Development of pH-sensitive pectinate/alginate microspheres for colon drug delivery

The purposes of this study were to develop and evaluate calcium pectinate/alginate microspheres (PAMs) and to exploit their pH-sensitive properties for colon-targeted delivery of encapsulated cisplatin. PAMs were prepared using an electrospraying method. The PAMs, as cores, were then coated with Eudragit S100 using a polyelectrolyte multilayer coating technique in aqueous solution. The morphology of the microspheres was observed under scanning electron microscopy. In vitro drug release studies were performed in simulated gastrointestinal fluid, and the results indicated that approximately 5 % of the cisplatin was released from the Eudragit S100-coated PAMs, and 51 % of the cisplatin was released from the uncoated PAMs at 1 h. The release of cisplatin from the Eudragit S100-coated PAMs was more sustained in simulated gastric fluid than in simulated intestinal fluid due to the increased solubility of the coating polymer in media with pH >7.0. Drug release from the Eudragit S100-coated PAMs was best described by the Higuchi’s square root model. From these results, it was concluded that Eudragit S100-coated PAMs are a potential carrier for delivery of cisplatin to the colon.     

Eudragit Coating of Chitosan-Prednisolone Conjugate Microspheres and In Vitro Evaluation of Coated Microspheres

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37°C. Ch‐SP-MS were spherical, with a mean size of 4.5 μm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 μm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.     

Modulated release of 5-fluorouracil from pH-sensitive and colon targeted pellets: An industrially feasible approach

Pellets, reliant on pH-sensitivity and time-dependency for drug delivery, provide one of the most versatile opportunities for targeting colon. 5-Fluorouracil (5-FU) loaded pellets were prepared by extrusion-spheronization using Avicel^® PH101 as a spheronization aid and hydroxypropylmethylcellulose K4M (HPMC K4M) solution as a binder. A 3² full factorial design was employed to optimize spheronization speed and time. Obtained pellets were evaluated for flow properties, pellet size, roundness and aspect ratio. Optimized batch was coated in a bottom-spray fluidized bed processor (FBP) with an inner coat of sustained release polymer Eudragit NE30D and an outer coat of pH-sensitive polymer Eudragit FS30D. The coating levels were statistically optimized and in vitro drug release was monitored by changing pH media method. Optimized system with 15% inner and outer coating levels revealed t_50% (time required for 50% drug release) to be about 9?h while almost complete drug was released in 24?h (98.71?±?1.33%) with highest dissolution efficiency (DE_24h) of 58.71%. The optimization model was validated; the predicted and experimental/actual values for validation batch (M1) were in close tolerance and the standard error (SE) was also small. Drug release was also studied at pH 7.4. Scanning electron microscopy (SEM) demonstrated average coating thickness to be 32.50?±?3.0 µm. Hence, the present study provides constructive results for colon targeting of 5-FU pellets with industrially feasible processes.     

Eudragit coating of chitosan-prednisolone conjugate microspheres and in vitro evaluation of coated microspheres

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37°C. Ch-SP-MS were spherical, with a mean size of 4.5 μm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 μm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.     

pH-sensitive and mucoadhesive microspheres for duodenum-specific drug delivery system

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21?±?18 μmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2?h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2?h, while nearly 90% of the drug was released within 6?h after transferring into SPDF.     

Eudragit S100 coated microsponges for Colon targeting of prednisolone

Context: Microsponge is a novel approach for targeting the drug to the colon for the management of colon ailments such as inflammatory bowel disease.

Objective: Prednisolone loaded microsponges (PLMs) were prepared and coated with Eudragit S 100 (ES) and evaluated for colon-specific drug delivery.

Materials and methods: PLMs were prepared using quasi emulsion solvent diffusion technique using ethyl cellulose, triethylcitrate (1% v/v, plasticizer) and polyvinyl alcohol (Mol. Wt. 72?kDa, emulsifying agent). The developed microsponges were compressed into tablets via direct compression technique using sodium carboxymethyl cellulose (Na CMC) and magnesium stearate as super-disintegrant and lubricant, respectively. The tablets were then coated with ES to provide protection against harsh gastric environment and manifest colon-specific drug release.

Results: PLMs were found to be nano-porous spherical microstructures with size around 35?µm and 86% drug encapsulation efficiency. Finally, they were compressed into tablets which were coated with Eudragit S 100 In vitro drug release from ES coated tablets was carried out at various simulated gastrointestinal fluids i.e. 1?hr in SGF (pH 1.2), 2 to 3?h in SIF (pH 4.6), 4–5?h in SIF (pH 6.8), and 6–24?h in SCF (pH 7.4) and the results showed the biphasic release pattern indicating prolonged release for about 24?h.

Discussion and conclusion: In vitro drug release studies revealed that drug starts releasing after 5?h by the time PLMs may enter into the proximal colon. Hence maximum amount of drug could be released in the colon that may result in reduction in dose and dose frequency as well as side effects of drug as observed with the conventional dosage form of prednisolone.     

pH-Sensitive and mucoadhesive microspheres for duodenum-specific drug delivery system

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21?±?18 μmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2?h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2?h, while nearly 90% of the drug was released within 6?h after transferring into SPDF.     

Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions.

Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin.

Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0?±?1.7% and 46.0?±?1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4?months at room temperature and at 4?°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution.

Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.     

Release profiles of theophylline from microspheres consisting of dextran derivatives and cellulose acetate butyrate: effect of polyion complex formation

The objective of this study was to evaluate the utility of mixtures among oppositely charged dextran derivatives as constituents of a controlled release microsphere. Carboxymethyldextran (CMD) and dextran sulfate (DS) were used as polyanions, and [2-(diethylamino) ethyl] dextran (EA) and [2-hydroxypropyltrimethylammonium] dextran (CDC) as polycations. The microspheres consisting of hydrophilic and hydrophobic polymers were prepared by emulsion-solvent evaporation method. The mixtures, CMD/EA, CMD/CDC, DS/EA, and DS/CDC, were used as hydrophilic polymers, because they can interact with each other to form polyion complexes for the improvement of sustained-release performances. Cellulose acetate butyrate and theophylline were used as a model hydrophobic polymer and a model drug, respectively. The yield of microspheres was excellent (more than 95%). According to observation, by scanning election microscopy (SEM) microspheres were spherical with a rough surface. The in vitro drug release from microspheres was examined in the JP XIV first fluid, pH 1.2, and second fluid, pH 6.8, at 37°C, and 100 rpm. In the DS/CDC system, drug release was depressed by formation of a polyion complex and not affected by pH of dissolution medium. The release rate was modulated by the ratio of hydrophilic and hydrophobic matrix. This particulate system, in which the polyion complex matrix is strengthened by a hydrophobic polymer, is a promising formulation for drug delivery.     

Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer

COX-2 inhibitors have demonstrated beneficial effects in colorectal cancer. The purpose of this study was to prepare and evaluate the colon specific microspheres of COX-2 inhibitors using valdecoxib as a model drug. Mucoadhesive core microspheres were prepared using chitosan as polymer and entrapped within Eudragit S 100 for colon targeting. FTIR spectrum of selected, coated microspheres showed peaks of valdecoxib at 3377, 3250, 1334 and 1155 cm⁻¹. XRD showed amorphous character and DSC showed depressed broad endotherm of valdecoxib at 169.07°C, which may be attributed to dilution effect by the amorphous polymer. The coated microspheres were spherical with an average size of 90 μm. Storage of the microspheres at 40°C/75% relative humidity for 6 months indicated no significant drug degradation. The coated microspheres did neither release the drug in acidic pH of stomach (pH 1.2) nor in small intestinal pH between 5 to 6.8, and the release started at pH 7.4, indicting perfect colonic delivery. The coated microspheres pretreated with phosphate buffer pH 7.4 for 30 min, when applied to mucosal surface of freshly excised goat colon, showed good mucoadhesion. The drug release at pH 7.4 and good mucoadhesive property of the microspheres make the system ideal for colonic delivery.     

Preparation and characterization of chitosan microspheres containing doxifluridine

Chitosan microspheres containing 5-fluorouracil (5-FU), tegafur (FT), and doxifluridine (DFUR) were prepared by the dry-in-oil method using silicone oil with no surfactant as a dispersion medium. For DFUR-containing chitosan microspheres (DFUR-M), reacetylation with acetic anhydride or coating using chitosan and glutaraldehyde was performed. DFUR-M, reacetylated DFUR-M, and chitosan-coated DFUR-M were investigated on in vitro drug release, and the former two microspheres were examined for in vivo degradation after subcutaneous (s.c.) implantation in mice, and in vivo plasma concentration-time profiles after s.c. implantation in rats. The present method gave fairly large microspheres purely composed of chitosan and drug because of no use of surfactant, which showed the mean particle diameters of 300-900 µm and the drug contents of 4-22% (w/w). Encapsulation efficiency of DFUR was higher than that of 5-FU and FT. DFUR-M and reacetylated DFUR-M exhibited spherical shape except chitosan-coated DFUR-M. DFUR-M showed high initial rapid release, which was suppressed to some extent by reacetylation or chitosan coating. DFUR-M and reacetylated DFUR-M subcutaneously implanted were gradually degraded, and approximately half or a little more of the microspheres disappeared from the implanted site at 3 weeks postimplantation. DFUR-M and reacetylated DFUR-M implanted subcutaneously gave similar plasma concentration-time profiles of DFUR, which did not indicate prolonged release in vivo. DFUR-containing chitosan microspheres with fairly large size and good drug content could be obtained by the present preparation but remained to be improved for drug release properties.     

Basic Coating Polymers for the Colon-Specific Drug Delivery in Inflammatory Bowel Disease

During acute attacks of inflammatory bowel disease, the luminal pH of the colon decreases significantly. This drop in pH can be exploited by developing coated dosage forms with acid-soluble coating polymers to achieve topical drug delivery to the colon. Two batches of minitablets, a conventional and a swellable formulation, were prepared by direct compression and coated with different amounts of either Eudragit® E or AEA® in a small coating pan. The release of the model drug dexamethasone from the coated tablets was measured spectrophotometrically at pH 2.0, 4.0, 5.0, and 6.8 and different stirring rates (100–200 rpm) to simulate the influence of pH and hydrodynamic stress on drug release. In general, lag times of drug release, determined as the time points of a 5% drug release, were longer with AEA-coated cores compared to those coated with Eudragit E, resulting from a lower polymer dissolution rate and water permeability of this film. In low pH media, drug release was dependent on the stirring rate because the onset of drug release is determined by the time required for dissolution of the basic polymer films. At pH 6.8, lag times from nonswelling tablets coated with Eudragit E, for which drug release only begins after complete erosion of the polymer film, are not significantly affected by hydrodynamic stress. Drug release from AEA-coated cores is determined by the slow drug diffusion through the polymer film. Lag times from tablets with swelling properties, for which drug release is induced by disruption of the basic polymer films due to water penetration and subsequent core swelling, are not significantly affected by hydrodynamic stress. Additional coating layers such as an intermediate hydroxypropylcellulose (HPC) layer and an enteric outer layer do not influence the lag times of drug release, nor does a 2-hr pretreatment of the entire dosage form in acidic media.     

Basic coating polymers for the colon-specific drug delivery in inflammatory bowel disease

During acute attacks of inflammatory bowel disease, the luminal pH of the colon decreases significantly. This drop in pH can be exploited by developing coated dosage forms with acid-soluble coating polymers to achieve topical drug delivery to the colon. Two batches of minitablets, a conventional and a swellable formulation, were prepared by direct compression and coated with different amounts of either Eudragit® E or AEA® in a small coating pan. The release of the model drug dexamethasone from the coated tablets was measured spectrophotometrically at pH 2.0, 4.0, 5.0, and 6.8 and different stirring rates (100-200 rpm) to simulate the influence of pH and hydrodynamic stress on drug release. In general, lag times of drug release, determined as the time points of a 5% drug release, were longer with AEA-coated cores compared to those coated with Eudragit E, resulting from a lower polymer dissolution rate and water permeability of this film. In low pH media, drug release was dependent on the stirring rate because the onset of drug release is determined by the time required for dissolution of the basic polymer films. At pH 6.8, lag times from nonswelling tablets coated with Eudragit E, for which drug release only begins after complete erosion of the polymer film, are not significantly affected by hydrodynamic stress. Drug release from AEA-coated cores is determined by the slow drug diffusion through the polymer film. Lag times from tablets with swelling properties, for which drug release is induced by disruption of the basic polymer films due to water penetration and subsequent core swelling, are not significantly affected by hydrodynamic stress. Additional coating layers such as an intermediate hydroxypropylcellulose (HPC) layer and an enteric outer layer do not influence the lag times of drug release, nor does a 2-hr pretreatment of the entire dosage form in acidic media.     

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

ABSTRACT

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

Preparation of alginate microspheres by water-in-oil emulsion method for drug delivery: Effect of Ca2+ post-cross-linking

Alginate microspheres were prepared by a water-in-oil emulsion solvent diffusion method. The alginate microspheres were post-cross-linked with Ca²⁺ ions. Influence of Ca²⁺ concentration on the characteristics and drug release behaviors of alginate microspheres was evaluated. Blue dextran was used as a water-soluble model drug. The non-cross-linked alginate microspheres were less than 100 μm in size and had a spherical shape. The cross-linked alginate microspheres were also spherical in shape with a rougher surface but their particle sizes were larger than 100 μm. The drug encapsulation efficiency of the non-cross-linked alginate microspheres was very high (82%). The drug encapsulation efficiency of alginate microspheres cross-linked with 5% and 10% Ca²⁺ concentrations were similar to the non-cross-linked microspheres. The in vitro drug releases of the cross-linked alginate microspheres showed prolong release profiles. The cumulative release of blue dextran decreased as the Ca²⁺ concentration increased. Thus, Ca²⁺-post-cross-linked alginate microspheres show possibility for use as controlled-release drug carriers.     

Dissolution Characteristics of Polycaprolactone-Polylactide Microspheres of Chlorpromazine

Abstract

Studies were conducted on the preparation of controlled release polycaprolactone-polylactide microcapsules of chlorpromazine and on release of the drug from the microcapsules in pH 7.0 buffer medium. A wide range of release rates of the drug was obtained by simple change in the polymer system. Chlorpromazine was released from the microspheres in a biphasic manner consisting of an initial fast release phase followed by a slow-release phase. Increasing the drug content increased the initial drug release rate but no significant drug loading effect on the second stage dissolution rate was noted. There was no significant effect of particle size on the drug release rate from the microspheres. The swelling property of the microspheres and the agglomerate nature of the sieve fractions may complicate the drug release kinetics and obscure the particle size effect on dissolution rate.     

Nanosponge-based pediatric-controlled release dry suspension of Gabapentin for reconstitution

Abstract

Context: Gabapentin was selected to formulate oral controlled release dry suspension because of short biological half life of 5–7?h and low bioavailability (60%). Gabapentin is a bitter drug so an attempt was made to mask its taste.

Objective: To formulate and evaluate controlled release dry suspension for reconstitution to increase the bioavailability and to control bitter taste of drug.

Materials and methods: Cyclodextrin based nanosponges were synthesized by previously reported melt method. The nanosponge–drug complexes were characterized by FTIR, DSC and PXRD as well as evaluated for taste and saturation solubility. The complexes were coated on Espheres by a suspension layering technique followed by coating with ethyl cellulose and Eudragit RS-100. A dry powder suspension for reconstitution of the microspheres was formulated and evaluated for taste, redispersibility, in vitro dissolution, sedimentation volume, leaching and pharmacokinetics.

Results and discussion: The complexes showed partial entrapment of drug nanocavities. Significant decrease in solubility (25%) was observed in the complexes than pure drug in different media. The microspheres of nanosponge complexes showed desired controlled release profile for 12?h. Insignificant drug leaching was observed in reconstituted suspension during storage for 7 days at 45?°C/75% RH. Nanosponges effectively masked the taste of Gabapentin and the coating polymers provided controlled release of the drug and enhanced taste masking. The results of in vivo studies showed increase in bioavailability of controlled release suspension by 24.09% as compared to pure drug.

Conclusion: The dry powder suspension loaded with microspheres of nanosponges complexes can be proposed as a suitable controlled release drug delivery for Gabapentin.     

Study on hydrophilic 5-fluorouracil release from hydrophobic poly(ϵ-caprolactone) cylindrical implants

Hydrophilic 5-fluorouracil (5-FU) loaded cylindrical poly(?-caprolactone) (PCL) implants with different implant diameters (2, 4 and 8?mm), different drug loadings (25% and 50%) and end-capping were fabricated and characterized. The implant structure, drug content and molecular weight of PCL after 120 days drug release were investigated. The in vitro release results showed that, when the drug loading was the same, drug release was fastest for the implant with a diameter of 2?mm and slowest for the implant with a diameter of 8?mm; for the implants with the same diameters, the release of drug from the implants with 50% drug loading was faster than that from the implants with 25% drug loading; however, this effect of drug loading decreased with the increase of implant diameter; in addition, 5-FU was released slightly slower from the end-capped implants than from the corresponding uncapped implants; the drug release data for all the uncapped implants were best fit with the Ritger-Peppas model. Drug release from the hydrophobic implants was found to be dominated by diffusion mechanism. Scanning electron microscopy images and drug content measurements revealed that 5-FU release took place gradually from the exterior region to the interior region of the implants.     

Formulation and Compaction of Microspheres

Abstract

The factors affecting the tabletability of formulations containing uncoated and/or coated microspheres were discussed by presenting a case study. The size and shape, as well as surface properties of microspherical particles, the type and amount of coating agent, selection of the external additives, and the rate and magnitude of the pressure applied were found to be the most critical factors to be considered in order to obtain and maintain the desired drug release properties of the microspheres. It was found that microcrystalline cellulose was needed in order to produce satisfactory beads in terms of size, shape and surface characteristics. The microsphere formulations, which were found to be highly sensitive to lubrication, were more compressible than their powder forms, but produced much weaker tablets. When coated with Surelease, increasing the amount of coating on the pellets reduced the tensile strength of their compacts. Compaction of the microspheres at high velocities resulted in a decrease in the tensile strength values and an increase in the volumetric strain recovery values. Dissoultion studies revealed that, regardless of the amount of coating applied, the coated microspheres lost their sustained release properties during compaction.     

Controlled drug delivery systems based on thiolated chitosan microspheres

The aim of the present study was to verify the potential of chitosan-thio-butyl-amidine (TBA) microspheres as carrier systems for controlled drug delivery. In this study microspheres were prepared utilizing water in oil (w/o) emulsification solvent evaporation technique. A concentration of 0.5% of chitosan-TBA conjugate displaying 100 µM thiol groups per gram polymer was used in the aqueous phase of the emulsion in order to prepare microspheres. The obtained non-aggregated free-flowing microspheres were examined with conventional light microscope as well as scanning electron microscopy (SEM). The microscopic images indicated that the prepared chitosan-TBA microspheres were of spherical shape and smooth surface while microparticles obtained from the unmodified chitosan were of porous structure and non-spherical shape. Particle size distribution was determined to be in the range from 1 to 59 µm. The free thiol group content of chitosan-TBA microspheres prepared with an aqueous phase of pH 2, 5, and 6.5 were determined to be 71.4, 49.4, and 8.2 µM/g polymer, respectively. Furthermore, results attained from in vitro release studies with fluorescein isothiocyanate labelled dextran (FITC-dextran) loaded chitosan-TBA microspheres showed a controlled release rate for more than three hours while the control reached the maximum peak level of release already within an hour. According to these results, chitosan-TBA microspheres seem to be a promising tool in transmucosal drug delivery for poorly absorbed therapeutic agents.