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1.
The aim of this work was to understand the influence of different formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres prepared by O/O emulsion solvent evaporation method, employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose polymers. Formulation variables studied included concentration of Eudragit S in the internal phase and the ratios between; internal to external phase, drug to Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres were evaluated by carrying out in vitro release studies and determination of particle size, production yield, and encapsulation efficiency. In addition, morphology of microspheres was examined using optical and scanning electron microscopy. Emulsion solvent evaporation method was found to be sensitive to the studied formulation variables. Particle size and encapsulation efficiency increased by increasing Eudragit S concentration in the internal phase, ratio of internal to external phase, and ratio of Eudragit S to the drug. Employing Eudragit S alone in preparation of the microspheres is only successful in forming acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S and ethylcellulose blend microspheres were able to control release under acidic condition and to extend drug release at high pH. The stability studies carried out at 40°C/75% RH for 6 months proved the stability of the optimized formulation. From the results of this investigation, microencapsulation of mesalamine in microspheres using blend of Eudragit S and ethylcellulose could constitute a promising approach for site-specific and controlled delivery of drug in colon.  相似文献   

2.
The purpose of this research was to prepare floating microspheres consisting of (1) calcium silicate as porous carrier; (2) orlistat, an oral anti-obesity agent; and (3) Eudragit S as polymer, by solvent evaporation method and to evaluate their gastro-retentive and controlled-release properties. The effect of various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behavior, percentage drug entrapment, and in vitro drug release was studied. The gamma scintigraphy of the optimized formulation was performed in albino rabbits to monitor the transit of floating microspheres in the gastrointestinal tract. The orlistat-loaded optimized formulation was orally administered to albino rabbits, and blood samples collected were used to determine pharmacokinetic parameters of orlistat from floating microspheres. The microspheres were found to be regular in sphae and highly porous. Microsphere formulation CS4, containing 200 mg calcium silicate, showed the best floating ability (88%±4% buoyancy) in simulated gastric fluid as compared with other formulations. Release pattern of orlistat in simulated gastric fluid from all floating microspheres followed Higuchi matrix model and Peppas-Korsmeyer model. Prolonged gastric residence time of over 6 hours was achieved in all rabbits for calcium silicate-based floating microspheres of orlistat. The enhanced elimination half-life observed after pharmacokinetic investigations in the present study is due to the floating nature of the designed formulations.  相似文献   

3.
The purpose of this research was to investigate whether Eudragit S100 microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Microspheres were prepared using water-in oil-in water emulsion solvent evaporation technique with polysorbate 20 as a dispersing agent in the internal aqueous phase and polyvinyl alcohol (PVA)/polyvinyl pyrrolidone as a stabilizer in the external aqueous phase. The use of smaller internal aqueous-phase volume (50 μL) and external aqueous-phase volume (25 mL) containing PVA in the manufacturing process resulted in maximum encapsulation efficiency (81.8%±0.9%). PVA-stabilized microspheres having maximum drug encapsulation released 2.5% insulin at pH 1.0 in 2 hours. In phosphate buffer (pH 7.4), microspheres showed an initial burst release of 22% in 1 hour with an additional 28% release in the next 5 hours. The smaller the volumes of internal and external aqueous phase, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA-stabilized microspheres demonstrated spherical particles with smooth surface, and laser diffractometry revealed a mena particle size of 32.51±20 μm. Oral administration of PVA stabilized microspheres in normal albino rabbits (equivalent to 6.6 IU insulin/kg of animal weight) demonstrated a 24% reduction in blood glucose level, with maximum plasma glucose reduction of 76±3.0% in 2 hours and effect continuing up to 6 hours. The area under the percentage glucose reduction-time curve was 93.75%. Thus, our results indicate that Eudragit S100 microspheres on oral administration can protect insulin from proteolytic degradation in the gastrointestinal tract and produce hypoglycemic effect.  相似文献   

4.
Microparticles of naproxen with Eudragit L100 and Aerosil were prepared by the emulsion solvent diffusion method in order to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal anti-inflammatory drugs after oral ingestion. The process of preparation involved the use of ethanol as good solvent, dichloromethane as a bridging liquid, water as poor solvent, Aerosil as anti-adhesion agent, and sodium dodecyl sulfate to aid in the dispersion of the drug and excipients into the poor solvent. The obtained microparticles were evaluated for micromeritic properties, yield, encapsulation efficiency, drug physical state, and drug release properties. The influence of formulation factors and preparation condition (polymer/naproxen ratio, Aerosil/polymer ratio, and the initial difference of temperature between the solvent and nonsolvent) on the properties of the microparticles were also examined. The resultant microparticles were finely spherical and uniform with high incorporation efficiency (>79%) and yield (>71%). The incorporation efficiency was enhanced with increasing the ratio of excipients to drug and the initial difference of temperature between the solvent and nonsolvent. The mean diameter of the microparticles was influenced by all of the manufacturing parameters. Studies carried out to characterize the micromeritic properties of formulations, such as flowability and packability, showed that microparticles were suitable for further pharmaceutical manipulation (e.g., capsule filling). Drug release studies of the microparticles confirmed the gastroresistance, and mathematical studies showed that the drug released followed a Hixon and Crowell kinetic. These microparticles represent a simple method for the preparation of drug-loaded enteric microparticles with desired micromeritic properties and gastroresistance release.  相似文献   

5.
In this study, we investigated the in vitro characteristics of mefenamic acid (MA) microparticles as well as their effects on DNA damage. MA-loaded chitosan and alginate beads were prepared by the ionotropic gelation process. Microsponges containing MA and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. The microparticles were characterized in terms of particle size, surface morphology, encapsulation efficiency, and in vitro release profiles. Most of the formulation variables manifested an influence on the physical characteristics of the microparticles at varying degrees. We also studied the effects of MA, MA-loaded microparticles, and three different polymers on rat brain cortex DNA damage. Our results showed that DNA damage was higher in MA-loaded Eudragit microsponges than MA-loaded biodegradable chitosan or alginate microparticles.  相似文献   

6.
This paper describes the formulation of a biodegradable microparticulate drug delivery system containing clodronate, a bisphosphonate intended for the treatment of bone diseases. Microspheres were prepared with several poly(D,L-lactide-co-glycolide) (PLGA) copolymers of various molecular weights and molar compositions and 1 poly(D,L-lactide) (PDLLA) homopolymer by a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation procedure. Critical process parameters and formulation variables (ie, addition of stabilizing agents) were evaluated for their effect on drug encapsulation efficiency and clodronate release rate from microparticles Well-formed clodronate-loaded microspheres were obtained for all polymers by selecting suitable process parameters (inner water/oil volume ratio 1∶16, temperature-raising rate in the solvent evaporation step 1°C/min, 2% wt/vol NaCl in the external aqueous phase). Good yields were obtained in all batches of clodronate microspheres (above 60%); drug encapsulation efficiencies ranged between 49% and 75% depending on the polymer used. Clodronate release from all copolymer microspheres was completed in about 48 hours, while those from PDLLA microspheres required about 20 days. The change of microsphere composition by adding a surfactant such as Span 20 or a viscosing agent such as carboxymethylcellulose extended the long-term release up to 3 months. Clodronate was successfully entrapped in PLGA and PDLLA microspheres, and drug release could be modulated from 48 hours up to 3 months by suitable selection of polymer, composition, additives, and manufacturing conditions. Published: July 11, 2001.  相似文献   

7.
Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision, and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical agents, and it consists of porous polymeric microspheres, typically 10–50 μm in diameter, loaded with active agents. Eudragit RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of drug release. Microsponges of nearly 98% encapsulation efficiency and 60–70% porosity were produced. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.KEYWORDS: hydroxyzine HCl, microsponges, oil in oil emulsion solvent diffusion, skin delivery  相似文献   

8.
Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision, and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical agents, and it consists of porous polymeric microspheres, typically 10–50 μm in diameter, loaded with active agents. Eudragit RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of drug release. Microsponges of nearly 98% encapsulation efficiency and 60–70% porosity were produced. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.  相似文献   

9.
Zidovudine (AZT) is commonly used to treat patients with AIDS, but it is limited by toxicity and high dosing needs. Alternative formulations have been proposed to overcome these drawbacks. The objective of this study was to evaluate process-related variables like hydration and sonication time, rotation speed of evaporation flask, and the effects of charge-inducing agent and centrifugation on zidovudine entrapment and release from niosomes. Formulation of zidovudine niosomes was optimized by altering the proportions of Tween, Span and cholesterol. The effect of process–related variables like hydration time, sonication time, charge-inducing agent, centrifugation and rotational speed of evaporation flask on zidovudine entrapment and release from niosomes was evaluated. The effect of changes in osmotic shock and viscosity were also evaluated. Non-sonicated niosomes were in the size range of 2-3.5 μm and sonicated niosomes formulated with Tween 80 and dicetylphosphate (DCP) had a mean diameter of 801 nm. Zidovudine niosomes formulated with Tween 80 entrapped high amounts of drug and the addition of DCP enhanced drug release for a longer time (88.72% over 12 h). The mechanism of release from Tween 80 formulation was the Fickian type and obeyed first-order release kinetics. Niosomes can be formulated by proper adjustment of process parameters to enhance zidovudine entrapment and sustainability of release. These improvements in zidovudine formulation may be useful in developing a more effective AIDS therapy.  相似文献   

10.
Lysozyme was encapsulated within biodegradable poly(D, L-lactide-co-glycolide) microspheres by a double emulsion solvent evaporation method for studying its release mechanism associated with protein stability problems. When urea, a protein unfolding agent, was added into the incubation medium lysozyme release rate from the microspheres increased with the increase in urea concentration. The enhanced lysozyme release was attributed to the suppression of protein aggregation, to the facilitated diffusion of unfolded lysozyme by an efficient reptile motion of unfolded protein molecules through porous channels in microspheres, and to the largely decreased extent of nonspecific protein adsorption onto the enlarged surface area of degrading polymer microspheres in the presence of urea. Encapsulating lysozyme in an unfolded form within PLGA microspheres was attempted by using urea as an excipient. This new urea-based formulation exhibited a more sustained lysozyme release profile than the control formulation, and released lysozyme from the microspheres showed a much less amount of lysozyme dimer population while maintaining a correct conformation after refolding in the incubation medium. This study provides new insights for the formulation of protein encapsulated PLGA microspheres.  相似文献   

11.
Characterization of 5-fluorouracil microspheres for colonic delivery   总被引:1,自引:0,他引:1  
The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 22 to 55 μm, and the size of the coated microspheres ranged from 103 to 185 μm. The core microspheres sustained the drug release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat ratio of 1∶7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram, and in vitro drug release after storage at 40°C/75% relative humidity for 6 months.  相似文献   

12.
The purpose of this research was to develop the taste-masked microspheres of intensely bitter drug ondansetron hydrochloride (OSH) by spray-drying technique. The bitter taste threshold value of OSH was determined. Three different polymers viz. Chitosan, Methocel E15 LV, and Eudragit E100 were used for microsphere formation, and the effect of different polymers and drug–polymer ratios on the taste masking and release properties of microspheres was investigated. The microspheres were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, Drug loading, in vitro bitter taste evaluation, and drug-release properties. The taste masking was absent in methocel microspheres at all the drug–polymer ratios. The Eudragit microspheres depicted taste masking at 1:2 drug–polymer ratio whereas with Chitosan microspheres the taste masking was achieved at 1:1 drug–polymer ratio. The drug release was about 96.85% for eudragit microspheres and 40.07% for Chitosan microspheres in 15 min.  相似文献   

13.
The purpose of the present study was to model the effects of the concentration of Eudragit L 100 and compression pressure as the most important process and formulation variables on the in vitro release profile of aspirin from matrix tables formulated with Eudragit L 100 as matrix substance and to optimize the formulation by artificial neural network. As model formulations, 10 kinds of aspirin matrix tablets were prepared. The amount of Eudragit L 100 and the compression pressure were selected as causal factors. In vitro dissolution time profiles at 4 different sampling times were chosen as responses. A set of release parameters and causal factors were used as tutorial data for the generalized regression neural, network (GRNN) and analyzed using a computer. Observed results of drug release studies indicate that drug release rates vary widely between investigated formulations, with a range of 5 hours to more than 10 hours to complete dissolution. The GRNN model was optimized. The root mean square value for the trained network was 1.12%, which indicated that the optimal GRNN model was reached. Applying the generalized distance function method, the optimal tablet formulation predicted by GRNN was with 5% of Eudragit L 100 and tablet hardness 60N. Calculated difference (f 1 2.465) and similarity (f 2 85.61) factors indicate that there is no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network, GRNN, to assist in development of extended release dosage forms.  相似文献   

14.
The purpose of this study was to improve the stability of cloricromene (AD6) in ophthalmic formulations and its drug availability at the ocular level. To this end, AD6-loaded polymeric nanoparticle suspensions were made using inert polymer resins (Eudragit RS100 and RL100). We modified the quasi-emulsion solvent diffusion technique by varying some formulation parameters (the drug-to-polymer ratio, the total drug and polymer amount, and the stirring speed). The chemical stability of AD6 in the nanosuspensions was assessed by preparing some formulations using (unbuffered) isotonic saline or a pH 7 phosphate buffer solution as the dispersing medium. The formulations were stored at 4°C, and the rate of degradation of AD6 was followed by high performance liquid chromatography (HPLC). The obtained nanosuspensions showed mean sizes and a positive surface charge (ζ-potential) that make them suitable for an ophthalmic application; these properties were maintained upon storage at 4°C for several months. In vitro dissolution tests confirmed a modified release of the drug from the polymer matrixes. Nanosuspensions prepared with saline solution and no or lower amounts of surfactant (Tween 80) showed an enhanced stability of the ester drug for several months, with respect to an AD6 aqueous solution. Based on the tecnological results, AD6-loaded Eudragit Retard nanoparticle suspensions appear to, offer promise as a means to improving the shelf life and bioavailability of this drug after ophthalmic application. Published: March 24, 2006  相似文献   

15.
In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices.  相似文献   

16.
The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract fromPhyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2×3 factorial design, where Eudragit E concentration and compression force were the in-dependent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formuations in order to achieve less water sorption and improve the release of the extract from the tablets. Published: April 27, 2007  相似文献   

17.
The purpose of this research was to evaluate in vitro transnasal sustained-release ability of sorbitan monostearate (SMS) organogels in isopropyl myristate (IM). Organogels were prepared containing SMS (2.5%–20%) and water (5%–25%) in IM and analyzed microscopically for phase behavior. The effect of Tween surfactants on gel strength and in vitro nasal diffusion of propranolol is reported. The in vitro nasal release retardant effect of SMS and Tween 20 was investigated using factorial design. The microscopic changes in structure of organogel during in vitro nasal diffusion were studied. The water-holding capacity of SMS organogels in IM increased with SMS concentration. The release retardant effect with incorportation of cosurfactant was of the order of Tween 80> Tween 60> Tween 20. Gel strengthening and increased viscosity were evident with increased concentration of SMS and Tween 20. The 3-dimensional network of SMS molecules controls the diffusional drug release. The organogel system on nasal mucosa during diffusion is dynamic in nature and changes continuously with the time of diffusion. The water penetration in the organogel network results in percolation and emulsification of organogel, thus affecting the release. Organogels provided an effective barrier for diffusion of propranolol. The surface epithelium lining and the granular cellular structure of treated nasal mucosa were intact.  相似文献   

18.
The purpose of this study was to develop formulations and systematically evaluate in vitro performances of buccoadhesive patches of propranolol hydrochloride using the hydrophobic polymer Eudragit L-100 as the base matrix. The hydrophilic polymers Carbopol 934 and polyvinyl pyrrolidone (PVP) K30 were incorporated into the Eudragit patches, to provide the patches with bioadhesive properties and to modify the rate of drug release. The patches, which were prepared by the solvent casting method, were smooth and elegant in appearance; were uniform in thickness, weight, and drug content; showed no visible cracks; and showed good folding endurance. A 32 full factorial design was employed to study the effect of independent variables like hydrophilic polymers Carbopol 934 and PVP K30, which significantly influenced characteristics like swelling index, ex vivo mucoadhesive strength, in vitro drug release, and ex vivo residence time. A stability study of optimized Eudragit patches was done in natural human saliva; it was found that both drug and buccal patches were stable in human saliva. It can be concluded that the present buccal formulation can be an ideal system to improve the bioavailability of the drug by avoiding hepatic first-pass metabolism. Published: June 22, 2007  相似文献   

19.
Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 μm, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.  相似文献   

20.
The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow size distributions with one size fraction comprising 70–80% of the yield. Scanning electron microscopy and quantitative Fourier transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism.  相似文献   

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