Synthesis and evaluation of sucrose‐containing polymeric hydrogels for oral drug delivery

Biodegradable and biocompatible copolymeric hydrogels based on sucrose acrylate, N‐vinyl‐2‐pyrrolidinone, and acrylic acid were designed and synthesized. Because of the growing importance of sugar‐based hydrogels as drug delivery systems, these new pH‐responsive sucrose‐containing copolymeric hydrogels were investigated for oral drug delivery. The sucrose acrylate monomer was synthesized and characterized. The copolymeric hydrogel was synthesized by free‐radical polymerization. Azobisisobutyronitrile (AIBN) was the free‐radical initiator employed and bismethyleneacrylamide (BIS) was the crosslinking agent used for hydrogel preparations. Homopolymeric vinyl pyrrolidone hydrogels were also prepared by the same technique. The hydrogels were characterized by differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy. Equilibrium swelling studies were carried out in enzyme‐free simulated gastric and intestinal fluids (SGF and SIF, respectively). These results indicate the pH‐responsive nature of the hydrogels. The gels swelled more in SIF than in SGF. A model drug, propranolol hydrochloride (PPH), was entrapped in these gels and the in vitro release profiles were established separately in both enzyme‐free SGF and enzyme‐free SIF. The drug release was found to be faster in SIF. About 93 and 99% of the entrapped drug was released over a period of 24 h in SGF and SIF, respectively. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2597–2604, 2002     

Thermoreversible hydrogel. XVII. Investigation of the drug release behavior for [N‐isopropylacrylamide‐co‐trimethyl acrylamidopropyl ammonium iodide‐co‐3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate] copolymeric hydrogels

A series of copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm), trimethyl acrylamidopropyl ammonium iodide (TMAAI), and 3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (DMAPS). Results showed that the swelling ratios of these copolymeric hydrogels increased with an increase of TMAAI content. The drug release behavior of the ionic thermosensitive hydrogels related to their ionicity and drug types. Results indicated that the release ratio of caffeine in the hydrogels was not affected by the ionicity of hydrogels, but increased with increasing of the swelling ratio. The anionic solute (phenol red) strongly interacted with cationic hydrogel (very large K_d), so the phenol red release ratio in cationic gels was very low. On the other hand, CV was adsorbed only on the skin layer of the cationic hydrogel because of the charge repulsion, and released rapidly. Therefore the release ratio was highest for cationic hydrogel to cationic drug. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1592–1598, 2002     

pH‐reversible hydrogels. IV. Swelling behavior of the 2‐hydroxyethyl methacrylate‐co‐acrylic acid‐co‐sodium acrylate copolymeric hydrogels

A series of 2‐hydroxyethyl methacrylate (HEMA) and sodium acrylate (SA50) copolymeric gels were prepared from HEMA and the anionic monomer SA50 with various molar ratios. The influence of SA50 on the copolymeric gels on their swelling behavior in deionized water at different temperatures and various pH buffer solutions was investigated. Results indicated that the poly(2‐hydroxyethyl methacrylate) (PHEMA) hydrogels exhibited an overshooting phenomenon in their dynamic swelling behavior. The maximum overshooting value decreased with increasing of the temperature. The same results were also found in the HEMA/SA50 copolymeric gels with a lower SA50 content. On the contrary, the overshooting phenomenon for HEMA/SA50 copolymeric gels with a higher content of SA50 was exhibited only under higher temperature (over 35°C). These copolymer gels were used to assess drug release and drug delivery in this article. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1360–1371, 2001     

pH‐thermoreversible hydrogels. I. Synthesis and swelling behaviors of the (N‐isopropylacrylamide‐co‐acrylamide‐co‐2‐hydroxyethyl methacrylate) copolymeric hydrogels

A series of pH‐thermoreversible hydrogels that exhibited volume phase transition was synthesized by various molar ratios of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and 2‐hydroxyethyl methacrylate (HEMA). The influence of environmental conditions such as temperature and pH value on the swelling behavior of these copolymeric gels was investigated. Results showed that the hydrogels exhibited different equilibrium swelling ratios in different pH solutions. Amide groups could be hydrolyzed to form negatively charged carboxylate ion groups in their hydrophilic polymeric network in response to an external pH variation. The pH sensitivities of these gels also depended on the AAm content in the copolymeric gels; thus the greater the AAm content, the higher the pH sensitivity. These hydrogels, based on a temperature‐sensitive hydrogel, demonstrated a significant change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a dehydrated network response to small variations of temperature. pH‐thermoreversible hydrogels were used for a study of the release of a model drug, caffeine, with changes in temperature. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 221–231, 1999     

Influence of MEOBiPA content on the properties of novel photoluminescent thermosensitive hydrogels

In order to establish a dual functional hydrogel, a special monomer, methacryloyloxy‐ethylene‐oxy‐carbonyl bis[4‐(phenyl‐isopropyl)phenyl]amine (MEOBiPA), was prepared from bis[4‐(phenyl‐isopropyl)phenyl]‐4‐cyanophenyl amine and 2‐hydroxyethyl methacrylate. Subsequently, a series of thermosensitive hydrogels was obtained through copolymerization of N‐isopropyl acrylamide (NIPAAm) with MEOBiPA by UV irradiation (named the NM series). The effect of MEOBiPA content on the swelling behavior, mechanical properties and drug release behavior of the hydrogels was further investigated. Results showed that the swelling ratios of the NM copolymeric hydrogels decreased from 4.73 to 1.74 g g^?1 when the MEOBiPA content in the hydrogel increased from 0.1 to 0.9 mol%. Both gel strength and crosslinking density of the NM hydrogels increased with increasing MEOBiPA. Conversely, the thermosensitive behavior of NM hydrogels significantly decreased upon increase of MEOBiPA content. Likewise, the caffeine release ratio also decreased from 70% to 25%. Notably, the intensity of photoluminescence increased with increasing MEOBiPA content in the hydrogels. Further, the corresponding copolymers of the hydrogels were prepared using free radical polymerization. The UV absorbance and photoluminescent behavior of the MEOBiPA, NIPAAm/MEOBiPA copolymeric hydrogels and their corresponding copolymers in different polar solvents were also investigated. © 2015 Society of Chemical Industry     

Thermoreversible hydrogels X: Synthesis and swelling behavior of the (N‐isopropylacrylamide‐co‐sodium 2‐acrylamido‐2‐methylpropyl sulfonate) copolymeric hydrogels

A series of thermosensitive hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm) and sodium‐2‐acrylamido‐2‐methylpropyl sulfonate (NaAMPS). Factors such as temperature and initial total monomer concentration and different pH solutions were investigated. Results indicated that the more the NaAMPS content in hydrogel system, the higher the swelling ratio and the gel transition temperature; the higher the initial monomer concentration, the lower the swelling ratio. The result also indicated that the NIPAAm/NaAMPS copolymeric hydrogels had different swelling ratios in various pH environments. The present gels showed a pH‐reversible property between pH 3 and pH 10 and thermoreversibility. The swelling ratios of copolymeric gels were lower in a strong alkaline environment because the gels were screened by counterions. Finally, the drug release behavior of these gels was also investigated in this article. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 1760–1768, 2000     

Thermoreversible hydrogels. XIX. Synthesis and swelling behavior and drug release behavior for the N‐isopropylacrylamide/poly(ethylene glycol) methylether acrylate copolymeric hydrogels

A series of thermosensitive copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm) and poly(ethylene glycol) methylether acrylate (PEGMEA_n), which was synthesized from acryloyl chloride and poly(ethylene glycol) mono methylether with three oxyethylene chain lengths. Investigation of the effect of the chain length of oxyethylene in PEGMEA_n, and the amount of the PEGMEA_n in the NIPAAm/PEGMEA_n copolymeric gels, on swelling behavior in deionized water was the main purpose of this study. Results showed that the swelling ratio for the present copolymeric gels increased with increasing chain length of oxyethylene in PEGMEA_n and also increased with increase in the amount of PEGMEA_n in the copolymeric gels. However, the gel strength and effective crosslinking density of these gels decreased with increase in swelling ratio. Some kinetic parameters were also evaluated in this study. Finally, the drug release and drug delivery behavior for these gels were also assessed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1683–1691, 2003     

Swelling and drug‐release behavior of the poly(AA‐co‐N‐vinyl pyrrolidone)/chitosan interpenetrating polymer network hydrogels

A series of novel hydrogels were prepared from acrylic acid (AA), N‐vinyl pyrrolidone (NVP), and chitosan by photopolymerization. The swelling behavior, gel strength, and drug release behavior of the poly(AA/NVP) copolymeric hydrogels and corresponding interpenetrating polymer network hydrogels were investigated. Results showed that the swelling ratios for the present hydrogels decreased with an increase of NVP content in the gel, but the gel strength increased with an increase of NVP content in the gel. Results also showed that the drug‐release behavior for the gels is related to the ionicity of drug and the swelling ratio of the gel. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2135–2142, 2004     

Effect of fluorinated hydrophobic monomer on the drug release behavior for the thermosensitive hydrogels

Three series of copolymeric gels based on N‐isopropylacrylamide (NIPAAm) and perfluoroalkyl methacrylate such as 2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate (OFPMA), 4,4,5,5,6,7,7,7‐octafluoro‐2‐hydroxy‐6‐(trifluoromethyl)heptyl methacrylate (OFHHMA), and 3,3,4,4,5,6,6,6‐octafluoro‐5‐(trifluoromethyl)hexyl methacrylate (OFHMA), were prepared by emulsion polymerization. The effect of perfluoroalkyl methacrylate and sodium lauryl sulfate (SLS), which can act as a surfactant and a pore‐forming agent, on the equilibrium swelling ratio and mechanical properties of the present hydrogels was investigated. Results show that hydrophobic monomers made the swelling ratio of the gel decrease and the mechanical property of the gel increase; however, SLS exhibits a contrary result. In addition, the effect of perfluoroalkyl methacrylate on the drug release behavior was also investigated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4661–4667, 2006     

Delivery of bupivacaine included in poly(acrylamide‐co‐monomethyl itaconate) hydrogels as a function of the pH swelling medium

Copolymeric hydrogels of poly(acrylamide‐co‐monomethyl itaconate) (A/MMI) crosslinked with N,N′‐methylenbisacrylamide (NBA) were synthesized as devices for the controlled release of bupivacaine (Bp). Two compositions of the copolymer, 60A/40MMI and 75A/25MMI, were studied. A local anesthetic was included in the feed mixture of polymerization (2–8 mg Bp/tablet) and by immersion of the copolymeric tablets in an aqueous solution of the drug. A very large amount of Bp (36–38 mg Bp/tablet) was included in the gels by sorption due to interactions between the drug and the side groups of the hydrogels. Swelling and drug release were in accordance with the second Fick's law at the first stages of the processes. The swelling behavior of these copolymers depended on the pH of the medium. The equilibrium swelling degree (W_∞) was larger at pH 7.5 (W_∞ ≈ 90 wt %) than at pH 1.5 (W_∞ ≈ 52–64 wt %) due to the ionization of the side groups of the copolymer. Release of the drug also depended on the pH of the swelling medium; at pH 7.5, about 60% of the included drug was released, and at pH 1.5, about 80% was released. Bp release was controlled by the comonomer composition of the gels, their drug‐load, and the pH of the swelling medium. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 327–334, 2002     

Effect of porosigen and hydrophobic monomer on the fast swelling–deswelling behaviors for the porous thermoreversible copolymeric hydrogels

A series of porous thermoreversible copolymeric hydrogels were prepared from N‐isopropylacrylamide (NIPAAm) and hydrophobic monomers such as 2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate (OFPMA) and n‐butyl methacrylate (BMA) and CaCO₃ or poly(ethylene glycol) 8000 (PEG8000) as porosigen by emulsion polymerization. The effect of hydrophobic monomers and porosigens on the fundamental properties, such as equilibrium swelling ratio, swelling kinetics, gel strength, crosslinked densities, etc., and fast swelling–deswelling behavior for the present copolymeric hydrogels were investigated. Results showed that the deswelling rates for the gels porosigened by CaCO₃ were more rapid than those gels foamed by PEG8000. Results also showed that the swelling rates for the gel foamed by CaCO₃ were higher than those for the gel foamed by PEG8000. At the same time, results also showed that the gels with OFPMA foamed by CaCO₃ exhibit a faster swelling–deswelling behavior than those gels with BMA. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3152–3160, 2006     

Thermoreversible hydrogels. II. Effect of some factors on the swelling behavior of N,N-dimethylacrylamide and n-butoxymethyl acrylamide copolymeric gels

A series of thermoreversible hydrogels are prepared from the various molar ratios of N,N-dimethylacrylamide (DMA), n-butoxymethyl acrylamide (nBMA), and N,N′-methylenebisacrylamide (NMBA). The influences of the amount of DMA in the copolymeric gels, temperature, and polymerization media on the swelling behaviors in water are investigated. Results indicate that the higher the DMA content in the hydrogel systems the higher the swelling ratio and the gel transition temperature. The effects of the gel thickness on the swelling ratio for DMA/nBMA copolymeric gels indicate that the equilibrium swelling time and diffusion coefficient for the thinner gel (1.5 mm) from the dried state to the completely swollen state are obviously faster than are those for the thicker gels (2.0 and 3.5 mm). The effects of the different polymerization media on the swelling ratio for DMA/nBMA copolymeric gels also show that the larger the solvent molecular size and the poor miscibility of the monomer and solvent the higher the swelling ratio and the diffusion coefficient. The drug release in these copolymeric gel systems are also investigated. © 1997 John Wiley & Sons, Inc. J Appl Polm Sci 65:909–916, 1997     

pH–thermoreversible hydrogels. II. Synthesis and swelling behaviors of N-isopropylacrylamide-co-acrylic acid-co-sodium acrylate hydrogels

A series of pH–thermoreversible hydrogels are prepared from the three molar ratios of N-isopropylacrylamide (NIPAAm) and acrylic acid neutralized 50 mol % by sodium hydroxide (SA50) and N,N′-methylene bisacrylamide (NMBA). The influence of the environmental conditions, such as temperature and pH values, on the swelling behavior of these copolymeric gels is also investigated in this article. Results show that the hydrogels bearing negative charges exhibit different equilibrium swelling ratios under various pH media. The pH sensitivities of these gels also strongly depend on the molar ratio of SA50 in the copolymeric gels; thus, the more the SA50 content, the higher the gel pH sensitivity. These hydrogels exhibited thermosensitivity demonstrating a larger change of the equilibrium swelling ratio in aqueous media under temperature changes. An overshooting phenomenon is observed from the gel swelling kinetics under high-temperature conditions. The said hydrogels are also used to investigate the release of model drugs in this study. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1955–1967, 1999     

Thermoreversible hydrogels. I. Synthesis and effect of a hydrophobic monomer on swelling behaviors of thermoreversible gels prepared by copolymerizing N-alkoxyalkylacrylamide with butyl acrylate

A series of copolymeric gels were prepared from N-alkoxyalkylacrylamide and n-butyl acrylate (BA) at various feed ratios. The effect of the content of BA in the copolymer on the gel behaviors is discussed. The respective crosslinked copolymer exhibits a gel transition behavior, collapsing and shrinking above gel transition temperature but swelling and reexpanding below gel transition temperature. By utilizing this character, these copolymeric gels could be used for drug release or drug delivery systems. The drug released from the copolymeric gels was plotted as M_t/M_∞ versus t, where M_t/M_∞ is the fraction of drug released at given time t. In this experiment, crystal violet and caffeine were chosen as model drugs. The deswelling-kinetics experiments with caffeine showed that a water pocket was formed within the gel matrix when the gel deswelled rapidly. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 1477–1484, 1997     

Synthesis and swelling properties of 2‐hydroxyethyl methacrylate‐co‐1‐vinyl‐3‐(3‐sulfopropyl)imidazolium betaine hydrogels

A series of 2‐hydroxyethyl methacrylate/1‐vinyl‐3‐(3‐sulfopropyl)imidazolium betaine (HEMA/VSIB) copolymeric gels were prepared from various molar ratios of HEMA and the zwitterionic monomer VSIB. The influence of the amount of VSIB in copolymeric gels on their swelling behavior in water and various saline solutions at different temperatures and the drug‐release behavior, compression strength, and crosslinking density were investigated. Experimental results indicated that the PHEMA hydrogel and the lower VSIB content (3%) in the HEMA/VSIB gel exhibited an overshooting phenomenon in their dynamic swelling behavior, and the overshooting ratio decreased with increase of the temperature. In the equilibrium water content, the value increased with increase of the VSIB content in HEMA/VSIB hydrogels. In the saline solution, the water content for these gels was not affected by the ion concentration when the salt concentration was lower than the minimum salt concentration (MSC) of poly(VSIB). When the salt concentration was higher than the MSC of poly(VSIB), the deswelling behavior of the copolymeric gel was more effectively suppressed as more VSIB was added to the copolymeric gels. However, the swelling behavior of gels in KI, KBr, NaClO₄, and NaNO₃ solutions at a higher concentration would cause an antipolyelectrolyte phenomenon. Besides, the anion effects were larger than were the cation effects in the presence of a common anion (Cl^?) with different cations and a common cation (K⁺) with different anions for the hydrogel. In drug‐release behavior, the addition of VSIB increased the drug‐release ratio and the release rate. Finally, the addition of VSIB in the hydrogel improved the gel strength and crosslinking density of the gel. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 2888–2900, 2001     

Thermoreversible hydrogels XIII: Synthesis and swelling behaviors of [N-isopropylacrylamide-co-sodium 2-acrylamido-2-methylpropyl sulfonate-co-N,N-dimethyl(acrylamido propyl) ammonium propane sulfonate] copolymeric hydrogels

A series of copolymeric hydrogels were prepared from various molar ratios of N-isopropylacrylamide (NIPAAm), sodium-2-acrylamido-2-methylpropyl sulfonate (NaAMPS) and N,N′-dimethyl(acrylamido propyl) ammonium propane sulfonate (DMAAPS). The swelling behaviors of these copolymeric hydrogels were investigated in various saline solutions. The result showed that the phase transition temperatures of these gels changed insignificantly, and the thermosensitivity, in contrast, diminished. In addition, the copolymer gels exhibited polyelectrolytic behavior under lower salt concentration (10⁻⁵∼10⁻¹ M), exhibited a nonionic gel (like NIPAAm) behavior at the salt concentration from 0.1 to 0.4 M, and showed an antipolyelectrolytic behavior (polyzwitterionic effect) at a salt concentration over 0.4 M. Finally, the presented coplymeric gels are investigated for use in drug release application.     

pH/thermoreversible hydrogels III: Synthesis and swelling behaviors of (N-isopropylacrylamide-co-acrylic acid) copolymeric hydrogels

A series of pH-thermoreversible hydrogels exhibiting volume phase transition were synthesized by three degrees of neutralization (DN) of acrylic acid (AA) and N-isopropylacrylamide (NIPAAm). The influence of environmental conditions, such as temperature and pH, on the swelling behavior of these copolymeric gels is investigated in this article. Results show that the negatively charged hydrogels exhibit different equilibrium swelling ratios at different pH values depending on the ionic composition. The pH-sensitivities of these gels also strongly depend on the DN of AA in the copolymeric gels. The results show that the higher the DN, the higher the gel pH-sensitivity. These hydrogels based on a temperature-sensitive hydrogel demonstrate a larger change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a collapsed dehydrated network in response to a variation of temperature. On the other hand, a significant phenomenon that was found in the gel swelling kinetics was an overshooting under high temperature conditions. The presented hydrogels were used for release of model drugs that occur at the changes of surrounding conditions, such as temperature and pH, in this study. It was also found that the higher the DN of AA, the higher the gel transition temperature and the larger the release in a high temperature environment and, at the same time, the larger the swelling ratios.     

pH‐sensitive hydrogels based on bovine serum albumin for anticancer drug delivery

Protein conjugates consisting of hydroxyethyl methacrylate and acrylic acid monomers in the presence of bovine serum albumin (BSA) were prepared by gamma irradiation to examine the potential use of these hydrogels in the controlled drug release systems. The study parameter was the BSA content in the as‐prepared conjugates. Polymers were characterized with FTIR, scanning electron microscopy (SEM), and swelling studies. The polymerization reaction caused the rearrangement of the BSA carbonyl hydrogen bonding and finally led to the modification of the BSA secondary structure as proved by FTIR. SEM proved that the prepared conjugates matrices are porous, with a three‐dimensional interconnected microstructure. The swelling kinetics of the hydrogels and the release dynamics of an anticancer model drug (flutamide) have been studied. High equilibrium swelling values, up to 1550%, could be observed and were correlated with the increase in pH, temperature, and BSA content. The mechanism of swelling changed from Fickian to non‐Fickian by reducing the acidity of the medium. This study proved that there is a direct relationship between the protein content in the conjugates and both the loaded and the released drug. These pH responsive conjugates may be exploited for the delivery of flutamide. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and characterization of 2‐hydroxyethylmethacrylate/2‐(3‐indol‐yl)ethylmethacrylamide‐based novel hydrogels as drug carrier with in vitro antibacterial properties

In this study, a new cationic monomer 2‐(3‐indol‐yl)ethylmethacrylamide (IEMA) derived from tryptamine was synthesized in a single step and characterized by Fourier transform infrared (FTIR), ¹H‐NMR, and ¹³C‐NMR. Then, one‐step preparation of novel poly[2‐hydroxyethylmethacrylate‐c‐2‐(3‐indol‐yl)ethylmethacrylamide], or p(HEMA‐c‐IEMA), copolymeric hydrogels has been performed successfully with IEMA and 2‐hydroxyethylmethacrylate (HEMA) as monomers using free radical aqueous polymerization. The hydrogels were characterized with scanning electron microscopy, FTIR, elemental analysis, thermogravimetric analysis, and texture profile analysis instruments. p(HEMA‐c‐IEMA) hydrogels were used for swelling, diffusion, drug release, and antibacterial activity studies. The drug‐release behavior of the hydrogels was determined as a function of time at 37 °C in pH 1.2 and 7.2. The swelling and drug‐release studies showed that an increased IEMA amount caused a higher increase in swelling and drug‐release values. Additionally, zero‐order, first‐order, and Higuchi equation kinetic models were applied to the drug‐release data, and the data fit well in the Higuchi model, and the Peppas power‐law model was applied to the release mechanism. Finally, the antibacterial activities of the hydrogels were screened against Gram‐positive bacteria (Bacillus cereus and Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium). © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45550.     

Colon‐specific oral delivery of vitamin B2 from poly(acrylamide‐co‐maleic acid) hydrogels: An in vitro study

Hydrogels, composed of poly(acrylamide‐co‐maleic acid) were synthesized and the release of vitamin B₂ from these gels was studied as a function of the pH of the external media, the initial amount of the drug loaded, and the crosslinking ratio in the polymer matrix. The gels containing 3.8 mg of the drug per gram gel exhibit almost zero‐order release behavior in the external media of pH 7.4 over the time interval of more than their half‐life period (t_1/2). The amount of the drug loaded into the hydrogel also affected the dynamic release of the encapsulated drug. As expected, the gels showed a complete swelling‐dependent mechanism, which was further supported by the similar morphology of the swelling and release profiles of the drug‐loaded sample. The hydrophilic nature of the drug riboflavin does not contribute toward the zero‐order release dynamics of the hydrogel system. On the other hand, the swelling osmotic pressure developed between the gels and the external phase, due to loading of the drug by equilibration of the gels in the alkaline drug solution, plays an effective role in governing the swelling and release profiles. Finally, the minimum release of the drug in the swelling media of pH 2.0 and the maximum release with zero‐order kinetics in the medium of pH 7.4 suggest that the proposed drug‐delivery devices have a significant potential to be used as an oral drug‐delivery system for colon‐specific delivery along the gastrointestinal (GI) tract. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1133–1145, 2002; DOI 10.1002/app.10402