Review of Disintegrants and the Disintegration Phenomena.

Disintegrant is one of the most important components in a typical tablet dosage form. It is responsible for ensuring the break-up of the tablet matrix upon ingestion. Disintegrants act by different mechanisms, and a number of factors may affect their performance. It is important for formulators to understand how disintegrants function so as to be able to judiciously use disintegrants to develop optimized formulations. If the formulator is required to implement the quality by design paradigm while developing a tablet formulation, it would be important to determine the impact of component ranges and process variations on tablet performance and of particular importance, tablet disintegration. Thus, a better understanding of the mechanisms of disintegrants and the tablet disintegration processes can be critical to product design success. This review aims to provide an overview of tablet disintegrants and the disintegration processes with particular focus on the factors affecting the functionalities of disintegrants. An updated compendium of different techniques employed to evaluate disintegrant action and measure disintegration time is also provided. The objective of this review is to assemble the knowledge about disintegrants and the measurement of tablet disintegratability so that the information provided could be of help to tablet formulation development.

[1]  Peter Kleinebudde,et al.  A new apparatus for real-time assessment of the particle size distribution of disintegrating tablets. , 2014, Journal of pharmaceutical sciences.

[2]  A. Stamm,et al.  A Comparative Evaluation of the Properties of some Tablet Disintegrants , 1980 .

[3]  P. Di Martino,et al.  Evaluation of Different Fast Melting Disintegrants by Means of a Central Composite Design , 2005, Drug development and industrial pharmacy.

[4]  T Nagai,et al.  Disintegration of the aspirin tablets containing potato starch and microcrystalline cellulose in various concentrations. , 1969, Chemical & pharmaceutical bulletin.

[5]  Kunio Ito,et al.  Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone. , 2002, Chemical & pharmaceutical bulletin.

[6]  A H de Boer,et al.  The role of water uptake on tablet disintegration. Design of an improved method for penetration measurements. , 1986, Pharmaceutica acta Helvetiae.

[7]  J. Remon,et al.  Crosslinked starch as a disintegrating agent , 1990 .

[8]  R. Davé,et al.  Novel use of superdisintegrants as viscosity enhancing agents in biocompatible polymer films containing griseofulvin nanoparticles , 2015 .

[9]  K Y Weon,et al.  Optimization study on the formulation of roxithromycin dispersible tablet using experimental design , 2000, Archives of pharmacal research.

[10]  E. Khalil,et al.  Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant. , 1998, Drug development and industrial pharmacy.

[11]  L. Cartilier,et al.  Characterization of moving fronts in cross-linked amylose matrices by image analysis , 1996 .

[12]  Xiaorong He,et al.  Development of a rapidly dispersing tablet of a poorly wettable compound: formulation DOE and mechanistic study of effect of formulation excipients on wetting of celecoxib. , 2008, International journal of pharmaceutics.

[13]  Chun-Ren Chen,et al.  Investigation of the Dissolution Difference between Acidic and Neutral Media of Acetaminophen Tablets Containing a Super Disintegrant and a Soluble Excipient , 1997 .

[14]  W. Lowenthal Mechanism of action of tablet disintegrants. , 1973, Pharmaceutica acta Helvetiae.

[15]  M. Hussain,et al.  Ion-exchange resins as drug delivery carriers. , 2009, Journal of pharmaceutical sciences.

[16]  M. C. Bonferoni,et al.  Disintegrants in Solid Dosage Forms , 1990 .

[17]  S. S. Kornblum,et al.  A new tablet disintegrating agent: cross-linked polyvinylpyrrolidone. , 1973, Journal of pharmaceutical sciences.

[18]  A La Manna,et al.  Disintegrating force as a new formulation parameter. , 1984, Journal of pharmaceutical sciences.

[19]  S. Neau,et al.  Crospovidone interactions with water. I. Calorimetric study of the effect of Polyplasdone particle size on its uptake and distribution of water. , 2014, Journal of pharmaceutical sciences.

[20]  C. Nyström,et al.  Studies on direct compression of tablets XXI. Investigation of bonding mechanisms of some directly compressed materials by strength characterization in media with different dielectric constants (relative permittivity) , 1990 .

[21]  P. Akkaramongkolporn,et al.  Evaluation of Some Anionic Exchange Resins as Potential Tablet Disintegrants , 2014 .

[22]  Parind Mahendrakumar Desai,et al.  Understanding disintegrant action by visualization. , 2012, Journal of pharmaceutical sciences.

[23]  C. Liew,et al.  Influence of disintegrants in different substrate physical form on dimensional recovery of multi-component tablet. , 2014, International journal of pharmaceutics.

[24]  D. F. Steele,et al.  Dynamic Vapor Sorption Properties of Sodium Starch Glycolate Disintegrants , 2005, Pharmaceutical development and technology.

[25]  S. Gattani,et al.  Formulation and Evaluation of Bi-layer Tablet of Metoclopramide Hydrochloride and Ibuprofen , 2008, AAPS PharmSciTech.

[26]  E Shotton,et al.  Effect of intragranular and extragranular disintegrating agents on particle size of disintegrated tablets. , 1976, Journal of pharmaceutical sciences.

[27]  R. Hoover,et al.  Starch from Hull-less Barley: Ultrastructure and Distribution of Granule-Bound Proteins , 2003 .

[28]  L. Augsburger,et al.  Evaluation of the Functional Equivalence of Crospovidone NF from Different Sources. I. Physical Characterization , 2001, Pharmaceutical development and technology.

[29]  Karen De Clerck,et al.  Wicking properties of various polyamide nanofibrous structures with an optimized method , 2011 .

[30]  Christopher T. Rhodes,et al.  Evaluations of the Mechanism of Disintegrant Action , 1982 .

[31]  G. K. Bolhuis,et al.  Improvement by super disintegrants of the properties of tablets containing lactose, prepared by wet granulation , 1983, Pharmaceutisch Weekblad.

[32]  C. Liew,et al.  Moistening Liquid-Dependent De-aggregation of Microcrystalline Cellulose and Its Impact on Pellet Formation by Extrusion–Spheronization , 2014, AAPS PharmSciTech.

[33]  L. Augsburger,et al.  Functionality comparison of 3 classes of superdisintegrants in promoting aspirin tablet disintegration and dissolution , 2005, AAPS PharmSciTech.

[34]  E. Kissa,et al.  Wetting and Wicking , 1996 .

[35]  C. Liew,et al.  Assessment of disintegration of rapidly disintegrating tablets by a visiometric liquid jet-mediated disintegration apparatus. , 2013, International journal of pharmaceutics.

[36]  R. Jiménez-Castellanos,et al.  Disintegrating efficiency of croscarmellose sodium in a direct compression formulation , 1997 .

[37]  Garnet E. Peck,et al.  The Swelling & Water Uptake of Tablets III: Moisture Sorption Behavior of Tablet Disintegrants , 1994 .

[38]  D. Derle,et al.  Effect of Polacrilin Potassium as Disintegrant on Bioavailability of Diclofenac Potassium in Tablets : a Technical Note , 2012, AAPS PharmSciTech.

[39]  Griet Van Vaerenbergh,et al.  Continuous manufacturing: the future in pharmaceutical solid dosage form manufacturing , 2015 .

[40]  G. Alderborn Tablets and compaction , 2007 .

[41]  H. Vromans,et al.  Studies on tableting properties of lactose. VIII. The effect of variations in primary particle size, percentage of amorphous lactose and addition of a disintegrant on the disintegration of spray-dried lactose tablets , 1987 .

[42]  C. Rhodes,et al.  Studies of the Utility of Cross Linked Polyvinlpolypyrrolidine as a Tablet Disintegrant , 1980 .

[43]  Peter Kleinebudde,et al.  Systematic classification of tablet disintegrants by water uptake and force development kinetics , 2014, The Journal of pharmacy and pharmacology.

[44]  P. L. Gould,et al.  The Effect of Recompression on the Swelling Kinetics of Wet Massed Tablets, Containing ‘Super’ Disintegrants , 1985 .

[45]  W Lowenthal,et al.  Mechanism of action of starch as a tablet disintegrant. V. Effect of starch grain deformation. , 1972, Journal of pharmaceutical sciences.

[46]  S. Gaisford,et al.  Solution calorimetry to monitor swelling and dissolution of polymers and polymer blends , 2006 .

[47]  Energetics of tablet disintegration , 1989 .

[48]  J. Carstensen,et al.  Methods for the assessment of the stability of tablet disintegrants. , 1991, Journal of pharmaceutical sciences.

[49]  I. Antal,et al.  Drug excipients. , 2006, Current medicinal chemistry.

[50]  G. Alebiowu,et al.  Effects of starches on the mechanical properties of paracetamol tablet formulations. II. Sorghum and plantain starches as disintegrants. , 2003, Acta pharmaceutica.

[51]  W. Lowenthal,et al.  Mechanism of action of starch as a tablet disintegrant. I. Factors that affect the swelling of starch grains at 37 degree. , 1966, Journal of pharmaceutical sciences.

[52]  I. Rashid,et al.  Characterization of chitin-metal silicates as binding superdisintegrants. , 2009, Journal of pharmaceutical sciences.

[53]  R. Parikh,et al.  Improving the tablet characteristics and dissolution profile of ibuprofen by using a novel coprocessed superdisintegrant: A technical note , 2007, AAPS PharmSciTech.

[54]  Nidhi Garg,et al.  Co-processed excipients: a patent review. , 2012, Recent patents on drug delivery & formulation.

[55]  P. Colombo,et al.  The role of bond weakening by liquids in the disintegration of tablets , 1992 .

[56]  I. Rashid,et al.  A novel superdisintegrating agent made from physically modified chitosan with silicon dioxide. , 2008, Drug development and industrial pharmacy.

[57]  T. Tabata,et al.  Formulation study for lansoprazole fast-disintegrating tablet. III. Design of rapidly disintegrating tablets. , 2003, Chemical & pharmaceutical bulletin.

[58]  S. Wan,et al.  A Study of the Swelling of Tablet Excipients Using Video Recording , 1990 .

[59]  K. A. Khan,et al.  Water-sorption properties of tablet disintegrants. , 1975, Journal of pharmaceutical sciences.

[60]  Montserrat Miñarro,et al.  The use of the SeDeM Diagram expert system to determine the suitability of diluents-disintegrants for direct compression and their use in formulation of ODT. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[61]  P. Lakshmi,et al.  Effect of synthetic super disintegrants and natural polymers in the preparation of donepezil hydrochloride fast disintegration films , 2014 .

[62]  J. Rhie,et al.  The effect of aging on the dissolution of wet granulated tablets containing super disintegrants , 1993 .

[63]  Xianghong Ma,et al.  Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets , 2014, PloS one.

[64]  D. Derle,et al.  Mechanism of disintegrant action of polacrilin potassium: Swelling or wicking? , 2012 .

[65]  Mrudula H. Bele,et al.  Effect of Sorbed Water on Disintegrant Performance of Four Brands of Polacrilin Potassium NF , 2011, AAPS PharmSciTech.

[66]  Chengyu Wang,et al.  Formulation and evaluation of nanocrystalline cellulose as a potential disintegrant. , 2015, Carbohydrate polymers.

[67]  A. Sakr,et al.  Tablet Dosage Forms , 2009 .

[68]  L. Augsburger,et al.  The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets , 2005, AAPS PharmSciTech.

[69]  K. Frömming,et al.  Sorption properties of cross-linked insoluble polyvinylpyrrolidone. , 1981, Journal of pharmaceutical sciences.

[70]  Parind Mahendrakumar Desai,et al.  Functionality of Disintegrants and Their Mixtures in Enabling Fast Disintegration of Tablets by a Quality by Design Approach , 2014, AAPS PharmSciTech.

[71]  S. Neau,et al.  Crospovidone interactions with water. II. Dynamic vapor sorption analysis of the effect of Polyplasdone particle size on its uptake and distribution of water. , 2014, International journal of pharmaceutics.

[72]  Jens Frahm,et al.  Tablet disintegration studied by high-resolution real-time magnetic resonance imaging. , 2014, Journal of pharmaceutical sciences.

[73]  H. Jung,et al.  Superdisintegrants: Characterization and Function , 2013 .

[74]  A. Sheela,et al.  Development of polymer-bound fast-dissolving metformin buccal film with disintegrants , 2015, International journal of nanomedicine.

[75]  Peter Kleinebudde,et al.  Performance of tablet disintegrants: impact of storage conditions and relative tablet density , 2015, Pharmaceutical development and technology.

[76]  W. Lowenthal,et al.  Mechanism of action of starch as a tablet disintegrant IV: effect of medicaments and disintegrants on mean pore diameter and porosity. , 1971, Journal of pharmaceutical sciences.

[77]  L. Augsburger,et al.  Evaluation of the Functional Equivalence of Crospovidone NF from Different Sources. II. Standard Performance Test , 2001, Pharmaceutical development and technology.

[78]  G. K. Bolhuis,et al.  The effect of particle size of disintegrants on the disintegration of tablets , 1981, Pharmaceutisch weekblad.

[79]  Kozo Takayama,et al.  Evaluation of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera. , 2002, Chemical & pharmaceutical bulletin.

[80]  J. Schwartz,et al.  The Binding and Disintegrant Properties of the Corn Starch Fractions: Amylose and Amylopectin , 1978 .

[81]  Z. Chowhan,et al.  Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability. , 1990, Journal of pharmaceutical sciences.

[82]  E. H. Melvin,et al.  Starch Granule Swelling in Water Vapor Sorption , 1952 .

[83]  IBRAHIM KHATTAB,et al.  Effect of Mode of Incorporation of Disintegrants on the Characteristics of Fluid‐bed Wet‐granulated Tablets , 1993, The Journal of pharmacy and pharmacology.

[84]  Sarsvatkumar Patel,et al.  Effect of Particle Size and Compression Force on Compaction Behavior and Derived Mathematical Parameters of Compressibility , 2006, Pharmaceutical Research.

[85]  S. Rossi,et al.  Investigation on bonding and disintegration properties of pharmaceutical materials , 1996 .

[86]  M. Aulton Pharmaceutics : the science of dosage form design , 2002 .

[87]  Immediate drug release from solid oral dosage forms. , 2005, Journal of pharmaceutical sciences.

[88]  E. Kissa Dispersions: Characterization, Testing, and Measurement , 1999 .

[89]  N. Peppas,et al.  A physical analysis of the phenomenon of tablet disintegration , 1988 .