The Effect of Formulation on the Antimicrobial Activity of Cetylpyridinium Chloride in Candy Based Lozenges

Purpose. The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. Methods. In vivo activity was investigated using six volunteers by determining the reduction in colony forming units recoverable from the oropharynx after sucking each lozenge separately on different days. In vitro determinations investigated the relative activity of aqueous solutions of the lozenges, the effect on activity of additional active ingredients, pH and lozenge base ingredients against separate inocula of each of the test organisms Staphylococcus aureus, Streptococcus pyogenes and Candida albicans. Results. Both in vivo and in vitro results showed that the pH of the dissolved lozenge solution was the single most influential readily adjustable formulation parameter which significantly influenced the activity of cetylpyridinium chloride activity in candy based lozenges. Conclusions. Lozenges containing cetylpyridinium chloride as the active ingredient should be formulated at a pH greater than 5.5.     

Lack of In Vivo/In Vitro Correlations for 50 mg and 250 mg Primidone Tablets

Purpose. To determine if large differences in the in vitro dissolution profiles for primidone tablets would result in significant bioavailability differences. Methods. Two separate bioavailability studies were conducted. The first study used 18 healthy subjects and compared the bioavailability of an old 50 mg tablet formulation, a new 50 mg tablet formulation, and a suspension containing 50 mg/ml of primidone. The second study enrolled 24 subjects who were to receive a new 250 mg tablet formulation, two lots of an old 250 mg tablet formulation and a 250 mg tablet from a second manufacturer. In vitro dissolution was conducted over 90 minutes, using USP 23 Apparatus 2 at 50 rpm, with 900 ml of water. Results. Dissolution at 90 minutes for the old and new 50 mg tablets was approximately 20% and 100%, respectively. The dissolution of the four 250 mg tablets ranged from approximately 30% to 100%. The 50 mg tablet that dissolved slower had a longer Tmax and a 14% lower Cmax than the more rapidly dissolving tablet, but the AUC(0–) values differed by only 3%. Only nine subjects completed the 250 mg study because of side effects. The differences in Cmax and AUC(0–) among the four 250 mg tablets were less than 7%. Conclusions. Even though there were large differences in the in vitro dissolution of the 50 mg and the 250 mg primidone tablets, the two 50 mg tablets were shown to be bioequivalent, as were the four 250 mg tablets.     

In Vitro/In Vivo Comparison of Drug Release and Polymer Erosion from Biodegradable P(FAD-SA) Polyanhydrides—A Noninvasive Approach by the Combined Use of Electron Paramagnetic Resonance Spectroscopy and Nuclear Magnetic Resonance Imaging

Purpose. The purpose of this study was to compare drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides in vitro and in vivoin real time and with minimal disturbance of the investigated system. Methods. P(FAD-SA) 20:80 and P(FAD-SA) 50:50 polymer tablets were loaded with the spin probe 3-carboxy-2,2,5,5-tetramethyl-pyrrollidine-1-oxyl (PCA) and implanted subcutaneously in the neck of rats or placed in 0.1 M phosphate buffer. 1.1 GHz EPR spectroscopy experiments and 7T MRI studies (Tl and T2 weighted) were performed. Results. A front of water penetration was visible by MRI in vitro in the case of P(FAD-SA) 20:80, but not for P(FAD-SA) 50:50. For both polymers, the thickness of the tablets decreased with time and a insoluble, easy deformable residue remained. Important processes such as edema, deformation of the implant, encapsulation and bioresorption were observable by MRIin vivo. P(FAD-SA) 50:50 was almost entirely absorbed by day 44, whereas an encapsulated residue was found for P(FAD-SA) 20:80 after 65 days. The EPR studies gave direct evidence of a water penetration induced changes of the microenvironment inside the tablet. EPR signals were still detectable in P(FAD-SA) 20:80 implants after 65 days, while the nitroxide was released in vitro within 16 days. Conclusions. Important parameters and processes such as edema, deformation of the tablet, micro viscosity inside the tablet and encapsulation can be monitored in real time by the combined use of the noninvasive techniques MRI and EPR leading to better understanding of the differences between the in vitroandin vivo situation.     

明目蒺藜丸联合聚乙烯醇滴眼液治疗干眼症的临床研究

目的 制备他达拉非片并考察其体内外释药特性。方法 以溶出度为评价指标,筛选他达拉非片各辅料用量及包衣增重。用相似因子（f₂）法比较自制制剂与参比制剂在0.5% SDS溶液、含0.5% SDS的0.1 mol/L的盐酸溶液、含0.5% SDS的pH 4.5醋酸钠缓冲液、含0.5% SDS的pH 6.8磷酸盐缓冲液中溶出曲线的相似性。比较二者在Beagle犬体内的药动学特征。结果 他达拉非片处方为他达拉非20 mg、乳糖50M 227.625 mg、羟丙基纤维素L 10.5 mg、交联羧甲基纤维素钠19.6 mg、SDS 0.525 mg、微晶纤维素M102 70 mg、硬脂酸镁1.75 mg,包衣增质量范围2%～4%。自制与参比制剂在4种溶出介质中的f₂均大于65,二者体外溶出行为相似。2种制剂在Beagle体内的药动学参数AUC_0~t、C_max、t_max均无显著性差异,自制他达拉非片的相对生物利用度为（101.67±8.99）%。结论 成功制备他达拉非片,其体外溶出和体内药动学行为与参比制剂相似。     

The Effect of Cetylpyridinium Chloride (CPC) on the Cell Surface Hydrophobicity and Adherence of Candida albicansto Human Buccal Epithelial Cells in Vitro

Purpose. This study examined the effects of cetylpyridinium chloride (CPC) on cell surface hydrophobicity (CSH) and adherence of blastospores of Candida albicans(MEN strain) to human buccal epithelial cells (EEC) in vitro. Methods. The effect of CPC treatment of either C. albicans blastospores or BEC on their subsequent adherence was determined using ³⁵SO₄ labelled blastospores in association with a Percoll gradient. The effects of CPC treatment of blastospores on their CSH was determined using Hydrophobic Interaction Chromatography. Results. Treatment of exponential and stationary phase blastospores with CPC (50 µg mL^–1) for 0.5–30 minutes, or with CPC (0.5–50 µg mL^–1) for 15 minutes resulted in significant reductions in both blastospore CSH and adherence to BEC in vitro. No correlation was apparent (r < 0.8) between reduced CSH and reduced blastospore adherence following treatment with CPC (0.5–50 µg mL^–1). Significantly reduced adherence of C. albicans (stationary or exponential growth phases) to human EEC was also observed following treatment of BEC with CPC (50 µg mL^–1) for 0.5–30 minutes or with CPC (0.5–50 µg mL^–1) for 15 minutes. Antiadherence effects were observed at both sub and super-minimum inhibitory concentrations of CPC. Conclusions. It is suggested that, whilst the ability of CPC to reduce the CSH of C. albicans may contribute to its reduced adherence to human BEC in vitro, reduced CSH is only one of several possible factors that contribute to the observed antiadherence effects.     

In Vivo Evaluation of Acyclovir Prodrug Penetration and Metabolism Through Rat Skin Using a Diffusion/Bioconversion Model

Purpose. In order to evaluate the in vivo penetration of prodrugs which undergo metabolism in skin, we analyzed thein vivo penetration profiles of acyclovir prodrugs based on a two-layer skin diffusion model in consideration of metabolic process. Methods. Acyclovir prodrugs (e.g., valerate, isovalerate and pivarate) were used as model prodrugs and the amounts excreted in urine were measured after percutaneous application. In vivo penetration profiles were then estimated by employing a deconvolution method and the penetration of acyclovir prodrugs was analyzed using a diffusion model. Subsequently, diffusion, partitioning and metabolic parameters were compared under in vitro and in vivo conditions. Results. Although total penetration amounts at the end of the experiment were similar for the three prodrugs, the ratio of intact prodrug to total penetration amount differed significantly. Moreover, the excretion and absorption profiles were also very different for each prodrug. Enzymatic hydrolysis rate constants calculated under in vivo conditions were considerably larger than those obtained in the skin homogenate and in vitro penetration experiments. Conclusions. The present skin diffusion/bioconversion model combined with computer analysis enables us to comprehensively account for diffusion, partitioning and metabolism during in vivo percutaneous absorption. Nevertheless, different enzymatic hydrolysis rate constants obtained under bothin vivo and in vitro conditions demonstrate the difficulty of obtaining accurate values for in vivo enzymatic activity from related in vitro experiments.     

Evaluation of the in Vivo Disintegration of Solid Dosage Forms of a Bile Acid Sequestrant in Dogs Using γ-Scintigraphy and Correlation to in Vitro Disintegration

Purpose. To evaluate the in vivo disintegration behavior of tablets and capsules of a bile acid sequestrant, DMP 504, in beagle dogs and to assess the significance of the in vitro disintegration of the dosage forms on subsequent in vivo behavior in order to draw possible in vitro-in vivo correlations. Methods. Tablet and capsule formulations of a bile acid sequestrant, DMP 504, were formulated with samarium oxide and neutron activated to produce radioactive ¹⁵³Sm to noninvasively evaluate their in vivo behavior in beagle dogs by -scintigraphy. A four-way crossover design was completed (n = 4) in which (a) tablets from two different batches were administered under the fasted condition and manufactured using different lots of drug substance where one batch exhibited relatively faster in vitro disintegration time (30 min) than the other tablet batch, which resulted in slower disintegration (45 min), (b) a capsule formulation was administered to fasted beagles, and (c) the tablet having slower in vitro disintegration was also administered in the fed state, and its in vivo disintegration was compared to that observed in the fasted state. Results. Tablets manufactured using a lot of DMP 504 having relatively fast in vitro disintegration (30 min) resulted in relatively rapid in vivo disintegration time (15 min) in the fasted condition. This in vivo disintegration time was comparable to the in vivo disintegration of the capsules (17 min) even though the in vitro capsule disintegration time was considerably faster (2 min). Tablets prepared using a drug substance that provided a longer in vitro disintegration time (45 min) resulted in a slower in vivo disintegration (63 min). There was no difference observed in the in vivo disintegration behavior in fasted and fed dogs for the tablets that provided slower in vitro disintegration. Conclusion. In vivo disintegration of tablets of the bile acid sequestrant DMP 504 correlated with in vitro disintegration times. -Scintigraphy continues to be a good tool to use during early stages of product development to investigate in vivo performance of dosage forms. The results of this study provided evidence that the physical chemical specifications of the drug substance may not always be indicative of in vitro or in vivo performance of tablet dosage form, even when formulation and process are not changed.     

In Vitro/in Vivo Correlation of the Bioadhesive Properties of a Buccal Bioadhesive Miconazole Slow-Release Tablet

An in vitro–in vivo correlation study was performed on the bioadhesive properties of three buccal formulations based on modified starch (drum-dried waxy maize)/polyacrylic acid mixtures. Mixtures containing 10 mg miconazole nitrate, characterized by a different in vitro detachment force and work of adhesion, were evaluated for their bioadhesive properties in human volunteers. The results obtained showed that no significant difference could be seen among the formulations in vivo. The in vitro method showed no significant influence of miconazole nitrate on the bioadhesion properties of the polymers, while the in vivo adhesion time of the pure polymer mixtures was significantly higher than for the polymers containing miconazole. The results from the in vitro method thus did not correlate well with the in vivo data. The in vitro method provided information only on the initial bioadhesion and no correlation could be made with the residence time of the tablet in the oral cavity.     

Effect of Omeprazole on Diazepam Disposition in the Rat: in Vitro and in Vivo Studies

Purpose. The inhibitory effects of omeprazole on diazepam metabolism in vitro and in vivo are compared in the rat. Methods. 3-hydroxylation and N-demethylation of diazepam was investigated in the presence of a range of omeprazole concentrations (2-500µM) in hepatic microsomes and hepatocytes. Zero order infusions together with matched bolus doses of omeprazole were used to achieve a range of steady state plasma concentrations (10-50mg/ L) and to study the diazepam-omeprazole interaction in vivo. Results. The 3-hydroxlation pathway was more prone to inhibition (K_Is 108 ± 30 and 28 ± 11 µM in microsomes and hepatocytes, respectively) than the demethylation pathway (K_Is of 226 ± 76 and 59 ± 27 µM in microsomes and hepatocytes, respectively). In both in vitro systems, the mechanism of inhibition was competitive with Km/K_I ratios larger than 1 for the 3HDZ pathway and smaller than 1 for the NDZ pathway. There was an omeprazole concentration dependent decrease in diazepam clearance in vivo which could be modelled using a simple inhibition equation with a K_I of 57µM (19.8mg/L). In contrast there was no statistically significant change in the steady state volume of distribution for diazepam in the presence of omeprazole. Conclusions. The in vivo K_I for the omeprazole: diazepam inhibition interaction shows closer agreement with the K_I values obtained in hepatocytes than with those observed in microsomes.     

Prediction of in Vivo Tissue Distribution from in Vitro Data. 2. Correlation Between in Vitro and in Vivo Tissue Distribution of a Homologous Series of Nine 5-n-Alkyl-5-Ethyl Barbituric Acids

Purpose. To evaluate the ability to determine accurate in vivo tissue-to-unbound plasma distribution coefficients (Kpu_e) from in vitro data. Methods. Fresh pieces of fifteen rat tissues/organs were incubated at 37°C with a homologous series of nine barbiturates covering a wide range of lipophilicity (Log P 0.02 to 4.13). Steady-state in vivo Kpu _e values were estimated from the tissue and plasma concentrations following simultaneous dosing by constant rate i.v. infusion of all nine barbiturates. Drug concentrations in the tissues and media were determined by HPLC with UV or mass spectrometric detection. Results. The pharmacokinetics of the barbiturate series following constant rate i.v. infusion indicated a range of clearance (0.49 to 30 ml.min^\-1.kg^\-1) and volume of distribution at steady state (0.51 to 1.9 l.kg^\-1) values. Good agreement was observed between the in vitro and in vivo Kpu values, although for the most lipophilic barbiturates the in vitro data underpredicted the in vivo tissue distribution for all tissues. Conclusions. The in vitro system for predicting the extent of in vivo tissue distribution works well for compounds of widely differing lipophilicity, although for the most lipophilic drugs it may result in an underprediction of in vivo values.     

Thermophysical Properties of Some Pharmaceutical Excipients Compressed in Tablets

Purpose. Thermophysical properties of three tableting excipients; microcrystalline cellulose, lactose and dicalcium phosphate dihydrate were observed to evaluate their ability to resist temperature induced changes in tablet form. Methods. Two thermophysical parameters, thermal diffusivity and specific heat, were measured by a pulse heating method. The materials were also evaluated by differential scanning calorimetry (DSC). Results. Microcrystalline cellulose in tablet form was found to be rather insensitive to heating and cooling treatments, even though the tablets seemed to remain in a stressed state four weeks after tableting. This stress, indicated by low temperature anomalies, was observed by the pulse method, but not by DSC. When magnesium stearate was incorporated as a lubricant within the microcrystalline cellulose powder, the thermophysical parameters indicated that the internal structure of the tablets changed with heating and cooling. Magnesium stearate eliminated the low temperature anomalies as well. The heat treatment changed the thermophysical properties of tablets made of the crystalline excipients lactose and dicalcium phosphate dihydrate, permanently causing irreversible structural changes. Conclusions. The melting of the lubricant together with enhanced stress relaxation in the structure of microcrystalline cellulose most probably caused the improved thermal diffusivity. The observed thermophysical changes with the crystalline excipients were due to changes in tablet's structure and material. The combination of methods used was found to be an accurate and reliable way to obtain useful information on the structural changes and material relaxations of intact tablets during temperature treatment and age-related changes in material properties.     

京尼平苷体内外微透析回收率的研究

目的 探究京尼平苷在自制线性微透析探针上的体内外回收率与灌流速度、药物浓度、透析膜长之间的关系。方法 采用HPLC测定微透析样品浓度,考察不同灌流速度、不同药物浓度和不同透析膜长对体外正向和体外反向回收率、体内反向回收率的影响。结果 自制探针性质稳定;探针回收率与京尼平苷的药物浓度无关,与灌流速度成反比,随透析膜长增加而增加;体外的正向与反向探针回收率有显著性差异（P<0.01）,而体内反向回收率低于体外反向回收率,与体外正向回收率无显著性差异;新探针体内回收率大于使用过1次的探针体内回收率（P<0.05）。结论 在京尼平苷的皮肤药动学研究中,宜采用体内反向回收率或体外正向回收率作为药物的探针回收率来校正。     

国产盐酸二甲双胍片与国际公认参比制剂溶出度比较

目的建立盐酸二甲双胍片溶出度测定方法,并分别比较250 mg及500 mg 2种规格国产盐酸二甲双胍片与国际公认参比制剂的溶出曲线。方法分别以水、0.1 mol·L-1盐酸、pH 4.0及pH 6.8磷酸盐缓冲溶液为溶出介质,采用桨法进行体外溶出度试验。用高效液相-紫外分光光度法(HPLC-UV)测定溶出介质中药物含量,并采用溶出度相似因子(f2值)分别评价国产片(每片250 mg)与日本橙皮书Glycoran(每片250 mg)、国产片(每片500 mg)与欧盟上市Merck SantéS.A.S(每片500 mg)在各pH介质中的相似性。结果每片250 mg的2种制剂在各溶出介质中,15 min内的溶出百分率均>85%。在0.1 mol·L-1盐酸的溶出介质中,国产盐酸二甲双胍片(每片500 mg)与欧盟上市Merck SantéS.A.S(每片500 mg)的溶出曲线f2值为78.5(>50);在水、pH 4.0及pH 6.8磷酸盐缓冲溶液的溶出介质中,2种制剂的溶出曲线f2值均<50。结论 2种规格为每片250 mg的盐酸二甲双胍片溶出行为相似。除0.1 mol·L-1的盐酸介质外,2种规格为每片500 mg的盐酸二甲双胍片在各种溶出介质中的溶出行为不相似。     

Effect of Concentration and Degree of Saturation of Topical Fluocinonide Formulations on In Vitro Membrane Transport and In Vivo Availability on Human Skin

Purpose. The thermodynamic acitvity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. Methods. Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. Results. Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. Conclusions. From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.     

Brain Penetration and In Vivo Recovery of NMDA Receptor Antagonists Amantadine and Memantine: A Quantitative Microdialysis Study

Purpose. To determine free brain concentrations of the clinically used uncompetitive NMDA antagonists memantine and amantadine using microdialysis corrected for in vivo recovery in relations to serum, CSF and brain tissue levels and their in vitro potency at NMDA receptors. Methods. Microdialysis corrected for in vivo recovery was used to determine brain ECF concentrations after steady-state administration of either memantine or amantadine. Additionally CSF, serum, and brain tissue were analyzed. Results. Following 7 days of infusion of memantine or amantadine (20 and 100 mg/kg/day respectively) whole brain concentrations were 44-and 16-fold higher than free concentrations in serum respectively. The free brain ECF concentration of memantine (0.83 ± 0.05 M) was comparable to free serum and CSF concentrations. In case of amantadine, it was lower. A higher in vivo than in vitro recovery was found for memantine. Conclusions. At clinically relevant doses memantine reaches a brain ECF concentration in range of its affinity for the NMDA receptor and close to its free serum concentration. This is not the case for amantadine and different mechanisms of action may be operational.     

新型抗菌肽PDK160在皮肤及软组织感染局部治疗中的应用

目的研究新型抗菌肽PDK160在皮肤及软组织感染局部治疗中的应用以及作用机制。方法采用体外杀菌试验、溶血性试验、耐药性试验等评价抗菌肽PDK160在小鼠体内创面感染模型和猪皮肤体外感染中的抗菌效果。结果抗菌肽PDK160在体外对革兰阳性菌和革兰阴性菌均具有广谱杀菌作用。另外,PDK160的强效杀微生物活性和广谱抗菌活性与溶血活性无关。PDK160在小鼠的创面感染和猪皮肤感染体外模型中,表现出明显的抗感染效果。在小鼠皮下或局部应用不会导致任何不良反应。结论PDK160可能是局部治疗感染的一种新的治疗方法,值得进一步的研究。     

Effect of antacids on aspirin dissolution and bioavailability

The in vitrodissolution profile, in vitroand in vivobuffering characteristics, and single-dose bioavailability of various buffered aspirin tablet formulations were studied. Buffering agents,such as magnesium and aluminum hydroxides (formulations B and C) or magnesium carbonate and aluminum glycinate (formulation D), significantly increased the rate of aspirin dissolution from solid dosage forms as compared to an unbuffered tablet (formulation A). The extent of aspirin absorption was equivalent with all formulations;however, the faster rate of dissolution (t₅₀ and t₉₀)with buffered formulations resulted in earlier and higher peak concentration of salicylate compared to that with unbuffered formulation, following a two-tablet dose in the fasting state. A comparison of the in vivobuffer capacity of a four-tablet dose of formulations B and D was performed in the postcibal state at the time of maximal meal-induced acid secretion, using a radiotelemetry procedure for determination of pH. Formulation B prolonged the interval of elevation of intragastric pH > 3 for 32 min as compared to 12 min for D.     

硝苯地平控释片体内外相关性溶出方法研究

目的 开发相应的能区分和反映参比制剂与自研制剂之间释放差异的溶出方法,使自研制剂与参比制剂体外释放达到最大程度的匹配,从而为生物等效性试验提供体内外更具相关性的研究。方法 采用美国药典(USP)溶出2法(桨法)作为质量控制方法;另采用流池法作为溶出区分性方法,评估不同实验参数下的溶出结果。结果 优化并确立方法为开环系统,流速3.0 mL·min^-1,加1/2勺玻璃珠。该方法可以有效区分处方和生产工艺变化对产品溶出的影响。以此法为基础所得到的体外溶出速率和溶出度与体内药动学研究结果一致。结论 本研究所开发的流池法适合作为硝苯地平控释片的溶出区分性方法,并具备一定的体内体外相关性。     

Improved Prediction of In Vivo Peroral Absorption from In Vitro Intestinal Permeability Using an Internal Standard to Control for Intra- and Inter-Rat Variability

Purpose. To evaluate the use of an in vitrointestinal permeability model to predict rat and human absorption as well as to evaluate the use of an internal standard to control for intra- and inter-rat variability. Methods. In vivoperoral absorption and in vitro steady-state intestinal permeability coefficients were determined in the rat for a variety of structurally different compounds with different physicochemical properties including: progesterone, hydrocortisone, salicylic acid, caffeine, clonidine, p-aminoclonidine, UK-14304, oxymetazoline, mannitol, PEG 900, PEG 4000, and a number of novel hydrophilic chemical entities. Results. The intestinal permeability coefficients determined in vitro could be used to predict the peroral absorption of a compound in both the rat and human. Normalizing the permeability of a test compound to an internal standard, e.g. mannitol, greatly improved the prediction of peroral absorption. Conclusions. The use of an internal standard can aid in the prediction of the peroral absorption of a test compound, in particular, for one that has moderate absorption in the range of 20–80%. Moreover, these methods would appear to be a useful means to improve the prediction of other absorption models as well, such as the Caco-2 cell systems and in-situ perfusion methods.     

In Vivo ESR Studies on Pharmacokinetics and Metabolism of Parenteral Lipid Emulsion in Living Mice

Purpose. We applied non-invasive and real-time method with in vivo ESR spectroscopy to determining pharmacokinetics and metabolism of lipid emulsion as a drug carrier in living mice. Methods. A spin-labeled triglyceride (SL-TG) was newly synthesized and lipid emulsion containing SL-TG was prepared. In vivo ESR spectra in mice were observed after intravenous administration of the lipid emulsion. Results. In vivo ESR spectra consisted of three components, coinciding with the in vitro spectra of SL-TG particles, free and immobilized fatty acids. The amount of the components depended on both the observing domain and the period after administration. In the chest, all three components were observed, while SL-TG particle was lacking in the abdomen. The half-life of the lipid particles in the chest was 2 hr. Conclusions. Non-invasive and real-time analysis of drug carriers in living animal is successfully accomplished using an in vivo ESR method.