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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

Propranolol-HCl, a water soluble drug, was bound to Indion 254, a cation exchange resin, and the resulting resinate was microencapsulated with polystyrene using an oil-in-water emulsion-solvent evaporation method with a view to achieve prolonged drug release in simulated gastric and intestinal fluid. The effect of various formulation parameters on the characteristics of the microcapsules was studied. The diameter of the resinate-loaded polystyrene microcapsules increased with increase in the concentration of emulsion stabilizer and coat/core ratio and decreased with increase in the volume of organic disperse phase. The variation in the size of the microcapsules appeared to be related with the inter-facial viscosity which was influenced by the viscosity of both the aqueous dispersion medium and the organic disperse phase. The resinate encapsulation efficiency and hence the drug entrapment efficiency of the microcapsules increased with increase in the concentration of emulsion stabilizer and coat/core ratio and decreased with increase in the volume of organic disperse phase. These characteristics were found to depend on the extent of formation of fractured microcapsules and subsequent partitioning of the resinate into the aqueous dispersion medium. The degree of fracture on the microcapsules depended on the viscosity of the aqueous dispersion medium and the organic disperse phase. The uncoated resinate discharged the drug quite rapidly following the typical particle diffusion process. Although the desorption of the drug from the resinate was independent of pH of the dissolution media, increase in ionic strength increased the drug desorption. On the other hand, release of drug from the coated resinate was considerably prolonged and followed a diffusion controlled model. The prolongation of drug release was dependent on the uniformity of coating which was influenced by the formulation parameters. The drug release from the microcapsules was also found to be independent of pH of the dissolution media and increased with increase in ionic strength. The pH-independent release of the drug from both the uncoated and microencapsulated resinate was due to pH-independent solubility of the drug and high equilibrium concentration of the resinate in both the dissolution media. Polystyrene appeared to be a suitable polymer to provide prolonged release of propranolol independent of pH of the dissolution media.

Ethylcellulose microcapsules containing theophylline were prepared by the phase-separation coacervation process induced by non-solvent addition in the presence of variable amounts of polyisobutylene. No statistical difference was evident between the different sized microcapsules with respect to their drug content, wall thickness and in-vitro drug dissolution profiles. Poly-isobutylene was, however, found to influence the release profiles of drug to a great extent. An increase in polyisoburylene concentration retarded the release of theophylline from the microcapsules due to the formation of smaller and spheroidal coacervate droplets in larger volumes, which resulted in the formation of more evenly coated microcapsules. Although the release of theophylline from the microcapsules was found to fit both the first order and diffusion controlled release processes, differential rate treatment indicated that the overall release, in fact, was governed by diffusion controlled process.

Sodium alginate and carboxymethyl locust bean gum (CMLBG) were reticulated in an aqueous solution of AlCl3, and this novel interpenetrating network (IPN) hydrogel encapsulated about 93–98% glipizide. The degree of reticulation in the spherical IPN beads was confirmed by Fourier transform infrared spectroscopy, elemental analysis, neutralization equivalent determination, tensile strength testing, and differential scanning calorimetry analysis. An increase in the CMLBG weight ratio and the degree of crosslinking in the IPN was found to increase mean dissolution time of the encapsulated drug. The dissolution efficiency was found to be much higher in the medium at pH 7.4 than at pH 1.2. The swelling of IPN depended on the pH of the medium, and accordingly, monitored the drug release for a period of 8 h. The anomalous drug transport mechanism was presumed to be operative. High performance liquid chromatography (HPLC) analysis showed the drug's stability in the IPN during encapsulation. The IPN showed significant hypoglycemic activity on male Wistar rats for up to 10 h. This could be beneficial for diabetic patients for achieving control over blood glucose levels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

This work embodies studies, performed with micropellet type dosage forms of Pentazocine Hydrochloride (Pz-HCl), using single and composite matrices of Eudragit RS100 (RS) and RL100 (RL). The effects of formulation parameters on various dosage form criteria - namely drug loading, particle size distribution, release profiles etc. have been investigated. Results indicate, that the two polymers can be successfully combined to produce different changes in release kinetics, with simple modifications of coating composition and initial drug loads.

Nonionic surfactants like polysorbates (Tweens) and co-surfactant like propylene glycol are used in pharmaceutical dosage forms, like microemulsion of diazepam. These additives interfere significantly with the estimation of diazepam by UV spectrophotomery method. The aim of this work was to develop a first-order derivative UV-spectrophotometry method that can estimate diazepam in presence of Tween-20 and propylene glycol. The experimental results clearly suggested that, in comparison with the UV-spectrophotometry method, the first-order derivative UV-spectrophotometry is a simple method to estimate diazepam with sufficient accuracy, specificity, and precision even in the presence of 282-times Tween-20 and 2,072-times propylene glycol.

Alginate matrix tablet of diltiazem hydrochloride (DTZ), a water-soluble drug, was prepared using sodium alginate (SAL) and calcium gluconate (CG) by the conventional wet granulation method for sustained release of the drug. The effect of formulation variables like SAL/CG ratio, drug load, microenvironmental pH modulator, and processing variable like compression force on the extent of drug release was examined. The tablets prepared with 1:2 w/w ratio of SAL/CG produced the most sustained release of the drug extending up to 13.5 h. Above and below this ratio, the drug release was faster. The drug load and the hardness of the tablets produced minimal variation in drug release. The addition of alkaline or acidic microenvironmental modulators did not extend the release; instead, these excipients produced somewhat faster release of diltiazem. This study revealed that proper selection of SAL/CG ratio is important to produce alginate matrix tablet by wet granulation method for sustained release of DTZ.

This study describes the formulation of rapidly disintegrating, fast dissolving diazepam tablets intended for use in the oral cavity. The tablets were prepared by the conventional wet granulation method using solid dispersion of the drug with PEG-4000 and/or PEG-6000. A 3 2 factorial design was used to reduce the number of experimental runs and to obtain several formulations by which tablets disintegrated within 3 min and released 85％ of the drug in less than 30 min. Several tablet formulations prepared with diSerent amounts of PEGs in solid dispersion met the above two criteria. However, tablets which were prepared with PEG-4000 alone at the lowest concentration disintegrated in the shortest time (32.12 sec) and released 85％ of the drug most rapidly (11.03 min). Key words―fast dissolving tablet; factorial design; optimization; solid dispersion; diazepam; polyethylene-glycol (PEG)

Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 mum, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.

The objective of this study was to develop a multiunit sustained release dosage form of diltiazem using a natural polymer from a completely aqueous environment. Diltiazem was complexed with resin and the resinate-loaded carboxymethyl xanthan (RCMX) beads were prepared by interacting sodium carboxymethyl xanthan (SCMX), a derivatized xanthan gum, with Al(+3) ions. The beads were evaluated for drug entrapment efficiency (DEE) and release characteristics in enzyme free simulated gastric fluid (SGF, HCl solution, pH 1.2) and simulated intestinal fluid (SIF, USP phosphate buffer solution, pH 6.8). Increase in gelation time from 5 to 20 min and AlCl(3) concentration from 1 to 3% decreased the DEE respectively from 95 to 79% and 88.5 to 84.6%. However, increase in gum concentration from 1.5 to 2.5% increased the DEE from 86.5 to 90.7%. The variation in DEE was related to displacement of drug from the resinate by the gel forming Al(+3) ions. While 75-82% drug was released in 2 h in SGF from various beads, 75 to 98% drug was released in 5 hour in SIF indicating the dependence of drug release on pH of dissolution media. Although the beads maintained their initial integrity throughout the dissolution process in both media, as evident from scanning electron microscopic studies, the faster release in SGF was accounted for higher swelling of the beads in SGF than in SIF. When release data (up to 60%) was fitted in power law expression, the drug release was found to be controlled by diffusion with simultaneous relaxation phenomena.

A micropellet dosage form was developed using ethyl cellulose as a polymer with a view to achieve a controlled release oral drug delivery system for theophylline. Drugpolymer ratios and stirring speeds were found to influence the size-distribution of micropellets. Time required for 50% release of theophylline from micropellets was found to vary linearly with the drug content and reciprocal of diameter of micropellets. Invitro release of theophylline from micropellets, having different drug-polymer ratios and different sizes, was found apparently to follow both the First-order release and Diffusion controlled release processes. By differential rate treatment it was found that the overall release, in fact, followed diffusion controlled process.

Xanthan gum (XG) was derivatized to sodium carboxymethyl xanthan gum (SCMXG) and then cross-linked with aluminium ions (Al(+3)) to prepare BSA-loaded microparticles (MPs) from a completely aqueous environment. The derivatized gum was characterized by various physical methods. Discrete and spherical BSA-loaded MPs were obtained from SCMXG solution, the pH of which was adjusted to 6 and 7 and the BSA entrapment efficiency was found to reach as high as 82%. The protein release in acidic dissolution medium was faster than that in alkaline dissolution medium and was accounted for the higher swelling ratio of the MPs in acidic environment. Moreover, the pH of the gum solution used to prepare the MPs also influenced the swelling and consequently protein release considerably.

Aceclofenac, a non-steroidal antiinflammatory drug, is used for posttraumatic pain and rheumatoid arthritis. Aceclofenac fast-dispersible tablets have been prepared by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time, disintegration time, drug content, in vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t(50%) and t(80%)) decreased with increase in the level of croscarmellose sodium. Where as, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions. It is concluded that fast-dispersible aceclofenac tablets could be prepared by direct compression using superdisintegrants.

Furosemide-loaded calcium alginate (ALG), calcium alginate-polyethyleneimine (ALG-PEI) and alginate-coated ALG-PEI (ALG-PEI-ALG) beads were prepared by ionotropic/polyelectrolyte complexation method to achieve controlled release of the drug. Effects of several formulation factors on the characteristics of the beads were investigated. Although variation in formulation factors did not influence the drug-loading efficiency (DLE) of ALG beads, rapid release of the drug in simulated intestinal fluid (SIF) could not be prevented. PEI treatment of ALG beads, however, prolonged the drug release considerably. Ionic interaction, as appeared from FTIR studies, between alginate and PEI led to the formation of polyelectrolyte complex membrane, the thickness of which was dependent on the conditions of PEI treatment as demonstrated by scanning electron microscopy (SEM). The membrane acted as a physical barrier to drug release from ALG-PEI beads. Alginate coating of ALG-PEI beads further prolonged the release of the drug by increasing membrane thickness and reducing swelling of the beads possibly by blocking the surface pores. Differential scanning calorimetry (DSC) study indicated that drug was not degraded by PEI treatment. The release data from ALG-PEI beads showed a good fit in power law expression, whereas the release data from ALG-PEI-ALG beads were found to fit in modified power law expression, and the mechanism of drug release changed from super case II transport to nearly Fickian transport, depending on the degree of gelation and formation of polyelectrolyte complex membrane.

Propranolol-HCl-loaded calcium alginate (ALG) beads, propranolol-resin complex (resinate)-loaded calcium alginate (RALG) beads and polyethyleneimine (PEI)-treated RALG (RALG-PEI) beads were prepared by ionotropic gelation/polyelectrolyte complexation method. The beads were evaluated and compared in respect of drug entrapment efficiency (DEE) and release characteristics in simulated gastric fluid (SGF, 0.1(N) HCl, pH 1.2) and simulated intestinal fluid (SIF, phosphate buffer, pH 6.8). DEE of RALG beads was considerably higher than that of ALG beads containing unresinated drug. However, DEE of RALG beads decreased with increase in both gelation time and concentration of the gel forming Ca2+ ions due to drug displacement from resinate. PEI treatment of RALG beads further decreased DEE as the polycation also displaced the drug from the resinate. The release of drug from all the beads was slow and incomplete in SGF owing to considerably less swelling of the beads and the decrease in drug release from the beads followed the order: RALG-PEI