Release from or through a Wax Matrix System. V. Applicability of the Square-Root Time Law Equation for Release from a Wax Matrix Tablet

Abstract

The control of drug release is a topic of much interest. Matrix systems are often used as a method to control drug release. Higuchi mathematically showed the drug release properties of matrix systems, 2) and numerous investigations have been carried out since then. According to the Higuchi equation, releases occur infinitely without regard to the amount of soluble component. A point or region where the release process begins to deviate from the Higuchi equation should appear when the amount of soluble component is finite, as is usual with the preparation of a matrix system. A matrix system as a controlled drug-release system may be more useful if its entire release process can be analyzed.Some troublesome situations such as coverage and thickness of wax should be taken into account when a wax matrix system is prepared using the melt method. Therefore a wax matrix system prepared from a physical mixture of a soluble component and wax powder was chosen to obtain the basic release properties. [3][4][5] Applying the Higuchi equation to release in various manners from the wax matrix tablet, release properties and the applicability of the equation or how release processes deviate from the equation were examined. ExperimentalMaterials The samples reported in the previous papers were used. [3][4][5][6] They were isoniazid JP (INZ, Yukigousei Yakuhin Kogyo Co., Japan) and hydrogenated caster oil (HCO, Kawaken Fine Chemical Co., Japan) as a wax powder. The mean diameter of INZ and HCO was 10.6 and 10.3 mm, respectively. Preparation of Physical Mixture for Wax MatrixThe mixed weight ratio of INZ to HCO powder was fixed at 7 : 3. The appropriate amounts of INZ and HCO powder were physically mixed using an automatic mixer (type S 10, Taiyo Kagaku Kogyo Co., Japan) for 10 min. 3-5)Preparation of Wax Matrix Tablets The amounts of physical mixture used were 0.30, 0.50, and 1.00 g for tablets 10 mm in diameter. The physical mixture was put into a die and compressed at 124.8 MPa with a flat-faced punch (model Clean Press Correct 12 HUK, Kikusui Co., Ltd., Japan). These were used for measurement of release from the whole surface of tablet and are abbreviated as T 3 , T 5 , and T 10 based on the amount of the wax matrix tablet. Preparation of Wax Matrix Tablets for Release from Single FlatFaced SurfaceThe wax matrix tablet of 0.50 g (T 5 ) was placed at the center of a die of 16 mm and an appropriate amount of HCO powder was added. Then the content was compressed at 62.5 MPa for measurement of release from the single flat-faced surface of tablets. These tablet are abbreviated as F 10 based on the release surface and tablet diameter. 3)Preparation of Wax Matrix Tablets for Release from Curved Side Surface Using the physical mixture of 0.50 g and an appropriate amount of HCO powder, three-layered tablets 10 mm in diameter were prepared with compression force of 124.8 MPa for measurement of release from the curved side surface of wax matrix tablets. The tablets are abbreviated as C 10 based on the release surface and tablet diameter....

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

“…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.…”

“…The released amount was determined by the absorbance at 290 nm. 1) In the release test, the sample was enclosed in a mesh-type sinker to prevent it from floating.…”

“…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.…”

“…Applicability of the square-root time law equation was examined by using the ratio of re- Using the penetration coefficient P (ϭD(e/t)), Eq. 1 was expressed as 1,5) :…”

“…1) So the Higuchi equation should be corrected by using the released amount. The modified Higuchi equation was named as the H-my equation.…”