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.

The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble drug in human body, using a solid dispersion technique (hot melt extrusion). The solid dispersion was prepared by cooling the hot melt of the drug in the carrier (Vitamin E TPGS and PVP). The dissolution rate of formulation 1 from a novel formulation prepared by solid dispersion technique was equal to release of formulation 6 (40% of eprosartan mesylate is in contrast to teveten ®) within 60 min (Table 1). The oral bioavailability of new eprosartan mesylate tablet having vitamin E TPGS and PVP K29 was tested on rats and dogs. Of the absorption enhancer and polymer tested, vitamin E TPGS and PVP K29, resulted in the greatest increases of AUC in animals (about 2.5-fold increase in rat and dog). When eprosartan mesylate was mixed with the absorption enhancer and polymer in a ratio of 2.94:2:1, vitamin E TPGS and PVP K29 improved eprosartan mesylate bioavailability significantly compared with the conventional immediate release (IR) tablet Teveten ® (formulation 7). These results show that solid dispersion using vitamin E TPGS and PVP K29 is a promising approach for developing eprosartan mesylate drug products.

Design of experiment provides a quality risk management to the manufacturing process of a product. This study was performed to select the water amount and identify the critical process parameters for wet granulation. Design of experiment, one of the quality by design approaches, was used in the study. The manufacturing process of valsartan and paravastatin fixed-dose combination tablets involves wet granulation, drying, sieving, blending and tableting. For wet granulation, a 3-factorial (granulating time, agitator speed and the amount of granulating water), 2-level (granule density and dissolution), 1-center (n = 3) point was used in the design of experiment batches and analyzed using Design Expert Software. Previously, this formulation was found to show good assay and content uniformity. Thus, only physical properties, bulk density and dissolution were evaluated for the design of experiment study. The amount of granulating water was identified as an important factor affecting the mean dissolution (p < 0.05) in contrast to the granulating time and agitator speed. Present results indicated that granulating time (6 to 10 min), amount of granulating water (40 to 60 g) and agitator speed (150 to 250 rpm) were optimal for wet granulation of valsartan and pravastatin fixed-dose combination tablets.

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Bacillus polyfermenticus KJS-2 (Bp2) was isolated from Bispan Ⓡ , a commercially available probiotics consisting of more than 4 strains. The objective of this study was to investigate the effect of three-layer coating on the stabilty of Bp2. Bp2 was microencapsulated with sodium alginate using an air atomizer. The Bp2 loaded pellets were also coated with HFP-chitosan and HPMCP for oral delivery system. When compared to the uncoated Bp2, the survival of the three-layer coated Bp2 increased to approximately 63% (p<0.01) in a 30% ethanol solution, 54% (p<0.05) in an artificial gastric juice (pH 2), and 53% (p<0.05) in the bile acid (pH 5). When coated beads were stored at 100 o C and 130 o C, Bp2 in coated beads was very stable (p<0.01) compared to uncoated Bp2.