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

Abstract

To control release of a drug is a topic of much interest. The wax matrix system was one method often used to control drug release, and its release properties were mathematically shown by Higuchi.2-4) Some basic properties of release from and through the wax matrix layer prepared from a physical mixture of water-soluble component and hydrogenated castor oil were obtained in previous papers. 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. It was also believed that a reservoir type wax matrix tablet having a fixed surface area may provide more basic release property, and some of the basic release properties obtained were shown in previous papers. 1,5,6) Here, generalization of the release process through the wax matrix layer was examined using a reservoir device tablet having a matrix layer prepared from a physical mixture of lactose and hydrogenated castor oil. The lag time was analyzed by the Higuchi equation and the actual release process after the lag time was analyzed using the zero-order release kinetic equation. ExperimentalThe following descriptions are closely similar to those in previous papers. 1,5) Materials 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. The mean diameters (mm) of INZ, LAC and HCO are 10.6, 9.4 and 10.3, respectively. The true density (g/cm 3 ) of LAC and HCO are 1.53 and 1.03, 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 by an automatic mixer (model S 10, Taiyo Kagaku Kogyo Co.) for 10 min.The physical mixture was put into a die 10 mm in diameter. After flattening the surface with a 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, this tablet was placed at the center of the bottom of a die 16 mm in diameter and 600 mg of HCO was added. Then, the contents were compressed at 62.5 MPa.This system was called the LAC : HCO/INZ system. Release Test Release measurements were carried out in 900 ml distilled water at a paddle rotation speed of 100 rpm at 37°C. The reservoir device tablet was placed in the dissolution apparatus (model NTR-VS, Toyama Sangyo Co., Ltd.) coupled to a flow cell set in a double-beam spectrophotometer (model 200-20, Hitachi Ind. Co.) via a micro tube pump (model MP-3, Tokyo Rikakikai Co., Ltd.), and pe...

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.…”

“…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.…”

“…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.…”