**2.4 Differential scanning calorimetry**

360 New Advances in the Basic and Clinical Gastroenterology

that this mucoadhesive formulation can deliver paclitaxel effectively when given by oral route without additional active pharmaceutical ingredient as an absorption enhancer (Lee et al., 2004; Hong et al., 2004; I. H. Lee et al., 2005, Shin et al., 2009). As an endeavor to formulate more efficient oral paclitaxel formulations, we have prepared oil-based paclitaxel formulations with monoolein, saturated triglycerides and emulsifiers. Monoolein was included in the formulation as a main ingredient due to its high bioadhesiveness (Nielsen et al., 1998) and its ability to release the encapsulated drug in a controlled fashion (Clogston et al., 2005a, 2005b). Triglycerides were added since they can solubilize paclitaxel efficiently (Kan et al., 1999). To access the effectiveness of the formulations, pharmacokinetic and anti-

Distilled monoolein (RYLOTM MG 19, > 90 % pure) was purchased from Danisco Ingredients, Denmark. Paclitaxel was obtained from Samyang Genex (Korea) and Indena S.P.A. (Italy). Cremophor EL, Tween 80 and triglycerides (triacetin, tributyrin, tricaproin, tricaprylin, tricaprin and trilaurin) were purchased from Sigma Chemical Co. (St. Louis,

The compositions of the oral paclitaxel formulations used in the experiments are summarized in Tables 2 and 3. Paclitaxel formulations with various triglycerides (Table 2) were prepared as follows: Paclitaxel in amorphous form was dissolved completely at 10 mg/ml in mixtures of oils consisting of monoolein, triglycerides and Tween 80 by sonication for 30 s. Some of the oral paclitaxel formulations were semi-solid or solid wax at ambient temperatures with the melting points of 30 ~ 50 C, and therefore had to be warmed before

In Table 3, Paclitaxel, amorphous or crystalline, was dissolved completely in excess amount of methylene chloride and mixed subsequently with tricaprylin. Methylene chloride was evaporated completely to prepare paclitaxel/tricaprylin solution by vacuum evaporation (BUCHI rotavapor R-200, Germany) at 40 C for 1 h. The content of methylene chloride was determined by gas chromatography and was less than 100 ppm in the paclitaxel/tricaprylin solution. Monoolein and Tween 80 were added to the paclitaxel/tricaprylin solution and mixed completely by sonication for 30 s. A formulation that does not contain paclitaxel, eG2, was also prepared for control. The oral paclitaxel formulations were semi-solid wax with the melting temperature of 33 ~ 35 C, and were warmed to body temperature before feeding. Dispersions of the oral paclitaxel formulations (G8, G9, and G10) were prepared by adding 2.3 times (by volume) of distilled water or syrup to the formulation G2 (also will be referred

Male ICR and Balb/c athymic mice, 7 weeks old, were purchased from Orient Bio Co. (Seoul, Korea) and Japan SLC (Japan), respectively, and maintained 1 week. Animal care

tumor efficacy studies were performed in mice models.

**2.2 Preparation of oral paclitaxel formulations** 

to as DHP107) and by vortexing or sonicating for 1 min.

**2. Materials and methods** 

**2.1 Materials** 

oral feeding.

**2.3 Animals** 

MO).

Differential scanning calorimetry (DSC) was performed to obtain the heating thermograms of paclitaxel and the formulations in Table 2 (DSC 821e, Mettler Toledo, Columbus, OH, equipped with Intracooler, Haake EK90/MT, Haake, Denmark) at a heating scan rate of 5 C/min. Scans were made with samples contained in hermetically sealed aluminum crucibles (ME-27331, Mettler Toledo). Initial heating scans were reported for paclitaxel and the formulations in Table 2. In case of the formulations, thermal history did not alter the heating thermograms if the samples were cooled to – 20 C before reheating.
