles

The thermal gelation of hydroxypropylmethylcellulose (HPMC) solutions has been studied as a function of sodium dodecyl sulfate (SDS) concentration with and without griseofulvin, a model particulate BCS Class II drug by rheological measurements of gelation temperature (Tgel), steady-state viscosity (η) at 25°C, and ζ-potential. Polymer adsorption on the drug was demonstrated by a decrease in η and potential in the absence of SDS. Griseofulvin had a synergistic effect on gelation which was attributed to an effective spanning of associated hydrophobic polymeric regions through interactions with the adsorbed polymer. Adding SDS offsets this effect on Tgel shielding hydrophobic interactions. Higher SDS concentrations had no effect on the particles surface as evidenced by constant ζ-potential and Tgel. Yet, polymeric chains are saturated and larger surfactant aggregates account for the increase in viscosity. Understanding the gelation mechanism and complex interactions of HPMC with surfactants and drugs is necessary for the design of pharmaceutical products and optimization of their performance properties.

Fast drying of biocompatible polymer films loaded with poorly water-soluble drug nano-particles via low temperature forced convection

Fast drying of nano-drug particle laden strip-films formed using water-soluble biocompatible polymers via forced convection is investigated in order to form films having uniform drug distribution and fast dissolution. Films were produced by casting and drying a mixture of poorly water soluble griseofulvin (GF) nanosuspensions produced via media milling with aqueous hydroxypropyl methylcellulose (HPMC E15LV) solutions containing glycerin as a plasticizer. The effects of convective drying parameters, temperature and air velocity, and film-precursor viscosity on film properties were investigated. Two major drying regimes, a constant rate period as a function of the drying conditions, followed by a single slower falling rate period, were observed. Films dried in an hour or less without any irreversible aggregation of GF nanoparticles with low residual water content. Near-infrared chemical imaging (NIR-CI) and the content uniformity analysis indicated a better drug particle distribution when higher viscosity film-precursors were used. Powder X-ray diffraction showed that the GF in the films retained crystallinity and the polymorphic form. USP IV dissolution tests showed immediate release (~20 min) of GF. Overall, the films fabricated from polymer-based suspensions at higher viscosity dried at different conditions exhibited similar mechanical properties, improved drug content uniformity, and achieved fast drug dissolution.

Effect of lapatinib on hepatic parenchymal enhancement on gadoxetate disodium (EOB)-enhanced MRI scans of the rat liver

The purpose of this study was to investigate the effect of lapatinib treatment on hepatic parenchymal enhancement on Gd-EOB-MRI scans in rat. Institutional animal review board approval was received prior to the commencement of all studies. Five rats received a single oral dose of 100 mg/kg/day lapatinib for 7 consecutive days. The controls (n = 5) were given 0.5 % (w/v) aqueous hydroxypropyl methyl cellulose containing 0.1 % (v/v) Tween 80 for 7 days. After the acquisition of gadoxetate disodium-enhanced MR images using 0.025 mmol gadolinium/kg, their livers were subjected to pathologic study to determine the expression level of organic anion-transporting polypeptide 1 (oatp1) and multi-drug resistance-associated protein 2 (mrp2). Relative enhancement of the liver was similar in both groups. At the hepatobiliary phase, which in rats occurs 3 min after the injection of Gd-EOB, it was 0.90 ± 0.06 in lapatinib-treated rats and 0.84 ± 0.08 in the controls (p = 0.30). There was also no difference in the expression level of oatp1 and mrp2. In rats, the administration of lapatinib for 7 days had no effect on hepatic parenchymal enhancement on Gd-EOB-MRI scans.

Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

Scratch resistance of plasticized hydroxypropyl methylcellulose (HPMC) films intended for tablet coatings

Scratch resistance (SR) of externally plasticized hydroxypropyl methylcellulose (HPMC) films intended for tablet film coatings was studied. Special attention was paid to effects of short-term aging and ultraviolet (UV) treatment on the SR properties of these films. Controlled scratching of the films was performed with a Lloyd LRX materials tester featuring a spherical steel tip. Scratch surface profiles were measured by scanning white light interferometry (SWLI). The influence of using an external plasticizer on the SR was studied by comparing scratch dimensions in non-plasticized films to samples plasticized either with glycerol or polyethylene glycol (PEG) 400. The study demonstrates that both the amount and type of plasticizer influences the SR of aqueous HPMC films. It also shows that SWLI can quantitatively evaluate the effect of plasticizer content and aging on the SR of pharmaceutical films. This knowledge could be used to optimize pharmaceutical film coating formulations.

Influence of surfactant properties on thermal behavior and sol–gel transitions in surfactant‐HPMC mixtures

AbstractFour surfactants, namely, sodium n‐decyl sulfate (SDeS), sodium n‐hexadecyl sulfate (SHS), sodium n‐dodecyl sulfate (SDS), and Triton X‐100, were used as additives to study thermal behavior and sol–gel transformations in dilute aqueous hydroxypropyl methyl cellulose (HPMC)/surfactant mixtures using micro‐differential scanning calorimetry. The influence of anionic surfactant, SDS on the gelation varied with SDS concentration where the sol–gel transition started at a higher temperature. Shape of the thermograms changed from single mode to dual mode at the SDS concentration of 6 mM and higher. SDeS and SHS, however, resulted in “salt‐in” effect of a different magnitude during gelation. Triton X‐100, being a non‐ionic surfactant, showed a minor “salt‐out” effect on the thermo‐gelation process. On the basis of different thermal behavior of anionic and non‐ionic surfactant/HPMC systems, a mechanism is proposed explaining how the chemical structure and electro‐charge of the surfactants affect the polymer/surfactant binding and polymer/polymer aggregation because of hydrophobic interaction during the sol–gel transition. © 2009 Wiley Periodicals, Inc. Journal of Applied Polymer Science, 2009

Improving flow properties of ibuprofen by fluidized bed particle thin-coating

The surfaces of ibuprofen particles (d50 42μm) were modified by coating the particles with diluted aqueous hydroxypropyl methylcellulose (HPMC) solution in an instrumentated top-spray fluid bed granulator. The objective was to evaluate whether an extremely thin polymer coating could be an alternative to granulation in enhancing powder flow and processing properties. The studied variables were inlet air temperature and spray rate. The treated powders showed a clear improvement in flow rate as measured with a flow meter designed for powders with poor flow properties. The particle size was determined using optical microscopy and image analysis. The particle size, size distribution and circularity of the treated and untreated ibuprofen batches showed no difference from each other. Consequently, the improvement in flow properties can be attributed to the trace amounts of hydroxypropyl methylcellulose applied onto the particle surfaces. In conclusion, fluidized bed particle thin-coating (PTC) alters the surface of ibuprofen powder particles and improves the flow properties of ibuprofen powder with changes in neither particle size, size distribution nor morphology.

Effect of SDS on the gelation of hydroxypropylmethylcellulose hydrogels

Thermal behavior of aqueous hydroxypropylmethylcellulose (HPMC)/surfactant mixtures was studied in the dilute concentration regime using micro-differential scanning calorimetry (DSC). The surfactant used was sodium n-dodecyl sulfate (SDS). The heat capacity of HPMC gel with various concentrations of SDS was much higher than that of the pure HPMC gel. The addition of SDS at different concentrations showed dissimilar influences on the gelation of HPMC; SDS at lower concentrations (≤6 mM) did not affect gelation temperature significantly except for enhancing the heat capacity whilst SDS at higher concentrations (≥6 mM) not only resulted in the gelation of HPMC at higher temperatures but also changed the pattern of the gelation thermograph from a single mode to a bimodal. On the basis of the observed thermal behavior of HPMC/SDS systems, the mechanism behind the sol-gel transition was discussed in terms of the properties of the surfactant and their influences on the extent of polymer/surfactant binding and polymer/polymer hydrophobic association. Gelation kinetics was analysed using the results from the DSC measurements. The kinetic parameters were determined.

Buoyancy-Driven Path Instabilities of Bubble Rising in Simple and Polymer Solutions of Hele–Shaw Cell

The buoyancy-driven path instabilities of an air bubble rising in a Hele–Shaw cell are examined as a function of the ratio of the gravitational and the capillary forces, i.e., the Eötvös number ( Eo ) of the bubble, for pure water, aqueous isopropyl alcohol (IPA) solutions, and aqueous hydroxypropyl methyl cellulose (HPMC) solutions. In the simple solutions, when Eo exceeds a threshold value, the motion of the bubble center can be categorized into three regimes: (1) a zigzag path for small Eo , (2) a straight path for intermediate Eo , and (3) another zigzag path accompanied by changes in the bubble for larger Eo ; these transitions occur irrespective of the fluid we examined. For HPMC solutions with concentrations lower than 0.001 g/100 mL, three different trajectories–a damped vibrational motion without changes in the bubble shape, a straight trajectory, and another damped vibrational motion accompanied by changes in the bubble shape–are observed as Eo increases. However, such path instabilities are suppressed for HPMC solutions with concentrations higher than 0.005 g/100 mL. Moreover, path instabilities occur when the Strouhal number exceeds a threshold of 0.2, which leads to the oscillation of the periphery length of the bubble for any of the solutions we studied.

Aqueous HPMCAS coatings: Effects of formulation and processing parameters on drug release and mass transport mechanisms

The major aim of the present work was to study the effects of various formulation and processing parameters on the resulting drug release kinetics from theophylline matrix pellets coated with aqueous hydroxypropyl methylcellulose acetate succinate (HPMCAS) dispersions. The plasticizer content, coating level and curing conditions significantly affected the release patterns in 0.1 M HCl, whereas no major effects were observed in phosphate buffer, pH 7.4. Due to the significant size of the HPMCAS particles (being in the micrometer range), their coalescence was particularly crucial and not complete upon coating. Consequently, at low coating levels continuous water-filled channels connected the bead cores with the release medium through which the drug could rapidly diffuse, resulting in high release rates even at low pH. In contrast, at high coating levels such continuous connections did not exist (due to the increased number of polymer particle layers), and drug release was controlled by diffusion through the macromolecular network resulting in much lower release rates in 0.1 M HCl. Importantly, pellet curing at elevated temperature and ambient relative humidity or exposure to elevated relative humidity at room temperature did not significantly alter the microstructure of the coatings, leading to only slightly decreased drug release rates. In contrast, pellet curing at elevated temperature combined with elevated relative humidity induced significant further polymer particle coalescence, resulting in a change of the underlying drug release mechanism and significantly reduced drug release rates.

Structural and kinetic modification of aqueous hydroxypropylmethylcellulose (HPMC) induced by electron beam irradiation

Aqueous solutions of 10 and 20 wt% hydroxypropylmethylcellulose (HPMC) were irradiated with different doses to make gel films. The gel fraction of the film increased sharply above a critical dose upon increase of the dose and then decreased gradually after passing a maximum. The scission/cross-linking ratio and the critical dose were determined with the aid of Charlesby–Rosiak equation as 0.52 and 9 kGy for the 10 wt% gel and 0.43 and 14 kGy for the 20 wt% gel, respectively. The gel fraction for the 20 wt% HPMC film was lower at low dose and higher at high dose than that for the 10 wt% film. The behavior of the swelling ratio of the gel film was just opposite to that of the gel fraction. The cross-linking density of the gel estimated from the Flory theory increased linearly with the irradiation dose at low dose, passed through a maximum around 100 and 160 kGy for 10% and 20% films, respectively, and decreased at high dose. These results suggest a competition of scission and cross-linking induced by the indirect effect of irradiation. Dielectric-relaxation measurements by time-domain reflectometry and RF impedance/material analyzer revealed two characteristic relaxations of chain motions around 100 MHz and of orientation of free water around 20 GHz. From the dose dependence of the dielectric-relaxation parameters determined by fitting to a combined equation of the Cole–Cole type and of the KWW type, a coupling of motions of HPMC molecules and water molecules was strongly suggested. The critical dose for gelation was coincident with the dose for the maximum of τ h and the minimum of Δ ε h together with the minimum of τ m and the maximum of Δ ε m , where τ h and Δ ε h denote the relaxation time and the relaxation strength for water molecular motion and τ m and Δ ε m the corresponding ones for HPMC molecular motion. The characteristic behavior is discussed in terms of an increase of the affinity between HPMC and water and the constrained molecular motion in the gel network.

A novel technique for imaging film coating defects in the film-core interface and surface of coated tablets

Confocal laser scanning microscopy (CLSM) was introduced and examined as a novel technique for imaging film-core interface and surface defects of film-coated tablets. Tablets of acetylsalicylic acid, microcrystalline cellulose (MCC) and lactose monohydrate were film-coated with aqueous hydroxypropyl methylcellulose using an instrumented side-vented pan coater. The film coatings were applied using 100- and 500-kPa spraying air pressures. The CLSM images of the coating surface were compared with surface roughness measurements using a laser profilometer and an optical roughness analyzer. The spraying air pressure affected the film-core interface and the occurrence of coating defects. With the lower spraying pressure the aqueous coating solution penetrated into the tablet core, the core components migrated to the coating layer, and the film coating surface was clearly rougher compared to the higher spraying pressure. Storage at 25°C/60% RH or 40°C/75% RH for 3 months expanded the MCC-containing tablet core impaired the film structure and increased the film roughness. Based on the present results, CLSM is an effective tool for imaging film-core interface and surface defects of film-coated tablets. The CLSM images are supported by the results obtained with the other surface roughness measuring techniques.

Swelling and drug release behavior of tablets coated with aqueous hydroxypropyl methylcellulose phthalate (HPMCP) nanoparticles

Organic solvent-based enteric coating technology using hydroxypropyl methyl cellulose phthalate (HPMCP) has been developed for many years due to low water solubility of HPMCP. In this work, aqueous HPMCP nanoparticles (HPMCP-NPs) were prepared by neutralization emulsification method using HPMCP powder and ammonium hydroxide (NH 4OH) in the absence of any organic solvent and emulsifier. Tablets for enteric use were coated with HPMCP-NP dispersions having different degree of neutralization that was manipulated by ion-exchange process. Disintegration and dissolution behavior of coated tablets were investigated using UV-visible spectrophotometer based on USP method (pH 1.2 and at 37 °C) and simulated intestinal fluid (pH 6.8 and at 37 °C for 60 min), respectively. The ion-exchange process, which was directly achieved by the protonation of dissociated carboxylic acid group of the aqueous HPMCP-NPs, was introduced as a useful way to control the release rate of drug and hydrophobic nature of HPMCP coating layer with a view for pharmaceutical application. The drug release and swelling were increased with increase in conductivity of aqueous HPMCP-NPs. On the other hand, particle size and polydispersity were decreased with increase in degree of neutralization.

Effect of nicotinamide on the properties of aqueous HPMC solutions

The effect of nicotinamide on the properties of aqueous hydroxypropylmethylcellulose (HPMC) solutions was studied. Rheological studies showed that solutions of HPMC of concentration less than 3.0 w/v.% did not form gels and exhibited Newtonian flow patterns at 25 °C. The inclusion of nicotinamide increased the viscosity of HPMC solutions, which indicates that nicotinamide expanded the HPMC coils in aqueous solution. When the temperature of the solutions was raised, they formed gels that were detected by viscometry and oscillation tests as abrupt increases in viscosity, storage modulus and loss modulus and an abrupt decrease in loss angle. Nicotinamide exhibited a salting in effect on the HPMC solutions resulting in an increase in gelation temperatures and cloud points. These effects are considered to be due to the hydrogen-bonding of nicotinamide to HPMC molecules, which was suggested by a shift to a longer wavelength of the UV spectra of aqueous nicotinamide solutions by the addition of HPMC. These results suggested that nicotinamide has affinity with the hydrophilic groups of HPMC.

Pinning of phase separation of aqueous solution of hydroxypropylmethylcellulose by gelation

Opalescence of the aqueous solution of hydroxypropylmethylcellulose (HPMC) induced by heating has been studied in terms of the phase diagram and the phase separation dynamics. The cloud point curve and the sol-to-gel transition curve intersected with each other at about 55°C. Just above the cloud-point curve at which the spinodal curve has its minimum, a ring-like scattering pattern appeared corresponding to the spinodal decomposition. Temporal growth of the scattering function in the course of phase separation was studied by a time-resolved light scattering technique. The gelation pinned the phase separation (spinodal decomposition) of the aqueous HPMC solution.

Influence of aqueous coatings on the stability of enteric coated pellets and tablets

Pancreatin pellets, placebo pellets and tablets containing vitamin B 2 were coated with various aqueous and organic enteric polymers, HPMCAS, HP, Eudragit® L 100-55, Eudragit® L 30 D-55, CAP, CAT, CMEC and PVAP, comparatively investigated and tested for storage stability. With the exception of Eudragit® L 100-55 and Eudragit® L 30 D-55, higher amounts of coating material were needed to achieve gastro-resistance with aqueous coating than with organic coating. Film formation from aqueous dispersions of micronized HP 55 was affected by the degree of micronization and was improved by reducing the particle size of the polymer. Undercoating was another suitable measure to decrease the amount of coating material required. The choice of plasticizer was of special importance in the aqueous dispersions, and type and quantity must be appropriate for the polymer applied. Non-polymeric plasticizers such as triethyl citrate (TEC) evaporated along with water during the spraying or drying process and high temperatures promoted such losses. The moisture-sensitive pancreatic enzymes were damaged both by humidity and heat during aqueous coating. The extent of damage was dependent on the coating equipment used. Upon storage, coatings obtained from aqueous dispersions showed changes in enteric performance or release characteristics as a consequence of three chemical/physical mechanisms: hydrolysis of ester linkages in the polymer or plasticizer, evaporation of the plasticizer, delayed film formation. The active ingredient pancreatin induced hydrolysis of the ester based film-former hydroxypropyl methylcellulose acetate succinate (HPMCAS). However, even without the influence of enzymes, the phthalic ester groups of aqueous hydroxypropyl methylcellulose phthalate (HP) were partly cleaved after 11 months storage. In HPMCAS-coated pancreatin pellets, the plasticizer glyceryl triacetate was almost completely hydrolyzed by the enzymes, whilst triethyl citrate was lost by evaporation through permeable packaging material at elevated temperatures. Open storage at elevated temperatures and humidities caused changes in the surface structure of HPMCAS coatings, consisting of a smoothing of the originally somewhat porous film and sticking. When applied to vitamin B 2 tablets, Eudragit® L 100-55, Opadry® enteric (PVAP) and Aqoat® (HPMCAS) proved to be quite stable aqueous enteric coatings, whereas cellulose acetate phthalate CAP or cellulose acetate trimellitate CAT coatings as ammonia-neutralized aqueous solution or as water-based pseudolatex Aquateric® were unstable when stored under stress conditions.