Sticking and Picking in Pharmaceutical Tablet Compression: An IQ Consortium Review.

Sticking and picking during tablet manufacture has received increasing interest recently, as it causes tablet defects, downtime in manufacturing, and yield losses. The capricious nature of the problem means that it can appear at any stage of the development cycle, even when it has been deemed as low risk by models, tests, and previous experience. In many cases, the problem manifests when transferring the process from one manufacturing site to another. Site transfers are more common now than in previous times because of the multinational nature of drug product manufacturing and the need for redundancy in manufacturing networks. Sticking is a multifactorial problem, so one single "fix" is unlikely to solve it completely, and "solutions" addressing one problem may exacerbate another. A broad-based strategy involving the API, formulation, tablet tooling, and the manufacturing process is the most likely approach to provide a robust and lasting solution. When faced with a sticking problem for the first or subsequent time, the formulator should address, in a structured way, a range of possible causes and remedies. In this article, we focus on current research and practice; on some of the common causes of sticking; mitigation and resolution strategies and solutions; and possible future directions in research.

[1]  Marcial Gonzalez,et al.  A nonlocal contact formulation for confined granular systems , 2011, 1107.4607.

[2]  M. Sherry Ku,et al.  Use of the Biopharmaceutical Classification System in Early Drug Development , 2008, The AAPS Journal.

[3]  Fernando Muzzio,et al.  Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC). , 2016, International journal of pharmaceutics.

[4]  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.

[5]  Krystan Reed,et al.  Tablet sticking: Using a ‘compression toolbox’ to assess multiple tooling coatings options , 2015 .

[6]  Naveen K. Bejugam,et al.  Tablet formulation of an active pharmaceutical ingredient with a sticking and filming problem: direct compression and dry granulation evaluations , 2015, Drug development and industrial pharmacy.

[7]  C. Leopold,et al.  Novel aspects on the direct compaction of ibuprofen with special focus on sticking , 2017 .

[8]  A. Narang,et al.  Decoupling the contribution of dispersive and acid-base components of surface energy on the cohesion of pharmaceutical powders. , 2014, International journal of pharmaceutics.

[9]  Michael Leane,et al.  A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms , 2015, Pharmaceutical development and technology.

[10]  Wenli Zhang,et al.  Novel application method of talcum powder to prevent sticking tendency and modify release of esomeprazole magnesium enteric-coated pellets , 2015, Pharmaceutical development and technology.

[11]  V. Balaram Recent advances in the determination of elemental impurities in pharmaceuticals – Status, challenges and moving frontiers , 2016 .

[12]  Ajit S. Narang,et al.  Molecular Basis of Crystal Morphology-Dependent Adhesion Behavior of Mefenamic Acid During Tableting , 2013, Pharmaceutical Research.

[13]  Toshiyuki Niwa,et al.  Influence of compression pressure and velocity on tablet sticking. , 2010, Chemical & pharmaceutical bulletin.

[14]  Satu Lakio,et al.  Single-step Coprocessing of Cohesive Powder via Mechanical Dry Coating for Direct Tablet Compression. , 2017, Journal of pharmaceutical sciences.

[15]  Joseph Kushner Utilizing quantitative certificate of analysis data to assess the amount of excipient lot-to-lot variability sampled during drug product development , 2013, Pharmaceutical development and technology.

[16]  Mike Tobyn,et al.  Multivariate analysis in the pharmaceutical industry: enabling process understanding and improvement in the PAT and QbD era , 2015, Pharmaceutical development and technology.

[17]  Marianthi Ierapetritou,et al.  Real time monitoring of powder blend bulk density for coupled feed-forward/feed-back control of a continuous direct compaction tablet manufacturing process. , 2015, International journal of pharmaceutics.

[18]  P. Schmidt,et al.  Influence of Compacted Hydrophobic and Hydrophilic Colloidal Silicon Dioxide on Tableting Properties of Pharmaceutical Excipients , 2005, Drug development and industrial pharmacy.

[19]  Changquan Calvin Sun,et al.  Mini review: Mechanisms to the loss of tabletability by dry granulation. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[20]  Caly Chien,et al.  Effect of food on abiraterone pharmacokinetics: a review , 2017 .

[21]  Preetanshu Pandey,et al.  A quality by design approach to scale-up of high-shear wet granulation process , 2016, Drug development and industrial pharmacy.

[22]  A Sabir,et al.  Formulation and process optimization to eliminate picking from market image tablets. , 2001, International journal of pharmaceutics.

[23]  Vivek S. Dave,et al.  Excipient variability and its impact on dosage form functionality. , 2015, Journal of pharmaceutical sciences.

[24]  K. Morris,et al.  Modeling of adhesion in tablet compression. II. Compaction studies using a compaction simulator and an instrumented tablet press. , 2004, Journal of pharmaceutical sciences.

[25]  Gudrun A Fridgeirsdottir,et al.  Support Tools in Formulation Development for Poorly Soluble Drugs. , 2016, Journal of pharmaceutical sciences.

[26]  S. Byrn,et al.  Stability of pharmaceutical salts in solid oral dosage forms , 2017, Drug development and industrial pharmacy.

[27]  P. Schmidt,et al.  Investigation of compacted hydrophilic and hydrophobic colloidal silicon dioxides as glidants for pharmaceutical excipients , 2004 .

[28]  Maunu Toiviainen,et al.  Continuous manufacturing of tablets with PROMIS-line - Introduction and case studies from continuous feeding, blending and tableting. , 2016, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[29]  S. Srčič,et al.  Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients , 2016, Acta pharmaceutica.

[30]  John N. Staniforth Use of Hydrogenated Vegetable Oil as a Tablet Lubricant , 1987 .

[31]  C. Shang,et al.  Modelling of the break force of tablets under diametrical compression. , 2013, International journal of pharmaceutics.

[32]  Ben Forbes,et al.  The influence of electrostatic properties on the punch sticking propensity of pharmaceutical blends , 2017 .

[33]  H. Mangal,et al.  Roll compaction/dry granulation: Suitability of different binders. , 2016, International journal of pharmaceutics.

[34]  Fernando J. Muzzio,et al.  Continuous Powder Mixing , 2015 .

[35]  Fernando J. Muzzio,et al.  Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes , 2016 .

[36]  P. Kleinebudde,et al.  Effect of roll-compaction and milling conditions on granules and tablet properties. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[37]  S. Schumann,et al.  The effects of chromium nitride ion bombardment treatment of tablet tooling on tablet adherence , 1992 .

[38]  John F. Gamble,et al.  Understanding the effect of API changes in pharmaceutical processing , 2017 .

[39]  John N. Staniforth,et al.  Aspects of Pharmaceutical Tribology , 1989 .

[40]  D. F. Steele,et al.  The mechanical properties of compacts of microcrystalline cellulose and silicified microcrystalline cellulose. , 2000, International journal of pharmaceutics.

[41]  A. Narang,et al.  Decoupling the Contribution of Surface Energy and Surface Area on the Cohesion of Pharmaceutical Powders , 2014, Pharmaceutical Research.

[42]  Divyakant Desai,et al.  Lubrication in tablet formulations. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[43]  Clive J Roberts,et al.  Characterising the surface adhesive behavior of tablet tooling components by atomic force microscopy , 2011, Drug development and industrial pharmacy.

[44]  Changquan Calvin Sun,et al.  Mechanism and Kinetics of Punch Sticking of Pharmaceuticals. , 2017, Journal of pharmaceutical sciences.

[45]  C. Sun,et al.  Modulating Sticking Propensity of Pharmaceuticals Through Excipient Selection in a Direct Compression Tablet Formulation , 2018, Pharmaceutical Research.

[46]  J. Kushner,et al.  Scale-up model describing the impact of lubrication on tablet tensile strength. , 2010, International journal of pharmaceutics.

[47]  P. Kleinebudde,et al.  Roll compaction/dry granulation: Comparison between roll mill and oscillating granulator in dry granulation , 2012, Pharmaceutical development and technology.

[48]  Bo Lang,et al.  Hot-melt extrusion – basic principles and pharmaceutical applications , 2014, Drug development and industrial pharmacy.

[49]  Richard L. Schild,et al.  Application of imaging based tools for the characterisation of hollow spray dried amorphous dispersion particles. , 2014, International journal of pharmaceutics.

[50]  Bozena Michniak-Kohn,et al.  Mixing order of glidant and lubricant--influence on powder and tablet properties. , 2011, International journal of pharmaceutics.

[51]  Matthew Roberts,et al.  Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations , 2003, The Journal of pharmacy and pharmacology.

[52]  C. Ghoroi,et al.  Influence of particle properties on powder bulk behaviour and processability. , 2017, International journal of pharmaceutics.

[53]  Hisakazu Sunada,et al.  Effect of water content on sticking during compression , 1997 .

[54]  R. E. Gordon,et al.  Utilization of differential scanning calorimetry in the compatibility screening of ibuprofen with the stearate lubricants and construction of phase diagrams , 1984 .

[55]  I. Larson,et al.  The role of physico-chemical and bulk characteristics of co-spray dried L-leucine and polyvinylpyrrolidone on glidant and binder properties in interactive mixtures. , 2015, International journal of pharmaceutics.

[56]  M. S. Ku,et al.  A biopharmaceutical classification-based Right-First-Time formulation approach to reduce human pharmacokinetic variability and project cycle time from First-In-Human to clinical Proof-Of-Concept , 2012, Pharmaceutical development and technology.

[57]  K. El-Say,et al.  COMPARATIVE STUDY AMONG DIFFERENT TECHNIQUES TO IMPROVE THE PHYSICAL AND TECHNICAL PROPERTIES PREVAILING TO COMPRESSION OF POORLY FLOWING AND HIGHLY COHESIVE DRUG , 2010 .

[58]  David S. Jones,et al.  Hot melt extrusion – processing solid solutions? , 2014, The Journal of pharmacy and pharmacology.

[59]  R. Greenwood,et al.  Application of external lubrication during the roller compaction of adhesive pharmaceutical formulations , 2013, Pharmaceutical development and technology.

[60]  W. Stagner,et al.  Application of multivariate methods to evaluate the functionality of bovine- and vegetable-derived magnesium stearate. , 2014, Journal of pharmaceutical sciences.

[61]  William Early,et al.  An evaluation of process parameters to improve coating efficiency of an active tablet film-coating process. , 2012, International journal of pharmaceutics.

[62]  P. Kleinebudde,et al.  Critical evaluation of root causes of the reduced compactability after roll compaction/dry granulation. , 2015, Journal of pharmaceutical sciences.

[63]  R C Rowe,et al.  Process control and scale-up of pharmaceutical wet granulation processes: a review. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[64]  J. Strong,et al.  Scanning Electron Microscope Observations of Powder Sticking on Punches during a Limited Number (N < 5) of Compactions of Acetylsalicylic Acid , 2017, Pharmaceutical Research.

[65]  D. F. Steele,et al.  The Use of a Modified Resin for Studying the Internal Structure of Microcrystalline Cellulose Particles , 1998 .

[66]  M. H. Rubinstein,et al.  Structure-lubricity evaluation of magnesium stearate , 1988 .

[67]  Stephen Edge,et al.  Adsorption of an Amine Drug onto Microcrystalline Cellulose and Silicified Microcrystalline Cellulose Samples , 2003, Drug development and industrial pharmacy.

[68]  K. Hapgood,et al.  Investigation of the potential for direct compaction of a fine ibuprofen powder dry-coated with magnesium stearate , 2015, Drug development and industrial pharmacy.

[69]  D. Lapham,et al.  Gas adsorption on commercial magnesium stearate: Effects of degassing conditions on nitrogen BET surface area and isotherm characteristics. , 2017, International journal of pharmaceutics.

[70]  T. Shinbrot,et al.  Use of a static eliminator to improve powder flow. , 2009, International journal of pharmaceutics.

[71]  K. Terada,et al.  Imprinting on empty hard gelatin capsule shells containing titanium dioxide by application of the UV laser printing technique , 2014, Drug development and industrial pharmacy.

[72]  J. Mitchell,et al.  Effects of crystal habit on the sticking propensity of ibuprofen-A case study. , 2017, International journal of pharmaceutics.

[73]  Ahmad Aljaberi,et al.  Functional performance of silicified microcrystalline cellulose versus microcrystalline cellulose: a case study , 2009, Drug development and industrial pharmacy.

[74]  C Vervaet,et al.  Continuous direct compression as manufacturing platform for sustained release tablets. , 2017, International journal of pharmaceutics.

[75]  P. Schmidt,et al.  Investigation of the glidant properties of compacted colloidal silicon dioxide by angle of repose and X-ray photoelectron spectroscopy. , 2006, European journal of pharmaceutics and biopharmaceutics.

[76]  Hong Wen,et al.  Systematical approach of formulation and process development using roller compaction. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[77]  J. Polli,et al.  Impact of Biopharmaceutics Classification System-based biowaivers. , 2010, Molecular pharmaceutics.

[78]  Troy Shinbrot,et al.  An observed correlation between flow and electrical properties of pharmaceutical blends , 2009 .

[79]  Dolapo Olusanmi,et al.  Measuring the sticking of mefenamic acid powders on stainless steel surface. , 2015, International journal of pharmaceutics.

[80]  Changquan Calvin Sun Dependence of ejection force on tableting speed—A compaction simulation study , 2015 .

[81]  G. Finet,et al.  Influence of the morphogranulometry and hydrophobicity of talc on its antisticking power in the production of tablets. , 2005, International journal of pharmaceutics.

[82]  T. Laich,et al.  Untersuchung schmiermittelabhängiger Kenngrössen an einer Exzentertablettenpresse ausgerüstet mit einem externen Schmiersystem , 1998 .

[83]  C. Leopold,et al.  A novel technique for the visualization of tablet punch surfaces: Characterization of surface modification, wear and sticking. , 2017, International journal of pharmaceutics.

[84]  H. Takeuchi,et al.  Prediction of effects of punch shapes on tableting failure by using a multi-functional single-punch tablet press , 2017, Asian journal of pharmaceutical sciences.

[85]  Erin M. Hansuld,et al.  A review of monitoring methods for pharmaceutical wet granulation. , 2014, International journal of pharmaceutics.

[86]  Srimanta Sarkar,et al.  Influence of the Punch Head Design on the Physical Quality of Tablets Produced in a Rotary Press. , 2017, Journal of pharmaceutical sciences.

[87]  G. P. McCarthy,et al.  Physicochemical comparison between microcrystalline cellulose and silicified microcrystalline cellulose , 1998 .

[88]  Christel A. S. Bergström,et al.  The Need for Restructuring the Disordered Science of Amorphous Drug Formulations , 2017, Pharmaceutical Research.

[89]  Matthew Roberts,et al.  Effect of punch tip geometry and embossment on the punch tip adherence of a model ibuprofen formulation , 2004, The Journal of pharmacy and pharmacology.

[90]  A. Narang,et al.  Effect of crystal habits on the surface energy and cohesion of crystalline powders. , 2014, International journal of pharmaceutics.

[91]  John F. Gamble,et al.  Monitoring process induced attrition of drug substance particles within formulated blends. , 2014, International journal of pharmaceutics.

[92]  Fernando J. Muzzio,et al.  Characterizing continuous powder mixing using residence time distribution , 2011 .

[93]  P. Schmidt,et al.  Mechanism of glidants: investigation of the effect of different colloidal silicon dioxide types on powder flow by atomic force and scanning electron microscopy. , 2004, Journal of pharmaceutical sciences.

[94]  Koichi Wada,et al.  Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. , 2011, International journal of pharmaceutics.

[95]  A. Kara,et al.  An application for zirconia as a pharmaceutical die set , 2004 .

[96]  Changquan Calvin Sun,et al.  Systematic evaluation of common lubricants for optimal use in tablet formulation , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[97]  C. Sun,et al.  Ribbon thickness influences fine generation during dry granulation. , 2017, International journal of pharmaceutics.

[98]  Alexander Krok,et al.  Numerical investigation into the influence of the punch shape on the mechanical behavior of pharmaceutical powders during compaction , 2014 .

[99]  T. Shinbrot,et al.  AFM study of hydrophilicity on acetaminophen crystals. , 2012, International journal of pharmaceutics.

[100]  P. Kleinebudde,et al.  Evaluation of lubrication methods: How to generate a comparable lubrication for dry granules and powder material for tableting processes , 2014 .

[101]  P. Schmidt,et al.  Preparation and optimization of l-leucine as lubricant for effervescent tablet formulations , 1995 .

[102]  Manabu Ito,et al.  Development of new shaped punch to predict scale-up issue in tableting process. , 2014, Journal of pharmaceutical sciences.

[103]  H. Ishihara,et al.  Studies on the mechanism of printing film-coated tablets containing titanium dioxide in the film by using UV laser irradiation , 2009, Drug development and industrial pharmacy.

[104]  P. Schmidt,et al.  Optimization of an effervescent tablet formulation containing spray dried L-leucine and polyethylene glycol 6000 as lubricants using a central composite design. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[105]  I. Larson,et al.  Effect of the deformability of guest particles on the tensile strength of tablets from interactive mixtures. , 2016, International journal of pharmaceutics.

[106]  Changquan Calvin Sun Materials science tetrahedron--a useful tool for pharmaceutical research and development. , 2009, Journal of pharmaceutical sciences.

[107]  G. Bolhuis,et al.  BONDING CHARACTERISTICS BY SCANNING ELECTRON-MICROSCOPY OF POWDERS MIXED WITH MAGNESIUM STEARATE , 1978 .

[108]  Changquan Calvin Sun,et al.  Powder properties and compaction parameters that influence punch sticking propensity of pharmaceuticals. , 2017, International journal of pharmaceutics.

[109]  M. Ghadiri,et al.  Tribo-electrification of active pharmaceutical ingredients and excipients , 2012 .

[111]  M. Davies,et al.  Scanning probe microscopy in the field of drug delivery. , 2007, Advanced drug delivery reviews.

[112]  T De Beer,et al.  Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation. , 2017, International journal of pharmaceutics.

[113]  I. Larson,et al.  Relationship between surface concentration of L-leucine and bulk powder properties in spray dried formulations. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[114]  M. Rutland,et al.  AFM Colloidal Probe Measurements Implicate Capillary Condensation in Punch-Particle Surface Interactions during Tableting. , 2017, Langmuir : the ACS journal of surfaces and colloids.

[115]  M. H. Rubinstein,et al.  Tablet lubricants I. Theory and modes of action , 1981 .

[116]  C. Leopold,et al.  Evaluation of the suitability of various lubricants for direct compaction of sorbitol tablet formulations. , 2013 .

[117]  J. Kushner,et al.  A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes. , 2014, Journal of pharmaceutical sciences.

[118]  P. Leterme,et al.  Relation between structural characteristics of talc and its properties as an antisticking agent in the production of tablets. , 2003, European Journal of Pharmaceutical Sciences.

[119]  Mohammad Hassan Khalid,et al.  Effect of roll compaction on granule size distribution of microcrystalline cellulose–mannitol mixtures: computational intelligence modeling and parametric analysis , 2017, Drug design, development and therapy.

[120]  Niklas Sandler,et al.  Pneumatic dry granulation: potential to improve roller compaction technology in drug manufacture , 2011, Expert opinion on drug delivery.

[121]  Thomas De Beer,et al.  Process Analytical Technology for continuous manufacturing of solid-dosage forms , 2015 .

[122]  John F. Gamble,et al.  Monitoring and end-point prediction of a small scale wet granulation process using acoustic emission , 2009, Pharmaceutical development and technology.

[123]  T Flanagan,et al.  Biopharmaceutical aspects and implications of excipient variability in drug product performance , 2017, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[124]  R. Kelly,et al.  Salt disproportionation: A material science perspective. , 2017, International journal of pharmaceutics.

[125]  I. C. Sinka,et al.  Break force and tensile strength relationships for curved faced tablets subject to diametrical compression. , 2013, International journal of pharmaceutics.

[126]  Gordon L. Amidon,et al.  Prediction of Solubility and Permeability Class Membership: Provisional BCS Classification of the World’s Top Oral Drugs , 2009, The AAPS Journal.

[127]  Ratnesh Lal,et al.  Multidimensional atomic force microscopy for drug discovery: a versatile tool for defining targets, designing therapeutics and monitoring their efficacy. , 2010, Life sciences.

[128]  M Krumme,et al.  The influence of engravings on the sticking of tablets. Investigations with an instrumented upper punch. , 1999, Pharmaceutical development and technology.

[129]  John W. Jones,et al.  Determination of process variables affecting drug particle attrition within multi-component blends during powder feed transmission , 2017, Pharmaceutical development and technology.

[130]  P. Leterme,et al.  Study of talcs as antisticking agents in the production of tablets. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[131]  Sandeep Kumar,et al.  Application of a hot-melt granulation process to enhance fenofibrate solid dose manufacturing , 2016, Drug development and industrial pharmacy.

[132]  Ahmad Almaya,et al.  A Demonstration of Mixing Robustness in a Direct Compression Continuous Manufacturing Process. , 2017, Journal of pharmaceutical sciences.

[133]  F. Neville,et al.  Colloidal Silica Particle Synthesis and Future Industrial Manufacturing Pathways: A Review , 2016 .

[134]  M. Roberts,et al.  Effect of lubricant type and concentration on the punch tip adherence of model ibuprofen formulations , 2004, The Journal of pharmacy and pharmacology.

[135]  A. Narang,et al.  Effect of milling temperatures on surface area, surface energy and cohesion of pharmaceutical powders. , 2015, International journal of pharmaceutics.

[136]  K. Danjo,et al.  Effect of Temperature on the Sticking of Low Melting Point Materials , 1993 .

[137]  Joseph P. Neilly,et al.  A material sparing method for quantitatively measuring tablet sticking , 2011 .

[138]  T. Andersson,et al.  Preformulation investigation and challenges; salt formation, salt disproportionation and hepatic recirculation , 2017, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[139]  Jinjiang Li,et al.  Lubricants in Pharmaceutical Solid Dosage Forms , 2014 .

[140]  C. Leopold,et al.  A comparative study on the sticking tendency of ibuprofen and ibuprofen sodium dihydrate to differently coated tablet punches , 2018, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[141]  K. Pathak,et al.  Pharmaceutical product development technologies based on the biopharmaceutical classification system. , 2009, Die Pharmazie.

[142]  C. Leopold,et al.  Investigation of the tableting behavior of Ibuprofen DC 85 W , 2018, Drug development and industrial pharmacy.

[143]  M. Tobyn,et al.  The use of colloid probe microscopy to predict aerosolization performance in dry powder inhalers: AFM and in vitro correlation. , 2006, Journal of pharmaceutical sciences.

[144]  W. Abdelwahed,et al.  DESIGHN AND EVALUATION OF A NEW FORMULATIONS OF ENALAPRIL MALEATE 20 MG TABLET IN A TIME EFFICIENT AND ON A LARGE INDUSTRIAL SCALE , 2014 .