Dielectric relaxation studies and dissolution behavior of amorphous verapamil hydrochloride.

Verapamil hydrochloride (VH) is a very popular calcium channel blocker. Solubility of its crystalline form in the blood reaches only 10-20%. Thus, it seems to be very important to improve its bioavailability. In this article, we show that the preparation of the amorphous form of VH enhance its dissolution rate. In addition we performed dielectric measurements to describe molecular dynamics of this active pharmaceutical ingredient (API). Since examined sample is typical ionically conducting material, to gain information about structural relaxation we employed the dielectric modulus formalism. The temperature dependence of the structural relaxation time can be described over the entire measured range by a single Vogel-Fulcher-Tamman (VFT) equation. From the VFT fits the glass transition temperature was estimated as T(g) = 320.1 K. Below glass transition temperature one clearly visible secondary relaxation, with activation energy E(a) = 37.8 kJ/mol, was reported. Deviations of experimental data from KWW fits on high-frequency flank of alpha-peak indicate the presence of an excess wing in tested sample. Based on Kia Ngai's coupling model we identified the excess wing as true Johari-Goldstein process.

[1]  M Paluch,et al.  Classification of secondary relaxation in glass-formers based on dynamic properties. , 2004, The Journal of chemical physics.

[2]  P. Madden,et al.  Conductivity-viscosity-structure: unpicking the relationship in an ionic liquid. , 2007, The journal of physical chemistry. B.

[3]  N. Rahman,et al.  Spectrophotometric method for the determination of verapamil hydrochloride in pharmaceutical formulations using N-bromosuccinimide as oxidant. , 2004, Farmaco.

[4]  John T. Fourkas,et al.  Supercooled liquids : advances and novel applications , 1997 .

[5]  A. Bansal,et al.  Physical stability and solubility advantage from amorphous celecoxib: the role of thermodynamic quantities and molecular mobility. , 2004, Molecular pharmaceutics.

[6]  H. Vogel,et al.  Das Temperaturabhangigkeitsgesetz der Viskositat von Flussigkeiten , 1921 .

[7]  P. Royall,et al.  The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems. , 1999, International journal of pharmaceutics.

[8]  R. Shanker,et al.  Dielectric relaxation and crystallization of ultraviscous melt and glassy states of aspirin, ibuprofen, progesterone, and quinidine. , 2007, Journal of pharmaceutical sciences.

[9]  S. Yamamura,et al.  Glassy state of pharmaceuticals. II. Bioinequivalence of glassy and crystalline indomethacin. , 1987, Chemical & pharmaceutical bulletin.

[10]  George Zografi,et al.  The Molecular Mobility of Supercooled Amorphous Indomethacin as a Function of Temperature and Relative Humidity , 1998, Pharmaceutical Research.

[11]  M. Hanaya,et al.  Microscopic observation of a peculiar crystallization in the glass transition region and β-process as potentially controlling the growth rate in triphenylethylene , 1999 .

[12]  Bruno C. Hancock,et al.  Molecular Mobility of Amorphous Pharmaceutical Solids Below Their Glass Transition Temperatures , 1995, Pharmaceutical Research.

[13]  K. L. Ngai,et al.  An extended coupling model description of the evolution of dynamics with time in supercooled liquids and ionic conductors , 2003 .

[14]  R. Forbes,et al.  The use of gravimetry for the study of the effect of additives on the moisture-induced recrystallisation of amorphous lactose , 1998 .

[15]  P. Di Martino,et al.  Molecular mobility of the paracetamol amorphous form. , 2000, Chemical & pharmaceutical bulletin.

[16]  Bruno C. Hancock,et al.  Interpretation of relaxation time constants for amorphous pharmaceutical systems. , 2000, Journal of pharmaceutical sciences.

[17]  C. Angell,et al.  Formation of Glasses from Liquids and Biopolymers , 1995, Science.

[18]  K L Ngai,et al.  Similarity of relaxation in supercooled liquids and interacting arrays of oscillators. , 1999, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[19]  Graham Williams,et al.  Non-symmetrical dielectric relaxation behaviour arising from a simple empirical decay function , 1970 .

[20]  Y Aso,et al.  Relationship between the crystallization rates of amorphous nifedipine, phenobarbital, and flopropione, and their molecular mobility as measured by their enthalpy relaxation and (1)H NMR relaxation times. , 2000, Journal of pharmaceutical sciences.

[21]  N. Lambov,et al.  Study of Verapamil hydrochloride release from compressed hydrophilic Polyox-Wsr tablets. , 1999, International journal of pharmaceutics.

[22]  T. Arita,et al.  Dissolution behavior and bioavailability of phenytoin from a ground mixture with microcrystalline cellulose. , 1976, Journal of pharmaceutical sciences.

[23]  T. Nagai,et al.  Stability and several physical properties of amorphous and crystalline form of indomethacin. , 1980, Chemical & pharmaceutical bulletin.

[24]  Ravi M Shanker,et al.  Calorimetric relaxation in pharmaceutical molecular glasses and its utility in understanding their stability against crystallization. , 2008, The journal of physical chemistry. B.

[25]  Bernhard Heintz,et al.  Clinical Pharmacokinetics of Vasodilators , 1998, Clinical pharmacokinetics.

[26]  Excess wing in the dielectric loss of glass formers: A johari-goldstein beta relaxation? , 2000, Physical review letters.

[27]  K. Kamiński,et al.  Dielectric relaxation study on tramadol monohydrate and its hydrochloride salt. , 2010, Journal of pharmaceutical sciences.

[28]  L. Carpentier,et al.  Dynamics of the Amorphous and Crystalline α-, γ-Phases of Indomethacin , 2006 .

[29]  H. Wagner,et al.  The dielectric modulus: relaxation versus retardation , 1998 .

[30]  G. P. Johari,et al.  Viscous Liquids and the Glass Transition. III. Secondary Relaxations in Aliphatic Alcohols and Other Nonrigid Molecules , 1971 .

[31]  Chandan Bhugra,et al.  Role of thermodynamic, molecular, and kinetic factors in crystallization from the amorphous state. , 2008, Journal of pharmaceutical sciences.

[32]  M. Eichelbaum,et al.  Pharmacokinetics of (+)-, (-)- and (+/-)-verapamil after intravenous administration. , 1984, British journal of clinical pharmacology.

[33]  B. Bagchi,et al.  Decoupling of tracer diffusion from viscosity in a supercooled liquid near the glass transition , 1997 .

[34]  G L Amidon,et al.  Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data: verapamil hydrochloride, propranolol hydrochloride, and atenolol. , 2004, Journal of pharmaceutical sciences.

[35]  B. Makower,et al.  Sugar Crystallization, Equilibrium Moisture Content and Crystallization of Amorphous Sucrose and Glucose , 1956 .

[36]  B. Perissutti,et al.  Controlled release of verapamil hydrochloride from waxy microparticles prepared by spray congealing. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[37]  A. Bansal,et al.  Devitrification of amorphous celecoxib , 2005, AAPS PharmSciTech.

[38]  Robert Simha,et al.  The glass transition and the nature of the glassy state , 1976 .

[39]  Madalena Dionísio,et al.  Molecular motions in amorphous ibuprofen as studied by broadband dielectric spectroscopy. , 2008, The journal of physical chemistry. B.

[40]  G. Zografi,et al.  Crystal nucleation and growth of indomethacin polymorphs from the amorphous state , 2000 .

[41]  A. Rajabi-Siahboomi,et al.  Investigation of the polymorphic transformations from glassy nifedipine , 2003 .

[42]  Ravi M Shanker,et al.  Dielectric studies of molecular motions in amorphous solid and ultraviscous acetaminophen. , 2005, Journal of pharmaceutical sciences.

[43]  M. Hanaya,et al.  β-Molecular Rearrangement Process, But Not an α-Process, as Governing the Homogeneous Crystal-Nucleation Rate in a Supercooled Liquid , 1996 .

[44]  M. Descamps,et al.  Plastic and glassy crystal states of caffeine. , 2005, The journal of physical chemistry. B.

[45]  Bruno C. Hancock,et al.  Crystallization of indomethacin from the amorphous state below and above its glass transition temperature. , 1994, Journal of pharmaceutical sciences.

[46]  Deliang Zhou,et al.  Thermodynamics, molecular mobility and crystallization kinetics of amorphous griseofulvin. , 2008, Molecular pharmaceutics.

[47]  M. Paluch,et al.  Decoupling of the dc conductivity and (α-) structural relaxation time in a fragile glass-forming liquid under high pressure , 2002 .

[48]  C. Lacabanne,et al.  Dielectric study of the molecular mobility and the isothermal crystallization kinetics of an amorphous pharmaceutical drug substance. , 2004, Journal of pharmaceutical sciences.

[49]  M. Oguni,et al.  Generation and extinction of a crystal nucleus below the glass transition temperature , 1997 .

[50]  C. Rustichelli,et al.  Properties of the racemic species of verapamil hydrochloride and gallopamil hydrochloride. , 1999, International journal of pharmaceutics.

[51]  M. Hanaya,et al.  Numerical and morphological approach to the mechanism of homogeneous-nucleation-based crystallization in o-terphenyl , 1998 .

[52]  W. Sawicki Pharmacokinetics of verapamil and norverapamil from controlled release floating pellets in humans. , 2002, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[53]  K. Ngai Correlation between the secondary β-relaxation time at Tg and the Kohlrausch exponent of the primary α-relaxation , 1998 .

[54]  M. Eichelbaum,et al.  Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of L- and D-verapamil examined with a stable isotope technique. , 1984, British journal of clinical pharmacology.

[55]  A. Rajabi-Siahboomi,et al.  Application of percolation theory in the study of an extended release Verapamil hydrochloride formulation. , 2008, International journal of pharmaceutics.

[56]  G. Fulcher,et al.  ANALYSIS OF RECENT MEASUREMENTS OF THE VISCOSITY OF GLASSES , 1925 .