Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid.

To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI-20 °C < RDI-80 °C < RDI-196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.

Combination of submicroemulsion and phospholipid complex for novel delivery of ursodeoxycholic acid.

The objective of this study was to prepare and characterize ursodeoxycholic acid submicron emulsion (UA-SME) loaded with ursodeoxycholic acid phytosomes (UA-PS) and optimize the process variables. A screening experiment with response surface methodology with Box-Behnken design (BBD) was used to optimize the process parameters of UA-SME. The blood concentrations of UA after oral administration of UA-SME and UA coarse drug were assayed. The optimum process conditions were finally obtained by using a desirability function. It was found that stirring velocity, homogenization pressure and homogenization cycles were the most important variables that affected the particles size, polydispersity index and entrapment efficiency of UA-SME. Results showed that the optimum stirring velocity, homogenization pressure and cycles were 16 000 rpm, 60 MPa and 10 cycles, respectively. The mean diameter, polydispersity index and entrapment efficiency of UA-SME were 251.9 nm, 0.241 and 74.36%, respectively. Pharmacokinetic parameters of UA and UA-SME in rats were Tmax 2.215 and 1.489 h, Cmax 0.0364 and 0.1562 µg/mL, AUC0-∞ 3.682 and 13.756 µg h/mL, respectively. The bioavailability of UA in rats was significantly different (p < 0.05) after oral administration of UA-SME compared to those of UA coarse drug. This was due to improvement of the hydrophilicity and lipophilic property of UA-SME.

[Pathogens of prostatitis and their drug resistance: an epidemiological survey].

OBJECTIVE: To investigate the epidemiological features of the pathogens responsible for prostatitis in the Changshu area, and offer some evidence for the clinical treatment of prostatitis. METHODS: This study included 2 306 cases of prostatitis that were all clinically confirmed and subjected to pathogenic examinations in 3 hospitals of Changshu area from 2008 to 2012. Neisseria gonorrhoeae, mycoplasma urealyticum and chlamydia trachomatis were detected by nucleic acid amplification ABI 7500, the bacterial data analyzed by VITEK-2 Compact, the drug-resistance to antibacterial agents determined using the WHONET 5.6 software, and the enumeration data processed by chi-square test and curvilinear regression analysis using SPSS 19.0. RESULTS: The main pathogens responsible for prostatitis were found to be Staphylococcus haemolyticus (30%), Staphylococcus epidermidis (12%), Enterococcus faecalis (9%), Escherichia coli (6%), Staphylococcus warneri and Staphylococcus aureus (3%), Mycoplasma urealyticum (8%), chlamydia trachomatis (5%) and Neisseria gonorrhoeae (6%). Statistically significant increases were observed in the detection rates of Escherichia coli (chi2 = 17.56, P<0.05), Mycoplasma urealyticum (chi2 = 8.73, P<0.05), Chlamydia trachomatis (chi2 = 8.73, P<0.05) and Enterococcus (chi2 = 8.22, P<0.05), but not in other pathogens. The resistance rates of Gram-positive bacteria to erythromycin and benzylpenicillin G were both above 45%, but with no significant difference between the two, those of Oxacillin (chi2 = 10.06, P<0.05) and Cefoxitin (chi2 = 9.89, P<0.05) were markedly increased, but those of quinolones, gentamycin and clindamycin remained low, except rifampicin (chi2 = 11.09, P<0.05). The resistance rates of Gram-negative bacteria to cefazolin and ampicillin were relatively high (mean 57.3%), and those to ceftriaxone (chi2 = 11.26, P<0.05) and trimethoprim sulfamethoxazole (chi2 =11.00, P< 0.05) significantly high; those to amikacin, cefepime, piperacillin/tazobactam and imipenem remained at low levels with no significant changes. However, the resistance rates of mycoplasma urealyticum to ciprofloxacin (chi2 = 11.18, P<0.05) and azithromycin (chi2 = 9.89, P<0.05) were remarkably increased. CONCLUSION: Gram-positive bacteria are the major pathogens responsible for prostatitis, but Escherichia coli, enterococcus and sexually transmitted disease pathogens are found to be involved in recent years. Quinolones and aminoglycosides are generally accepted as the main agents for the treatment of Gram-positive bacterial infection. However, rational medication for prostatitis should be based on the results of pathogen isolation and drug sensitivity tests in a specific area.

D-Alpha-tocopherol acid polyethylene glycol 1000 succinate, an effective stabilizer during solidification transformation of baicalin nanosuspensions.

Baicalin nanosuspensions, stabilized with 10% TPGS (relative to the weight of baicalin), were transformed into nanosuspensions powders by solidification process. Solidification methods for this transformation included freeze-drying, spray drying or vacuum drying. High pressure homogenization was applied for production of baicalin nanosuspensions used TPGS, SDS, P188, HPMC and MC as stabilizer, respectively. The influence of the different solidification transformation methods on the redispersibility of solid drug nanosuspensions was systemically investigated, such as freeze-drying, spray drying and vacuum drying. Each method was applied with three grades of process stresses called as "conservative", "moderate" and "aggressive" conditions, and the redispersibility index (RDI) of nanosuspensions stabilized by stabilizers (such as TPGS, SDS, P188, HPMC and MC) during those process was investigated. The results showed that there was significant difference in RDI of nanosuspensions after solidification process. The RDI(a) (1.09, 1.01, 1.05, 0.99), RDI(b) (1.03, 0.99, 1.06, 1.02) and RDI(c) (1.01, 1.01, 1.09, 1.08) of nanosuspensions stabilized by TPGS were more small during different solidification process, compared with those of nanosuspensions stabilized by other stabilizer. It was concluded that the baicalin nanosuspensions were subjected to agglomeration or crystal growth during solidification transformation, especially at high aggressive stress conditions. Meanwhile, compared to other stabilizer, the TPGS was more effective for stability of baicalin nanosuspensions, which could exhibit higher affinity to the drug crystal and stronger surface adsorption at different solidification stresses.