US 2007/0148240 Al  5  Jun.28,2007  Ingredients  Polyvinyl Pyrrolidone (PVP K-30)  Isopropyl Alcohol  Purified Water  Sucrose  Starch  Talc  Amount  40 g  300 ml  200 ml  400 g  800 g  900 g  INGREDIENT  1. The Cores:  2. The Drug Coating Layer:  Itraconazole  Hydroxypropyl Methylcellulose (HPMC)  Methylene Chloride  Ethanol  AMOUNT  1155 g  600 g  945  g  6900 ml  12600 ml  (A) Materials and Method for Preparation of the Cores:  [0062]  The cores were prepared using the following ingre› dients:  [0063]  The cores were produced by a three-step process.  The first step included dissolving 40 g of PVP K-30 in 300  ml of isopropyl alcohol with stirring and then mixing with  200 ml of distilled water, which produced a binder solution.  The second step included mixing 800 g of starch and 900 g  of talc together. The final step included putting sucrose into  a fluidized bed granulator (such as Glatt or Huttlin) and  spraying the PVP K-30 binder solution produced in the first  step onto the sucrose, while at the same time adding the  starch-talc mixture to the sucrose, to form the cores. The  cores were further dried under warm air.  [0064]  The dried cores were then passed through an  18-inch sieve once and a 20-inch sieve once. the cores  having the size within 18-20 mesh were retained for use in  the manufacturing of the granules of the present invention.  (B) Materials and Method for Preparation of the Drug  Coating Layer  [0065]  The drug coating layer was prepared using the  following ingredients:  [0066]  The drug coating layer was prepared by mixing  1026 g of HPMC and 600 g of itraconazole, followed by  adding 12600 ml of ethanol to the mixture until all of the  ingredients were thoroughly mixed. Then, 6900 ml of meth› ylene chloride were added to the mixture until all of the  ingredients were completely dissolved to form the drug  coating layer.  (C) Method for Making the Pharmaceutical Formulation:  [0067]  The drug coating layer-coated granules were pre› pared by placing the 1074 g of the 18-20 mesh cores as  described in (A) into a fluidized-bed centrifuge granulator  (Glatt). The drug coating layer as described in (B) was  sprayed, as a mist-like solution, onto the cores while the  Glatt was in operation to form wet granules, which were  further dried to form the drug coating layer-coated granules  of the present pharmaceutical formulation.  [0069]  The cores and the drug coating layer of the phar› maceutical formulation of Example 3 were the same as those  described in Examples 1-2, except that the pharmaceutical  formulation of Example 3 contained a protective layer,  which was used as a seal coating for the drug coating layer.  The pharmaceutical formulation of Example 3 contained the  following ingredients:  [0070]  The protective layer was prepared by adding dis› tilled water to PEG 20,000, followed by stirring until PEG  20,000 was completely dissolved.  [0071]  After the drug coating layer-coated granules were  made and dried in the Glatt, the protective layer was sprayed  onto the drug coating layer-coated granules while the Glatt  was still centrifuging to coat the protective layer onto the  granules. The protective layer-coated granules were then  dried to form the pharmaceutical formulation of the present  invention.  [0072]  The cores and the drug coating layer of the phar› maceutical formulation of Example 4 were the same as  described in Examples 1-3. Additionally, Example 4 con› tained a protective layer which was prepared according to  the same procedure as described in Example 3, except for  the quantities of the protective layer ingredients. The phar› maceutical formulation of Example 4 was prepared using the  following ingredients:  INGREDIENT  1. The Cores:  2. The Drug Coating Layer:  Itraconazole  Hydroxypropyl Methylcellulose (HPMC)  Methylene Chloride  Ethanol  3. The Protection Layer:  Polyethylene glycol (PEG) 20000  Distilled Water  AMOUNT  1155 g  600 g  945 g  6900 ml  12600 ml  27 g  270 ml  INGREDIENTS  Itraconazole  Hydroxypropyl Methylcellulose (HPMC)  Methylene Chloride  Ethanol  AMOUNT  600 g  1026 g  6900 ml  12600 ml  [0068]  The cores and the drug coating layer of the phar› maceutical formulation of Example 2 were prepared accord› ing to the procedures described in Example 1 except that the  quantity of the cores used in Example 2 was different from  that in Example. The pharmaceutical formulation of  Example 2 contained the following ingredients:  EXAMPLE 2  EXAMPLE 1  EXAMPLE 3  EXAMPLE 4 