The inclusion complex of CBZ with β-CD (in 1:1 molar ratio) was obtained by the kneading method of complexation in solid state. This molar ratio was chosen on technical requirements for obtaining the final product, i.e., acceptable weight, oral dispersion and mechanical properties for both the compressible powder and chewable tablets. The actual formation of the 1:1 inclusion complex was proved by post synthesis (kneading) physical–chemical characterization and by dissolution experiments. The physical mixture maintaining the same 1:1 molar ratio was used as reference. In the present study, it was not necessary to calculate a stability constant because the lower 1:1 molar ratio was chosen due to reasons related to the tablet weight requirements. Available literature data [13 (link),14 (link),15 (link),21 (link)] indicated values of Ks of 376.5–636 M−1 for various phase solubility diagrams of AL type. All reported phase solubility diagrams exhibited slopes of less than 1, proving the existence of a 1:1 molar ratio complex.
For the physical mixture, the necessary amounts of the raw components were sieved and accurately weighted (to yield 1:1 molar ratio) and then physically mixed for 15 min in an agate mortar, at the room temperature, in order to obtain a homogeneous powder.
For the inclusion complex synthesis by kneading, 0.25 mmol of CBZ and 0.25 mmol of β-CD, in 1:1 molar ratio, were thoroughly mixed together in a mortar, with vigorous trituration, for about 3 h. During this process, an appropriate volume of 70% ethanol solution was added until a homogeneous paste was obtained. The resulting paste was further triturated for 1 h. Then, the obtained product was dried, at room temperature, for 24 h. The solid dried mixture was passed through sieve no. VI [25 ]. The solid dispersion was stored in the desiccator, over anhydrous calcium chloride, until use.
The formulation of chewable tablets with 200 mg of CBZ, the exact composition, the used pressure and their pharmacotechnical characterization were performed as described in a previous paper [26 ]. The powder for direct compression contained the active ingredient—the inclusion complex CBZ-β-CD at a molar ratio of 1:1—and F-MELT®, Fuji’s patented F-MELT® system, which was specifically designed for Oral Disintegrating Tablets.
For the physical mixture, the necessary amounts of the raw components were sieved and accurately weighted (to yield 1:1 molar ratio) and then physically mixed for 15 min in an agate mortar, at the room temperature, in order to obtain a homogeneous powder.
For the inclusion complex synthesis by kneading, 0.25 mmol of CBZ and 0.25 mmol of β-CD, in 1:1 molar ratio, were thoroughly mixed together in a mortar, with vigorous trituration, for about 3 h. During this process, an appropriate volume of 70% ethanol solution was added until a homogeneous paste was obtained. The resulting paste was further triturated for 1 h. Then, the obtained product was dried, at room temperature, for 24 h. The solid dried mixture was passed through sieve no. VI [25 ]. The solid dispersion was stored in the desiccator, over anhydrous calcium chloride, until use.
The formulation of chewable tablets with 200 mg of CBZ, the exact composition, the used pressure and their pharmacotechnical characterization were performed as described in a previous paper [26 ]. The powder for direct compression contained the active ingredient—the inclusion complex CBZ-β-CD at a molar ratio of 1:1—and F-MELT®, Fuji’s patented F-MELT® system, which was specifically designed for Oral Disintegrating Tablets.
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