Sustained Release Matrices Research Articles

Morphology of new zwitterionic copolymer matrices for sustained drug release

Morphology of new zwitterionic copolymer matrices for sustained drug release

Evaluation of Galactomannan from <i>Gleditsia Sinensis</i> Lam. as Sustained Release Material in Colonic Drug Delivery

The galactomannan from endosperm of G. sinensis seeds was used as sustained release material in the matrix tablets prepared at different concentration of 5, 10 and 15 % corresponding to formulations of G5, G10 and G15, for the release of theophylline. The drug release behaviors of the systems were investigated, including the swelling and morphological studies and texture analysis. The dissolution tests were conducted in 0.1 M hydrochloric acid and pH 6.8 phosphate buffered saline. The results of release studies demonstrated that G10 with 10 % galactomannan concentration showed a better control of the drug release profiles. The percents of cumulative drug released in 24 h were 98.8, 90.2 and 83.4 % for G5, G10 and G15, respectively. All the systems exhibited the typical morphological behavior of a swellable matrix. Results of texture analysis on the swollen tablets confirmed that diffusion drug release mechanism played the major role in G10 and G15 systems while the drug delivery kinetic towards an erosion/relaxation mechanism for G5 matrix tablets.

Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water-soluble drugs II. In-vivo evaluation

Abstract Objectives Lipid-based liquid crystals formed from phytantriol (PHY) and glyceryl monooleate (GMO) retain their cubic-phase structure on dilution in physiologically relevant simulated gastrointestinal media, suggesting their potential application as sustained-release drug-delivery systems for poorly water-soluble drugs. In this study the potential of PHY and GMO to serve as sustained-release lipid vehicles for a model poorly-water-soluble drug, cinnarizine, was assessed and compared to that of an aqueous suspension formulation. Methods Small-angle X-ray scattering was used to confirm the nanostructure of the liquid-crystalline matrix in the presence of the selected model drug, cinnarizine. Oral bioavailability studies were conducted in rats, and disposition of lipid and drug in segments of the gastrointestinal tract was determined over time. Differences in the digestibility and stability of formulations under digestion conditions were investigated using an in-vitro lipolysis model. Key findings The oral bioavailability of cinnarizine using the PHY formulation was 41%, compared to 19% for the GMO formulation and 6% for an aqueous suspension. The PHY formulation provided a Tmax for cinnarizine of 33 h, with absorption apparent up to 55 h after administration. In contrast, the Tmax for the GMO formulation was only 5 h. The PHY formulation was retained in the stomach for extended periods of time, with 56% of lipid remaining in the stomach after 24 h, in contrast to less than 1% of the GMO formulation after 8 h, suggesting that gastric retention was a key aspect of the prolonged period of absorption, which correlated with the formulations' relative susceptibility to in-vitro lipolysis and degradation. Conclusions PHY provides a dramatic sustained-release effect for cinnarizine on oral administration, which is linked to gastric retention of the formulation and its ability to resist digestive processing. Poorly digested liquid crystal lipid formulations therefore offer a novel class of sustained-release matrices for oral administration.

Use of Silk Protein, Sericin, as a Sustained-Release Material in the Form of a Gel, Sponge and Film

To evaluate the usability of silk protein (sericin, SC) as a sustained-release material, the physicochemical properties of SC and the release profiles of model drugs from SC gel, sponge and film were studied. Heat aids the dissolution of SC. The molecular weight of SC tended to decrease as the heating temperature and heating time increased. The gel and sponge formed by SC were moldable and consisted of high molecular weight SC polymers (250 kDa and about 400 kDa). SC film was easily broken and exhibited elastic distortion. The addition of moisture-retaining plasticizer (glycerin and sorbitol) improved the film-forming characteristics of SC. The results suggested that SC is practical as a moldable gel and sponge, and as a tensible film. To evaluate the release profiles of small molecules, fluorescein isothiocyanate-dextran ((1) FD4, 4 kDa and (2) FD70, 70 kDa) were used as two model drugs with significantly different molecular weights, and fluorescein isothiocyanate-albumin ((3) FA, 66 kDa) was used as a charged drug. Each was formulated in SC gel, sponge and film. In each preparation, the release rate of the model drugs tended to be FA<FD70<FD4. FA, which has a large molecular weight and negative charge, was released for the longest period of time (≥1 week) from each preparation. The results suggest that SC is usable as an aqueous sustained-release material for high molecular weight drugs. Furthermore, if the drug is charged, its release can be sustained for an extended time.

Formulation and Characterization of Floating Gelucire Matrices of Metoprolol Succinate

The aim of the current investigation was to formulat e floating sustained-release matrices of metoprolol succinate using Gelucire 43/01 and Gelucire 44/14 by a melt-solidification technique. The in vitro and in vivo characteristics of the prepared matrices were evaluated. The in vitro drug release studies performed in 0.1 N HCl revealed a proportional increase in drug release pattern with increased concentration of Gelucire 44/14. Drug release data were analyzed by various mathematical models, and the mean dissolution time, Dissolution Efficiency, and similarity factor (f2) were determined in optimizing formulations. Differential scanning calorimetry and Fourier transform infrared spectroscopy showed no chemical interaction between drug and carriers studied. The in vitro floating characteristics of Gelucire matrices were greater than 12 h with good in vivo gastric retention. The results indicate that Gelucire 43/01 is an appropriate carrier for the development of sustained-release floating drug delivery systems and Gelucire 44/14, a highly hydrophilic and lipophilic balance (HLB) excipient, acts as release enhancer in the formulations studied.

Hydroxypropylated starches of varying amylose contents as sustained release matrices in tablets

Waxy corn, Hylon VII, and common corn starches were hydroxypropylated to low and high levels, and their sustained release properties and matrix characteristics were studied. Hydroxypropylation had a stronger impact on Hylon VII and common corn starch matrices than on waxy corn ones, suggesting that the behavior of starch tablet was dominated by its amylose content. The introduction of hydroxypropyl groups increased the water holding capacity of all starches and resulted in more fluid-like and softer matrices with increased chain mobility for amylose-containing starches. There was a decrease in the tablet porosity and in the storage modulus of swollen tablets of Hylon VII and common corn starches after hydroxypropylation. Microscopic analyses revealed smoother and less porous tablet structure upon hydroxypropylation of all starches. Hydroxypropylation improved the sustained release ability of amylose-containing starch matrices, and conferred additional resistance to the hydrolytic action of pancreatin under simulated gastrointestinal conditions. However, hydroxypropylation had a detrimental impact on drug release from waxy corn starch matrices.

Solid lipid extrudates as sustained-release matrices: The effect of surface structure on drug release properties

The study focused on the structural characterization of sustained-release lipid matrices prepared by solid lipid extrusion. Drug-containing lipid extrudates were locally analyzed in order to identify differences between the chemical and structural composition of surface and core elements. Independent of the lipid the dissolution from the outer extrudate surfaces was slower compared with dissolution from surfaces prepared by cutting the extrudate. The burst effect was higher for the cross-sections indicating more drug was exposed on these surfaces. The release from glycerol trimyristate (Dynasan 114 ®) extrudates was slower compared with glycerol palmitostearate (Precirol ATO 5 ®) extrudates. By solid-state analysis using DSC, ATR-FTIR and SEM measurements the differences between surface material and core material could be attributed mainly to morphological differences. Chemical differences between the core and the outer surface were not relevant. The differences between the surfaces might be explained by the friction induced temperature increase during extrusion in the die plate. The obtained results and a proposed scheme were used to explain the influence of different formulation/processing parameters, such as drug particle size and milling on the drug dissolution behaviour. Small drug particles and intact extrudates are a means of minimizing the burst release.

Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: Establishment of level A IVIVC

The purpose of this study was to examine a level A in vitro–in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer–Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

In Vitro Evaluation of Theophylline Matrices using Xyloglucan

Xyloglucan is a water soluble polysaccharide extracted from the beans of Tamarindus Indica. Very few publications are found related to its use for preparing oral sustained release swellable matrix. The purpose of this investigation was to prepare sustained release matrices using Xyloglucan and investigate the effects of polymer level, diluents type, pH and ionic strength of the dissolution medium, basket rotational speed, and swelling isotherms on drug release. Tablet formulations containing 50% theophylline as a drug model, Xyloglucan cold water soluble (20%, 30 and 40%) and different diluents (Avicel PH-101, lactose and dibasic calcium phosphate) were prepared. The formulation containing 30% Xyloglucan water soluble and Avicel was selected as best formulation because it gives controlled release profile and tested for swelling isotherms, drug release in different dissolution media, and different basket rotational speed. Percent drug release from formulations containing 50% theophylline, 30% Xyloglucan water soluble, and Avicel PH-101 was 34.2% at 6 hours, 35.6% with lactose, and 30.9% with Emcompress. ANOVA two-way analysis showed a change in drug release rate when polymer percent was increased at the 5% significance level. Different diluents, different dissolution media, and different basket rotational speeds did not significantly change the drug release. The mechanism of drug release appears to follow anomalous relaxation for swellable matrix.

New co-polymer zwitterionic matrices for sustained release of verapamil hydrochloride

Stable co-polymer [vinyl acetate-co-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate, p(VA-co-DMAPS)] latex of different compositions has been synthesized for the first time by emulsifier-free emulsion copolymerization. The unusual >>overshooting<< behavior of the co-polymer tablets has been explained by the formation of specific clusters from the opposite oriented dipoles-zwitterionic species. The change of their concentration with the DMAPS unit fraction (mDMAPS), pH and ionic strength has been considered responsible for the differences observed in the swelling kinetics. The results obtained prove that mDMAPS and ionic strength could be used to control the swelling degree of the p(VA-co-DMAPS) matrices and their sustained drug delivery. In this way, p(VA-co-DMAPS) matrices could be effectively used to control the sustained release of drugs with basic properties like verapamil hydrochloride from model tablets.

In vitro evaluations of konjac glucomannan and xanthan gum mixture as the sustained release material of matrix tablet

The objective of the present investigations was to develop sustained release matrix tablets with a mixture of the polysaccharides, konjac glucomannan (KGM) and xanthan gum (XG), as the sustained release material. A simple enzymatic procedure was selected to mimic the environment of colon in vitro assessments. The concentration of β-mannanase solution in mimic colon media was determined by comparing the hydrolytic ability of the mimic colon solution with that of 4% (w/v) rat cecal content media. In vitro, investigations were carried out to characterize the drug release process. The model drug cimetidine released from polysaccharides gel layer of matrix tablets over 10 h. It was shown that the synergistic interaction between konjac glucomannan and xanthan gum in the gel phase affects on the drug diffusion, which can effectively retard the drug release from the matrix tablets. Further research on the mixed polysaccharides indicated that there was a strong synergistic interaction between KGM and XG in solution and in the gel phase. The experimental results predicted that the polysaccharide mixtures of konjac glucomannan and xanthan gum has a good potential to be applied to sustained release drug delivery systems.

Effect of Particle Size, Compaction Force and Presence of Aerosil 200 on the Properties of Matrices Prepared from Physical Mixture of Propranolol Hydrochloride and Eudragit RS or RL

Objective Eudragits are widely used polymers in the production of oral sustained release dosage forms. The application of these polymers in the production of inert insoluble matrices has been investigated. However the effect of particle size, compaction force and presence of Aerosil 200 as a glidant on the properties of Eudragit RS and RL matrices prepared by direct compression of their physical mixtures with drug have not been fully investigated. This study was performed in order to investigate the effect of above mentioned factors on physicomechanical and release properties of propranolol hydrochloride and Eudragit RS or RL matrices. Materials and Methods Polymers were separated to different size fractions using series of sieves. Matrices were prepared in 1:3 ratio by direct compression of physical mixture of drug and polymer. To study the effect of Aerosil 200, matrices were prepared from different size fractions containing 1%w/w Aerosil 200. To investigate the effect of compaction force, the 125-177µm size fraction of polymer was chosen and compression carried out at 5, 10, 15, 20 and 30 kN compaction force. Matrices were characterized for their hardness and dissolution. Results The results showed that due to decrease in tablet hardness the release rate increased with increase in polymer particle size. Drug release rates were almost the same for both polymers at similar particle size range. The same trend was also observed for matrices containing Aerosil 200. Addition of Aerosil 200 decreased the rate of drug release from all matrices except those prepared from 250-350 µm size fraction. This was attributed to increase in the tablet hardness. Increase in compaction force from 5kN to 20kN increased the tablet hardness and consequently decreased the release rate, however, further increase in compaction force from 20 to 30 kN did not significantly affect the release rates of drug. Conclusion Polymer particle size, presence of Aerosil and compaction force are important factors affecting drug release from Eudragit RS or RL matrices. Eudragit RS and RL polymers alone are not suitable for preparation of sustained release matrices containing water soluble drugs.

Solid lipid extrusion of sustained release dosage forms

The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5 ®) and glyceryl trimyristate (Dynasan 114 ®), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 °C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 °C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.

Drug/Cyclodextrin Solid Systems in the Design of Hydrophilic Matrices: A Strategy to Modulate Drug Delivery Rate

The aim of this study was to investigate how the delivery rate of erodible sustained-release hydrophilic matrices intended for the delivery of poorly soluble drugs can be optimized through the incorporation of drug/cyclodextrin binary systems. Carvedilol (CAR), a sparingly water-soluble antihypertensive drug, was selected as a model for the study. As first, we attempted to improve CAR apparent solubility by association with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and then incorporated CAR/HPbetaCD binary systems in sustained-release tablets made of poly(ethyleneoxide) (PEO). Solid CAR/HPbetaCD binary systems were prepared by physical mixing, kneading, co-melting and freeze-drying methods and characterized by DSC and X-ray powder diffractometry. The amount of CAR dissolved from all the HPbetaCD-containing systems was higher than pure CAR, the co-molten and freeze-dried products showing the best dissolution performance. The incorporation of the binary systems in PEO tablets resulted in a CAR release rate much higher than tablets containing only CAR. It was found that the time necessary to achieve complete release from the tablet was linearly related to the dissolution parameters of CAR/HPbetaCD powders. In the case of co-molten and freeze-dried products, all CAR content could be released in about 12 and 10 h, respectively. Our results demonstrate that the incorporation of drug/cyclodextrin solid systems in erodable PEO matrices intended for the delivery of poorly water-soluble drugs is useful to modulate the release rate by controlling the dissolution properties of the drug inside the tablet.

Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems

A new class of surfactants with glycerate headgroups, that form viscous lyotropic liquid crystalline phases in excess water, have been investigated for their potential to provide sustained release matrices for depot drug delivery. Oleyl glycerate and phytanyl glycerate were used as representative surfactants of this new class, and their behaviour compared with that of glyceryl monooleate (GMO). The surfactants were found to form reverse hexagonal phase (H II) in excess water, and the matrices were loaded with a series of model hydrophobic and hydrophilic drugs, (paclitaxel, irinotecan, glucose, histidine and octreotide), and the release kinetics determined. In all cases, the release behaviour obeyed Higuchi kinetics, with linear drug release versus square root of time. The H II phases released model drugs slower than the GMO cubic phase matrix. The oleyl glycerate matrix was found to consistently release drug faster than the phytanyl glycerate matrix, despite both matrices being based on H II phase. To further demonstrate the potential utility of these materials as drug depot delivery systems, an injectable precursor formulation for octreotide was also prepared and demonstrated to provide controlled release for the peptide. The stability of the H II phase to likely in vivo breakdown products was also assessed.

Release characteristics and bioactivity of gelatin-tricalcium phosphate membranes covalently immobilized with nerve growth factors

The gelatin-tricalcium phosphate membranes were cross-linking with low concentration glutaraldehyde solution (GTG). This material has good mechanical property, biocompatibility, and is feasible for surgical manipulation. For axonal regeneration, nerve growth factors (NGF) were immobilized onto the composite (GTG) with carbodiimide. The purpose of this study was to evaluate the release characteristics and bioactivity of NGF after covalent immobilization onto the GTG membranes (GEN). NGF immobilized onto and released from the composite was quantified using ELISA method. PC 12 cells were cultured on the GTG and GEN composites. Cell survival, cytotoxicity, and cellular activity were evaluated by total protein content, LDH activity, and MTT assay respectively. Neurite outgrowth assay was used to evaluate the biological activity of NGF released from GEN composite. From ELISA measurement, the releasing curve for NGF showing two distinctive parts with different slopes indicated that NGF were released from the composite in diffusion-controlled mechanism and degradation-controlled mechanism respectively. While culturing with PC 12 cells, LDH leakage results implied that whether GTG composite cross-linked with NGF or not showed little cytotoxicity. The total protein content and cellular activity of PC 12 cells were lower on GTG and GEN membranes than control group. However, 56%±3.98 of PC 12 cells showed significant neurite outgrowth on GEN membranes which was statistically higher than GTG without NGF immobilization. In addition, sustained release of bioactive NGF for two months had been demonstrated by neurite outgrowth assay. From these experiments, it can be concluded that the technique used in the present study is capable of immobilizing NGF onto GTG membranes covalently and remaining the bioactivity of NGF. Therefore, GEN composite can be materials for sustained release of bioactive NGF and a candidate for future therapeutic application in nerve repair.

New Nanophase Separated Intelligent Amphiphilic Conetworks and Gels

AbstractAmphiphilic conetworks (APCN) are new materials composed of covalently bonded otherwise immiscible hydrophilic and hydrophobic polymer chains. The amphiphilic nature of these new crosslinked polymers is indicated by their swelling ability in both hydrophilic and hydrophobic solvents. Special synthetic techniques have been developed for the preparation of these new unique materials, such as poly(2‐hydroxyethyl methacrylate)‐l‐polyisobutylene (PHEMA‐l‐PIB), poly(methacrylic acid)‐l‐polyisobutylene (PMAA‐l‐PIB) and poly(N,N‐dimethylaminoethyl methacrylate)‐l‐polyisobutylene (PDMAEMA‐l‐PIB) (‐l‐ stands for linked by). Due to their unique architecture, macrophase separation of the immiscible components is prevented by the chemical bonding in the conetworks. As a results, phase separation leads to nanodomains with usually 2‐20 nm domain sizes as shown by AFM measurements. The nanophase separated morphology may also lead to smart temperature responsive gels with high mechanical stability, such as in the case of poly(N,N‐dimethylaminoethyl methacrylate)‐l‐polyisobutylene APCNs as discovered during these studies. In another approach, poly(2‐hydroxyethyl methacrylate)‐l‐polyisobutylene and poly(methacrylic acid)‐l‐polyisobutylene APCNs were prepared by a special two‐step process. The new PMAA‐l‐PIB polyelectrolyte APCNs possess smart (intelligent) reversible pH‐responsive properties in aqueous media. These unique conetwork structures and properties of these new emerging materials may lead to numerous new potential applications, such as smart materialk products, sustained drug release matrices, biomaterials, nanohybrids, nanotemplates etc.

Carbon Dioxide Emulsion Assisted Loading of Polymer Microspheres toward Sustained Release Materials

An organic solvent-free method for encapsulating progesterone at high loadings within micron-sized inert latex polymer beads is reported. This approach makes use of a polymeric surfactant to emulsify carbon dioxide into an aqueous latex suspension. In this way, preformed approximately 4 microm polystyrene (PS) microparticles surface-grafted with poly(N-vinylpyrrolidone) (PVP) were plasticized and swollen followed by rapid partitioning of progesterone into the polymer matrix. The as-prepared polystyrene beads incorporated over 10% progesterone by weight while maintaining their initial size and morphological uniformity. Dissolution experiments were also carried out to obtain the release profile of progesterone entrapped within the PVP/PS particles.

수성미세채널을 형성하는 서방성 매트릭스 장용정을 이용한 탐스로신의 방출제어

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate

Solid-state compatibility and in vitro dissolution of direct-compressed sustained-release matrices of polyvinylacetate (PVAc) and polyvinylpyrrolidone (PVP) containing ibuprofen as a model drug were studied. Polyvinylalcohol (PVA) was used as an alternative water-soluble polymer to PVP. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) were used for characterizing solid-state polymer–polymer and drug–polymer interactions. The mechanical treatment for preparing physical mixtures of polyvinyl polymers and the drug (i.e. simple blending or stressed cogrinding) was shown not to affect the physical state of the drug and the polymers. With the drug–polymer mixtures the endothermic effect due to drug melting was always evident, but a considerable modification of the melting point of the drug in physical binary mixtures (drug:PVP) was observed, suggesting some interaction between the two. On the other hand, the lack of a significant shift of the melting endothermic peak of the drug in physical tertiary drug–polymer mixtures revealed no evidence of solid-state interaction between the drug and the present polymers. Sustained-release dissolution profiles were achieved from the direct-compressed matrices made from powder mixtures of the drug and PVAc combined with PVP, and the proportion of PVAc in the mixture clearly altered the drug release profiles in vitro. The drug release from the present matrix systems is controlled by both diffusion of the drug through the hydrate matrix and the erosion of the matrix itself.