Characterisation of Biodegradable Microspheres Containing Dehydro-Iso-Androsterone

Abstract

Poly-DL-lactide (PLA) and poly-DL-lactide-co-glycolide (DL-PGA) micromatrices (PharmazomesTM) containing dehydro-isoandrosterone (DHEA), a weak androgen, were prepared by a solvent evaporation process. Micromatrices with increasing drug loading as well as increasing polymer molecular weight were prepared. The morphology of these systems depended on the drug loading, the polymer molecular weight and polymer composition. Increasing the drug loading or polymer molecular weight resulted in increasingly irregular microparticles being formed. DSC thermograms did not reveal the presence of crystalline DHEA in micromatrices containing 10 to 50% DHEA loading. However crystalline DHEA was observed in microspheres heated to above the glass transition temperature of the polymer. Xray analysis of 30% DHEA micromatrices established the presence of crystalline DHEA in the micromatrices. The percent release of DHEA from the micromatrices, into 40% ethanol at 37°C, increased with increasing DHEA loading. The dissolution of DHEA from drug-polymer compressed discs of constant surface area was proportional to the square root of time indicating matrix controlled release.     

Kinetics and Mechanism of Drug Release From Calcium Alginate Membrane Coated Tablets

Compressed tablets containing guaifenesin (model drug), calcium acetate (reactant) and pharmaceutical excipients were prepared. The tablets were coated with calcium alginate hydrogel using a novel, self-correcting membrane coating technique. Effects of coating time, the type of alginate polymer and pH of the dissolution medium on the rate of drug release were evaluated. In distilled water, zero order drug release profiles were obtained from the coated tablets. The release rate decreased with an increase in the coating time (increased coat thickness) and molecular weight of alginate polymer. The release rate constants correlated with model for spherical reservoir system and, were used to calculate permeability of guaifenesin in the calcium alginate coatings. Alginate polymer with higher guluronic acid content provided acid stable coating and higher molecular weight polymer produced membrane with lower permeability for guaifenesin.     

Development of molecularly imprinted polymer as sustain release drug carrier for propranolol HCL

Applications of molecularly imprinted polymer (MIPs), is rapidly increasing, especially in the drug delivery field. Molecularly imprinted polymers are the molecular traps, which can entrap the specific molecule and also control its release. Polymer complexes were prepared with and without propranolol HCl as templates, MAA (methacrylic acid) as monomer and EGDMA (ethyleneglycol dimethacrylate) as crosslinker by solvent polymerization technique. Drug release pattern from these polymer complexes were compared and maximum drug release in 12?h was consider to optimize the ratio of MAA and EGDMA. Since, the maximum propranolol HCl release from polymer complex was low (62.15%) in optimized batch, inclusion complex of drug with β-cyclodextrin were prepared for the higher drug release (80.32%). The selected polymer complexes were treated with methanol for complete removal of the drug to form MIPs. These MIPs were reloaded with the drug and subjected for drug release. The release patterns from reloaded MIP’s were observed to be slightly quicker than their corresponding MIP’s.     

Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500?nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.     

Formulation factors affecting drug release from poly(lactic acid) (PLA) microcapsule tablets

A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid) (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375 to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug release from the microcapsule was influenced by the polymer ratios and increased with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and the PLA were directly compressed independently to form microcapsule and matrix tablets, respectively. Drug release from the microcapsule tablets was significantly lowered (p < .001) compared to matrix tablets or free microcapsule (free microcapsule > matrices > microcapsule tablets). We also investigated the effect of tablet adjuvants, compression pressures, and microcapsule loading on the tablet performance in terms of friability, hardness, porosity, tensile strength, and the release kinetics of PB. The drug release rate increased with increasing compression pressure in the case of Emcompress or lactose, but not Avicel. The drug release rate was three- to fivefold increased with sodium starch glycolate compared to tablets without a disintegrant. With an increase in microcapsule loading, a decrease in the drug release rate was observed; however, the tablet performance remained satisfactory. The morphology of the microcapsules was monitored microscopically after the dissolution and the disintegration of tablets. The drug release accelerated with compression pressures and microcapsule loading from the tablets due to mechanical destruction of the microcapsule wall, which was more clearly seen after disintegration and dissolution of the tablets. Our data suggest that the PLA microcapsule can be tableted to make a SR product without significantly affecting its release kinetics.     

Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

Kinetic Release of Theophylline from Hydrophilic Swellable Matrices

The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg ± 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.     

Effect of Polymer Loading on Drug Release from Film-Coated Ibuprofen Pellets Prepared by Extrusion-Spheronization

Many factors are capable of influencing the mechanism of drug release from pellets prepared by extrusion-spheronization. This study was designed to elucidate the effect of polymer type and loading and the effect of processing variables on the rate and mechanism of drug release from ibuprofen pellets coated using aqueous polymeric dispersions. Qualitative and quantitative assessment of the success of the film coating process and the quality of the resultant films is made using scanning electron microscopy and in-vitro dissolution testing. The importance of plasticizer in polymeric film formation is also discussed. Uncoated pellets containing 60, 70 and 80% ibuprofen were coated with aqueous polymeric dispersions of polymethacrylates, ethylcellulose and silicone elastomer films. The high drug loading of these pellets adds special interest to this study. Drug release from uncoated pellets appears to follow first-order kinetics. The application of a polymeric membrane to uncoated cores has the effect of retarding drug release. There appears to be a critical coating level below which core coverage by the polymer is incomplete, drug release is diffusion controlled and first-order release kinetics are observed. Above a defined polymer level, drug release appears to be membrane controlled and zero-order kinetics are observed. The presence of plasticizer in the polymeric film imparts a hydrophilic component to an otherwise hydrophobic membrane. This enhances the penetration of aqueous solvent into the pellet core during in-vitro dissolution testing, increasing the rate of drug release. Scanning electron micrographs reveal the nature of these hydrophilic pores, beneath which a fine tortuous skeletal network of drug-depleted core is exposed.     

Effect of Polymer Loading on Drug Release from Film-Coated Ibuprofen Pellets Prepared by Extrusion-Spheronization

Abstract

Many factors are capable of influencing the mechanism of drug release from pellets prepared by extrusion-spheronization. This study was designed to elucidate the effect of polymer type and loading and the effect of processing variables on the rate and mechanism of drug release from ibuprofen pellets coated using aqueous polymeric dispersions. Qualitative and quantitative assessment of the success of the film coating process and the quality of the resultant films is made using scanning electron microscopy and in-vitro dissolution testing. The importance of plasticizer in polymeric film formation is also discussed. Uncoated pellets containing 60, 70 and 80% ibuprofen were coated with aqueous polymeric dispersions of polymethacrylates, ethylcellulose and silicone elastomer films. The high drug loading of these pellets adds special interest to this study. Drug release from uncoated pellets appears to follow first-order kinetics. The application of a polymeric membrane to uncoated cores has the effect of retarding drug release. There appears to be a critical coating level below which core coverage by the polymer is incomplete, drug release is diffusion controlled and first-order release kinetics are observed. Above a defined polymer level, drug release appears to be membrane controlled and zero-order kinetics are observed. The presence of plasticizer in the polymeric film imparts a hydrophilic component to an otherwise hydrophobic membrane. This enhances the penetration of aqueous solvent into the pellet core during in-vitro dissolution testing, increasing the rate of drug release. Scanning electron micrographs reveal the nature of these hydrophilic pores, beneath which a fine tortuous skeletal network of drug-depleted core is exposed.     

Development of a cyclodextrin-based nasal delivery system for lorazepam

A new drug delivery system containing hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a mucoadhesive polymer was developed with the aim to overcome the limitations connected with the nasal application of drugs with low water solubility. Lorazepam, free or as cyclodextrin inclusion complex, was loaded into mucoadhesive microparticles by spray drying, using hydroxypropylmethyl cellulose (HPMC), carbomer, and HPMC/carbomer interpolymer complex (IPC) as mucoadhesive components. Differential scanning calorimetry (DSC) indicated the presence of drug crystalline areas in microparticles loaded with free lorazepam, whereas in those loaded with HP-beta-CD inclusion complex, the drug was amorphous. Zeta potential measurement revealed that the polymer was the main component on the surface of the microparticles. The swelling rate and mucoadhesive properties of the microparticles were determined by the polymer type used in formulation. IPC- and carbomer-based microparticles showed superior swelling rate and mucoadhesion compared with the HPMC-based microparticles (p < .05). Drug loading into the polymer matrix decreased the swelling rate as well as the mucoadhesive properties of microparticles (p < .05), whereas the presence of HP-beta-CD in the matrix did not induce any additional reduction of those parameters (p > .05). The in vitro dissolution studies demonstrated that the microparticles containing the lorazepam inclusion complex displayed 1.8-2.5 times faster drug release compared with those containing free lorazepam. The change in the drug release rate could be connected with improved drug solubility inside the polymer matrix due to inclusion complex formation, as well as to the reduction in crystallinity following complexation, as confirmed by DSC studies.     

Kinetic Release of Theophylline from Hydrophilic Swellable Matrices

The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg ± 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.     

Development of Polysaccharide-Based Colon Targeted Drug Delivery Systems for the Treatment of Amoebiasis

ABSTRACT

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30–40% drug release during the initial 4–5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18–24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

Preparation and characterization of ibuprofen-loaded microspheres consisting of poly(3-hydroxybutyrate) and methoxy poly (ethylene glycol)-b-poly (D,L-lactide) blends or poly(3-hydroxybutyrate) and gelatin composites for controlled drug release

Poly-(3-hydroxybutyrate) (P(3HB)) is a biodegradable and biocompatible polymer that has been used to obtain polymer-based drug carriers. However, due to the high crystallinity degree of this polymer, drug release from P(3HB) microspheres frequently occurs at excessive rates. In this study, two strategies for prolonging ibuprofen release from P(3HB)-based microspheres were tested: blending with poly(D,L-lactide)-b-polyethylene glycol (mPEG-PLA); and obtaining composite particles with gelatin (GEL). SEM micrographs showed particles that were spherical and had a rough surface. A slight decrease of the crystallinity degree of P(3HB) was observed only in the DSC thermogram obtained from unloaded-microspheres prepared from 1:1 P(3HB):mPEG-PLA blend. For IBF-loaded microspheres, a reduction of around 10 °C in the melting temperature of P(3HB) was observed, indicating that the crystalline structure of the polymer was affected in the presence of the drug. DSC studies also yielded evidence of the presence of a molecular dispersion coexisting with a crystalline dispersion in the drug in the matrix. Similar results were obtained from X-ray diffractograms. In spite of 1:1 mPEG-PLA:P(3HB) blends having contributed to the reduction of the burst effect, a more controlled drug release was provided by the use of the 3:1 P(3HB):mPEGPLA blend. This result indicated that particle hydration played an important role in the drug release. On the other hand, the preparation of P(3HB):GEL composite microspheres did not allow control of the IBF release.     

In-vitro evaluation of sustained-release dyphylline tablets

Dyphylline tablets were prepared by direct compression of mixtures of the drug, emcompress and different ratios of hydroxypropyl methylcellulose (HPMC) or cellulose acetate phthalate (CAP). Physical properties of the prepared tablets and the drug release in 0.1 N HC1 and phosphate buffer, pH 7.4 were investigated.

All tablets were found to satisfy the USP requirements regarding content, weight uniformity and friability. Hardness was greatly enhanced and thickness was slightly increased by increasing the polymer ratio in tablet formulations. Disintegration time of the dyphylline tablets was delayed by the presence of either HPMC or CAP and there was a direct relationship between the polymer ratio and the disintegration time. Considerable retardation in the rate and extent of drug release from the prepared tablets in both dissolution liquids was observed. As the polymer ratio increased in the tablet formulations, the drug release was significantly inhibited.     

pH dependent hydrolysis and drug release behavior of chitosan/poly(ethylene glycol) polymer network microspheres

Semi-interpenetrating polymer network (IPN) microspheres of chitosan and poly(ethylene glycol) PEG were prepared for controlled release of drugs. A new method for the chemical crosslinking of chitosan microspheres containing isoniazid (INH) as a model drug is proposed and evaluated. The method consists of the exposure of microspheres to the vapor of crosslinking agent that act in gaseous phase under mild conditions. The structural analysis of the microspheres was carried out by FTIR-analysis. The swelling behavior, hydrolytic degradation, structural changes of the microspheres and loading capacity (LC) of the microspheres for INH were investigated. The prepared microspheres have shown 93% drug loading capacity, which suggested that these semi-IPN microspheres are suitable for controlled release of drugs in an oral sustained delivery system. © 2001 Kluwer Academic Publishers     

In vitro drug release study of methacrylate polymer blend system: effect of polymer blend composition,drug loading and solubilizing surfactants on drug release

The application of polymers as the drug delivery systems for treating oral infections is a relatively new area of research. The present study was to test the release of the antibacterial drug chlorhexidine diacetate (CHDA), the antifungal drug Nystatin (NYS) and the antiviral drug acyclovir (ACY) from polymer blends of poly(ethyl methacrylate) and poly(n-hexyl methacrylate) of different compositions. The effects of polymer blend composition, drug loading and solubilizing surfactants on the release of the drugs have been studied. Measurements of the in vitro rate of drug release showed a sustained release of drug over extended periods of time. Drug release rates decreased with increasing PEMA content in polymer blends. CHDA release rates increased steadily with increasing drug load. The drug release rates increased with the addition of surfactants. This study demonstrates that the three therapeutic agents show a sustained rate of drug release from polymer blends of PEMA and PHMA over extended periods of time. By varying polymer blend compositions as well as the drug concentration (loading), it is possible to control the drug release rates to a desired value. The drug release rate is enhanced by addition of surfactants that solubilize drugs in the polymer blends.     

Development of a Cyclodextrin-Based Nasal Delivery System for Lorazepam

A new drug delivery system containing hydroxypropyl-β-cyclodextrin (HP-β-CD) and a mucoadhesive polymer was developed with the aim to overcome the limitations connected with the nasal application of drugs with low water solubility. Lorazepam, free or as cyclodextrin inclusion complex, was loaded into mucoadhesive microparticles by spray drying, using hydroxypropylmethyl cellulose (HPMC), carbomer, and HPMC/carbomer interpolymer complex (IPC) as mucoadhesive components. Differential scanning calorimetry (DSC) indicated the presence of drug crystalline areas in microparticles loaded with free lorazepam, whereas in those loaded with HP-β-CD inclusion complex, the drug was amorphous. Zeta potential measurement revealed that the polymer was the main component on the surface of the microparticles. The swelling rate and mucoadhesive properties of the microparticles were determined by the polymer type used in formulation. IPC- and carbomer-based microparticles showed superior swelling rate and mucoadhesion compared with the HPMC-based microparticles (p < .05). Drug loading into the polymer matrix decreased the swelling rate as well as the mucoadhesive properties of microparticles (p < .05), whereas the presence of HP-β-CD in the matrix did not induce any additional reduction of those parameters (p > .05). The in vitro dissolution studies demonstrated that the microparticles containing the lorazepam inclusion complex displayed 1.8–2.5 times faster drug release compared with those containing free lorazepam. The change in the drug release rate could be connected with improved drug solubility inside the polymer matrix due to inclusion complex formation, as well as to the reduction in crystallinity following complexation, as confirmed by DSC studies.     

Properties of Hot-Melt Extruded Theophylline Tablets Containing Poly(Vinyl Acetate)

The objectives of this study were to investigate the properties of poly(vinyl acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of theophylline from matrix tablets prepared by hot-melt extrusion. A physical mixture of drug, polymer, and drug release modifiers was fed into the equipment and heated inside the barrel of the extruder. The cylindrical extrudates were either cut into tablets or ground into granules and compressed with other excipients into tablets. Due to the low glass transition temperature of the PVAc, the melt extrusion process was conducted at approximately 70°C. Theophylline was used as the model drug in this study. Theophylline was present in the extrudate in its crystalline form and was released from the tablets by diffusion. The Higuchi diffusion model and percolation theories were applied to the dissolution data to explain the drug release properties of the matrix systems. The release rate was shown to be dependent on the granule size, drug particle size, and drug loading in the tablets. Water-soluble polymers were demonstrated to be efficient release rate modifiers for this system.     

Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate)

The objectives of this study were to investigate the properties of poly(vinyl acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of theophylline from matrix tablets prepared by hot-melt extrusion. A physical mixture of drug, polymer, and drug release modifiers was fed into the equipment and heated inside the barrel of the extruder. The cylindrical extrudates were either cut into tablets or ground into granules and compressed with other excipients into tablets. Due to the low glass transition temperature of the PVAc, the melt extrusion process was conducted at approximately 70°C. Theophylline was used as the model drug in this study. Theophylline was present in the extrudate in its crystalline form and was released from the tablets by diffusion. The Higuchi diffusion model and percolation theories were applied to the dissolution data to explain the drug release properties of the matrix systems. The release rate was shown to be dependent on the granule size, drug particle size, and drug loading in the tablets. Water-soluble polymers were demonstrated to be efficient release rate modifiers for this system.     

Molecular Properties of Propranolol Hydrochloride Prepared as Drug-Resin Complexes

Drug-resin complexes, as well as physical dispersions, containing varying contents of propranolol were prepared. The molecular properties of samples were investigated by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and infrared (IR) spectroscopy. In addition, the USP paddle method was used to determine the release behavior of drug from various formulations prepared from the samples. The data from DSC and XRPD indicated that the molecular state of drug in the complexes was amorphous, whereas that in the physical dispersions exhibited the crystalline state of pure drug. These results suggested that the molecule of drug prepared as drug-resin complexes was monomolecularly dispersed in the resin bead. The IR study provided evidence that demonstrated the interaction between the drug and resin in the complexes. The release behavior of drug from the complexes was governed by the cross-linkage structure and equilibrium treatment of drug exchange of resin.