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.     

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.     

Preparation and In Vitro Evaluation of Chitosan Microspheres Containing Prednisolone: Comparison of Simple and Conjugate Microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

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.     

In Vitro Evaluation of Albumin Microspheres Containing Actinomycin D

Albumin microspheres containing actinomycin D were prepared by the heat stabilization method. The compata-bility of the drug with magnetite and the optimum stability of the drug in different pH were studied. Drug loaded albumin microspheres containing magnetite showed good magnetic response. Release of the drug was slow and continued for 7 days exhibiting sustained release property. The difference as regards to the size, shape, drug content and release rate from freshly prepared and freeze dried drug loaded albumin microspheres was negligible.     

In Vitro Evaluation of Albumin Microspheres Containing Actinomycin D

Abstract

Albumin microspheres containing actinomycin D were prepared by the heat stabilization method. The compata-bility of the drug with magnetite and the optimum stability of the drug in different pH were studied. Drug loaded albumin microspheres containing magnetite showed good magnetic response. Release of the drug was slow and continued for 7 days exhibiting sustained release property. The difference as regards to the size, shape, drug content and release rate from freshly prepared and freeze dried drug loaded albumin microspheres was negligible.     

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.     

Comparison of simple Eudragit microparticles loaded with prednisolone and Eudragit-coated chitosan-succinyl-prednisolone conjugate microparticles: Part I. Particle characteristics and in vitro evaluation as a colonic delivery system

Objective: Simple Eudragit microparticles loaded with prednisolone and chitosan-succinyl-prednisolone conjugate microparticles coated with Eudragit were prepared and characterized in vitro in order to obtain their basic features as a colonic delivery system.

Materials and methods: Both types of microparticles were prepared by the emulsification-solvent evaporation modified somewhat from the previous one. Their particle size, shape and their drug content were investigated, and in vitro release profiles were examined using JP-15 1st fluid (pH 1.2), JP-15 2nd fluid (pH 6.8) and PBS (pH 7.4) as release media. Furthermore, the regeneration of conjugate microparticles from Eudragit-coated microparticles was investigated under the same incubation conditions.

Results: Simple Eudragit S100 (EuS) microparticles (ES-M) were almost spherical, ca. 1.2 μm diameter, and PD content ca. 3.7% (w/w). Conjugate microparticles (CS-M1) and EuS-coated conjugate microparticles (CS-M1/S) had particle sizes of ca. 2.8 and 15.3 μm, respectively, and PD contents of 5.4 and 2.1% (w/w), respectively. ES-M exhibited suppressed release at pH 1.2, gradual release at pH 6.8 and rapid release at pH 7.4. CS-M1 showed no release at pH 1.2, and very slow release at pH 6.8 and 7.4. CS-M1 regenerated poorly from CS-M1/S at pH 6.8.

Conclusions: Simple Eudragit micrparticles and Eudragit-caoted conjugate microparticles, prepared by the present methods, were found in vitro to be possibly useful as the delivery systems of PD to the lower intestine, although there were differences in their release rate and morphological features.     

Cellulose Acetate Trimellitate Microspheres Containing NSAIDS

Indomethacin and ketoprofen (non-steroidal anti-inflammatory drugs) were incapsulated with cellulose acetate trimellitate, enteric polymer, using a spray drying technique.

Organic solutions of polymer and drug were prepared in different weight ratios and sprayed, achieving drug loaded microspheres.

The obtained spray dried microparticles were characterized in terms of yield of production, shape, size, morphological characteristics and drug content.

The in vitro drug release tests, carried out using a pH change method with a flow-through cell apparatus, show a typical delayed drug release due to the pH-dependent solubility of the polymer.     

Dissolution Characteristics of Polycaprolactone-Polylactide Microspheres of Chlorpromazine

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.     

Preparation and Evaluation of Methotrexate-Loaded Biodegradable Polyanhydride Microspheres

Methotrexate-loaded biodegradable polyanhydride microspheres were prepared by modified hot-melt technique and aqueous solvent evaporation technique. The effect of particle size, drug loading and microencapsulation technique on the in vitro drug release was studied. The in vitro release of methotrexate was evaluated using an automated flow-through cell system. The release profile consisted of burst release and sustained release phases. The burst release from the microspheres prepared by the modified technique was lower than that from the aqueous solvent evaporation technique. In addition, the microspheres with lower loadings released smaller amounts during the burst release phase. For a given loading and processing technique, the amount released by burst decreased with an increase in particle size. The microspheres prepared by the modified hot-melt technique with 10% loading and 177-250 μm size fraction gave desirable prolonged release. This formulation was tested in vivo in rats by subcutaneous implantation. The peak serum level of methotrexate was reached between 15-18 hours compared to that between 0-3 hours observed following the administration of an equivalent dose of methotrexate solution. No microspheres were found at the site of implantation at 48 hours post-implantation.     

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.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Evaluation of Tableted Microspheres of Dipyridamole

Microspheres of dipyridamole were prepared by solvent evaporation methods. The effect of additives Avicel PH 101, and beta cyclodextrin on the release rate of tableted microspheres were studied. Incorporating Avicel or beta cyclodextrin increased the dipyridamole release rates in tableted microspheres. Beta cyclodextrin was found to be a good additive for microsphere tablets to increase the drug release rates without causing disintegration.     

Preparation of Novel Cationic Copolymer Microspheres and Evaluation of Their Function by In Vitro and In Vivo tests as Ph-Sensitive Drug Carrier Systems

ABSTRACT

Novel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior whenthe pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.     

Preparation and Characteristics of Gelatin Microspheres

Abstract

Gelatin microspheres are prepared by emulsification of a aqueous gelatin solution in a oily phase containing a surfactant, gelation by cooling, dehydration by isopropanol and cross-linking by formaldehyde. The pH, the gelatin concentration in the aqueous solution and the surfactant concentration in the oily phase have some influence on the size distribution of unloaded and loaded microspheres and on the drug contents of microspheres.     

提高采收率用聚(N-羟甲基丙烯酰胺-丙烯酰胺)微球的反相微乳液聚合及其性能

以煤油为连续相,50.0wt%N-羟甲基丙烯酰胺(N-MAM)、丙烯酰胺(AM)单体水溶液为分散相,Span80/OP-10为乳化剂,依据拟三元相图配制了含50.6wt%油相、42.0wt%水相、7.4wt%Span80/OP-10(质量比6∶1)乳化剂相的W/O微乳液(质量分数)。以N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,在65℃过硫酸铵(APS)引发下进行反相微乳液聚合制备了纳米级交联P(AM/NMAM)微球。以微球粒径及溶胀性为考察指标,从单体配比、交联剂用量、引发剂用量及搅拌速率等方面对合成条件进行了优化。结果表明,在单体配比m(AM)∶m(N-MAM)为4∶1,交联剂MBAA用量0.60wt%、引发剂APS用量0.50wt%(以单体总质量计)、搅拌速率1000r/min的条件下合成的微球耐盐性好、吸水倍率高,在1.0×10~5 mg/L模拟地层水中可达18.40g/g。扫描电子显微镜(SEM)、透射电子显微镜(TEM)对微球形态的表征结果显示,其具有较好的球形度及单分散性,粒径分布均一,约为100nm左右。流变及岩心封堵实验表明微球胶乳具有良好的注入性,封堵效果显著,可实现逐级深部调剖。     

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 in vitro characteristics of lactoferrin-loaded chitosan microparticles

In order to achieve the delivery and controlled release of lactoferrin (LF), a biologically multifunctional protein, chitosan microparticles loaded with LF were prepared. Several types of chitosan microparticles containing LF were prepared by the w/o emulsification-solvent evaporation method, and the particle characteristics and release properties in JP 2nd fluid, pH 6.8, were examined. All kinds of microparticles were obtained at a yield of more than 75% (w/w). LF-loaded microparticles prepared by nonsonication and nonaddition of sulfate, named Ch-LF(N), showed high drug content, small particle size and spherical particle shape. Also, for release properties, Ch-LF(N) exhibited gradual drug release over 7 hr with less remaining in the microparticles. Considering the mucoadhesive properties of chitosan microparticles, Ch-LF(N) are suggested to be useful for gradual supply to topical diseased sites or for effective delivery to intestinal areas with abundant LF receptors.     

Cellulose acetate microspheres as floating depot systems to increase gastric retention of antidiabetic drug: formulation, characterization and in vitro-in vivo evaluation

Gastric emptying is a complex process that is highly variable and makes the in vivo performance of 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 hours utilizing floating or hydrodynamically controlled drug delivery systems. The objective of this investigation was to develop a floating, depot-forming drug delivery system for an antidiabetic drug based on microparticulate technology to maintain constant plasma drug concentrations over a prolonged period of time for effective control of blood sugar levels. Formulations were optimized using cellulose acetate as the polymer and evaluated in vitro for physicochemical characteristics and drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in healthy male albino mice. The shape and the surface morphology of the prepared microspheres were characterized by optical microscopy and scanning electron microscopy. In vitro drug release studies were performed and drug release kinetics were calculated using the linear regression method. Effects of stirring rate during preparation and polymer concentration on the size of microspheres and drug release were observed. The prepared microspheres exhibited prolonged drug release (more than 10 hours) and remained buoyant for over 10 hours. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 73% to 98% were obtained. The release rate decreased and the mean particle size increased at higher polymer concentrations. Stirring speed affected the morphology of the microspheres. This investigation revealed that upon administration, the biocompatible depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain orally given drug. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.