.
　　　　　　　

　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　in preparation 　　　　Jan. '012

　　　PAGE for PUBLICATION / FIELD [JPN] [ENG]
　　　PAGE for COLLABORATION [JPN] [ENG]

CONTENTS of MEMORANDUM s

§１.　Release of Drug from or through a Wax Matrix System

　　　I. Basic Release Properties of the Wax Matrix System
　　　II. Basic Properties of Release from or through the Wax Matrix Layer
　　　III. Basic Properties of Release through the Wax Matrix Layer
　　　IV. Genaralized Expression of the Release Process for a Reservoir Device Tablet
　　　V. Applicability of the Square-Root Law Equation for Release from a Wax Matrix Tablet
　　　VI. Analysis and Prediction of the Entire Release Process of the Wax Matrix Tablet

§２.　Dissolution of Solid Dosage Form

　　　I. Dissolution and Simulation Curves for Log-Normal Particle-Size-Distributed Model System
　　　II. Equations for the Dissolution of Nondisintegrating Tablet under the Sink Condition
　　　III. Equations for the Dissolution of a Nondisintegrating Single Component Tablet under a Nonsink Condition
　　　IV. Equation for the Non-sink Dissolution of a Monodisperse System
　　　V. New Form Equations for the Non-sink Dissolution of a Monodisperse System
　　　VI. Dissolution of Nondisintegrating Single Component Tables under Non-sink Condition
　　　VII. Effect of Shape on the Dissolution of Nondisintegrating Single Component Tablet under Non-sink Condition

§３.　Changes of Surface Area in the Dissolution Process of Crystalline Substances

　　　I. Changes of Surface Area in the Dissolution Process of Crystalline Substances 　
　　　II. Dissolution and Simulation Curves for Mixed Systems of Sieved Particles 　
　　　III. Dissolution and Simulation curves for Symmetrical Particle-Size Distributed Model Systems 　 　
　　　IV. Dissolution and Simulation Curves Estimated from Changes of Surface Area and Cube Root Law 　
　　　V. Dissolution and Simulation Curves for Log-Normal Particle-Size-Distributed Model Systems 　
　　　VI. Simulation of Dissolution of Crystalline Particle 　
　　　VII. Simulation of Dissolution of Crystalline Particle. II. 　

§４.　Physico-Chemical Properties of Glycyrrhiz Acid in Aqueous Media

　　　I. Surface-active Properties and Formation of Molecular Aggregate
　　　II. Effect on Flocculation-Deflocculation Behavior of Suspensions of Sulfathiazole and Graphite
　　　III. Solubilizing Properties for Dyes and Medicinal Substance
　　　IV. Emulsification of Oleic Acid
　　　V. Critical Micelle Concentration of Mixed Solutions of Glycyrrhizin and Sodium Cholate
　　　VI. Determination of Critical Micell Concentration of Sodium Cholate by Iodine Method
　　　VII. Emulsifying Ability of Glycyrrhizin and Stability of the Emulsions

.
　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　contents
　　　　　　　　　　§１.　Release of Drug from or through a Wax Matrix System
Yonezawa Y., Ishida S., Suzuki S., Sunada H..
　　The wax matrix layer was prepared from a physical mixture of wax powder and soluble component
　　　( When a wax matrix system is prepared from melted granules, troublesome factors
　　　　such as coverage and thickness of wax on the soluble component must be considered.)
　　To obtain basic properties, the wax matrix system was prepared from a physical mixture.
　　A modifed Higuchi equation , 　derivation of the H-my equation

I. Basic Release Properties of the Wax Matrix System
　　　　　Chem. Pharm. Bull., 49(11), 1448 - 1451 (2001)
　　　Release from the wax matrix tablet, examination of release direction
　　　The release rate constant obtained as 　g/min^1/2　 changed with the release direction.
　　　The release rate constant obtained as 　g/cm² min^1/2　 was almost the same.
　　　　It was suggested that the relrease property was almost the same and
　　　　the wax matrix structure was uniform independent of release surface or direction in a fixed mixing ratio.

II. Basic Properties of Release from or through the Wax Matrix Layer
　　　　　Chem. Pharm. Bull., 50( 2), 220-224 (2002)
　　　Release from or through the reservoir device wax matrix tablet
　　　Fundamentally, tortuosity can not be expressed by some meaningful factors, and is obtained as an experimental result.
　　　However, the tortuosity should be defined by the matrix structure, and the structure should be concerned with the porosity (ε).
　　　　as a result obtained was　　the totoursity(τ) value is ( nearly ) equal to ε^-2.

III. Basic Properties of Release through the Wax Matrix Layer
　　　　　Chem. Pharm. Bull., 50( 6), 814 - 817 (2002)
　　　Release from the reservoir device wax matrix tablet
　　　　m/S_o = (P/L) C_s t , 　　P= D(ε/τ)
　　　　m : the relreased amount , S_o : the surface area of matrix layer ,　　L : the thickness of matrix layer ，
　　　　P: the penetration coefficient,　D : the diffusion coefficient ,　C_s:the solubility
　　　　τ:the totoursity,　ε : the porpsity in the matrix layer
　　　　the totoursity value is ( nearly ) equal to ε^-2　was ascertained.

IV. Genaralized Expression of the Release Process for a Reservoir Device Tablet
　　　　　Chem. Pharm. Bull., 50( 9), 1219-1222 (2002)
　　　in the case of the totoursity value was ( nearly ) equal to ε^-2 ,
　　　　then the equation could be rewritten by using the porosity
　　　mL/ε³ = D S_o C_s ( t -T_f )
　　　　m : the relreased amount ,　　L : the thickness of matrix layer ， 　　ε : the porpsity in the matrix layer
　　　　S_o: the surface area of matrix layer ,　　D : the diffusion coefficient ,　　T_f ： the lag time

V. Applicability of Square-Root Time Law Equation for Release from a Wax Matrix Tablet
　　　　　Chem. Pharm. Bull., 51( 8), 904 - 908 (2003)
　　　Applicability Higuchi equation was examined.
　　　The estimated applicability was confirmed by the release measurements
　　　　　The remaining amount of drug in the matrix gradually decrease,
　　　　　and is insufficient to satisfy a derivation condition of Higuchi equation.

VI. Analysis and Prediction of the Entire Release Process of the Wax Matrix Tablet
　　　　　Chem. Pharm. Bull., 53( 8), 915 - 918 (2005)
　　　Simulated release amount increase infinitely when the Higuchi equation was applied.
　　　The remaining amount of drug in the matrix gradually decrease,
　　　　and is insufficient to satisfy a derivation condition of Higuchi equation.
　　　Higuchi equation was modified by taking into account of the released amount of drug.
　　　Modifcation of Higuchi's equation, named as the H-my equation 　　　　　　　　　　　　　　 cf
　　　　　For the commom case of εC_s << A in the initial state.
　　　Q(=m/S_o) = { P ( 2A - εC_s) C_s t }^1/2 was simplified as:
　　　Q(=m/S_o) = ( 2PAC_s t )^1/2　　　　　dQ/dt = ( PAC_s / 2t )^1/2 ，　　dm/dt = S_o ( P A C_s / 2 t )^1/2　
　　　　　　the A-value should be corrected by using the released amount (m)
　　　dm/dt = S_o { P(M_o- m) C_s / 2V_mt }^1/2　　　　　　　　　　　　　　　　　　 A = M_o/ V_m ,　M = M_o- m
　　　-dM/dt = S_o ( PMC_s / 2V_mt )^1/2　　　
　　　( M/M_o )^1/2 = 1 - S_o ( PC_s t / 2V_mM_o )^1/2 　　
　　　simulation　　m = M_o[ 1 - { 1 - S_o ( PC_s t / 2V_mM_o )^1/2 }² ]
　　　　the release process simulated by using the H-my equation fitted well with the mesured
　　　　　

.
　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　contents
　　　　　　　　　　§２.　Dissolution of Solid Dosage Form
Yonezawa Y., Shinohara I., Shirakura K., Kawase S., Sasaki M., Wada A., Jinde Y., Otsuka A., Sunada H..
　　　Derivation of several dissolution equations based on Hixson -Crowell equation
　　　　crystal habit
　　　　exact expression of Hixson-Crowell equation　　　　　　　　　　　　　　　　　　　another derivation
　　　　optional initial amount within the solubility; the z-law equation ，the Ln-z equation

I. Dissolution and Simulation Curves for Log-Normal Particle-Size-Distributed Model System
　　　　　Chem. Pharm. Bull., 38(11), 3107- 3111 (1990)
II. Equations for the Dissolution of Nondisintegrating Tablet under the Sink Condition
　　　　　Chem. Pharm. Bull., 39( 3), 769 - 772 (1991)
III. Equations for the Dissolution of a Nondisintegrating Single Component Tablet under a Nonsink Condition
　　　　　Chem. Pharm. Bull., 39(12), 3355 - 3358 (1991)

IV. Equation for the Non-sink Dissolution of a Monodisperse System
　　　　　Chem. Pharm. Bull., 42( 2), 349 - 353 (1994)
　　　Derivation of equation for dissolution with optional amount of crystalline particle within the solubility.
　　　1)　dissolution with any optional initial amount (M_o) within the solubility (M_s), 　M_o/M_s-value is a value other than 1/3
　　　　　the z-law equation： (M/M_o)^z = 1 - z k S_sp C_s t 　， 　z = 1/3 - M_o/M_s
　　　　　　M ( = M_o - m) ： the undissolved amount remainning in the solution
　　　　　　k: the intrinsic dissolution rate constant, 　　S_sp : the specific surface area, 　　　C_s: the solubility

V. New Form Equations for the Non-sink Dissolution of a Monodisperse System
　　　　　Chem. Pharm. Bull., 43( 2), 304 - 310 (1995)
　　　1)　dissolution with the initial amount (Mo) equal to 1/3 of the solubility (Ms), M_o/M_s-value is equal to 1/3
　　　　　the Ln-z equation : ln(M/M_o) = - k S_sp C_s t
　　　　　　M (= M_o - m)： the undissolved amount remainning in the solution
　　　　　　k: the intrinsic dissolution rate constant, 　　S_sp: the specific surface area, 　　　C_s: the solubility
　　　2)　dissolution with any optional initial amount around the solubility was examined
　　　　　the Lg-z equation : (m/M_o)^-1 = 1 + k S_sp C_s t

VI. Dissolution of Nondisintegrating Single Component Tables under Non-sink Condition
　　　　　Chem. Pharm. Bull., 43(11), 1961- 1965 (1995)
　　　　Applicability of the z-law equation and the Ln-z equations for dissolution of tablet were examined

VII. Effect of Shape on the Dissolution of Nondisintegrating Single Component Tablet under Non-sink Condition
　　　　　Chem. Pharm. Bull., 44( 5), 1043 - 1048 (1996)
　　　　Effect of tablet shape was examined using the z-law equation and the Ln-z equation were examined

the z-law equation and the Ln-z equation
1.　The Ln-z equation is useful to determine the intrinsic dissolution rate constant for dissolution of any optional initial amount .
　　　in the region Mo<Ms/3, 　the treated line gradully goes downward from the Ln-z equation line
　　　Mo = Ms/3, 　the treated line fitted well with he Ln-z equation line
　　　in the region Mo>Ms/3, 　the treated line gradully goes upward from the Ln-z equation line
　　　
2.　Once the intrinsic dissolution rate constant of a substance has been determined in advance,
　　the dissolution process of the substance with any optinal initial amount within solubility can be approximately predicted.

3.　Application for dissolution of multi-components tablet
　　the dissolution process could be roughly prospected when the volume fraction was introduced.
　　as the uniform weight of tablet can be used , a hydrodynamic effect can be neglected and
　　　the effect of additives can be evaluated

4.　

.
　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　contents
　　　　§３.　Changes of Surface Area in the Dissolution Process of Crystalline Substances
Yonezawa Y., Yamamoto A., Shinohara I., Otsuka A., Sunada H..
I. Changes of Surface Area in the Dissolution Process of Crystalline Substances 　
　　　　　Chem. Pharm. Bull., 36 (7), 2557 - 2561 (1988)
II. Dissolution and Simulation Curves for Mixed Systems of Sieved Particles 　
　　　　　Chem. Pharm. Bull., 37 (2), 467 - 470 (1989)
III. Dissolution and Simulation curves for Symmetrical Particle-Size Distributed Model Systems 　 　
　　　　　Chem. Pharm. Bull., 37 (5), 1362 - 1365 (1989)
　　　Dissolution of modelized particle-size distribution
　　　　dissolution process and estimation of an apparent particle size to define it

IV. Dissolution and Simulation Curves Estimated from Changes of Surface Area and Cube Root Law 　
　　　　　Chem. Pharm. Bull., 37 (7), 1889 - 1894 (1989)
　　　　Exact expression of Hixson-Crowell equations
　　　　　the Cube root law equation : (M/M_o)^1/3 = 1 - (1/3)k S_sp C_s t
　　　　　the Negative two-third law equation : (M/M_o)^-2/3 = 1+ (2/3)k S_sp C_s t
V. Dissolution and Simulation Curves for Log-Normal Particle-Size-Distributed Model Systems 　
　　　　　Chem. Pharm. Bull., 38 (4), 1024 - 1026 (1990)
　　　Dissolution of a generalized log-normal particle-size-distributied particles
　　　Prediction of a dissolution precess

VI. Simulation of Dissolution of Crystalline Particle 　
　　　　　J. Soc. Powder Tech., 27(9), 621-625 (1990)
VII.Simulation of Dissolution of Crystalline Particle. II. 　
　　　　　J. Soc. Powder Tech., 28(9), 567-571 (1990)

.
　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　contents
　　　　　　　　§４.　Physico-Chemical Properties of Glycyrrhizic Acid in Aqueous Media
Yonezawa Y., Iba K., Tatsumi T, Watanabe J., Sunada H., Otsuka A., Nakagaki M..
1. Surface-active Properties and Formation of Molecular Aggregate
　　　　　YAKUGAKU ZASSHI, 96 (2), 203 - 208 (1976)
2. Effect on Flocculation-Deflocculation Behavior of Suspensions of Sulfathiazole and Graphite
　　　　　J. Pharm. Sci., 67 (2), 151 - 154 (1978)
3. Solubilizing Properties for Dyes and Medicinal Substance
　　　　　YAKUGAKU ZASSHI, 101 (9), 829 - 835 (1981)
4. Emulsification of Oleic Acid
　　　　　YAKUGAKU ZASSHI, 103 (2), 203 - 208 (1983)
　　　Emulsifing ability
　　　Estimation of the emulsified particle size by means of a light absorption method.

5. Critical Micelle Concentration of Mixed Solutions of Glycyrrhizin and Sodium Cholate
　　　　　YAKUGAKU ZASSHI, 103 (10), 1085 - 1090 (1983)
6. Determination of Critical Micelle Concentration of Sodium Cholate by Iodine Method
　　　　　YAKUGAKU ZASSHI, 99 (2), 217 - 219 (1979)
　　　Applicabiliyt of the iodine method

7. Emulsifying Ability of Glycyrrhizin and Stability of the Emulsions
　　　　　J. Jpn. Cosmet. Sci. Soc., 8 (1), 61 - 66 (1984)

to HOME of Yonezawa　 [JPN] 　[ENG]　;　　
to PAGE for COLLABORATION [JPN]　[ENG]　　. PUBLICATION/FIELD [JPN]　[ENG],

E-Mail：yzw@meijo-u.ac.jp
Home of Physical Pharmacy ,
　Labo of Physical Pharmacy ,Faculty , University