Physical stability of pharmaceutical formulations: solid-state characterization of amorphous dispersions

Abstract The acceptable stability of the drug formulations is one of the basic requirements for pharmaceutical development and commercialization. The increasing application of enabling delivery techniques poses even more challenge to the drug physical stability of pharmaceutical formulations. After a brief review of regulatory requirements and recent drug recalls due to physical instability, we discuss the physical stability of the solid-state drug in amorphous dispersions with focus on analytical techniques, amorphous molecular mobility, drug-excipient interaction, and the effect of water.

[1]  George Zografi,et al.  The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state , 1990 .

[2]  Simon Bates,et al.  Characterization of amorphous API:Polymer mixtures using X-ray powder diffraction. , 2008, Journal of pharmaceutical sciences.

[3]  T. Haefele,et al.  Confocal Raman Microscopy in Pharmaceutical Development , 2010 .

[4]  Satyendra Kumar,et al.  Crystalline, liquid crystalline, and isotropic phases of sodium deoxycholate in water. , 2011, Journal of pharmaceutical sciences.

[5]  H. Levine,et al.  The concept of ‘structure’ in amorphous solids from the perspective of the pharmaceutical sciences , 2002 .

[6]  D. Bikiaris,et al.  Combining SEM, TEM, and micro-Raman techniques to differentiate between the amorphous molecular level dispersions and nanodispersions of a poorly water-soluble drug within a polymer matrix. , 2007, International journal of pharmaceutics.

[7]  Patrick J. Marsac,et al.  Estimation of Drug–Polymer Miscibility and Solubility in Amorphous Solid Dispersions Using Experimentally Determined Interaction Parameters , 2008, Pharmaceutical Research.

[8]  Zeren Wang,et al.  Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems. , 2009, Journal of pharmaceutical sciences.

[9]  Jun Huang,et al.  A Quality by Design approach to investigate tablet dissolution shift upon accelerated stability by multivariate methods. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[10]  M. Pikal,et al.  The glass transition and sub-T(g)-relaxation in pharmaceutical powders and dried proteins by thermally stimulated current. , 2009, Journal of pharmaceutical sciences.

[11]  L. S. Taylor,et al.  Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture. , 2009, Molecular pharmaceutics.

[12]  Thomas Rades,et al.  Melt extrusion and spray drying of carbamazepine and dipyridamole with polyvinylpyrrolidone/vinyl acetate copolymers. , 2008, Drug development and industrial pharmacy.

[13]  C. Roberts,et al.  The stability of solid dispersions of felodipine in polyvinylpyrrolidone characterized by nanothermal analysis. , 2011, International journal of pharmaceutics.

[14]  S. Šašiċ,et al.  Raman chemical mapping of low-content active pharmaceutical ingredient formulations. III. Statistically optimized sampling and detection of polymorphic forms in tablets on stability. , 2012, Analytical chemistry.

[15]  Feng Qian,et al.  Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant , 2013, Pharmaceutical development and technology.

[16]  Lian Yu,et al.  Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives , 2012, The AAPS Journal.

[17]  G Zografi,et al.  How does residual water affect the solid-state degradation of drugs in the amorphous state? , 1996, Journal of pharmaceutical sciences.

[18]  Bruno C. Hancock,et al.  Characteristics and significance of the amorphous state in pharmaceutical systems. , 1997, Journal of pharmaceutical sciences.

[19]  S. Itai,et al.  Evaluation of Crystallization Behavior on the Surface of Nifedipine Solid Dispersion Powder Using Inverse Gas Chromatography , 2013, Pharmaceutical Research.

[20]  H. Wikström,et al.  Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture , 2011, AAPS PharmSciTech.

[21]  G. Buckton,et al.  A study of the crystallisation of amorphous salbutamol sulphate using water vapour sorption and near infrared spectroscopy. , 2002, International journal of pharmaceutics.

[22]  C. Telang,et al.  Improved physical stability of amorphous state through acid base interactions. , 2009, Journal of pharmaceutical sciences.

[23]  Lawrence X. Yu,et al.  Crystallinity evaluation of tacrolimus solid dispersions by chemometric analysis. , 2012, International journal of pharmaceutics.

[24]  Thomas Rades,et al.  Relaxation and crystallization of amorphous carbamazepine studied by terahertz pulsed spectroscopy. , 2007, Journal of pharmaceutical sciences.

[25]  J. Authelin,et al.  A Practical Method to Predict Physical Stability of Amorphous Solid Dispersions , 2012, Pharmaceutical Research.

[26]  A. Saha,et al.  Formation of physically stable amorphous phase of ibuprofen by solid state milling with kaolin. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[27]  G. Van den Mooter,et al.  Review: physical chemistry of solid dispersions. , 2009, The Journal of pharmacy and pharmacology.

[28]  J. Tingstad.  PHYSICAL STABILITY TESTING OF PHARMACEUTICALS. , 1964, Journal of pharmaceutical sciences.

[29]  Lynne S Taylor,et al.  Evaluation of amorphous solid dispersion properties using thermal analysis techniques. , 2012, Advanced drug delivery reviews.

[30]  Chandra Vemavarapu,et al.  Use of Surfactants as Plasticizers in Preparing Solid Dispersions of Poorly Soluble API: Stability Testing of Selected Solid Dispersions , 2006, Pharmaceutical Research.

[31]  Karthik Nagapudi,et al.  Manufacture and performance evaluation of a stable amorphous complex of an acidic drug molecule and Neusilin. , 2011, Journal of pharmaceutical sciences.

[32]  S. Ohtake,et al.  Effect of water on the chemical stability of amorphous pharmaceuticals: I. Small molecules. , 2013, Journal of pharmaceutical sciences.

[33]  A. Sakr,et al.  Application of on-line Raman spectroscopy for characterizing relationships between drug hydration state and tablet physical stability. , 2005, International journal of pharmaceutics.

[34]  Bruno C. Hancock,et al.  Disordered drug delivery: destiny, dynamics and the Deborah number , 2002, The Journal of pharmacy and pharmacology.

[35]  L Yu,et al.  Amorphous pharmaceutical solids: preparation, characterization and stabilization. , 2001, Advanced drug delivery reviews.

[36]  Geoff G. Z. Zhang,et al.  Phase transformation considerations during process development and manufacture of solid oral dosage forms. , 2004, Advanced drug delivery reviews.

[37]  Peter Timmins,et al.  Physical stability and recrystallization kinetics of amorphous ibipinabant drug product by fourier transform raman spectroscopy. , 2011, Journal of pharmaceutical sciences.

[38]  R. Tan,et al.  Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy , 2011, Drug development and industrial pharmacy.

[39]  R. Suryanarayanan,et al.  Quantification of Crystallinity in Substantially Amorphous Materials by Synchrotron X-ray Powder Diffractometry , 2005, Pharmaceutical Research.

[40]  George Zografi,et al.  Assessing the performance of amorphous solid dispersions. , 2012, Journal of pharmaceutical sciences.

[41]  Y. Maitani,et al.  Influence of manufacturing factors on physical stability and solubility of solid dispersions containing a low glass transition temperature drug. , 2012, Chemical & pharmaceutical bulletin.

[42]  Jiao Yang,et al.  An improved kinetics approach to describe the physical stability of amorphous solid dispersions. , 2010, International journal of pharmaceutics.

[43]  Jukka Seppälä,et al.  Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine , 2008, Pharmaceutical Research.

[44]  Y. Khimyak,et al.  Amorphous drug-PVP dispersions: application of theoretical, thermal and spectroscopic analytical techniques to the study of a molecule with intermolecular bonds in both the crystalline and pure amorphous state. , 2009, Journal of pharmaceutical sciences.

[45]  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.

[46]  S. Byrn,et al.  Solid-state nuclear magnetic resonance spectroscopy--pharmaceutical applications. , 2003, Journal of pharmaceutical sciences.

[47]  Atsushi Sakurai,et al.  Polymer combination increased both physical stability and oral absorption of solid dispersions containing a low glass transition temperature drug: physicochemical characterization and in vivo study. , 2012, Chemical & pharmaceutical bulletin.

[48]  Yaochun Shen,et al.  Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging. , 2007, Journal of pharmaceutical sciences.

[49]  F. Vogt,et al.  Analysis of amorphous solid dispersions using 2D solid-state NMR and (1)H T(1) relaxation measurements. , 2010, Molecular pharmaceutics.

[50]  T. De Beer,et al.  In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[51]  J. Rantanen,et al.  Atomic Pairwise Distribution Function Analysis of the Amorphous Phase Prepared by Different Manufacturing Routes , 2012, Pharmaceutics.

[52]  M. Ticehurst,et al.  Characterisation of the influence of micronisation on the crystallinity and physical stability of revatropate hydrobromide. , 2000, International journal of pharmaceutics.

[53]  S. Hasegawa,et al.  Investigation of preparation methods on surface/bulk structural relaxation and glass fragility of amorphous solid dispersions. , 2012, International journal of pharmaceutics.

[54]  Emily F. Smith,et al.  Physical stability of ternary solid dispersions of itraconazole in polyethyleneglycol 6000/hydroxypropylmethylcellulose 2910 E5 blends. , 2008, International journal of pharmaceutics.

[55]  S. Brocchini,et al.  Characterization and stability of ternary solid dispersions with PVP and PHPMA. , 2011, International journal of pharmaceutics.

[56]  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.

[57]  Ping Gao,et al.  Enhanced bioavailability of a poorly soluble VR1 antagonist using an amorphous solid dispersion approach: a case study. , 2008, Molecular pharmaceutics.

[58]  Jingjun Huang,et al.  Drug-polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blend. , 2008, Journal of Pharmacy and Science.

[59]  Thomas Rades,et al.  Correlating thermodynamic and kinetic parameters with amorphous stability. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[60]  B. Macdonald,et al.  Package selection for moisture protection for solid, oral drug products. , 2010, Journal of pharmaceutical sciences.

[61]  George Z. Papageorgiou,et al.  Characterization of the distribution, polymorphism, and stability of nimodipine in its solid dispersions in polyethylene glycol by micro-Raman spectroscopy and powder x-ray diffraction , 2007, The AAPS Journal.

[62]  H. Gill,et al.  The importance of surface energetics of powders for drug delivery and the establishment of inverse gas chromatography. , 2007, Advanced drug delivery reviews.

[63]  I. Ivanisevic,et al.  Uses of X-Ray Powder Diffraction In the Pharmaceutical Industry , 2010 .

[64]  Lynne S Taylor,et al.  Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. , 2006, Journal of pharmaceutical sciences.

[65]  H. Brittain,et al.  Spectral methods for the characterization of polymorphs and solvates. , 1997, Journal of pharmaceutical sciences.

[66]  Yushen Guo,et al.  An Overview of Physical Stability of Pharmaceuticals , 2010 .

[67]  R. Suryanarayanan,et al.  Molecular Motions in Sucrose-PVP and Sucrose-Sorbitol Dispersions: I. Implications of Global and Local Mobility on Stability , 2011, Pharmaceutical Research.

[68]  A. Sakr,et al.  Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity. , 2005, International journal of pharmaceutics.

[69]  I. Ivanisevic.  Physical stability studies of miscible amorphous solid dispersions. , 2010, Journal of pharmaceutical sciences.

[70]  Deliang Zhou,et al.  Physical stability of amorphous pharmaceuticals: Importance of configurational thermodynamic quantities and molecular mobility. , 2002, Journal of pharmaceutical sciences.

[71]  S. Yoshioka,et al.  Feasibility of 19F-NMR for assessing the molecular mobility of flufenamic acid in solid dispersions. , 2009, Chemical & pharmaceutical bulletin.