[Self-assembly and in vitro and in vivo evaluation of spherical crystallized interferon for sustained delivery].

It is a challenging and important project to prolong the in vivo half life of protein and peptide drugs by physicochemical methods without new molecular entities generation. Protein crystallization provides a new strategy for improving the stability and in vivo delivery of these drugs. We show here that recombinant human interferon-alpha (rhIFN) can form spherical crystals. The physical and chemical features of the crystals were characterized, and drug dissolution was determined in vitro. The pharmacokinetics of crystallized interferon after sc injection in rabbit at 1.5 x 10(7) U x kg(-1) was compared to that of soluble form. The crystals were characterized as mono-dispersed spheres, with yield of > 80%, mean diameter size of about 16 microm and crystallinity of 23.2%. The in vitro dissolution behavior of crystallized rhIFN was featured as low initial burst release (21% within the first 2 h) and prolonged cumulative dissolution time up to 72 h without biological potency lost. After sc administration of soluble and crystallized interferon in rabbits, the peak time (T(max)) and half life (t1/2) were prolonged from (1.80 +/- 0.45) h and (1.35 +/- 0.35) h to (13.20 +/- 2.68) h and (10.68 +/- 1.97) h, respectively. The corresponding peak concentration decreased from (1 411.10 +/- 575.28) U x mL(-1) to (721.37 +/- 206.55) U x mL(-1). PK/PD analysis indicated that (96.87 +/- 20.30) % of relative bioavailability was obtained. The research results of this work will provide important academic value and application prospect for improving clinical therapeutic effect and development of biomacromolecules delivery system for protein and peptide drugs.

Synthesis of lamivudine stearate and antiviral activity of stearic acid-g-chitosan oligosaccharide polymeric micelles delivery system.

To increase lipophilicity of water-soluble antiviral drug, the prodrug of Lamivudine (LA), Lamivudine stearate (LAS) was synthesized via ester linkage between LA and stearic acid. After the esterification, the octanol-water partition coefficient (logP) of LA increased from -0.95 to 1.82. Stearic acid-g-chitosan oligosaccharide (CSO-SA) micelles have demonstrated fast internalization and accumulation ability to tumor cells. Herein, the CSO-SA with 3.79% amino substitution degree (SD) was prepared for loading LAS. The critical micelle concentration (CMC) of CSO-SA was about 0.032mg/ml. The micelles with 1mg/ml CSO-SA concentration had 460.8nm average diameters with a narrow size distribution and 29.7mV surface zeta potential. After LAS was incorporated, the micellar size decreased and the zeta potential increased. The LAS loaded CSO-SA micelles (CSO-SA/LAS) possessed high entrapment efficiency and drug loading. LA release from CSO-SA/LAS showed a pH-dependent behavior. The release rate of LA from CSO-SA/LAS increased significantly as the pH of release medium reduced from 7.4 to 6.2. CSO-SA/LAS presented a low cytotoxicity and high cellular uptake percentage of LAS against HBV transfected tumor cells (HepG2.2.15). In vitro anti-HBV activities of CSO-SA/LAS presented more conspicuous inhibitory effects on antigen expression and DNA replication compared with LA and LAS.

The effects of mixed MPEG-PLA/Pluronic copolymer micelles on the bioavailability and multidrug resistance of docetaxel.

A mixed micelle that comprised of MPEG-PLA (MPP) and Pluronic copolymers was developed for enhanced bioavailability and to overcome multidrug resistance of docetaxel in cancer therapy. The mixed micelles that sufficiently solubilized docetaxel were evaluated for the effect of Pluronic copolymers weight ratio on the mixed micelles with respect to drug loading and drug release. In vitro, cell viability and cytotoxicity studies in KB and KBv cells revealed that the mixed micellar formulations were more potent than the commercial docetaxel formulation (Taxotere). In vivo pharmacokinetics study in rats showed that the mixed micelles significantly enhanced the bioavailability of docetaxel (3.6 fold) than Taxotere. Moreover, antitumor activity assessed in KBv cancer xenograft BALB/C nude mice models showed that the mixed micelles significantly reduced the tumor size than the control (Taxotere). Clear differences in the intracellular uptake of docetaxel between MPP and mixed micelles were observed using confocal laser scanning microscopy. This study presents not only a new micelle structure for a diblock-triblock copolymer system, but also a method for enhanced bioavailability of docetaxel and to overcome some of the limitations on its multidrug resistance in cancer therapy.

Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation.

A microemulsion system of docetaxel was prepared and evaluated for its solubilization capacity and oral bioavailability improvement. Based on a solubility study and pseudo ternary phase diagrams, microemulsions of about 30 nm in mean diameter were formulated with improved solubilization capacity towards the hydrophobic drug, docetaxel. The o/w microemulsion formulation (M-3) composed of Capryol 90 (oil), Cremophor EL (surfactant) and Transcutol (co-surfactant) enhanced the solubility of docetaxel up to 30 mg/mL, which maintained solubilization capacity for 24 h even after it was diluted 20 times with normal saline. The three formulations did not show significant difference in the in vitro lipid digestion study. Both the ultrafiltration and dialysis studies revealed that the release of 80% of docetaxel was released from the microemulsions within 12 h in vitro. Compared to the commercial product Taxotere (0.025 microg/cm(2)), the apical to basolateral transport of docetaxel across the Caco-2 cell monolayer from the M-3 formulation (Capryol 90/Cremophor EL/Transcutol=29.4:24.9:12.4, w/w) was significantly improved (0.624 microg/cm(2), p < 0.01). Moreover, the oral bioavailability of the M-3 formulation in rats (34.42%) rose dramatically compared to that of the orally administered Taxotere (6.63%). This increase in bioavailability was probably due to the combined effect of the enhancement in solubility, the inhibition of P-gp efflux system and the increase in permeability. These results encourage further development of docetaxel microemulsions as an oral drug delivery system.

Preparation, characterization and in vitro intestinal absorption of a dry emulsion formulation containing atorvastatin calcium.

A redispersible dry emulsion (DE) formulation of atorvastatin calcium (AC) was developed to enhance the in vitro dissolution of AC, thereby increasing its gastrointestinal absorption. The spray-drying technology was used where Plurol Oleique CC 497 was chosen as the oil phase. Effects of carriers, surfactants, and homogenizers on the characteristics of DE containing AC were systematically investigated. The final formulation consisted of dextrin and Poloxamer 188 as carrier and surfactant, respectively, and was homogenized by a high pressure homogenizer before spray drying. The in vitro release of AC from the optimized DE was significantly higher than that of pure AC powder (76% vs. 30% at 24 hr). The in vitro intestinal absorption of AC from the DE formulation was 0.77 microg/cm(2) at 2 hr, which was a 2.33-fold increase compared to the pure unformulated AC powder. These results suggest that the oral dry emulsion formulation could improve the intestinal absorption of AC.

Enhanced electrostatic interaction between chitosan-modified PLGA nanoparticle and tumor.

In our previous study, lung tumor-specific targeting of paclitaxel was achieved in mice by intravenous administration of chitosan-modified paclitaxel-loaded PLGA nanoparticles (C-NPs-paclitaxel). Transient formation of aggregates in the blood stream followed by enhanced trapping in the capillaries was proposed as a mechanism of the lung-specific accumulation of paclitaxel. In the present study, the mechanism of tumor lung preferential accumulation of paclitaxel from C-NPs-paclitaxel was investigated. Zeta potential and in vitro cellular cytotoxicity (A549 cells and CT-26 cells) of C-NPs-paclitaxel, and in vitro uptake of coumarin 6 to these cells from chitosan-modified coumarin 6 containing PLGA nanoparticles (C-NPs-coumarin 6) were examined as a function of pH (6.8, 7.4 and 8.0). The zeta potential of C-NPs-paclitaxel increased as the medium pH became more acidic. In vitro uptake of coumarin 6 by A549 cells and CT-26 cells was enhanced at lower pH for C-NPs-coumarin 6. In vitro cytotoxicity experiment with C-NPs-paclitaxel demonstrated enhanced cytotoxicity as the pH became more acidic. Therefore, enhanced electrostatic interaction between chitosan-modified PLGA nanoparticles and acidic microenvironment of tumor cells appears to be an underlying mechanism of lung tumor-specific accumulation of paclitaxel from C-NPs-paclitaxel.

An investigation on intestinal absorption of a new anticancer drug, 2-methoxyestradiol.

In this paper, the intestinal absorptive property of a new anticancer drug, 2-methoxyestradiol (2ME2) was investigated by in situ rat intestinal recirculation perfusion experimental techniques. The results indicated that the concentrations of 2ME2 had no influence on absorption rate constant (ka) of 2ME2 and the small intestinal absorption of 2ME2 was a first-order process with passive diffusion mechanism within the concentration tested. 2ME2 was well absorbed at each intestinal segment except duodenum and the best site of intestinal absorption of 2ME2 was the ileum. In addition, the PH of drug perfusate and the concentration of SDS had significant effects on absorption kinetics. Faintly basic environment profitted small intestinal absorption of 2ME2. Tween 80 and SDS could not enhance the intestinal absorption of 2ME2. The above study provided a theoretical foundation for developing effective oral preparations with higher bioavailability to treat cancers. In addition, the improved ligation way for studying the best site of intestinal absorption of 2ME2, should be used extensively in related studies because of decreasing number of experimental rats and saving time.

[Progress in the development of crystallized proteins as drug delivery system].

Crystallization has been widely applied in pharmaceutical formulations as an effective approach to improve the stability and efficacy of small agents. However protein crystals are suffered from limitation in the drug delivery system due to their complex crystallization behaviors. With development of crystallization technologies and their industrial application, protein crystals are receiving more and more attentions as a novel delivery system for biomacromolecules. Crystals with thermodynamic stable structure can improve the physical and chemical stability of protein drugs and present a sustained release behavior. On the basis of pertinent literatures, this review introduces the recent research situation and development process of protein crystals as drug delivery system. Moreover, the crystallization process of proteins, as well as the preparation and potential application are discussed systematically.

Studies on PEG-modified SLNs loading vinorelbine bitartrate (I): preparation and evaluation in vitro.

In this study, the conjugate of PEG2000-stearic acid (PEG2000-SA) was used to prepare PEGylated solid lipid nanoparticles loading vinorelbine bitartrate (VB-pSLNs) by cold homogenization technique. The particle size and zeta potential of resulted VB-pSLNs ranged 180-250nm and 0-10mV, which were determined using a Zetasizer, respectively. Although the drug entrapment efficiency (EE) slightly decreased after the PEG modification of VB-SLNs, above 60 % EE could be reached. The drug release tests in vitro indicated the faster drug release from VB-pSLNs than that from VB-SLNs without PEG modification. To investigate the cellular uptake of VB-pSLNs, the chemical conjugate of octadecylamine-fluorescein isothiocynate (FITC-ODA) was synthesized, and was used as a fluorescence marker to incorporate into nanoparticles. The results from cellular uptake indicated that the phagocytosis of VB-pSLNs by RAW264.7 cells was inhibited effectively by the PEG modification of SLNs, while the uptake by cancer cells (MCF-7 and A549) could be improved significantly. The assay of anticancer activity in vitro demonstrated that the anticancer activity of VB was significantly enhanced by the encapsulation of SLNs and pSLNs due to the increased cellular internalization of drug. The results suggested that SLNs and pSLNs could be excellent carrier candidates to entrap VB for tumor chemotherapeutics.

Formulation, preparation and evaluation of an intravenous emulsion containing Brucea javanica oil and Coix Seed oil for anti-tumor application.

The purpose of this study was to prepare and evaluate the intravenous emulsion (BCOE) containing Brucea javanica oil (BJO) and Coix seed oil (CSO), which is used in anti-tumor treatment. The formulation and preparation of BCOE were systematically investigated. High-pressure homogenization, particle size distribution, zeta-potential and HPLC were carried out. The pharmacokinetics of the main component, oleic acid, and anti-tumor activity studies about the tumor growth inhibitory ratios (TGIR) and the mortality experiments were also employed to evaluate BCOE in vivo compared with BJO emulsion (BJOE) and CSO emulsion (CSOE) using S180 sarcoma-bearing mice. The final BCOE formulation was 10% (w/v) oils with BJO and CSO 3 : 1, 0.6% (w/v) Lipid E 80, 0.3% (w/v) Pluronic F-68 (F-68), 0.1% (w/v) sodium oleate and 2.5% (w/v) glycerin in water. The preparation conditions involved 70 degrees C for preparing the crude emulsion, 6 cycles for high-pressure homogenization at 500 bar, pH value was adjusted to 8.5 after high-pressure homogenization and 115 degrees C for 30 min in a rotating water bath for sterilization. The pharmacokinetics parameters showed the combination of BJO and CSO may not influence the elimination of BCOE and have no significant difference between BCOE and BJOE or CSOE. The data of TGIR and mortality indicated that BCOE could increase the anti-tumor activity of CSOE and reduced the toxicity of BJOE. The mortality study (BCOE 0, BJOE 63.3%, CSOE 13.3%) showed that BCOE greatly reduced the toxicity of BJOE and CSOE. Therefore, the development and application of BCOE will make an important contribution to anti-tumor therapy.

Pharmacodynamic comparison of prostaglandin E1 administered by different routes to rats.

The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.

Antitumor effect of paclitaxel-loaded PEGylated immunoliposomes against human breast cancer cells.

PURPOSE: The antitumor effect of paclitaxel-loaded PEGylated immunoliposome (PILs) was investigated in breast cancer cell lines and the xenograft model. METHODS: Herceptin was conjugated to paclitaxel-loaded PEGylated liposomes (PLs). In vitro cellular uptake and cytotoxicity of PILs were determined in breast cancer cell lines while in vivo antitumor efficacy was evaluated in the xenograft nude mouse model. RESULTS: The PILs formulation was able to significantly increase the HER2 mediated cellular uptake of paclitaxel compared to the PLs in cell lines overexpressing HER2 (BT-474 and SK-BR-3 cells). However, in the MDA-MB-231 cells, which express low levels of HER2, the difference between the PILs and PLs formulation was not significant. The biological activity of Herceptin was maintained throughout the conjugation process as exhibited by the antitumor dose-response curves determined for Herceptin itself, for the thiolated Herceptin alone and subsequently for the immunoliposome-coupled Herceptin. In BT-474 and SK-BR-3 cells, the cytotoxicity of the PILs was more potent than that of Taxol. Moreover, in in vivo studies, PILs showed significantly higher tumor tissue distribution of paclitaxel in the BT-474 xenograft model and more superior antitumor efficacy compared to Taxol and PLs. However, in the MDA-MB-231 xenograft model, PILs and PLs showed similar tumor tissue distribution as well as antitumor activity. CONCLUSIONS: These results suggest that HER2-mediated endocytosis is involved in the PILs formulation. The ability of the PILs formulation to efficiently and specifically deliver paclitaxel to the HER2-overexpressing cancer cells implies that it is a promising strategy for tumor-specific therapy for HER2-overexpressing breast cancers.

Improvement of the dissolution rate of nitrendipine using a new pulse combustion drying method.

Solid dispersions (SDs) of nitrendipine (NTD), a poorly water-soluble drug, were prepared with the Hypulcon pulse combustion dryer system, and the physicochemical properties of particles were investigated and compared with those of particles prepared with a spray dryer. The SD particles prepared with Hypulcon using Aerosil and Tween 80 as carriers showed improved properties over those prepared with a conventional spray dryer, such as smaller particle size, tighter particle size distribution, and no agglomeration. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that the drug in the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution was dispersed in an amorphous state. Fourier transformation IR spectroscopy indicated the presence of hydrogen bonds between NTD and Aerosil. Aerosil had greater ability to improve the dissolution of NTD than Sylysia and other polymers. The highest drug supersaturation concentration was maintained continuously during the dissolution test of the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution using Hypulcon. The good hydrophilicity and dispersibility of Aerosil, solubilization of Tween 80, and actions of shock waves and ultrasonic waves might account for the amorphization of NTD and improved dissolution rate of SDs. Pulse combustion drying with low drying costs and high thermal efficiency is a promising method for the preparation of SD particles with improved properties without using organic solvent.

Liposome formulation of paclitaxel with enhanced solubility and stability.

Despite its strong antitumor activity, paclitaxel (Taxol) has limited clinical applications due to its low aqueous solubility and hypersensitivity caused by Cremophor EL and ethanol which is the vehicle used in the current commercial product. In an attempt to develop a pharmaceutically acceptable formulation that could replace Taxol, a paclitaxel incorporated liposome has been constructed to improve solubility and physicochemical stability. The effect of various components of the liposome, including cholesterol and lipid, on the solubility and entrapment efficiency (EE) of paclitaxel was systematically investigated. The results showed that 5% (v/v) of polyethylene glycol 400 in the hydration medium of liposome significantly increased the solubility (up to 3.39 mg/mL) as well as the EE and the paclitaxel content in the liposome formulation composed of 10% (w/v) of S(100)PC with cholesterol (cholesterol-to-lipid molar ratio = 10:90). When sucrose (sugar-to-lipid molar ratio = 2.3) was added as a lyoprotectant during the freeze-drying of the liposome, physicochemical stability of liposome was significantly improved. Moreover, the cytotoxicity of the final liposome formulation against MDA-MB-231 human breast cancer cell line was not significantly different from that of Taxol. The enhanced aqueous solubility as well as the physicochemical stability of paclitaxel in the liposome formulation developed in this study could be a safer and effective alternative to the Cremophor EL and ethanol formulation.

Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome.

A sterically stabilized paclitaxel-loaded liposome tailored to target human breast cancer cells was developed, thereby promoting the efficiency of intracellular delivery of paclitaxel through receptor-mediated endocytosis. Results indicated that the targeting moiety (thiolated Herceptin) was successfully coupled to the distal reactive maleimide terminus of the poly (ethylene glycol)-phospholipid conjugate as well as being incorporated in the liposomal bilayers. The particle size of the PEGylated immunoliposome was maintained at about 200 nm. Confocal microscopy studies showed that the PEGylated immunoliposome was uptaken into the interior of the tumor cell through the receptor-mediated endocytosis pathway. The PEGylated immunoliposome showed substantially higher cellular uptake than the PEGylated liposome in cancer cells (BT-474 and SK-BR-3) over-expressing human epidermal growth factor receptor 2 (HER2) at 37 degrees C, while no difference was found in low HER2 expressing cells (MDA-MB-231) nor at low temperature (4 degrees C). Pharmacokinetics of paclitaxel in the PEGylated immunoliposome was compared with that in Taxol and in the PEGylated liposome in rats. The circulating time of paclitaxel in the PEGylated immunoliposome was prolonged compared to Taxol while slightly shortened than that in the PEGylated liposome. Therefore, the paclitaxel-loaded PEGylated immunoliposome using Herceptin could serve as a promising model for future tumor specific cancer therapy of HER2 over-expressing breast cancers.

Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation.

An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of improving the solubility of paclitaxel as well as the physicochemical stability of liposome in comparison to the current Taxol formulation. The use of 3% (v/v) Tween 80 in the hydration media was able to increase the solubility of drug. The addition of sucrose as a lyoprotectant in the freeze-drying process increased the stability of the liposome particles. There was no significant difference in the entrapment efficiency of paclitaxel between the conventional non-PEGylated liposomes and our PEGylated liposomes. Cytotoxicity in human breast cancer cell lines (MDA-MB-231 and SK-BR-3) of our paclitaxel formulation was less potent compared to Taxol after 24h incubation, but was equipotent after 72 h due to the slower release of drug from the liposome. Our PEGylated liposomes increased the biological half-life of paclitaxel from 5.05 (+/-1.52)h to 17.8 (+/-2.35)h compared to the conventional liposomes in rats. Biodistribution studies in breast cancer xenografted nude mouse model showed that our liposomes significantly decreased the uptake in reticuloendothelial system (RES)-containing organs (liver, spleen and lung) while increasing the uptake in tumor tissues after injection compared to Taxol or the conventional liposomal formulation. Moreover, the PEGylated liposome showed greater tumor growth inhibition effect in in vivo studies. Therefore, our PEGylated liposomal formulation of paclitaxel could serve as a better alternative for the passive targeting of human breast tumors.

Preparation of insulin loaded PLGA-Hp55 nanoparticles for oral delivery.

The aim of the present work was to investigate the preparation of PLGA nanoparticles (PNP) and PLGA-Hp55 nanoparticles (PHNP) as potential drug carriers for oral insulin delivery. The nanoparticles were prepared by a modified emulsion solvent diffusion method in water, and their physicochemical characteristics, drug release in vitro and hypoglycemic effects in diabetic rats were evaluated. The particle sizes of the PNP and PHNP were 150+/-17 and 169+/-16 nm, respectively, and the drug recoveries of the nanoparticles were 50.30+/-3.1 and 65.41+/-2.3%, respectively. The initial release of insulin from the nanoparticles in simulated gastric fluid over 1 h was 50.46+/-6.31 and 19.77+/-3.15%, respectively. The relative bioavailability of PNP and PHNP compared with subcutaneous (s.c.) injection (1 IU/kg) in diabetic rats was 3.68+/-0.29 and 6.27+/-0.42%, respectively. The results show that the use of insulin-loaded PHNP is an effective method of reducing serum glucose levels.

Enhanced immune responses induced by vaccine using Sendai virosomes as carrier.

Sendai virosomes can deliver encapsulated contents into the cytoplasm directly in a virus fusion-dependent manner. In this paper, Sendai virosomes-formulated melanoma vaccine was constructed and its anti-tumor effects were investigated. The melanoma vaccine was prepared by encapsulating mixture antigen into the Sendai virosomes. The antigen, mixture proteins were extracted from B(16) melanoma cells. The cytotoxic T lymphocyte (CTL) response level was evaluated by (51)Cr release method, and the change of CD4(+) and CD8(+) expression as well as the concentration of IgG in serum of immunized mice was measured. The results showed that Sendai virosomes-formulated melanoma vaccine can effectively elicit not only systemic immune response but also strong CTL response. Sendai virosomes can be used as an effective vector for use in anti-tumor vaccine therapy.

[Pharmacokinetic study of ketoprofen in rat by blood microdialysis technique].

AIM: To investigate the in vitro recovery and influencing factors of ketoprofen in microdialysis probe, and study the pharmacokinetic of unbound ketoprofen in rat after iv administration. METHODS: The recovery of ketoprofen was detected by a concentration difference method. After microdialysis probe was inserted into the jugular vein of male Wistar rats, the probe was infused with various concentrations perfusate. The in vivo recovery and the pharmacokinetics of unbound ketoprofen in rat were investigated. Dialysate samples were determined by HPLC. RESULTS: The recovery detected by gain was as the same as that by loss; the recovery was independent of the drug concentration surrounding the probe. The in vitro recovery was 28.75% by concentration difference method and the in vivo recovery was (40.3 +/- 2.7) % by retrodialysis method. After i.v. administration of ketoprofen in rat, T 1/2, AUC and CL of unbound ketoprofen were (181 +/- 16) min, (112 +/- 27) microg x min x mL(-1) and (0.22 +/- 0.05) L x min(-1), respectively. CONCLUSION: Microdialysis sampling can be used for the pharmacokinetic study of unbound ketoprofen in rat.

Preparation of roxithromycin-polymeric microspheres by the emulsion solvent diffusion method for taste masking.

Microspheres of roxithromycin with Eudragit S100 and silica were prepared by the emulsion solvent diffusion method to mask the bitter taste of the antibiotic. The effect of different polymers and drug-polymer ratios on the taste masking and the characteristics of the microspheres were investigated. It was found that Eudragit S100 was the best for masking the unpleasant taste of roxithromycin among the six kinds of polymers investigated. The results of DSC, X-ray diffraction and IR showed that there were several combinations of roxithromycin and Eudragit S100. The influence of other formulation factors, i.e. dichloromethane-acetone ratios and silica-polymer ratios on the properties of the microspheres were also examined. In conclusion, the results of the present study will be helpful for the preparation of oral forms of roxithromycin with an acceptable taste.