No abstract

The reliable in-line monitoring of pharmaceutical processes has been regarded as a key tool toward the full implementation of process analytical technology. In this study, near-infrared (NIR) spectroscopy was examined for use as an in-line monitoring method of the paracetamol cooling crystallization process. The drug powder was dissolved in ethanol-based cosolvent at 60°C and was cooled by 1°C/min for crystallization. NIR spectra acquired by in-line measurement were interpreted by principal component analysis combined with off-line characterizations via X-ray diffraction, optical microscopy, and transmission electron microscopy. The whole crystallization process appeared to take place in three steps. A metastable form II polymorph of paracetamol was formed and transformed into the stable form I polymorph on the way to the growth of pure form I by cooling crystallization. These observations are consistent with a previous focused beam reflectance method-based study (Barthe et al., Cryst Growth Des 8:3316-3322, 2008).

This study aimed to evaluate the long-term efficacy of entecavir (ETV) in adefovir (ADV)-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV-refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty-four patients were men, and their median age was 47 (25-69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3-8.0) log(10) copies/mL, and the median duration of ETV therapy was 24 (12-47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg-positive patients. In multivariate analysis, only initial virologic response at 3 months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387-7.120; P = 0.006). The patients with a virological response at 3 months had not only a significantly higher probability of achieving a virologic response (P < 0.001) but also lower probability of experiencing a virologic breakthrough (P = 0.043) than the patients without an early response. Viral breakthrough was observed in 29 patients during the follow-up period. Cumulative breakthrough rates at 6, 12, 24 and 36 months were 0%, 15%, 45% and 73%, respectively. ETV monotherapy may be considerably efficacious in cases with an initial virological response but its efficacy is attenuated by frequent emergence of ETV resistance in ADV-refractory CHB patients with prior LMV resistance.

No abstract

Although salmon-calcitonin (sCT) has been known as a potent drug for the treatment of osteoporosis, its oral dosage form products have not been commercially available primarily due to a poor oral bioavailability. Chitosan has been extensively examined as a potential oral absorption enhancer, whereas encapsulation with PLGA has been widely studied to address the delivery problems of typical peptide drug molecules. We investigated the mechanism and therapeutic effect of chitosan modification on the sCT-loaded PLGA nanoparticles. Chitosan was added onto these particles in two ways: by incorporation during W/O/W emulsification and by solid dipping. Particles were characterized by particle size analyzer, Zeta potential analyzer, scanning electron microscopy, and so forth. Nano-sized particles of 430-590 nm in fairly spherical shape with a narrow size distribution were produced. The PLGA encapsulation efficiency greater than 50% of added sCT was achieved regardless of chitosan modification. It turned out that sCT-loaded PLGA particles with chitosan modified during W/O/W emulsification (referred to as sCT-PLGA-CHT1) showed better therapeutic behavior in terms of sustained release effects as well as short-period hypocalcemic effects than the others. It was concluded that the beneficial effect was greatly associated with the formation of embedded structure of chitosan molecules when particles were modified with chitosan.