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A novel multilamellar vesicular delivery system was developed for the controlled release application. Multilamellar vesicles were prepared by thin film hydration and converted into proliposomes by freeze-drying. A model drug metoclopramide, a highly hydrophilic drug, was successfully encapsulated into proliposomes. The proliposomes produced were non-sticky, free-flowing powders. The proliposomes were formulated into a unit dosage form by combining with various excipients. The effect of different compositions such as type and concentration of phospholipid or hydrophilic polymer was investigared to optimize the formulation. The formation of multilamellar vesicles was confirmed by observing the process of hydration of proliposomes under an optical microscope. The spherical shape of vesicles was confirmed by transmission electron microscopy (TEM) and mean particle sizes were in the range of 1.3-2.5 microm, as measured by dynamic light scattering technique. Differential scanning calorimetry (DSC) study of formulations was conducted to understand the crystalline nature of drug in the vesicles. The results indicated a molecular level dispersion of drug into proliposomes with encapsulation efficiency up to 43%. Critical formulation parameters were identified to obtain a near zero order in vitro release pattern. Proliposomal formulations produced were suitable as multiparticulate drug delivery systems for the controlled release of a highly hydrophilic molecule.

The aim of the present study was to develop proliposomal formulations to enhance the oral bioavailability of exemestane by improving solubility, dissolution and/or intestinal permeability. Proliposomal powder formulations were prepared using different ratios of drug (exemestane), distearoyl-phosphatidylcholine (DSPC), cholesterol and dimyristoyl-phosphatidylglycerol (DMPG) by solvent evaporation method. The effect of phospholipid composition and drug:lipid ratio on in vitro performance of proliposomes was studied. Proliposomes were characterized for their particle size distribution, thermal characteristics by differential scanning calorimetry (DSC) and dissolution behavior. Further, the formulated proliposomes were subjected to in vitro permeation or transport studies using different models such as rat intestine, parallel artificial membrane permeability assay (PAMPA) and Caco-2 cell line. Proliposomes provided enhanced exemestane dissolution due to incorporation into the phospholipid bilayers and change in the physical state from crystalline to amorphous. The in vitro transport studies in rat intestine, PAMPA and Caco-2 models revealed that the proliposomes were successful in enhancing the permeation of exemestane. These proliposomal formulations of exemestane could provide improved oral bioavailability due to enhanced solubility, permeability and hence absorption.

Recently, there has been a great deal of research activity in the development of stimulus-responsive polymeric hydrogels. These hydrogels are responsive to external or internal stimuli and the response can be observed through abrupt changes in the physical nature of the network. This property can be favorable in many drug delivery applications. The external stimuli can be temperature, pH, ionic strength, ultrasonic sound, electric current, etc. A majority of the literature related to the development of stimulus-responsive drug delivery systems deals with temperature-sensitive poly(N-isopropyl acrylamide) (pNIPAAm) and its various derivatives. However, acrylic-based pH-sensitive systems with weakly acidic/basic functional groups have also been widely studied. Quite recently, glucose-sensitive hydrogels that are responsive to glucose concentration have been developed to monitor the release of insulin. The present article provides a brief introduction and recent developments in the area of stimulus-responsive hydrogels, particularly those that respond to temperature and pH, and their applications in drug delivery.

This study deals with the production of poly(DL-lactide-co-glycolide) (PLGA) microspheres using ethyl acetate as a dispersing solvent, a partially water soluble and less toxic solvent, by using emulsification and solvent diffusion/ evaporation techniques. PLGA 50 : 50 was used, having molecular weights, 12000 and 34000 with the end group capped (RG502, 503) and uncapped (RG502H, 503H) biodegradable polymers. The microspheres were loaded with nifedipine (NFD) as a model drug. Solvent removal from the embryonic microspheres was manipulated by adopting different techniques. These methods have shown a significant effect on the physicochemical and release characteristics of the microspheres. Rapid removal of the solvent resulted in microspheres with a loose matrix and large size. Use of higher molecular weight polymers increased the size of the microspheres as well as delayed release of the drug. The uncapped polymer has given a higher rate of diffusion when compared to the capped polymers. Thermal analyses showed a uniform molecular distribution of the drug in the polymer matrix. The mechanism of drug release from the PLGA microspheres followed the Fickian diffusion.

The study is concerned with the development of cellulose acetate microspheres by the o/w emulsification and solvent evaporation method in the presence of polyvinyl alcohol as an emulsifying agent. The influence of process parameters such as solvent mixture (acetone + dichloromethane) composition, concentration of the emulsifying agent and speed of stirring has been examined. The microspheres have been analysed for their size, drug loading capacity and release kinetics. Spherical and smooth surfaced microspheres with encapsulation efficiencies ranging between 73-98%, were obtained. Use of acetone in the oil phase drastically reduced the particle size. Slow drug release from microspheres occurred up to approximately 8 h and the release was found to be non-Fickian. An optimization procedure was employed to investigate and identify the key parameters affecting the properties of the microspheres. A 33 randomized full factorial design was used in the analyses of the data. A linear model with interactive terms was generated using a multiple linear regression approach. The statistical analysis confirms the significant effect of solvent composition and concentration of emulsifying agent on the drug release characteristics.

New spherically shaped cross-linked hydrogels of polyacrylamide-grafted guar gum were prepared by the emulsification method. These were selectively derivatized by saponification of the -CONH2 group to the -COOH group. The derived microgels were characterized by FTIR and elemental analyses. The derivatized microgels were responsive to pH and ionic strength of the external medium. The swelling of microgels increased when the pH of the medium changed from acidic to alkaline. Transport parameters, viz., solvent front velocity and diffusion coefficients were calculated from a measurement of the dimensional response of the microgels under variable pH conditions. The variation in pH changed the transport mechanism from Case II (in 0.1 N HCl) to non-Fickian (in pH 7.4 buffer), and these processes are relaxation-controlled. Ionic strength exerted a profound influence on the swelling of the microgels. Swelling was reversible and pulsatile with the changing environmental conditions. The pH-sensitive microgels were loaded with diltiazem hydrochloride and nifedipine (both antihypertensive drugs) and their release studies were performed in both the simulated gastric and intestinal pH conditions. The release was relatively quicker in pH 7.4 buffer than observed in 0.1 N HCl; the release followed non-Fickian transport in almost all the cases.

Hollow microspheres of cellulose acetate loaded with four cardiovascular drugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffusion-evaporation method. The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%. The microspheres had smooth surfaces, with free-flowing and good-packing properties. Scanning electron microscopy (SEM) confirmed their hollow structures, with sizes in the range 489-350 microm. The microspheres tended to float over the gastric media for more than 12 h. The drug loaded in hollow microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for more than 8 h. The release kinetics followed different transport mechanisms depending on the nature of the drug molecules.

Gastric emptying is a complex process, which is highly variable and makes in vivo performance of the drug-delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 h. The floating or hydrodynamically controlled drug-delivery systems are useful in such applications. The present review addresses briefly the physiology of the gastric emptying process with respect to floating drug-delivery systems. In recent years, the multiparticulate drug-delivery systems are used in the oral delivery of drugs. One of the approaches toward this goal is to develop the floating microspheres so as to increase the gastric retention time. Such systems have more advantages over the single-unit dosage forms. The development of floating microspheres involves different solvent evaporation techniques to create the hollow inner core. The present review addresses the preparation and characterization of the floating microspheres for the peroral route of administration of the drug.

This study is an attempt to prepare microspheres loaded with two antihypertensive drugs viz., nifedipine (NFD) and verapamil hydrochloride (VRP) using cellulose-based polymers viz., ethyl cellulose (EC) and cellulose acetate (CA). Emulsification and solvent evaporation methods were optimized using ethyl acetate as a dispersing solvent. The particles are spherical in shape and have smooth surfaces, as evidenced by the scanning electron microscopy. The microspheres were characterized for their particle size and distribution, tapped density and encapsulation efficiency. Smaller sized particles with a narrow size distribution were produced with EC when compared to CA matrices. Molecular level drug distribution in the microspheres was confirmed by differential scanning calorimetry. The microspheres were directly compressed into tablets using different excipients. The drug release from CA was faster than EC microspheres and, also, the VRP release was faster than NFD. The excipients used in tableting showed an effect on the release as well as the physical properties of the tablets.

This paper reports the development of new interpenetrating polymeric networks of sodium alginate with gelatin or egg albumin cross-linked with a common cross-linking agent, glutaraldehyde, for the in-vitro release of cefadroxil. The beads formed were characterized by Fourier transform infra-red spectroscopy, scanning electron microscopy and differential scanning calorimetry. Swelling/drying experiments were performed to compute the diffusion coefficients and the molecular mass between cross-links of the beads. The release results were evaluated using an empirical equation to understand the transport mechanism. The extent of cross-linking was studied in terms of the size and release characteristics of the beads. The experimental and derived quantities have been used to study their dependencies on the nature of the polymeric beads, transport mechanism, encapsulation efficiency and drug diffusion, as well as the cross-linking abilities of the polymers.

This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticles used as drug delivery systems. Methods of preparation, drug loading and drug release are covered. The most important findings on surface modification methods as well as surface characterization are covered from 1990 through mid-2000.

Solubility data of a hazardous pesticide like chlorpyrifos are important in order to determine its residual toxicity from soil and to understand its controlled release characteristics. In this paper, solubility of chlorpyrifos was measured by using gas chromatography in pure water, methanol, and water-methanol mixtures at 298.15, 303. 15, and 308.15K. The results indicate that chlorpyrifos is more soluble in methanol than in water. The solubility of chlorpyrifos in water can be enhanced by adding methanol to water. The effect of temperature on the solubility of chlorpyrifos was observed at higher methanol content in the mixture.

Polymeric sodium alginate microparticles were prepared by precipitating sodium alginate in methanol, followed by cross-linking with glutaraldehyde. The extent of cross-linking was controlled by the time of exposure to glutaraldehyde. The topology of microparticles was characterized by scanning electron microscopy (SEM), which indicated smooth surfaces. The equilibrium swelling experiments were carried out in water to observe the effect of cross-linking and drug loading for better utility of microparticles. It was found that swelling decreased, but drug loading increased, with an increase in cross-linking of the matrix.

Urea-formaldehyde (UF), polymerized in situ in aqueous media, is a rigid polymer that can be used in the controlled release of bioactive molecules. During the process of polymerization, liquid neem seed oil (NSO) was encapsulated at three different loadings, which was then replaced by diclofenac sodium (DS), the presence of which was confirmed by FTIR spectra. The nanocapsules thus prepared were evaluated for percentage loading of the drug, particle size and release characteristics. Thermal analysis and x-ray data were obtained to understand the physical nature of the encapsulated drug. The surface characteristics of the nanocapsules were studied using a scanning electron microscope. Particles in the size range around 500 nm were obtained. The percentage loading efficiency of NSO was approximately 90-95, whereas for DS, the loading efficiency was only 50-60%. Complete release of the drug from the matrices occurred in 24 h, whereas, at 8 h only 60% of the drug was released.

This paper presents experimental results on the successful encapsulation of a natural liquid pesticide 'neem (Azadirachta Indica A. Juss.) seed oil' hereafter designated as NSO, using sodium alginate (Na-Alg) as a controlled release (CR) polymer after crosslinking with glutaraldehyde (GA). The NSO-containing beads have been prepared by changing the experimental variables such as the extent of crosslinking and the amount of loading in order to optimize the process variables. The absence of chemical interactions between active ingredients and polymer as well as crosslinking agent was confirmed by FTIR spectral measurements. The SEM data indicated that the structure of the walls of the beads are smooth and nonporous. The swelling results indicated that swelling of the polymeric beads decreases with increasing exposure time to the crosslinking agent. However, no significant variation in swelling was observed with different amounts of NSO loading. In order to understand the crosslinkability and its effect on the NSO release patterns of the beads, an attempt was made to calculate the molar mass between crosslinks using the Flory-Rehner equation. The release data have been fitted to an empirical equation to estimate the kinetic parameters.

Poly(vinyl alcohol)-guar gum interpenetrating network microspheres were prepared by cross-linking with glutaraldehyde. Nifedipine, an antihypertensive drug, was loaded into these matrices before and after cross-linking to study its release patterns. The extent of cross-linking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Furthermore, the microspheres were characterized for drug entrapment efficiency, particle size, transport of water into the matrix and drug release kinetics. Scanning electron microscopic photographs confirmed the spherical nature and surface morphology. The mean particle size of the microspheres was found to be around 300 microm. The molecular transport phenomenon, as studied by the dynamic swelling experiments, indicated that an increase in cross-linking affected the transport mechanism from Fickian to non-Fickian. The in vitro release study indicated that the release from these microspheres is not only dependent upon the extent of cross-linking, but also on the amount of the drug loaded as well as the method of drug loading.