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In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages. more...

Gliclazide is a second-generation sulfonylurea compound used as a prescription medicine in the treatment of non insulin dependent diabetes mellitus (NIDDM) or type II diabetes. As a consequence of the poor aqueous solubility, the therapeutic efficacy of the drug in oral dosage form suffers from major drawbacks, e.g., inter-individual variable bioavailability. To overcome the same, various extended/sustained release (SR, matrix mediated) oral dosage formulations have been attempted and in the present communication, we report the use of a biocompatible and biodegradable anionic clay, known as Mg–Al layered double hydroxides (LDHs) to encapsulate the gliclazide drug by ex situ anion exchange process, to form LDH-GLZSR sustained release tablet, known as LDH-GLZSR. It was characterized structurally and compositionally by various analytical techniques. The LDH-GLZSR tablet was manufactured by direct compression method, followed by using microcrystalline cellulose as binder, crospovidone as disintegrator and magnesium stearate as lubricant. Different post formulation parameters of LDH-GLZSR tablets were evaluated and in vitro dissolution study was carried out in two pH conditions (1.2 for stomach and 6.8 for colon), comparing the same to a market available polymer based SR formulation (tablet) of the same drug, named as GLZ-SR to estimate the suitability of the former for a similar use. more...

In this study, carboxymethyl sulfate derivative (CLBS) of locust bean gum (LBG) was synthesized by varying the strength of sulfating reagent. CLBS was characterized by Fourier transform infrared (FTIR) spectroscopy, elemental analysis, and viscosity measurements. Furthermore, the degree of sulfation and carboxymethylation in CLBS was determined. Novel micro(hydro)gel particles of CLBS were fabricated in basic aluminum chloride solution and different concentration of diclofenac sodium was incorporated into these particles. Differential scanning calorimetry and FTIR analyses did not suggest any drug-polymer interaction. Spherical morphological structures of the particles were evident under scanning electron microscope. Regardless of the formulation variables, a maximum of ~60% drug entrapment efficiency was achieved. For a higher degree of substitution, CLBS particles disintegrated rapidly (~20 min) and released80% drug in acidic medium (pH1.2 and pH4.0) in 60 min. However, the particles liberated only ~60% drug in phosphate buffer medium (pH6.8) during this period. Following disintegration of the particles, the pH of gastric environment elevated. In stomach histopathology, the ulcers were scored and it was estimated that CLBS afforded ~86% protection to the gastric mucosa from ulceration. Thus, the micro(hydro)gel particles of CLBS-aluminium complex could be useful for immediate analgesic effect of the drug without any significant gastric distress. more...

Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD50) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma. more...

This study was undertaken to investigate correlation between the carboxymethylation-induced rheological changes and drug release characteristics of locust bean gum (LBG) matrix tablets. LBG was derivatized to carboxymethyl LBG (CMLBG) and characterized by (13)C NMR, FTIR and elemental analyses. Rheological studies revealed that LBG, in contact with water, produced a strong elastic gel which swelled less due to lower penetration of water resulting in slower drug release. On the other hand, CMLBG formed a viscous polymer solution through which higher influx of water resulted in rapid swelling of the matrix and faster drug release. Although the release from a particular matrix was dependent on drugs' solubilities, CMLBG matrix tablet produced faster release of all the drugs than LBG matrix tablets. In conclusion, rheological study appeared to be an useful tool to predict release of drugs from polysaccharide matrix tablets. more...

The superporous hydrogels (SPHs) have gained appreciation as drug delivery devices owing to their large water absorption capacity through interconnected pores. The polysaccharides are the attractive material for the design of SPHs largely due to the presence of hydrophilic functional groups in their structure and possibility of tailoring chemical structure of the polysaccharides. In addition, they have been reported to be nontoxic, biodegradable, and biocompatible and therefore, the concern of toxicity is expected to be less. Natural polysaccharides have been employed to synthesize higher generation SPHs through interpenetration/cross-linking with other synthetic polymeric chains. Several modifications have been done to improve the mechanical strength of SPHs in the swollen state. The gas blowing technique is mostly adopted for the creation of porous structures into polysaccharide-based SPHs. This chapter provides a comprehensive overview of the synthetic strategies and progress in the field of drug delivery and tissue engineering. The physicochemical properties and drug delivery attributes of chitosan (CS) and sodium alginate-based SPHs are discussed in detail. Research findings on polysaccharide-based SPHs other than CS and alginate are also summarized. more...

Tablets, compression coated with certain polysaccharides and intended for colon delivery, retain the integrity of the coat for an initial period of about 6 h (lag period) beyond which (post-lag period) the coat is degraded by colonic enzymes to induce drug release. This work was undertaken to investigate the factors which influence the integrity of the coat during the lag period. Core tablets containing two model drugs were compression coated with various amounts of carboxymethyl locust bean gum (CMLBG). In-vitro release of drugs, erosion of coat, and steady shear viscosity of CMLBG solutions having different concentrations and solution pH were determined. The viscosity of CMLBG that depended primarily on CMLBG concentration and partly on solution pH was responsible for erosion and integrity of the coat in the lag period. Evaluation of polymer viscosity could describe the integrity of coat of a polysaccharide coated tablet in the lag period. more...

This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca2+ ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen. more...

The purpose of this work was to evaluate different methods of cross-linking for developing diltiazem–resin complex loaded carboxymethyl xanthan gum (CMXG) hydrogel beads to achieve highest possible drug entrapment and extended release for effective cardio-protection. The hydrogel beads were prepared by ionic cross-linking and dual cross-linking using simultaneous (SIM) and sequential (SEQ) methods. Among the three methods, SEQ method produced smaller sized beads having higher drug entrapment efficacy and prolonged release characteristics as evidenced from mean dissolution time and diffusion coefficient of drug. Keeping the concentration of ionic cross-linker constant, increase in the amount of covalent cross-linker and cross-linking time decreased the drug release. Higher release of the drug in acid solution was attributed to the higher solubility of the basic drug and higher swelling of the matrices in acid solution. Comparison of FTIR spectra, drug content and dissolution profiles indicated that the drug was stable in the beads when kept under stress condition up to 3 months. In conclusion, the sequential method was found superior for producing CMXG hydrogel beads as a prolonged release delivery device in cardiovascular diseases. more...

The optimization is reported of various process parameters for the development of poly(lactic-co-glycolic acid, PLGA) coating on Mg–Al layered double hydroxide (LDH) nanoparticles intercalated with the anticancer drug methotrexate (MTX). Both double and single emulsion-solvent evaporation techniques were adapted to synthesize the PLGA coated, MTX drug loaded nanoparticles as above, with and without LDH. While keeping some of the process parameters constant, the homogenization speed, concentration of PLGA, LDH-MTX, MTX and surfactants, aqueous and organic phase volume involved in the synthesis of the PLGA-MTX and PLGA-LDH-MTX nanoparticles, were varied and evaluated to obtain the desired particle size range and drug entrapment efficiency for specific use. The optimized and a few selected unoptimized nanoparticles were further assessed for in vitro drug release kinetics and time and dose dependent in vitro cell viability bioassay, in vitro MTX uptake study using human osteosarcoma, MG-63 cell line. The in vivo pharmacokinetic study demonstrated the much higher therapeutic efficacy of the optimized PLGA-LDH-MTX and PLGA-MTX nanoparticles in terms of the enhanced half life of the drug and the slow clearance rate compared to those of the bare MTX drug. more...

Considering the pH dependent chemical stability of anticancer drug methotrexate (MTX), the present communication reports a new approach for intercalation of the same in a nanoceramic vehicle, magnesium aluminium layered double hydroxide (LDH), by ex situ anion exchange method at pH 7.00, using 0.3 M ammonium acetate solution for dissolution of the drug. This simple method ensures maximum stability of the drug at the above said pH, with no degradation byproduct (e.g., N10-methyl folic acid formed due to alkaline hydrolysis) under the given experimental conditions, compared to the similar approach, using 0.1 M sodium hydroxide solution, reported in our earlier work. Importantly, the above method leads to an enhanced drug loading of 32.3 wt%, compared to our previous reports. The cumulative release profile of MTX from LDH–MTX formulation in phosphate buffer saline (PBS) at pH 7.4 exhibited burst release initially which was taken care of by imparting a unique coating of poly(D,L-lactide-co-glycolide, PLGA) on the LDH–MTX nanostructure that reduces the toxicity due to local accumulation. Hence, the superiority of the above for use in cancer chemotherapy, over the conventional drug–polymer system has been established w.r.t the drug release profile and a possible hypothesis of the same has been suggested. The half maximal inhibitory concentration (IC50) of the MTX drug used in this study has been determined and the same has been used to estimate the time dependent (24, 48, 72 and 96 h) efficacy of the MTX loaded samples with/without polymer coating, on human colon tumour cells (HCT-116). more...

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO 2 –Na 2 O–ZnO–CaO–MgO–P 2 O 5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63–66% porous and 5–50 μm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas–Korsmeyer release pattern based on Fickian diffusion, while 0.5–1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass. more...

Silica xerogel and its PEG assisted derivatives were prepared by sol–gel method for controlled release of andrographolide. In vitro and in vivo release of andrographolide from the nano porous silica as well as PEG modified silica matrix were studied. Drug release from the matrix increased with increasing percentage of PEG and followed a biphasic pattern. The in vitro release profile followed zero order kinetics with erosion of the matrix for the first six hours and higuchi model with the diffusion mechanism for rest of the time period. Pharmacokinetic data revealed sustained release of the drug from silica–drug composite with higher elimination t1/2 than the pure drug. For all the formulations Level A in vitro-in vivo correlation (IVIVC) was established with (R2) > 0.98. Histology of different organs was carried out following in vivo administration of the drug-carrier composite. The histological examination demonstrated absence of any inflammatory or degenerative response with the formulations. Fourier transform infrared (FTIR) data revealed the coexistence of andrographolide in the silica matrix. Transmission electron microscope (TEM) images also unfold the repose matrix structure in PEG assisted derivatives than the pure matrix. This study discloses that silica gel and PEG assisted derivatives could be used as a biocompatible and sustained release device for andrographolide. more...

The effect of Ca(2+) ion concentration on swelling, erosion, and drug release mechanism of Ca(2+) ion cross-linked carboxymethyl xanthan gum (Ca-CMXG) matrices was investigated. By adding CaCl2 solution, carboxymethyl xanthan gum (CMXG) was converted into Ca-CMXG matrix, which was evaluated for swelling, erosion and drug release in different dissolution media. The amount of Ca(2+) ion alters the viscosity of gel layer formed around the matrices resulting in decreased water penetration into swollen layer. The changes in amount of Ca(2+) ion considerably influenced the swelling and erosion of the matrix leading to different drug release profiles. The simultaneous swelling and erosion of matrices that were controlled by the degree of cross-linking prejudiced the drug release mechanism. The release data fitted well into the Korsmeyer-Peppas equation and the combined effect of diffusion and erosion described the overall drug transport mechanism. more...

The objective of this work was to study the release behavior of prednisolone from calcium-cross-linked carboxymethyl xanthan gum (CMXG) tablets in dissolution medium having different pH values prevailing in the gastrointestinal lumen. Xanthan gum (XG) was derivatized to CMXG which was then cross-linked in situ with Ca(+2) ion during wet massing step of tablet preparation. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry studies did not show any drug-polymer interaction although the drug underwent solid-state transformation during compression as evident from X-ray diffraction analysis. In vitro release study demonstrated that increase in the amount of Ca(+2) ion decreased the drug release, and beyond a certain amount, the drug release increased. While increase in both drug load and tablet crushing strength decreased the drug release, increase in exposure time in acid solution of pH 1.2 increased the overall release of the drug. The mechanism of drug release was non-Fickian/anomalous. The results indicated that variation in the amount of Ca(+2) ion can modulate the drug release from CMXG matrix tablets as needed. more...

Herein, an aqueous solution of etherified locust bean polysaccharide (ELBP) containing lamivudine was reticulated in presence of trivalent aluminium (Al 3+ ) ions to nanoscale level (43.82–197.70 nm) by surfactant assisted homogenization-reticulation technique. The variation in aluminium chloride (AlCl 3 ) strength (1.5–3.5% (w/v)) and drug:ELBP weight ratio (0.11–0.43) affected the properties of the nanoreticulations. Regardless of the variables, a maximum of ∼44% drug entrapment efficiency was noted. In simulated intestinal fluid (phosphate buffer solution, pH 7.4), the drug release rate was inversely proportional to the strength of AlCl 3 ; but followed a proportional relationship with the drug:ELBP ratio. The mechanism of drug release shifted from Fickian diffusion to anomalous transport as the salt strength was increased above 2.5% (w/v). At intermediate drug:ELBP ratio, the drug release rate was regulated by polymer chain relaxation as opposed to simple diffusion mechanism. Fourier transform infrared spectroscopy did not show any evidence of chemical interaction between the drug and ELBP. Thermal analysis and X-ray diffraction studies suggested amorphous dispersion of drug in the nanoreticulations. Thus, the nanoreticulations were expected to absorb via intestine and phagocytosed by the virus-infected hepatic macrophages and hence could be useful for controlled delivery of lamivudine avoiding dose-dependent toxicity of the drug. more...

The application of interpenetrating polymer network (IPN) hydrogel tablets of tamarind seed polysaccharide and sodium alginate for controlled release of a water-soluble antihypertensive drug, propranolol HCl (PPL), was investigated. The IPN tablets loaded with PPL or PPL–resin complex (resinate) were prepared by a wet granulation/covalent cross-linking method. Fourier Transform Infrared Spectroscopic confirmed the cross-linking reaction and IPN formation, while X-ray Diffraction and Scanning Electron Microscopy studies confirmed the amorphous dispersion of the drug within the IPN tablets. The plain drug PPL showed complete release within 1 h, while drug release from the resinate was prolonged for 2.5 h and the IPN matrices showed drug release up to 24 h. The drug release rate from the IPN matrices was affected by polymer concentration and cross-linking time; the higher the cross-linking time, the slower was the drug release. The drug release mechanism was found to be of a non-Fickian type. more...

Sol/gel-derived silica gel was prepared at room temperature from tetraethyl orthosilicate precursor. The extracts of Terminalia chebula (Haritoki) were entrapped into the porous silica gel. Fourier transform infrared analysis revealed the proper adsorption of herbal values in the nanopores of the silica gel. Porosity was estimated by transmission electron microscope studies. The release kinetics of the extract in both 0.1 N HCl, pH 1.2, and Phosphate-buffer saline (PBS), pH 7.2, were determined using UV-Vis spectroscopy. Different dissolution models were applied to release data in order to evaluate the release mechanisms and kinetics. Biphasic release patterns were found in every formulation for both the buffer systems. The kinetics followed a zero-order equation for first 4 h and a Higuchi expression in a subsequent timeline in the case of 0.1 N HCl. In the case of PBS, the formulations showed best linearity with a first-order equation followed by Higuchi's model. The sustained release of the extract predominantly followed diffusion and super case II transport mechanism. The release value was always above the minimum inhibitory concentration. more...

Development and evaluation of xanthan gum-facilitated ethyl cellulose microsponges for controlled percutaneous delivery of diclofenac sodium In this study, xanthan gum-facilitated ethyl cellulose microsponges were prepared by the double emulsification technique and subsequently dispersed in a carbopol gel base for controlled delivery of diclofenac sodium to the skin. Scanning electron microscopy revealed the porous, spherical nature of the microsponges. Increase in the drug/polymer ratio (0.4:1, 0.6:1, 0.8:1, m/m) increased their yield (79.1-88.5 %), drug entrapment efficiency (50.0-64.1 %), and mean particle diameter (181-255 μm). Compared to the microsponges with high drug/polymer ratio (0.8:1, m/m), the flux of entrapped drug through excised rat skin decreased by 19.9 % and 17.0 %, respectively, for the microsponges prepared at low and intermediate drug/polymer ratios. When an equivalent amount of pure drug (not entrapped into microsponges) was dispersed into the gel base and the flux was compared, the microsponges (drug/polymer ratio 0.8:1, m/m) were found to reduce the flux by 33.3 %. Whether the drug was dispersed either in un-entrapped or entrapped form into the gel base, the drug permeation through rat skin followed Higuchi's diffusion kinetic model. The microsponges prepared at the lowest drug/polymer ratio exhibited a comparatively slower drug permeation profile and were hence considered most suitable for controlled drug delivery application. FTIR spectroscopy and DSC analyses indicated the chemically stable, amorphous nature of the drug in these microsponges. The gel containing these optimized microsponges was comparable to that of a commercial gel formulation and did not show serious dermal reactions. Hence, the microsponge system obtained at the lowest drug/polymer ratio could be useful for controlled release of diclofenac sodium to the skin. more...

Interpenetrating polymer network (IPN) matrices of sodium alginate and carrageenan were prepared for controlled release application. The propranolol-resin complex (resinate) loaded matrices were prepared by wet granulation/covalent crosslinking method and subsequently compressed into tablets. The SEM, DSC and XRD studies confirmed the amorphous nature of drug in the IPN matrix and FTIR confirmed the IPN formation and stability of drug within IPN matrix. The pure drug propranolol HCl showed rapid and complete dissolution within 60 min, while drug release from resinate was extended for 2.5 h and that from IPN tablets was still slower and drug release prolonged over 18 h. The crosslinking time of granules affected the release of drug from IPN matrix. more...

In this study, nanovesicles were developed for brimonidine tartrate by film hydration technique and dispersed in viscous carbopol solution for ocular delivery. Scanning electron microscopy revealed spherical shape of the vesicles. As high as 32.27% drug entrapment efficiency was achieved depending upon the surfactant/cholesterol molar ratio (7:4 to 7:8). The vesicles were in the size range of 298.0-587.9 nm. Release study showed a biphasic drug-release pattern for the lyophilized vesicular formulation in buffered saline solution, i.e., initial burst release followed by gradual release over the period of 8 h. On contrary, the isolated vesicles reduced the burst effect in 3 h by two to three times and the drug release was comparatively slower at the intermediate ratio in both cases. With variation in cholesterol content, the drug release followed either first order or Higuchi's kinetics. Physically the lyophilized vesicular formulations were more stable at refrigerated temperature. DSC and X-RD analyses indicated loss of drug crystallinity in the vesicles. FTIR spectroscopy did not reveal any interaction between drug and excipients. The lyophilized formulation showed better ocular hypotensive activity than marketed drops on albino rabbits and in vivo efficacy was sustained up to 7.5 h. Furthermore, the formulation was found to be non-irritant to the rabbit eye. Hence, the lyophilized vesicles, when dispersed in viscous carbopol solution, had the potential in reducing dosing frequency and could improve patient compliance. more...

The multi-layered hydrogel membranes of sodium alginate-hydroxypropyl methylcellulose-polyester were developed for controlled delivery of anti-inflammatory drug, diclofenac diethylamine through intact skin. The XRD studies indicated the amorphous dispersion of drug in the membranes. DSC analysis suggested that as cross-linking increases, the stiffer membranes were formed. The prepared membranes were permeable to water vapors depending upon the cross-link density. The in vitro drug diffusion through excised rat abdominal skin depends on the cross-link density and polymer concentration. The primary skin irritation study indicated that the prepared membranes were less irritant and safe for drug delivery across the skin. more...

Considering relatively fast drug release rate of Ca+2/gellan beads in phosphate buffer solution, a novel glipizide-loaded bead system was developed through ionotropic gelation of gellan with trivalent Al+3 ions and covalent cross-linking with glutaraldehyde (GA). Following GA-treatment, spherical Al+3/gellan beads contracted leaving wrinkles on bead surface. A maximum of 97.67% drug entrapment efficiency was achieved; however GA-treatment reduced the same by 11.89%. All the beads released only 10% drug in acidic medium in 2 h; however it was found 38–47% for Al+3/gellan beads and only 15% for GA-treated beads in weakly alkaline medium. The drug release did correlate well with their swelling behaviors. The anomalous drug transport mechanism shifted to super case II transport for GA-treated beads, where the polymer relaxation phenomenon was dominant. The drug was relatively stable, amorphous in the beads. Thus both GA-treated and -untreated Al+3/gellan beads could be useful carriers for the controlled oral delivery of glipizide. more...

Homopolymeric and interpenetrating network (IPN) hydrogel beads of ibuprofen (IBP), a nonsteroidal anti-inflammatory drug, were prepared using carboxymethyl xanthan and sodium alginate as polymers and AlCl3 as a cross-linking agent. Formation of IPN structure was examined using FTIR analysis. The effect of composition of the hydrogel beads and the amount drug load on the release of IBP was studied in acidic and phosphate buffer (PB) solution of pH 6.8. In accordance with the swelling behavior of the beads, drug release from the IPN beads in acidic solution was found to be confined within those from homopolymeric beads. On the other hand, drug release from IPN beads in PB solution was found to be less than those from the homopolymeric beads although the swelling of the beads followed the same trend as in an acidic solution. An increase in the drug load further decreased the drug release from all the beads in both the dissolution media. FTIR, XRD, and DSC analyses demonstrated the absence of any interaction between the drug and the polymers. The results indicated that IPN hydrogel beads provided more sustained release of IBP than homopolymeric beads. © 2011 Wiley Periodicals, Inc. Adv Polym Techn 30:1–11, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.20199 more...

Diltiazem HCl, a water soluble drug was bound to Indion 254®, a cation exchange resin and resulting drug–resin complex was entrapped within interpenetrating polymer network (IPN) microcapsules of gellan gum and egg albumin prepared by ionotropic gelation and covalent crosslinking method. The IPN microcapsules were characterized by SEM, DSC, TGA, XRD and FTIR analyses. The pure drug diltiazem showed rapid and complete dissolution within 60 min, while drug release from drug-resinate was extended for 3 h and that from IPN microcapsules was still slower. The ionically cross-linked microcapsules were capable of releasing drug up to 9 h, and that from dual crosslinked microcapsules was extended up to 15 h. The microcapsules which were prepared with higher concentration of glutaraldehyde released the drug more slowly. The release data were fitted to an empirical equation to determine the transport mechanism. more...

Polymethylmethacrylate (PMMA) coated microcapsules of diclofenac sodium (DFS) were prepared by a modified wa-ter-in-oil-in-water (W1/O/W2) emulsion solvent evaporation method using sodium alginate (SAL) as a matrix material in the internal aqueous phase (W1).Their performance with respect to controlled release of the drug in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated, and compared with non-matrix microcapsules prepared by the conventional W1/O/W2 emulsion solvent evaporation method. Scanning electron micrographs (SEM) revealed that all the microcapsules were discrete and spherical in shape; however, the surface porosity of the matrix microcap-sules appeared to be less than that of the non-matrix microcapsules. In case of non-matrix microcapsules, an increase in the volume of water in W1 phase resulted in decrease in the drug entrapment efficiency (DEE) along with increase in release of the drug in both SGF and SIF. While in case of matrix microcapsules increase in the amount of SAL in W1 phase and concentration of the coating polymer in organic phase led to increase in DEE of the matrix microcapsules and considerable decrease in the drug release in both SGF and SIF. No interaction between the drug and any of the polymers used to prepare microcapsules was evident from Fourier transform infra-red (FTIR) analysis. The matrix microcapsules prepared using higher concentration of SAL and PMMA released the drug following zero order or Case-II transport model. The matrix microcapsules appeared to be suitable for releasing lesser amounts of DFS in SGF and providing extended release in SIF. more...

Interpenetrating network (IPN) matrix tablets of diltiazem-HCl (DTZ) was prepared by wet granulation method using polyacrylamide-grafted-sodium alginate (PAam-g-SAL) co-polymer and sodium alginate (SAL) for sustained release of the drug. Formulation of IPN structure was examined using FTIR spectroscopy, and compatibility of the drug with the polymers was evaluated through FTIR, DSC, and XRD analyses. The effect of co-polymer/SAL ratios, drug load, and total polymer/calcium gluconate (CG) ratios on drug release in acidic and phosphate buffer solutions was investigated. The release of drug was controlled by the relative magnitude of swelling capacity of IPN matrix and viscosity of the gel formed following dissolution of the polymers. The swelling capacity of the matrix was governed by the formation of calcium alginate gel structure and the rigidity imparted by the co-polymer. The results indicated that IPN matrix tablets of PAam-g-SAL and SAL could be used for sustained release of DTZ. more...

The purpose of the study was to develop a multiunit sustained release dosage form of diltiazem hydrochloride using a natural polymer, sodium carboxymethyl xanthan gum and polyethyleneimine (PEI) from a completely aqueous environment. PEI treated diltiazem resin complex loaded beads were characterized by morphology, drug entrapment efficiency, in vitro and in vivo release behaviour. 40% and 80% drug was released in 2 hour in pH 1.2 and in 5 to 6 h in pH 6.8 respectively depending on the formulation variables. The prolonged release was attributed to decreased swelling of the beads due to PEI treatment. Maintaining the shape throughout the dissolution process, PEI treated diltiazem resin complex beads released the drug following non-Fickian transport phenomena. In vivo pharmacokinetic evaluation in rabbits shows slow and prolonged drug release when compared with diltiazem solution. The designed beads are suitable for prolonged release of a water soluble drug under a complete aqueous environment using natural gum. more...

In this study, carboxymethyl derivative of locust bean gum was prepared, characterized, and its gelling ability with different concentrations (1-5% w/v) of aluminum chloride (AlCl(3)) was utilized for the development of glipizide-loaded beads in a completely aqueous environment. The beads were spherical when observed under a scanning electron microscope. Increase in gelling ion concentration decreased the drug entrapment efficiency from 97.68% to 95.14%. The beads swelled more slowly in pH 1.2 KCl-HCl buffer and exhibited a slower drug release pattern than that observed in pH 7.4 phosphate buffer. Irrespective of the dissolution media, the drug release became slower at higher AlCl(3) concentration. The drug release in alkaline medium was found to be controlled by a combination of diffusion as well as polymer relaxation phenomena. Comparing the release profiles, it was observed that the beads treated with 5% AlCl(3) provided slower drug release up to 10 h in alkaline medium without any sign of disintegration and, thus, this formulation was selected for further studies. Fourier transform infrared (FTIR) spectroscopy indicated the stable nature of the drug in the beads. Differential scanning calorimetry and X-ray diffraction analysis showed that most of the drug remained in amorphous state in the beads. Stability study indicated no statistical significant difference in drug entrapment efficiency of the beads. In vivo activity of the beads was tested and a prolonged hypoglycemic effect was achieved. Hence, carboxymethyl locust bean beads could be a potential carrier for controlled oral delivery of glipizide. more...

An electrically responsive hydrolyzed polyacrylamide-grafted-sodium alginate (H-PAAm-g-SA)-based membrane-controlled transdermal drug delivery systems were developed and evaluated. The grafting reaction was confirmed by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. On application of electric stimulus, the swollen H-PAAm-g-SA hydrogel was deswelled in the vicinity of electrodes. The drug release was greater in the presence of electric stimulus when compared with passive diffusion, and it was found to be dependent on the applied electric current strength, concentration of H-PAAm-g-SA copolymer in the reservoir, and cross-link density of rate-controlling membrane. A pulsatile pattern of drug release was observed when the electric stimulus was switched "on" and "off." The skin histopathology study suggested that, after application of an electrical stimulus, changes were in the structure of stratum corneum. more...

Interpenetrating network (IPN) beads of sodium carboxymethyl xanthan (SCMX) and sodium alginate (SAL) were pre-pared by ionotropic gelation process using AlCl3 as a cross-linking agent. The effect of different formulation vari-ables like total polymer concentration, gelation time, concentration of cross-linking agent, and drug load on the extent of release of ibuprofen (IBP), a non steroidal anti-inflammatory drug, was examined. The formation of IPN structure was examined using Fourier Transform Infra-red (FTIR) analysis and the compatibility of the drug in the bead was evaluated through FTIR, X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) analyses. While increase in the concentration of total polymer, gelation time, and drug load decreased the drug release in both acidic (pH-1.2) and phosphate buffer (PB) solution (pH-6.8), increase in the concentration of cross-linking agent tended to increase the drug release. However, from all the formulations, the drug release in acidic medium was considerably slow and a maximum 14% of the loaded drug was released in 2 h. Complete drug release was achieved in PB solution within 210 to 330 min depending upon the formulation variables. The release of the drug followed non-Fickian transport process in acidic medium and case-II transport mechanism in PB solution and these release behaviour correlated well with the kinetics of dynamic swelling of IPN beads. The study indicated that the IPN beads of SCMX and SAL could be a suitable dosage form to minimize the drug release in acidic solution and to control the drug release in PB solution depending upon the need. more...

Diltiazem hydrochloride (DTZ) matrix tablets were prepared using polyacrylamide-grafted sodium alginate (PAam-g-SA) co-polymers having different percentages of grafting and their partially hydrolyzed products with a view to achieve sustained release of the highly water-soluble drug. PAam-g-SA co-polymers having different percentages of grafting were synthesized by free radical polymerization using acrylamide (Aam) as monomer and ammonium persulphate (APS) as initiator, and the resulting co-polymers were subjected to alkaline hydrolysis to produce their corresponding partially hydrolyzed co-polymers. Matrix tablets of DTZ were prepared by wet granulation using either PAam-g-SA co-polymers or partially hydrolyzed PAam-g-SA co-polymers. The effect of percentage grafting, drug load and calcium gluconate (CG), used as excipient, was studied in simulated gastrointestinal fluid. While the tablets prepared using the co-polymer having higher percentages of grafting provided faster drug release (100% in 5.5 h), the tablets prepared with the corresponding hydrolyzed co-polymer released the drug slowly (71% in 12 h). This behaviour in release appeared to be controlled by the relative magnitude of the viscosity and the swelling capacity of the copolymers. Moreover, increase in drug load tended to decrease the drug release from all types of tablets and increase in the amount of CG increased the drug release. FT-IR and DSC studies revealed the absence of any interaction between the drug and the co-polymers. The matrix tablet made of partially hydrolyzed graft co-polymer having the highest percentage of grafting provided the most sustained release of the drug. more...

This study was undertaken to develop tablets of diazepam-hydroxypropyl-β-cyclodextrin inclusion complex that disintegrate within 3 minutes and release 85% of drug within 30 minutes to provide rapid action of the drug through oro-mucosal route. Formation of inclusion complex was verified using X-ray diffraction and differential scanning calorimetric studies. Enhanced of aqueous solubility, as evident from phase solubility study, and dissolution of the drug were related with the formation of inclusion complex. Among the various formulations, tablet containing inclusion complex of drug/hydroxypropyl-β-cyclodextrin in a molar ratio of 1:2, and a combination of microcrystalline cellulose/lactose in a ratio of 4:1 disintegrated in 13 seconds and released 85% drug within 9 minutes. Addition of 10% w/w polyvinyl pyrrolidone in the tablet formulation further enhanced the drug release. Accelerated stability study indicated that mean dissolution time of the drug from the tablet did not change significantly within 6 months. more...

This review paper attempts to provide an overview in the fabrication and application of organic-inorganic based composites in the field of local drug delivery for bone. The concept of local drug delivery exists for a few decades. However, local drug delivery in bone and specially application of composites for delivery of drugs to bone is an area for potential research interest in the recent time. The advantages attained by an organic-inorganic composite when compared to its individual components include their ability to release drug, adopting to the natural environment and supporting local area until complete bone regeneration, which make them carriers of interest for local drug delivery for bone. more...

In this study, periodate oxidation of sodium alginate was controlled such that the oxidized alginate could form isolatable beads with Ca(+2) ions. The beads of oxidized alginate having a degree of oxidation 1 mol%, entrapped 89% flurbiprofen and released almost all of its content within 1.5 h in pH 7.2 phosphate buffer solution. The beads were covalently crosslinked with adipic dihydrazide (ADH) in addition to ionic crosslinks and were characterized. Scanning electron microscopy revealed that the beads were spherical having smooth surfaces. The drug entrapment efficiency decreased (90-86%) with increasing concentration of ADH (2-6% w/v) in the gelation medium. However, the beads prolonged the drug release in alkaline dissolution medium up to 8 h depending upon the concentration of ADH. The beads prepared with 2% ADH swelled more rapidly and led to faster drug release in either pH 1.2 HCl solution or pH 7.2 phosphate buffer solution. The swelling tendencies were reduced and the drug release became slower with higher concentrations in either fluid. The drug diffusion from the beads followed super case II transport mechanism. FTIR spectroscopy indicated stable nature of flurbiprofen in the beads and therefore had potential as sustained oral delivery system for the drug. more...

An electroresponsive drug delivery system was developed using poly(acrylamide-grafted-xanthan gum) (PAAm-g-XG) hydrogel for transdermal delivery of ketoprofen. The electrically sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under nitrogen atmosphere followed by alkaline hydrolysis. When a swollen PAAm-g-XG hydrogel was placed in between a pair of electrodes, deswelling of the hydrogel was observed in the vicinity of electrodes carrying the electric stimulus. The membrane-controlled drug delivery systems were prepared using drug-loaded PAAm-g-XG hydrogel as the reservoir and crosslinked with poly(vinyl alcohol) to form films as rate controlling membranes (RCM). The in vitro drug permeation study from the formulations was performed through excised rat abdominal skin. Drug permeation across the skin was greatly enhanced in the presence of electric stimulus as compared to passive diffusion and was found to be dependent upon the applied electric current strength and crosslink density of RCM. A pulsated pattern of drug release was observed as the electric stimulus was switched `on' and `off.' The skin histopathology study demonstrated that, after the application of an electrical stimulus, there were changes in the structure of stratum corneum and cell structure. These PAAm-g-XG hydrogel could be useful as transdermal drug delivery systems actuated by an electric signal to provide on-demand release of drugs. more...

Bovine serum albumin (BSA)-loaded carboxymethyl xanthan (CMX) microparticles were prepared following gelation of sodium carboxymethyl xanthan (SCMX) gum with different concentrations (1-5%) of aluminium chloride (AlCl3). The microparticles prepared using 1% AlCl3 were subsequently coated with 0.5% aqueous solution of either SCMX gum or sodium alginate. Both uncoated and coated microparticles were characterized for entrapment efficiency, surface morphology, particle size, in vitro release and protein stability. The uncoated microparticles became non-spherical and the mean diameter was found to increase with increasing AlCl3 concentration. Higher concentration of AlCl3 decreased BSA entrapment efficiency of the uncoated microparticles from 86-61%. Furthermore, BSA entrapment in coated microparticles was found lower (78-79%) than uncoated microparticles prepared using 1% AlCl3. Although, the uncoated microparticles released almost half of its content in NaCl-HCl buffer solution (pH 1.2) in 2 h, the alginate and xanthan coated microparticles did not liberate a substantial amount of entrapped protein within the same period and prolonged the release in PBS solution (pH 7.4) up to 10 and 12 h, respectively. The microparticles released the protein via diffusion and swelling of the polymer matrix. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that BSA integrity was well retained in the CMX microparticles. more...

A pH-sensitive graft co-polymer of polyacrylamide (PAAm) and sodium alginate (SA) was synthesized by free radical polymerization under a nitrogen atmosphere followed by alkaline hydrolysis. The co-polymer was characterized by Fourier transform infrared (FT-IR) spectroscopy, elemental analysis and thermogravimetric analysis (TGA). Ketoprofen-loaded graft co-polymer beads were prepared by ionotropic gelation/covalent cross-linking. The beads were characterized by swelling studies, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). A pulsatile swelling study indicated that the co-polymer exhibits considerable pH-sensitive behavior. Release of ketoprofen was significantly increased when the pH of the medium was changed from acidic to alkaline. Stomach histopathology of albino rats indicated that the beads were able to retard the release of the drug in the stomach, and gastric side-effects like ulceration, hemorrhage and erosion of gastric mucosa were diminished when the drug was entrapped into PAAm-g-SA-based pH-sensitive hydrogel beads. more...

Xanthan gum was derivatized to sodium carboxymethyl xanthan (SCMX) gum with a view to prepare bovine serum albumin (BSA)-loaded carboxymethyl xanthan (CMX) microparticles through interaction with metal ion in a completely aqueous environment. The effect of various formulation variables, such as a pH of SCMX gum solution, concentration of BSA and SCMX gum, and gelation time on BSA entrapment efficiency and release of the protein in different media were studied. While BSA entrapment efficiency was found to decrease with increase in gelation time and initial BSA loading, the same was found to increase with increase in concentration of SCMX gum. Although the release of BSA in acidic medium was almost equal to that in alkaline medium, as compared up to 2 hr, the release in alkaline medium was found to be prolonged to a different extent depending upon the formulation variables. Copyright © 2008 John Wiley & Sons, Ltd. more...

SUMMARY In this study, ionotropic gelation method was used for the preparation of ibuprofen-loadedcalcium alginate (CALG) and ethylenediamine (EDA) treated calcium alginate (EDA-CALG)microspheres. The effect of EDA-treatment on drug entrapment efficiency, particle size, morphology,swelling behavior and in vitro release characteristics of the microspheres was investigated byvarying its concentration from 0.5 to 2% (v/v). The reduction in drug entrapment efficiency by amaximum of 44.60% was noted for EDA-CALG microspheres compared to untreated CALGmicrospheres. The particle size and swelling index of EDA-CALG microspheres were reducedwith increasing EDA concentration. All the microspheres were observed to retain their sphericalshapes with rough surfaces. EDA-CALG microspheres prepared using 1% and 2% v/v EDA,released almost all of its content within 7 h in pH 6.8 phosphate buffer, however, CALGmicrospheres were found to release the same within 3 h. The intensity of melting endothermic peak ofibuprofen reduced significantly at lower drug load as experienced from DSC thermograms. The FT-IRspectrum of pure ibuprofen, ibuprofen-loaded CALG and EDA-CALG microspheres showed thecharacteristic band of C = O stretching vibration of ibuprofen. Hence, this study revealed thatEDA can be employed for the preparation of ibuprofen-loaded CALG microspheres to retard thedrug release to some extent.Key words: Ibuprofen; Alginate; Ethylenediamine; Microspheres; Ionotropic gelation more...

Novel pH-sensitive hydrogel beads were prepared using a hydrolyzed poly(acrylamide-g-xanthan) (PAAm-g-XG) copolymer from a complete aqueous environment and evaluated for targeting ketoprofen to the intestine. The PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The copolymer was characterized by FTIR spectroscopy, (1)H NMR spectroscopy, elemental analysis and thermogravimetric analysis. Pulsatile swelling study indicated that the copolymer exhibits considerable pH-sensitive behavior unlike pristine xanthan gum. Ketoprofen-loaded pH-sensitive beads were prepared by ionotropic gelation with Al(3 + ) ions. Release of drug from all the copolymeric beads was much lesser than that from pristine xanthan beads. Moreover, a maximum of 20% ketoprofen was released from the copolymeric beads in pH 1.2-5.5 during a period of 3 h, while a major portion of the drug was released in pH 6.8-7.4 gradually over a longer period. Pharmacodynamic activity and stomach histopathology of albino rats indicated that the beads were able to retard the drug release in stomach, and gastric side effects such as ulceration, hemorrhage and erosion of gastric mucosa were diminished when the drug was entrapped into PAAm-g-XG-based pH-sensitive beads. more...

This study was performed to assess and correlate in vitro drug release with in vivo absorption of prednisolone (PDL) from a colon-targeted tablet prepared by compression coating of core tablet. In vivo drug absorption study was conducted using a high performance liquid chromatographic (HPLC) method, which was developed and validated for the estimation of PDL in rabbit plasma. The calibration curve showed linearity in the concentration range of 0.05 to 50 μg/mL with the correlation coefficient (r) of 0.999. The method was specific and sensitive with the limit of detection (LOD) and lower limit of quantification (LLOQ) of 31.89±1.10 ng/mL and 96.63±3.32 ng/mL, respectively. The extraction recovery (ER) of PDL from three different levels of quality control (QC) samples ranged from 98.18% to 103.54%. In vitro drug release study revealed that less than 10% drug was released in 6.34 h and almost complete (98.64%) drug release was achieved in the following 6 h. In vivo drug absorption study demonstrated lower values of Cmax, AUCtotal, and protracted Tmax from compression-coated tablet. The results confirmed the maximum release of drug in the colon while minimizing release in the upper gastrointestinal tract (GIT). An excellent in vitro and in vivo correlation (IVIVC) was also achieved after considering the lag time. more...

This work was envisaged to develop compression-coated tablets using a blend of Ca+2 ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 ± 0.09 h and T rap of 6.50 ± 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 ± 0.08 h and T rap to 3.56 ± 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 ± 0.09 h) and short T rap (4.36 ± 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting. more...

The major aims of the present study were (1) to select a multiple-unit formulation that matched the in vitro dissolution profile of single-unit sustained-release commercial capsules, (2) to compare the sustaining/controlling efficacy of the selected multiple-unit formulation with that of the single-unit commercial conventional tablet and sustained-release capsules, and (3) to determine whether an in vitro-in vivo correlation exists for single- and multiple-unit formulations. Ibuprofen (20%-60% wt/wt)-loaded multiple-unit polystyrene microparticles were prepared by an emulsion-solvent evaporation method from an aqueous system. The in vitro release profiles obtained in phosphate buffer of pH 6.8 for drug-loaded polystyrene microparticles and for commercial sustained-release capsules (Fenlong-SR, 400 mg) were compared. Since the microparticles with 30% ibuprofen load showed a release profile comparable to that of the Fenlong-SR release profile, the microparticles with this drug load were considered to be the optimized/selected formulation and, therefore, were subjected to stability study and in vivo study in human volunteers. A single-dose oral bioavailability study revealed significant differences in C(max), T(max), t(1/2a), t(1/2e), K(a), K(e), and AUC between the conventional tablet and optimized or Fenlong-SR capsule dosage forms. However, all the parameters, with the exception of K(a) along with relative bioavailability (F) and retard quotient (R(Delta)), obtained from the optimized ibuprofen-loaded microparticles were lower than that obtained from the commercial Fenlong-SR formulation. Furthermore, linear relationship obtained between the percentages dissolved and absorbed suggests a means to predict in vivo absorption by measuring in vitro dissolution. more...

The purpose of this study was to examine the suitability of polystyrene-coated (PS-coated) microcapsules of drug-resin complex for achieving prolonged release of diltiazem-HCl, a highly water-soluble drug, in simulated gastric and intestinal fluid. The drug was bound to Indion 254, a cation-exchange resin, and the resulting resinate was microencapsulated with PS using an oil-in-water emulsion-solvent evaporation method. The effect of various formulation parameters on the characteristics of the microcapsules was studied. Mean diameter and encapsulation efficiency of the microcapsules rose with an increase in the concentration of emulsion stabilizer and the coat/core ratio, while the same characteristics tended to decrease with an increase in the volume of the organic disperse phase. The desorption of drug from the uncoated resinate was quite rapid and independent of the pH of the dissolution media. On the other hand, the drug release from the microcapsules was prolonged for different periods of time depending on the formulation parameters and was also found to be independent of the pH of the dissolution media. Both the encapsulation efficiency and the retardation of drug release were found to be dependent on the uniformity of coating, which in turn was influenced by the formulation parameters. Kinetic studies revealed that the desorption of drug from the resinate obeyed the typical particle diffusion process, whereas the drug release from the microencapsulated resinate followed the diffusion-controlled model in accordance with the Higuchi equation. PS appeared to be a suitable polymer to provide prolonged release of diltiazem independent of the pH of the dissolution media. more...