共查询到20条相似文献,搜索用时 31 毫秒
1.
The in vitro stability (temperature and pH) and dissolution study (pH 7.4 phosphate buffer solution and pH changed medium) of the enteric-coated microspheres containing Mycoplasma hyopneumoniae vaccine (MHV) were examined. The MHV microspheres were thermally more stable than the unencapsulated MHV. More than 90% of antigenicity was retained in the MHV microspheres for 3 weeks when stored at 4 degrees C. The MHV microspheres in pH 1.2 and pH 3.0 medium were more stable than the unencapsulated MHV. The MHV enteric-coated microspheres exhibited an excellent enteric function to prevent pH-related inactivation. The influence of particle size, CAP concentration and span 80 concentration on the MHV released from microspheres was also determined. The smaller the particle size, the higher the dissolution rate due to the larger surface area of the smaller particle. The higher the concentration of span 80 used, the more the greater the amount of MHV released. This was attributed to the more porous structure of microspheres prepared by the higher concentration of span 80. By increasing the CAP concentration, however, the release rate of MHV was decreased due to the larger amount of CAP and the more compact structure of microspheres. 相似文献
2.
The solvent evaporation method was employed to encapsulate Mycoplasma hyopneumoniae vaccine (MHV) using cellulose acetate phthalate (CAP) as an enteric coating material. Glucose was used as a diluent. The effect of some factors, such as encapsulating temperature, surfactant concentration, mechanical agitation and CAP concentration on the formation condition, particle size distribution, morphology, surface topography and antigen content of MHV microspheres, was investigated. The result indicates that the optimal operating conditions were: encapsulating temperatures, 20 degrees C; stirring speed, 400 rpm; span 80 concentration, 0.6; and 8 per cent of CAP concentration, 30 ml. The optimal condition can be used to prepare the desirable microspheres. The content uniformity of MHV microspheres was also indicated. 相似文献
3.
Ketoprofen gastroresistant microspheres were prepared by spray-drying using common pH dependent polymers, such as Eudragit S and L, CAP, CAT and HPMCP. The long ketoprofen recrystallization time was a serious hindrance to the preparation of microspheres having a drug content higher than 35%. Microspheres were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffractometry and in vitro dissolution studies, and used for the preparation of tablets. During this step, the compaction ability of the spray-dried powders was measured. While the compressibility of the microspheres containing the enteric cellulosic derivatives are not acceptable and different from those of the microcrystalline cellulose, the compaction properties of ketoprofen/Eudragit L or S microspheres are comparable to those of the Avicel PH 101. In vitro dissolution studies were performed on the microspheres and the tablets. All microspheres showed a good gastroresistance, but some differences among the five polymers in reducing drug release at low pH values are present. Acrylic polymers (Eudragit L or S) are considerably more effective than the cellulosic derivatives CAP and CAT, while the HPMCP profile is in an intermediate position. These differences are erased by the microspheres compression process. In HCl 0.1 N, the percentage of ketoprofen released from the tablets is always close to zero, independently from the polymer used. 相似文献
4.
To obtain a sustained-release dosage form with a lack of gastric unwanted effects, wax microspheres containing propranolol (I) were prepared by a congealable dispersion microencapsulation technique. The effects of the process variables; type of wax, speed of emulsification, amount of drug loaded, type and amount of emulsifier, were studied on the entrapment efficiency, angle of repose, dissolution efficiency (DE), in-vitro drug release and mean particle size of (I) microspheres, by a factorial design. The results showed that changes in the amount of emulsifier (Tween), 0.04% and 0.08%, the type of Tween (80 and 20) and the wax type; beeswax or ceresine, caused a significant decrease in the entrapment efficiency. All the variables had an effect on the angle of repose and particle size of the (I) microspheres. The only significant parameter affecting the DE was the nature of the wax. The drug release in pH 6.8 was affected by all the variables except the amount of emulsifier. The formulation with a 0.25:4 ratio of drug:ceresine wax and 0.04% of Tween 80 in 600 rpm emulsification speed showed a suitable multiparticulate delivery system for the retarded dissolution of entrapped active ingredients, allowing absorption only in the intestinal tract. 相似文献
5.
The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicate that quantity of emulsifying agent, time for stirring, drug-to-polymers ratio and speed of rotation affected the characteristics of microspheres. Microspheres were discrete, spherical, free flowing and showed a good percentage of drug entrapment efficiency. An in vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 32 full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X1) and stirring speed (X2) on dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency, particle size and t80. The best batch exhibited a high drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 µm. A sustained drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microspheres to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication. 相似文献
6.
C. W. Liao I. C. Cheng K. S. Yeh F. Y. Lin C. N. Weng 《Journal of microencapsulation》2013,30(3):285-297
Using formalin inactivated Actinobacillus pleuropneumoniae antigens and aqueous ethylcellulose dispersions, microspheres of oral vaccines were developed by a co-spray drying process. The present study attempted to determine whether the dosage formulations of microspheres could form enteric matrices. To assess the enteric characteristics, an in vitro dissolution test was performed with the AQ6-AP microspheres; 95% of the A. pleuropneumoniae protein was released within 3 h at pH 7, but there was no release at pH 1.5. The scanning microscopy revealed that the surface structure of AQ6-AP microspheres became porous at neutral pH. The SDS-PAGE analysis showed that the release rate of proteins from the microspheres was pH dependent not only for the AQ6-AP formulation but also when antigens of A. pleuropneumoniae were replaced with porcine serum. The results suggest that the A. pleuropneumoniae antigens were entrapped in the AQ6 microspheres under the acidic conditions. In a mouse model, oral immunization with AQ6-AP microspheres containing A. pleuropneumoniae evoked systemic IgG and mucosal IgA responses against A. pleuropneumoniae antigens. Thus, the present method may further provide an opportunity to develop oral vaccines and mucosal immunity. 相似文献
7.
Aim:
To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.Methods:
The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres.Results:
rhEPO was almost completely released from the PLGA microspheres in vitro, following zero-order release kinetics over approximately 30 d. After intramuscular injection (10 000 or 30 000 IU rhEPO/kg) in the rats, the serum rhEPO concentration reached maximum levels on d 1, then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism. A good linear correlation (R2=0.98) was obtained between the in vitro and in vivo release data. A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10 000 or 30 000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO.Conclusion:
The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month. 相似文献8.
Microencapsulation of the anti-inflammatory drug piroxicam and the anti-asthmatic drug theophylline was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Microspheres of both drugs that are different in the chemical nature and size were successfully encapsulated at a theoretical loading of 25% with the pH sensitive Eudragit S 100 polymer using the emulsion-solvent evaporation method. Solvent composition, stirring rate and the volume of the external phase were adjusted to obtain reproducible, uniform and spherical microspheres. The size distribution of microsphere batches generally ranged from 125-500 microm with geometric means close to 300 microm. Optical light microscopy was used to identify the microsphere shape. Drug loading was determined by completely dissolving the microspheres in an alkaline borate buffer at pH 10. In vitro dissolution studies were carried out on the microspheres at 37 degrees C (+/-0.5 degrees C) at 100 rpm with USP Dissolution Apparatus II using the procedure for enteric-coated products at two successive different pH media (1.2 and 6.5). Both preparations exhibited an initial rapid release in the acidic medium with theophylline showing a larger increase in the amount released during this stage. The drug release was sustained for both preparations at pH 6.5 with theophylline microspheres, showing more extended release. Drug release rate kinetics followed a Higuchi spherical matrix model for both microsphere preparations. 相似文献
9.
The solubility of non cross-linked chitosan in weak acid solutions restricts its utility in microspheres for drug delivery. The primary aim of this study was to produce pentasodium tripolyphosphate cross-linked chitosan microspheres with higher acid resistance for controlled release of ampicillin. The microspheres were prepared by two different microencapsulation procedures (by emulsification and by spray-drying) and characterized by their particle size, surface morphology, stability, drug entrapment efficiency and drug release. The size of the microspheres was <10 microm with a narrow size distribution. The entrapment of ampicillin in the microspheres was more than 80%. Stability of uncross-linked and cross-linked microspheres was affected by the pH of simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5). The inclusion of the enzymes pepsin and pancreatin did not affect the stability of the microspheres. The inclusion of lysozyme in phosphate buffer saline resulted in increased solubilization. The release of the drug was affected by cross-linking of microspheres with tripolyphosphate (TPP). The cross-linked microspheres were more stable in simulated gastric fluid and showed slower but sustained release of ampicillin. The antimicrobial activity of the released ampicillin was confirmed by Staphylococcus aureus bioassay. 相似文献
10.
In this study, the fluorescein isothiocyanate (FITC)-albumin distribution, the amount of FITC-albumin release and the degradation of poly (DL-lactic-co-glycolic acid) (PLGA) microspheres were evaluated. The higher the FITC-albumin concentration in the W1 phase, the higher the protein concentration and loading efficiency in the microspheres, the larger the particle size of microspheres. Confocal laser scanning microscopy (CLSM) showed that the FITC-albumin was distributed uniformly in the microspheres with a low concentration while it was aggregated at higher concentrations. The high protein concentration in the microspheres showed significantly large initial release (above 70% w/w) during the 10 days. A higher PVA concentration in the W2 phase resulted in a smaller particle size, higher protein contents and loading efficiency and decreased release rate. After a 10 day incubation period, the microspheres with a low FITC-albumin concentration had an almost spherical morphology, while microspheres with a high FITC-albumin concentration had a more distorted morphology, suggesting that rapid morphological changes and microspheres ruptures can be induced by an initial burst release. 相似文献
11.
We have produced biodegradable or enteric-coated microspheres containing camostat mesylate, a protease inhibitor, using a water-oil-water emulsion solvent evaporation method. The characteristics of the microspheres were determined. When polylactic acid, a biodegradable polymer, was used as a wall material, the optimized microsphere obtained showed a loading efficiency of almost 95% and had a mean diameter of 30 microm. This microsphere showed a sustained-release profile, with nearly 25% of drug being released at seven days in a dissolution test. When hypromellose acetate succinate (AS-HG type, with a high content of succinyl group) was used as an enteric wall material, optimized microspheres showed a loading efficiency of almost 80%. In this case, pH 3.0 citrate buffer was used as an internal aqueous phase, and citrate buffer containing 0.5% polyvinylalcohol was used as the external aqueous phase. These microspheres showed a rapid release profile in pH 6.8 buffer, whereas the release was extremely slow in pH 1.2 buffer. Hypromellose acetate succinate microspheres were also prepared containing 10% (w/w) N-benzoyl-dl-arg-4-nitroanilide as a model substrate for trypsin, with or without 5% (w/w) camostat. These microspheres were incubated in pH 6 or 7 buffer containing trypsin at 37 degrees C. When camostat was included in the microspheres, the substrate was protected from attack by trypsin, while in the absence of camostat, the released substrate was immediately attacked by trypsin to produce the degradation product N-benzoyl-dl-arginine. 相似文献
12.
The aim of this study was to demonstrate a sustained-release microparticulate dosage form for acyclovir via an in vitro study. Ethyl cellulose was selected as a model encapsulation material. All of the microspheres were prepared by an oil-in-water solvent evaporation technique. A 23 full factorial experiment was applied to study the effects of the viscosity of polymer, polymer/drug ratio, and polymer concentration on the drug encapsulation efficiency and the dissolution characteristics. The encapsulation efficiency of acyclovir in microspheres was in the range of 20.0-56.6%. Increase in the viscosity of ethyl cellulose and the ratio of CH2Cl2/ethyl cellulose increased drug encapsulation efficiency. The drug continuously released from microspheres for at least 12 h, and the release rate depended on the pH of the release medium. The sustained release characteristic was more prominent in the simulated intestine fluid than in the simulated gastric fluid. A faster release of drug was observed when a high viscosity polymer was used. The decomposition of acyclovir significantly decreased when encapsulated by ethyl cellulose, especially when stored at 37 and 50 °C. 相似文献
13.
《Pharmaceutical development and technology》2013,18(6):738-746
AbstractThe purpose was to improve the encapsulation efficiency of cetirizine hydrochloride (CTZ) microspheres as a model for water soluble drugs and control its release by applying response surface methodology. A 33 Box–Behnken design was used to determine the effect of drug/polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3), on the mean particle size (Y1), percentage encapsulation efficiency (Y2) and cumulative percent drug released for 12?h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations were evaluated for micromeritic properties and morphologically characterized by scanning electron microscopy (SEM). The relative bioavailability of the optimized microspheres was compared with CTZ marketed product after oral administration on healthy human volunteers using a double blind, randomized, cross-over design. The results revealed that the mean particle sizes of the microspheres ranged from 62 to 348?µm and the efficiency of entrapment ranged from 36.3% to 70.1%. The optimized CTZ microspheres exhibited a slow and controlled release over 12?h. The pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax, decreased Cmax and AUC0–∞ value of 3309?±?211 ng?h/ml indicating improved relative bioavailability by 169.4% compared with marketed tablets. 相似文献
14.
《Pharmaceutical development and technology》2013,18(5):1169-1174
To develop a long-acting injectable thienorphine biodegradable poly (d, l-lactide-co-glycolide) (PLGA) microsphere for the therapy of opioid addiction, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The thienorphine loaded PLGA microspheres were prepared by o/w solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, residual solvent content and sterility testing. The microspheres were sterilized by gamma irradiation (2.5 kGy). The results indicated that the morphology of the thienorphine PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 30.19?±?1.17 to 59.15?±?0.67μm and the drug encapsulation efficiency was influenced by drug/polymer ratio, homogeneous rotation speed, PVA concentration in the water phase and the polymer concentration in the oil phase. These changes were also reflected in drug release. The plasma drug concentration vs. time profiles were relatively smooth for about 25 days after injection of the thienorphine loaded PLGA microspheres to beagle dogs. In vitro and in vivo correlation was established. 相似文献
15.
Manju Rawat 《Journal of microencapsulation》2013,30(4):306-314
The present study aimed to develop an oral sustained release microparticulate system for acid labile enzyme-Serratiopeptidase. A 32 full factorial experiment was designed to study the effects of the external aqueous phase volume and stabilizer (Tween® 80) concentration on the entrapment and size of Eudragit S100 microspheres prepared by a modified double emulsion solvent evaporation technique. The results of analysis of variance tests for both effects indicated that the test is significant. The effect of external aqueous phase volume was found to be higher on the entrapment efficiency of microspheres (SSY1 = 1362.63; SSY2 = 250.13), whereas Tween® 80 produced a significant effect on size of microspheres (SSY1 = 944.01; SSY2 = 737.26). Scanning electron microscopy of microspheres demonstrated smooth surface spherical particles. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. Microspheres having maximum drug encapsulation (81.32 ± 3.97) released 4–5% enzyme at pH 1.2 in 2 h. The release of enzyme from microspheres followed Higuchi kinetics (R2 = 0.987). In phosphate buffer, microspheres showed an initial burst release of 25.65 ± 2.35% in 1 h with an additional 62.96 ± 4.09% release in the next 5 h. Thus, formulation optimization represents an economical approach for successful preparation of Eudragit S100 microspheres involving fewest numbers of experiments. 相似文献
16.
多柔比星海藻酸钙微球的制备及其载药、释药性质的研究 总被引:5,自引:0,他引:5
目的:考察多柔比星海藻酸钙微球的制备工艺及载药、释药性质。方法:考察不同处方微球的粒径、机械强度、降解等性质,筛选出最佳处方;以多柔比星为模型药物研究其对药物的承载能力及体外释药特性。结果:制备的微球圆整且分散性好,粒径均匀。多柔比星海藻酸钙微球的载药量达30%以上,包封率在90%以上;在体外37℃生理氯化钠溶液中释放显示具有缓释作用。结论:该微球对多柔比星具有较高的承载能力,并有较好的缓释作用,可满足临床治疗动脉栓塞需要。 相似文献
17.
Insulin encapsulation in reinforced alginate microspheres prepared by internal gelation. 总被引:2,自引:0,他引:2
Catarina M Silva António J Ribeiro Domingos Ferreira Francisco Veiga 《European journal of pharmaceutical sciences》2006,29(2):148-159
Insulin-loaded alginate microspheres prepared by emulsification/internal gelation were reinforced by blending with polyanionic additive polymers and/or chitosan-coating in order to increase the protection of insulin at simulated gastric pH and obtain a sustained release at simulated intestinal pH. Polyanionic additive polymers blended with alginate were cellulose acetate phtalate (CAP), Eudragit L100 (EL100), sodium carboxymethylcellulose (CMC), polyphosphate (PP), dextran sulfate (DS) and cellulose sulfate (CS). Chitosan-coating was applied by using a one-stage procedure. The influence of additive polymers and chitosan-coating on the size distribution of microspheres, encapsulation efficiency and release profile of insulin in simulated gastrointestinal pH conditions was studied. The mean diameter of blended microspheres ranged from 65 to 106 microm and encapsulation efficiency of insulin varied from 14 to 100%, reaching a maximum value when CS and DS were incorporated in the alginate matrix. Insulin release, at pH 1.2, was almost prevented by the incorporation of PP, DS and CS. When uncoated microspheres were transferred to pH 6.8, a fast dissolution occurred, independently of the additive polymer blended with alginate, and insulin was completely released. Increasing the additive polymer concentration in the alginate matrix and/or chitosan-coating the blended alginate microspheres did not promote a sustained release of insulin from microspheres at pH 6.8. 相似文献
18.
《Journal of microencapsulation》2013,30(3):250-261
Lysozyme and insulin were encapsulated in alginate gel microspheres using impinging aerosols method. High loadings of around 50% weight/dry microspheres weight were obtained with encapsulation efficiencies of at least 48%. Environmental scanning electron microscopy revealed smooth spherical hydrated microspheres (30–60?µm) in diameter. No lysozyme or insulin release was measured in simulated gastric fluid (HCl, pH 1.2, 37°C). Total insulin release occurred in simulated intestinal fluid (SIF; phosphate buffer saline, pH 7.4, 37°C) in 8?h following 2?h incubation in SGF and was found to retain 75% activity using the ARCHITECT® assay. Lysozyme was released completely in SIF in 10?h following 2?h incubation in SGF and was found to exhibit at least 80% bioactivity using the Micrococcus lysodeikticus assay. The absence of protein release in HCl and the retention of high levels of biological activity demonstrate the potential of alginate gel microspheres, for improving oral delivery of biopharmaceuticals. 相似文献
19.
S. K. Umadevi R. Thiruganesh S. Suresh K. Bhaskar Reddy 《Biopharmaceutics & drug disposition》2010,31(7):407-427
The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span‐85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41–80 µm. The swelling index was in the range 0.37–0.82 and the entrapment efficiency range was 51–75% for all the formulations. The optimised batch ACM13 released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non‐Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti‐inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
20.
目的:评价盐酸二甲双胍肠溶胶囊在不同p H条件下的溶出曲线。方法:参照2010版《中华人民共和国药典》附录X B、XD,采用桨法考察盐酸二甲双胍肠溶胶囊在pH分别为1.0、4.0、纯水条件下2h后调节为pH6.8磷酸缓冲液再溶出1h的溶出性能, HPLC法测定溶出液中二甲双胍浓度,DDSolver 1.0对溶出曲线进行分析。结果:盐酸二甲双胍肠溶胶囊在pH1.0、pH4.0及纯水2h内几乎不释放,而在pH6.8的磷酸盐缓冲液中45min内释放达90%以上。经软件DDSolver1.0分析3种pH条件下的溶出曲线是相似的。结论:该二甲双胍肠溶胶囊在不同pH条件下的溶出曲线是相似的,对于不同患者溶出性能一致,药品品质较佳。 相似文献