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).

No abstract

Two organic compounds with potential absorption enhancing effects, bile acids and transferrin, were examined by the gastro-intestinal (GI) absorption of therapeutic salmon calcitonin (sCT) as encapsulated by poly(lactide-co-glycolide) (PLGA) for the treatment of osteoporosis. The sCT-loaded PLGA nanocapsules were prepared by O/W emulsification approach. Either additive of a designated content was mixed with sCT dissolved in methanol. For bile acids, their content (0-7.5 mg to sCT 6 mg) was observed to have a substantial effect both on the emulsification process and the encapsulation efficiency. When 1.5 mg of bile acids was added, sCT-loaded PLGA nanocapsules of about 700 nm in diameter and with a fairly high encapsulation efficiency greater than 35% were produced. Accordingly, this formulation gave the most significant hypocalcemic effect in an in vivo experiment with SD rats. On the other hand, a too high bile acids loading resulted in a poor encapsulation efficiency of less than 7%. Two principal roles of bile acids were proposed: emulsifying agent and absorption enhancer. Transferrin, a human glycoprotein of 80 kDa molecular weight, turned out to have potential as absorption enhancer as well.

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.