Release from or through a Wax Matrix System. III. Basic Properties of Release through the Wax Matrix Layer.

Abstract

To control drug release is a topic of much interest. Wax matrix system was often used as one of methods to control drug release, and its release properties were mathematically expressed by Higuchi. [2][3][4] To control a drug release, it is important to obtain some basic properties of matrix system.When the matrix layer was prepared from melted granules of soluble component and wax, some factors such as surface coverage and thickness of melted wax on the surface of soluble component should be considered at least. On the other hand, when the wax matrix layer was prepared from a physical mixture of soluble component and wax, basic properties of matrix system can be estimated by connecting simple factors.It was considered that reservoir type wax matrix tablet having a fixed surface area may provide more basic release property. In the previous paper, 1) a reservoir device wax matrix tablet was prepared from a physical mixture of hydrogenated castor oil and drug (isoniazid) that was the same one in the reservoir. Hence basic release property from and through the wax matrix layer was investigated (abbreviated as INZ : HCO/INZ system). Then tortuosity as a basic property was suggested to be expressed by a function of the porosity.Here, basic release properties of drug (isoniazid) in the reservoir through the wax matrix layer prepared from the physical mixture of hydrogenated castor oil powder and soluble substance, i.e., lactose were investigated (abbreviated as LAC : HCO/INZ system). As a result, comparable release properties were obtained from both LAC : HCO/INZ and INZ : HCO/INZ systems. Hence it was suggested that the time begin to release the drug in reservoir through wax matrix layer and its release rate constant can be roughly prospected from the amount of matrix layer and mixed weight fraction of component in the matrix layer. ExperimentalMaterials Isoniazid JP (INZ, Yukigousei Yakuhin Kogyo Co.) was pulverized prior to use. Lactose (LAC, Meggle D80) was used as the water-soluble ingredient in the matrix layer. Hydrogenated castor oil (HCO, Kawaken Fine Chemical Co.) was used as the matrix substance.1,5) The mean diameters (mm) of INZ, LAC and HCO are 10.6, 9.4 and 10.3, respectively.Preparation of Reservoir Device Tablet Reservoir device tablets having a flat wax matrix layer were prepared. Lactose and hydrogenated castor oil powder were weighed at a given mixed weight ratio for the matrix layer, and were physically mixed together using an automatic mixer (model S 10, Taiyo Kagaku Kogyo Co.) for 10 min.The physical mixture was put into a die having a diameter of 10 mm. After flattening the surface by using the punch, a 50 mg amount of INZ was accumulated on the physical mixture. Then the contents were compressed at 124.8 MPa to make a two-layer tablet. The two-layer tablet was placed at the center of the bottom of a die having a diameter of 16 mm and 600 mg of HCO was added. Then, the contents were compressed at 62.5 MPa. The shape of prepared reservoir device tablet was the same one shown in the previous pape...

Release from or through a Wax Matrix System. VI. Analysis and Prediction of the Entire Release Process of the Wax Matrix Tablet

“…[5][6][7][8] In this case, following relationship was obtained when it was examined with reservoir device tablet. 5,6) P/Dϭe 3 (5) and tϭe Ϫ2 (6) Thus the same matrix showed different properties. It was supposed that the amount of drug decrease with release time, and the release process gradually deviate from the Higuchi equation.…”

“…1,[5][6][7][8][9] These were isoniazid JP (INZ, Yukigousei Yakuhin Kogyo Co.) and hydrogenated caster oil (HCO, K 3 wax ® , mp 84-88°C, Kawaken Fine Chemical Co.) as a wax powder. The mean diameter of INZ and HCO are 10.6 and 10.3 mm, respectively.…”

“…5,6) The thickness of the wax matrix tablet (L) was expressed as Lϭ1.02M m within the examined amount of wax matrix (M m ). 1,5,6) Therefore, e and A values are mostly defined by the amount of wax matrix and mixed weight ratio of the drug.…”

“…On the other hand, when a wax matrix system is prepared using a physical mixture of soluble component and wax, basic release properties can be estimated by connecting their basic properties and simple factors. [5][6][7][8] Therefore, applicability or validity of the H-my equation was examined by using the wax matrix tablets prepared from a physical mixture.…”

Release from or through a Wax Matrix System. IV. Generalized Expression of the Release Process for a Reservoir Device Tablet.

“…1,5) When the wax matrix system was prepared from melted granules of water-soluble component and wax, certain factors such as surface coverage and thickness of the melted wax on the surface of the soluble component should be considered. When the wax matrix system is prepared from a physical mixture of soluble component and wax, basic properties of the matrix system can be estimated by simple factors.…”