改善难溶性药物功效的一种新型给药系统——干酏剂的研究进展

干酏剂是一种将乙醇和药物同时包裹入水溶性聚合物壳内的固态微囊.乙醇的潜溶剂作用及喷雾干燥工艺可能产生的无定形药物,有利于包裹于干酏剂中的水难溶性药物快速分散并溶解于水性介质中,从而提高其溶出速率和生物利用度.本文综合近年来干酏剂研究的主要文献,从干酏剂的制剂成型工艺及机制、对难溶性药物体外溶出、体内吸收及生物利用度的影响,以及基于干酏剂的剂型设计及应用做一综述.     

Bioavailability of cyclosporin A dispersed in sodium lauryl sulfate-dextrin based solid microspheres

The purpose of this work was to develop a solid dispersion system containing cyclosporin A (CsA) in order to improve the bioavailability of poorly water-soluble CsA. Solid dispersion systems that are spherical in shape (CsA-microspheres) were prepared with varying ratios of CsA/sodium lauryl sulfate/dextrin using a spray-drying technique. The effects of sodium lauryl sulfate (SLS) and dextrin on the dissolution of CsA dispersed in SLS-dextrin based solid microspheres were investigated. The bioavailability of CsA-microspheres was compared with CsA powder alone and commercial Sandimmun in dogs. SLS significantly enhanced the dissolution of CsA from microspheres, while dextrin did not affect this. The CsA-microspheres at the CsA/SLS/dextrin ratio of 1/3/1, which gave the highest dissolution rate of CsA among the formula treated, was selected as an optimal formula for oral delivery. This formula gave significantly higher blood levels, area under the drug concentration-time curve (AUC) and maximum blood concentration of drug (Cmax) of CsA in dogs compared with the CsA powder alone. The AUC, Cmax and time to reach maximum blood concentration (Tmax) of CsA with CsA-microspheres was not significantly different from those after oral administration of Sandimmun, suggesting the similar bioavailability to Sandimmun in dogs. Our study demonstrates that the CsA-microspheres prepared with SLS and dextrin, with improved bioavailability of CsA, would be useful to deliver a poorly water-soluble CsA and could be applicable to other poorly water-soluble drugs.     

Poly(D,L-lactide-co-glycolide) encapsulated poly(vinyl alcohol) hydrogel as a drug delivery system

Purpose. The efficiency of encapsulation of water-soluble drugs in biodegradable polymer is often low and occasionally these microcapsules are associated with high burst effect. The primary objective of this study is to develop a novel microencapsulation technique with high efficiency of encapsulation and low burst effect. Method. Pentamidine was used as a model drug in this study. Pentamidine/polyvinyl alcohol (PVA) hydrogel was prepared by freeze-thaw technique. Pentamidine loaded hydrogel was later microencapsulated in poly(lactide-co-glycolide) (PLGA) using solvent evaporation technique. The microcapsules were evaluated for the efficiency of encapsulation, particle size, surface morphology, thermal characteristic, and drug release. Results. Scanning Electron Microscope (SEM) studies revealed that the microcapsules were porous. The microcapsules were uniform in size and shape with the median size of the microcapsules ranging between 27 and 94 m. The samples containing 10% PLGA showed nearly three times increase in drug loading (18-53%) by increasing the hydrogel content from 0-6%. The overall drug release from the microencapsulated hydrogel, containing 3% and 6% PVA, respectively, was significantly lower than the control batches. Conclusions. The use of a crosslinked hydrogel such as PVA can significantly increase the drug loading of highly water-soluble drugs. In addition, incorporation of the PVA hydrogel significantly reduced the burst effect and overall dissolution of pentamidine.     

Preparation of double-encapsulated microcapsules for mitigating drug loss and extending release.

The double-encapsulated microcapsules were prepared by the non-solvent addition, phase-separation method to form core material and, encapsulated with the O/W emulsion non-solvent addition method to increase drug loading and regulate drug release rate. The drug used was theophylline, which is water-soluble. Dichloromethane and n-hexane were used as the solvent and non-solvent, respectively. This study investigated how various core material and microcapsule EC/TH ratios affect the drug loss, particle size, surface morphology and release rate. The drug loss of the double-encapsuLated microcapsules was 12.8% less than that of microcapsules prepared by the O/W emulsion non-solvent addition method alone. The particle size of these double-encapsulated microcapsules decreased as the concentration of EC polymer was increased in the second encapsulation process. The roughness of their surface was also in proportion to the concentration of polymer solution used in the second encapsulation process. The dissolution study showed that the T20 of the double-encapsulated microcapsules ranged from 2-35.4 h, while that of the O/W emulsion non-solvent addition method microcapsules was from 2.7-7.7 h. The greater the level of EC in the polymer solution, the slower the release rate of the drug from the microcapsules when the EC was not over the critical amount.     

Enhanced dissolution rate of celecoxib using PVP and/or HPMC-based solid dispersions prepared by spray drying method

Celecoxib with low solubility and high permeability (BCS class II) in water is a non-steroidal anti-inflammatory drug used in the treatment of pain and inflammation, associated with rheumatoid arthritis, and several other inflammatory disorders. Also, it is a selective cyclooxygenase 2 inhibitor with low water solubility and high crystallinity. The objective of this study was to improve dissolution rate of celecoxib which was water-insoluble drug. Solid dispersions were prepared by spray drying as the solvent evaporation method. The dissolution behavior of solid dispersions was compared with Celebrex^® (Pfizer) as a control group in simulated gastric juice (pH 1.2, 0.5 % SLS. The characterization of the prepared solid dispersions is analyzed by scanning electron microscope, powder X-ray diffractometer, Fourier transform infrared spectroscopy and reverse phase-high performance liquid chromatography The best formulation was SD 8 in this study. It was the cumulative release of 97 % at 120 min. This study suggests that the solubility and bioavailability of poorly water-soluble celecoxib improved through the prepared solid dispersions by spray drying method.     

Preparation and in vitro evaluation of slow release ketoprofen microcapsules formulated into tablets and capsules.

Ketoprofen powder was encapsulated with Eudragit RL/RS polymer solutions in isopropanol-acetone 1:1, using a simple and rapid method. Microcapsules were prepared using Eudragit solutions with different RL/RS ratios. The encapsulation process produces free-flowing microcapsules with good drug content and marked decrease in dissolution rate. The retardation in release profile of ketoprofen from microcapsules was a function of the polymer ratio employed in the encapsulation process. In vitro release of ketoprofen from microcapsules either filled in gelatin capsules or compressed into tablets, using calcium sulphate as diluent, confirmed the efficiency of the encapsulation process for preparing prolonged release medication. A capsule formulation with optimum sustained-release profile was suggested.     

Microencapsulation of insulin using a W/O/W double emulsion followed by complex coacervation to provide protection in the gastrointestinal tract

Abstract

Microcapsules containing insulin were prepared using a combination of a W/O/W double emulsion and complex coacervation between WPI (used as a hydrophilic emulsifier) and CMC or SA with further spray drying of the microcapsules in order to provide protection in the gastrointestinal tract. The microcapsules prepared exhibited high encapsulation efficiency and showed the typical structure of a double emulsion. After spray drying of these microcapsules, the integrity of the W/O/W double emulsion was maintained and the biological residual activity remained high when using the combination of 180?°C inlet air temperature and 70?°C outlet air temperature. The microcapsules exhibited low solubility at pH 2 and high solubility at pH 7 so they might protect insulin at acid pH values in the stomach and release it at intestinal pH values. The microcapsules developed in this study seem to be a promising oral delivery vehicle for insulin or other therapeutic proteins.     

The effect of water to ethanol feed ratio on physical properties and aerosolization behavior of spray dried cromolyn sodium particles

Cromolyn sodium (CS) was spray dried under constant operation conditions from different water to ethanol feed ratios (50:50-0:100). The spray dried CS samples were characterized for their physicochemical properties including crystallinity, particle size distribution, morphology, density, and water/ethanol content. To determine quantitatively the crystallinity of the powders, an X-ray diffraction (XRD) method was developed using samples with different crystallinity prepared by physical mixing of 100% amorphous and 100% crystalline CS materials. The aerodynamic behavior of the CS samples was determined using an Andersen Cascade Impactor (ACI) with a Spinhaler at an air flow of 60 L/min. Binary mixtures of each spray dried CS powder and Pharmatose 325, a commercial alpha-lactose monohydrate available for DPI formulations, were prepared and in vitro aerosol deposition of the drug from the mixtures was analyzed using ACI to evaluate the effect of carrier on deposition profiles of the spray dried samples. CS spray dried from absolute ethanol exhibited XRD pattern characteristic for crystalline materials and different from patterns of the other samples. The crystallinity of spray dried CS obtained in the presence of water varied from 0% to 28.37%, depending on the ratio of water to ethanol in the feed suspensions. All samples presented different particle size, water/ethanol content, and bulk density values. CS particles spray dried from absolute ethanol presented uniform elongated shape whereas the other samples consisted mainly of particles with irregular shape. Overall, fine particle fraction increased significantly (p < 0.01) with decreasing d50% and water and ethanol content of spray dried CS samples. Significant difference (p < 0.01) in deposition profiles of the drug were observed between corresponding carrier free and carrier blended formulations. The difference in deposition profiles of CS aerosolized from various spray dried samples were described according to the particle size, shape, and water/ethanol contents of the powders. The results of this study indicate that enhanced aerosol performance of CS can be obtained by spray drying of the drug from suspensions containing > or = 87.5% v/v ethanol.     

Nanoencapsulation of a crystalline drug

The aim of this work was to assess the influence of various formulation parameters on the incorporation of a poorly water-soluble crystalline drug into nanoparticles. For this purpose, the influence of the polymer (polylactic acid, polysebacic acid terminated with lithocholic acid, and polysebacic acid-co-lithocholic acid) as well as the effect of the dispersion medium (aqueous phases at different temperatures, saline medium and ethanol) on the encapsulation was investigated. 3H-labelled drug was used in order to determine the loading efficiency by liquid scintillation counting. The solubility of the drug in the various polymer materials was assessed by differential scanning calorimetry (DSC). The solubility of the drug in the different dispersion media was then determined by gas chromatographic-mass spectrometric measurements. The highest loading ratios were obtained using poly (lactic acid) (PLA). However, the drug solubility in the polymers, determined by DSC analysis, cannot be considered as predictive for encapsulation efficiency. The study of the influence of the liquid outer phase showed that the encapsulation efficiency increased when the drug solubility in the dispersion medium (before acetone evaporation) decreased. These experiments made it possible to propose a mechanism to account for the leakage of the crystalline drug during the nanoprecipitation process. So, when acetone is eliminated by evaporation, the drug solubility in the dispersion medium decreases, leading to the formation of crystals. During nanoparticles storage, the crystals continue to grow, the nanoparticles serving as drug reservoirs. These findings highlight the importance of using a polymer with a specific affinity for the drug, and a dispersion medium with the lowest drug solubility to achieve an efficient encapsulation of a crystalline drug.     

Formulation and characterization of the microencapsulated entomopathogenic fungus Metarhizium anisopliae MA126

Abstract

Bioinsecticides are expected to be used for controlling major species of aphids. The present study explored a liquid phase coating technique for the formulation of microencapsulated conidia of the entomopathogenic fungus Metarhizium anisopliae MA126. Various parameters for microencapsulation were investigated. The biopolymers sodium alginate, hydroxypropyl methyl cellulose (HPMC) and chitosan were tested as coating materials. Calcium chloride was used as the cross-linking agent for converting soluble sodium alginate into an insoluble form. To improve the efficiency of microencapsulation, the additives of HPMC, dextrin, chitosan or HPMC/chitosan in various ratios (1 : 1, 1 : 3 and 3 : 1) were used as the coating materials. The particle size of a bare microcapsule was less than 30 µm. Larger size microcapsules were produced using vortex method by comparison with that using homogenization method. The latter method, however, was easy to scale up. The effect of coating materials on the morphology and encapsulation efficiency of the microcapsules was also studied. The best encapsulation efficiency (78%) was using HPMC as the additive of the coating material. The next was dextrin (70%). By measuring the germination rate, the results showed that the activity was ～80% of the initial after 6 months of storage at 4°C, while that of the bare conidia was less than 50% stored in identical conditions.     

Preparation and in vitro evaluation of slow release ketoprofen microcapsules formulated into tablets and capsules

Abstract

Ketoprofen powder was encapsulated with Eudragit RL/RS polymer solutions in isopropanol-acetone 1:1, using a simple and rapid method. Microcapsules were prepared using Eudragit solutions with different RL/RS ratios. The encapsulation process produces free-flowing microcapsules with good drug content and marked decrease in dissolution rate. The retardation in release profile of ketoprofen from microcapsules was a function of the polymer ratio employed in the encapsulation process. In vitro release of ketoprofen from microcapsules either filled in gelatin capsules or compressed into tablets, using calcium sulphate as diluent, confirmed the efficiency of the encapsulation process for preparing prolonged release medication. A capsule formulation with optimum sustained-release profile was suggested.     

Formulation optimization and characterization of spray dried microparticles for inhalation delivery of doxycycline hyclate

The local delivery of antibiotics in the treatment of infectious respiratory diseases is an attractive alternative to deliver high concentration of antimicrobials directly to the lungs and minimize systemic side effects. In this study, inhalable microparticles containing doxycycline hyclate, sodium carboxymethylcellulose, leucine and lactose were prepared by spray drying of aqueous ethanol formulations. Box-Behnken design was used to study the influence of various independent variables such as polymer concentration, leucine concentration, ethanol concentration and inlet temperature of the spray dryer on microparticle characteristics. The microparticles were characterized in terms of particle morphology, drug excipient interaction, yield, entrapment efficiency, Carr's index, moisture content, thermal properties, X-ray powder diffraction, aerosolization performance and in vitro drug release. The effect of independent variables on spray dryer outlet temperature was also studied. The overall shape of the particles was found to be spherical like doughnuts in the size range of 1.16-5.2 μm. The optimized formulation (sodium carboxymethylcellulose concentration 14% w/v, leucine concentration 33% w/v, ethanol concentration 36% v/v, inlet temperature of 140°C) exhibited the following properties: yield 56.69%, moisture content 3.86%, encapsulation efficiency 61.74%, theoretical aerodynamic diameter 3.11 μm and Carr's index 23.5% at an outlet temperature 77°C. The powders generated were of a suitable mass median aerodynamic diameter (4.89 μm) with 49.3% fine particle fraction and exhibited a sustained drug release profile in vitro.     

Preparation and in vitro characterization of amifostine biodegradable microcapsules.

The purpose of this project was to develop sustained release microcapsules of amifostine. The microcapsules were prepared using solvent evaporation technique. The effect of several formulation variables on the characteristics of the microcapsules was studied. The formulation variables studied were drug loading, polymer (polylactide-co-glycolide) (PLGA) concentration, and the amount of gelatin in the initial aqueous phase. The drug loading was studied at three different levels (5, 10, and 25 mg); the PLGA concentration was studied at two levels (500 and 1000 mg); and the amount of gelatin used ranged from 2 to 14 mg. In general, the microcapsules were less than 155 microm in diameter with median size between 50 and 80 microm. While the use of higher amounts of PLGA significantly increased the median size of the microcapsules, using higher amounts of amifostine had no significant effect, irrespective of the amount of PLGA. The use of gelatin, within the range 2-14 mg, did not show any significant effect on the particle size distribution. Scanning electron microscopy (SEM) of the microcapsules revealed that all nine formulations yielded spherical particles. The use of 500 mg PLGA with 10 or 25 mg amifostine yielded microcapsules with porous surfaces. The surface pores, however, were not present in microcapsules prepared using 1000 mg PLGA. The efficiency of encapsulation decreased significantly from 63 to 24% when the amount of amifostine increased from 5 to 25 mg in the formulations using 500 mg PLGA. Similarly, the efficiency of encapsulation decreased from 87 to 23% when the amount of PLGA was doubled to 1000 mg. An increase in the amount of amifostine in the formulation using 500 mg PLGA also resulted in a significant increase in initial drug release (from 20 to 62%) within the first hour. These results were consistent with the porous morphology of these microcapsules. In general, all batches of microcapsules showed 24-96 h sustained drug release.     

Survival of Beijerinckia sp. microencapsulated in carbohydrates by spray-drying

The encapsulation of Beijerinckia sp. cell suspension in different wall materials using the spray drying technique was performed. Mat dextrin, dehydrated glucose syrups, gum acacia and modified starch materials were tested. Cell viability assays were carried out before and after drying and during storage of the products. The surface area and characteristics of the encapsulated powders were examined using BET adsorption of N(2) and scanning electron microscopy, respectively. The residual moisture content and water activity of the powders were also determined. The best results were obtained with the dehydrated glucose syrup, which resulted in products with the greatest per cent survival during the drying process and subsequent storage period. The products obtained with the dehydrated glucose syrup showed more uniform microcapsule surfaces at lower A(w) values and residual moisture content.     

Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method

The microencapsulation vesicle (MCV) method is a liposome preparation technique that reproducibly produces liposomes with homogeneous particle sizes with a high encapsulation efficiency. Liposomes encapsulating water-soluble drugs, lipophilic drugs and an amphiphilic drug were prepared by the MCV method and the encapsulation efficiency of the drugs was examined. Three kinds of egg yolk lecithin with different iodine values, i.e., purified egg yolk lecithin (PEL), partially hydrogenated purified egg yolk lecithin (R-20) and completely hydrogenated purified egg yolk lecithin (R-5), were used for membrane materials in order to explore the possible effects of membrane rigidity or surface area on the encapsulation efficiency of the drug. Water-soluble 5-fluorouracil showed 12-15% encapsulation efficiency, which was higher than those reported in the literature (less than 10%). With the MCV method, theoretically the initial drug-containing water phase was always separated from the dispersion medium by the lecithin-containing oil phase, which was advantageous to maintaining a higher encapsulation efficiency of the water-soluble drug. The encapsulation efficiency of lipophilic ibuprofen and flurbiprofen was around 90%. As for ketoprofen and liposomes were not formed when using hydrogenated egg yolk lecithin R-5, while the encapsulation efficiency using PEL or R-20 was around 80%. Amphiphilic amitriptyline hydrochloride resulted in a slightly higher encapsulation efficiency when dissolved in the water than the chloroform. Among the three kinds of lecithin, the most unsaturated PEL tended to show a higher encapsulation efficiency, probably due to differences in the packing geometry of the hydrophobic carbon chains in the membrane bilayer. The encapsulation efficiency of these drugs strongly correlated to the logP(octanol/water) and also tended to correlate to the logP(chloroform/water) for the order of the logP(chloroform/water) was almost the same as the order of the logP(octanol/water) in the drugs examined. As far as the results of this study, the logP(octanol/water) was considered to be a better indicator of the encapsulation efficiency of a drug in the MCV method.     

Preparation of novel polymeric microspheres for controlled release of finasteride

The utility of the novel polycarbonate, poly(propylene carbonate maleate) (PPCM) to encapsulate and control the release of finasteride, via microspheres, was investigated. The PPCM microspheres loaded with finasteride were elaborated by a simple oil-in-water (O/W) emulsion-solvent evaporation method. Various manufacturing parameters, including the concentration of polymer in dichloromethane (DCM) and the polymer:finasteride ratios were altered to optimize process variables during the microspheres production. The effects of these changes on the characteristics of the microspheres were examined. The structure and morphology were characterized by wide-angle X-ray diffraction (WXRD) and scanning electron microscopy (SEM). The results showed that the mean diameter of microspheres was approximately 2mum, and had both smooth and spherical surfaces. Greater encapsulation efficiency was obtained by increasing the ratios of polymer:finasteride and the concentration of PPCM in DCM. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. The release profiles of finasteride from PPCM microcapsules were found to be biphasic with a burst release followed by a gradual release phase. A prolonged in vitro drug release profile was observed. After an initial burst, a continuous drug release was observed for up to 5-6 weeks.     

Sustained release of propranolol hydrochloride based on ion-exchange resin entrapped within polystyrene microcapsules

Propranolol-HCl, a water soluble drug, was bound to Indion 254, a cation exchange resin, and the resulting resinate was microencapsulated with polystyrene using an oil-in-water emulsion-solvent evaporation method with a view to achieve prolonged drug release in simulated gastric and intestinal fluid. The effect of various formulation parameters on the characteristics of the microcapsules was studied. The diameter of the resinate-loaded polystyrene microcapsules increased with increase in the concentration of emulsion stabilizer and coat/core ratio and decreased with increase in the volume of organic disperse phase. The variation in the size of the microcapsules appeared to be related with the inter-facial viscosity which was influenced by the viscosity of both the aqueous dispersion medium and the organic disperse phase. The resinate encapsulation efficiency and hence the drug entrapment efficiency of the microcapsules increased with increase in the concentration of emulsion stabilizer and coat/core ratio and decreased with increase in the volume of organic disperse phase. These characteristics were found to depend on the extent of formation of fractured microcapsules and subsequent partitioning of the resinate into the aqueous dispersion medium. The degree of fracture on the microcapsules depended on the viscosity of the aqueous dispersion medium and the organic disperse phase. The uncoated resinate discharged the drug quite rapidly following the typical particle diffusion process. Although the desorption of the drug from the resinate was independent of pH of the dissolution media, increase in ionic strength increased the drug desorption. On the other hand, release of drug from the coated resinate was considerably prolonged and followed a diffusion controlled model. The prolongation of drug release was dependent on the uniformity of coating which was influenced by the formulation parameters. The drug release from the microcapsules was also found to be independent of pH of the dissolution media and increased with increase in ionic strength. The pH-independent release of the drug from both the uncoated and microencapsulated resinate was due to pH-independent solubility of the drug and high equilibrium concentration of the resinate in both the dissolution media. Polystyrene appeared to be a suitable polymer to provide prolonged release of propranolol independent of pH of the dissolution media.     

Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles

The slow dissolution rate exhibited by poorly water-soluble drugs is a major challenge in the drug development process. Following oral administration, drugs with slow dissolution rates generally show erratic and incomplete absorption which may lead to therapeutic failure. The aim of this study was to improve the dissolution rate and subsequently the oral absorption and bioavailability of a model poorly water-soluble drug. Microparticles containing the model drug (griseofulvin) were produced by spray drying the drug in the absence/presence of a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant to improve the particle wetting and hence the dissolution rate. The spray dried particles were characterized and in vitro dissolution studies and in vivo absorption studies were carried out. The results obtained showed that the dissolution rate and absolute oral bioavailability of the spray dried griseofulvin/Poloxamer 407 particles were significantly increased compared to the control. Although spray drying griseofulvin alone increased the drug's in vitro dissolution rate, no significant improvement was seen in the absolute oral bioavailability when compared to the control. Therefore, it is believed that the better wetting characteristics conferred by the hydrophilic surfactant was responsible for the enhanced dissolution rate and absolute oral bioavailability of the model drug.     

Microencapsulation of eugenol by gelatin-sodium alginate complex coacervation

Present study describes microencapsulation of eugenol using gelatin-sodium alginate complex coacervation. The effects of core to coat ratio and drying method on properties of the eugenol microcapsules were investigated. The eugenol microcapsules were evaluated for surface characteristics, micromeritic properties, oil loading and encapsulation efficiency. Eugenol microcapsules possessed good flow properties, thus improved handling. The scanning electron photomicrographs showed globular surface of microcapsules prepared with core: coat ratio1:1.The treatment with dehydrating agent isopropanol lead to shrinking of microcapsule wall with cracks on it. The percent oil loading and encapsulation efficiency increased with increase in core: coat ratio whereas treatment with dehydrating agent resulted in reduction in loading and percent encapsulation efficiency of eugenol microcapsules.     

Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate

To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.