An Overview of Factors Affecting Superdisintegrants Functionalities
DOI:
https://doi.org/10.37285/ijpsn.2019.12.1.1Abstract
Disintegrants are an essential excipients in solid oral formulations. Superdisintegrants such as croscarmellose sodium, sodium starch glycolate, crospovidone and polacrilin potassium are among excipients added in immediate release and oral dispersible tablet formulations at low concentrations to counteract effects of compression and binder after administration. Hygroscopicity of superdisintegrants facilitates permeation of water into tablet matrix and cross-linkage reduces their solubility in water. This article describes factors which could affect functionality of superdisintegrants such as molecular and physicochemical factors (degree of cross-linkage and substitution, particle size, particle porosity and impurities); formulation and process factors (solubility and hygroscopicity of fillers and/or binders, incompatibility, pH, lubricants, mode of disintegrant addition, granulation, mixer shear rate, compression pressure and reworking) and aging and storage conditions.
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Keywords:
Superdisintegrant, Sodium starch glycolate, Croscarmellose sodium, Crospovidone, Polacrilin potassium, Disintegration, dissolution
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Published
2019-01-31
How to Cite
1.
Dilebo J, Gabriel T. An Overview of Factors Affecting Superdisintegrants Functionalities. Scopus Indexed [Internet]. 2019 Jan. 31 [cited 2024 Nov. 19];12(1):4355-61. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/270
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Review Articles
References
Abraham A, Olusanmi D, Ilott AJ, Good D, Murphy D, Mcnamara D, Jerschow A and Mantri RV (2016). Correlation of phosphorus cross-linking to hydration rates in sodium starch glycolate tablet disintegrants using MRI. J Pharm Sci 105:1907-1913.
Akbuga J and Ermantas K (1992). Role of disintegrants in temperature-and moisture-related physical changes of ketoconazole tablets. Pharmazie 47: 644-645.
Balasubramaniam J, Bindu K, Rao VU, Ray D, Haldar R and Brzeczko AW (2008). Effect of superdisintegrants on dissolution of cationic drugs. Dissolut Technol 15: 18-25.
Barabas ES and Adeyeye CM (1996). Crospovidone Anal Profiles Drug Subst Excipients 24: 87-163.
Barmpalexis P, Syllignaki P and Kachrimanis K (2018). A study of water uptake by selected superdisintegrants from the sub-molecular to the particulate level. Pharm Dev Technol 23: 476- 487.
Bele MH and Derle DV (2012). Mechanism of disintegrant action of polacrilin potassium: swelling or wicking? Acta Pharm Sin B 2: 70-76.
Bele MH and Derle DV (2011). Brand to brand variation in the disintegrant functionality of polacrilin potassium, NF. J Excipients and Food Chem 2: 53-63.
Bindra DS, Stein D, Pandey P and Barbour N (2014). Incompatibility of croscarmellose sodium with alkaline excipients in a tablet formulation. Pharm Dev Technol 19: 285-289.
Bolhuis GK, Kamp HV and Lerk CF (1986). On the similarity of sodium starch glycolate from different sources. Drug Dev Ind Pharm 12: 621-630.
Bolhuis GK, Smallenbroek AJ and Lerk CF (1981). Interaction of tablet disintegrants and magnesium stearate during mixing I: effect on tablet disintegration. J Pharm Sci 70: 1328-1330.
Borodkin S and Yunker MH (1970). Interaction of amine drugs with a polycarboxylic acid ion-exchange resin. J Pharm Sci 59: 481-486.
Bühler V (2005). Polyvinylpyrolidone Excipients for Pharma-ceuticals: Povidone, Crospovidone and Copovidone, Springer, Berlin, pp 1-247.
Chen CR, Cho SL, Lin CK, Lin YH, Chiang ST and Wu HLS (1998). Dissolution difference between acidic and neutral media of acetaminophen tablets containing a superdisintegrant and a soluble excipient. II. Chem Pharm Bull 46: 478-481.
Chen CR, Lin YH, Cho SL, Yen SY and Wu HLS (1997). Investigation of the dissolution difference between acidic and neutral media of acetaminophen tablets containing a superdisintegrant and a soluble excipient. Chem Pharm Bull 45: 509-512.
Chien YW, Nostrand PV, Hurwitz AR and Shami EG (1981). Drug-disintegrant interactions: binding of oxymorphone derivatives. J Pharm Sci 70: 709-710.
Desai PM, Liew CV and Heng PWS (2016). Review of disintegrants and the disintegration phenomena. J Pharm Sci 105: 2545-2555.
Desai PM, Liew CV and Heng PWS (2012). Understanding disintegrant action by visualization. J Pharm Sci 101: 2155-2164.
Di Martino P, Martelli S and Wehrlé P (2005). Evaluation of different fast melting disintegrants by means of a central composite design. Drug Dev Ind Pharm 31: 109-121.
Ekmekciyan N, Tuglu T, El-Saleh F, Muehlenfeld C, Stoyanov E and Quodbach J (2018). Competing for water: a new approach to understand disintegrant performance. Int J Pharm 548: 491-499.
Faroongsarng D and Peck GE (2008). The swelling and water uptake of tablets III: moisture sorption behavior of tablet disintegrants. Drug Dev Ind Pharm 1994; 20: 779-798.
Fransén N, Morin M, Björk E and Edsman K (2008). Physicochemical interactions between drugs and super-disintegrants. J Pharm Pharmacol 60: 1583-1589.
Gordon MS, Chalterjee B and Chowhan ZT (1990). Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability. J Pharm Sci 79: 43-47.
Gordon MS, Rudraraju VS, Dani K and Chowhan ZT (1993a). Effect of the mode of superdisintegrant incorporation on dissolution in wet granulated tablets. J Pharm Sci 82: 220-226.
Gordon MS, Rudraraju VS, Rhie JK and Chowhan ZT (1993b). The effect of aging on the dissolution of wet granulated tablets containing super disintegrants. Int J Pharm 9: 119-131.
Gould PL and Tan SB (1985). The effect of recompression on disintegrant efficiency in tablets prepared by wet granulation. Drug Dev Ind Pharm 11: 441-460.
Guest RT (2009). Croscarmellose Sodium. In Handbook of Pharmaceutical Excipients (Rowe RC, Sheskey PJ, and Quinn ME eds), Pharmaceutical Press, London, pp 206-208.
Hiew TN, Johan NAB, Desai PM, Chua SM, Loh ZH and Heng PWS (2016). Effect of moisture sorption on the performance of crospovidone. Int J Pharm 514: 322-331.
Hollenbeck RG (1988). Bioavailability of phenylpropanolamine HCl from tablet dosage forms containing croscarmellose sodium. Int J Pharm 47: 89-93.
Johnson JR, Wang LH, Gordon MS and Chowhan ZT (1991). Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution. J Pharm Sci 80: 469-471.
Khattab I, Menon A and Sakr A (1993). Effect of mode of incorporation of disintegrants on the characteristics of fluid-bed wet-granulated tablets. J Pharm Pharmacol 45: 687-691.
Kibbe AH (2009). Crospovidone. In Handbook of Pharmaceutical Excipients (Rowe RC, Sheskey PJ, and Quinn ME eds), Pharmaceutical Press, London, pp 208-210.
Kottke MK and Rudnic EM (2002). Tablet Dosage Forms. In Modern Pharmaceutics (Banker GS and Rhodes CT eds), Marcel Dekker, New York, pp 292-338.
Marais AF, Song M and de Villiers MM (2003). Effect of compression force, humidity and disintegrant concentration on the disintegration and dissolution of directly compressed furosemide tablets using croscarmellose sodium as disintegrant. Trop J Pharm Res 2: 125-135.
Markl D and Zeitler JA (2017). A review of disintegration mechanisms and measurement techniques. Pharm Res 34: 890-917.
Moreton RC (2008). Disintegrants in Tablets. In Pharmaceutical Dosage Forms: Tablets Rational Design and Formulation (Augsburger LL and Hoag SW eds), Informa Healthcare, New York, pp 217-250.
Nazmi M, Islam SMA, Bhuiyan MA and Reza S (2013). Effect of superdisintegrants and their mode of incorporation on disintegration time and release profile of carbamazepine from immediate release tablet. J App Pharm Sci 3: 80-84.
Palmieri A (2009). Polacrilin Potassium. In Handbook of Pharmaceutical Excipients (Rowe RC, Sheskey PJ, and Quinn ME eds), Pharmaceutical Press, London, pp 504-506.
Preetha B, Pandit JK, Rao VU, Bindu K, Rajesh YV and Balasubramaniam J (2008). Comparative evaluation of mode of incorporation of superdisintegrants on dissolution of model drugs from wet granulated tablets. Acta Pharm Sin 50: 229-236.
Quodbach J and Kleinebudde P (2016). A critical review on tablet disintegration. Pharm Dev Technol 21: 763-774.
Quodbach J and Kleinebudde P (2015). Performance of tablet disintegrants: impact of storage conditions and relative tablet density. Pharm Dev Technol 20: 762-768.
Quodbach J and Kleinebudde P (2014). Systematic classification of tablet disintegrants by water uptake and force development kinetics. J Pharm Pharmacol 66: 1429-1438.
Quodbach J, Moussavi A, Tammer R, Frahm J and Kleinebudde P (2014). Tablet disintegration studied by high-resolution real-time magnetic resonance imaging. J Pharm Sci 103: 249-255.
Rahman M, Roy S, Hasan S, Alam A, Jha MK, Ahsan Q and Ferdaus J (2011). Effect of mode of addition of disintegrants on dissolution of model drug from wet granulation tablets. Int J Pharm Sci Res 2: 84-92.
Rudnic EM, Kanig JL and Rhodes CT (1985). Effect of molecular structure variation on the disintegrant action of sodium starch glycolate. J Pharm Sci 74: 647-650.
Rudnic EM, Lausier JM, Chilamkurti RN and Rhodes CT (1980). Studies of the utility of cross linked polyvinylpolypyrrolidine as a tablet disintegrant. Drug Dev Ind Pharm 6: 291-309.
Rudnic EM, Kanig JL and Rhodes CT (1983). The effect of molecular structure on the function of sodium starch glycolate in wet granulated systems. Drug Dev Ind Pharm 9: 303-320.
Sacchetti M, Teerakapibal R, Kim K and Elder EJ Jr (2017). Role of water sorption in tablet crushing strength, disintegration, and dissolution. AAPS Pharm Sci Tech 18: 2214-2226.
Sarisuta N and Parrott EL (1988). Effects of temperature, humidity, and aging on the disintegration and dissolution of acetaminophen tablets. Drug Dev Ind Pharm 14: 1877-1881.
Shah S and Augsburger L (2001). Evaluation of the functional equivalence of crospovidone NF from different sources. I. physical characterization. Pharm Dev Technol 6: 39-51.
Sheen PC and Kim SI (1989). Comparative study of disintegrating agents in tiaramid hydrochloride tablets. Drug Dev Ind Pharm 15: 401-414.
Shotton E and Leonard GS (1976). Effect of intragranular and extragranular disintegrating agents on particle size of disintegrated tablets. J Pharm Sci 65: 1170-1174.
Smallenbroek AJ, Bolhuis GK and Lerk CF (1981). The effect of particle size of disintegrants on the disintegration of tablets. Pharm Weekbl Sci 3: 172-175.
Van Kamp HV, Bolhuis GK and Lerk CF (1983). Improvement by superdisintegrants of the properties of tablets containing lactose, prepared by wet granulation. Pharmaceutisch Week blad 5: 165-171.
Wren SAC, Alhusban F, Barry AR and Hughes LP (2017). Mechanistic understanding of the link between sodium starch glycolate properties and the performance of tablets made by wet granulation. Int J Pharm 529: 319-328.
Zarmpi P, Flanagan T, Meehan E, Mann J and Fotaki N (2017). Biopharmaceutical aspects and implications of excipient variability in drug product performance. Eur J Pharm Biopharm 111: 1-5.
Zhao N and Augsburger LL (2006a). The influence of product brand-to-brand variability on superdisintegrant performance a case study with croscarmellose sodium. Pharm Dev Technol 11: 179-185.
Zhao N and Augsburger LL (2006b). The influence of granulation on superdisintegrant performance. Pharm Dev Technol 11: 47-53.
Zhao N and Augsburger LL (2005). The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharm Sci Tech 6: E120-E126.
Akbuga J and Ermantas K (1992). Role of disintegrants in temperature-and moisture-related physical changes of ketoconazole tablets. Pharmazie 47: 644-645.
Balasubramaniam J, Bindu K, Rao VU, Ray D, Haldar R and Brzeczko AW (2008). Effect of superdisintegrants on dissolution of cationic drugs. Dissolut Technol 15: 18-25.
Barabas ES and Adeyeye CM (1996). Crospovidone Anal Profiles Drug Subst Excipients 24: 87-163.
Barmpalexis P, Syllignaki P and Kachrimanis K (2018). A study of water uptake by selected superdisintegrants from the sub-molecular to the particulate level. Pharm Dev Technol 23: 476- 487.
Bele MH and Derle DV (2012). Mechanism of disintegrant action of polacrilin potassium: swelling or wicking? Acta Pharm Sin B 2: 70-76.
Bele MH and Derle DV (2011). Brand to brand variation in the disintegrant functionality of polacrilin potassium, NF. J Excipients and Food Chem 2: 53-63.
Bindra DS, Stein D, Pandey P and Barbour N (2014). Incompatibility of croscarmellose sodium with alkaline excipients in a tablet formulation. Pharm Dev Technol 19: 285-289.
Bolhuis GK, Kamp HV and Lerk CF (1986). On the similarity of sodium starch glycolate from different sources. Drug Dev Ind Pharm 12: 621-630.
Bolhuis GK, Smallenbroek AJ and Lerk CF (1981). Interaction of tablet disintegrants and magnesium stearate during mixing I: effect on tablet disintegration. J Pharm Sci 70: 1328-1330.
Borodkin S and Yunker MH (1970). Interaction of amine drugs with a polycarboxylic acid ion-exchange resin. J Pharm Sci 59: 481-486.
Bühler V (2005). Polyvinylpyrolidone Excipients for Pharma-ceuticals: Povidone, Crospovidone and Copovidone, Springer, Berlin, pp 1-247.
Chen CR, Cho SL, Lin CK, Lin YH, Chiang ST and Wu HLS (1998). Dissolution difference between acidic and neutral media of acetaminophen tablets containing a superdisintegrant and a soluble excipient. II. Chem Pharm Bull 46: 478-481.
Chen CR, Lin YH, Cho SL, Yen SY and Wu HLS (1997). Investigation of the dissolution difference between acidic and neutral media of acetaminophen tablets containing a superdisintegrant and a soluble excipient. Chem Pharm Bull 45: 509-512.
Chien YW, Nostrand PV, Hurwitz AR and Shami EG (1981). Drug-disintegrant interactions: binding of oxymorphone derivatives. J Pharm Sci 70: 709-710.
Desai PM, Liew CV and Heng PWS (2016). Review of disintegrants and the disintegration phenomena. J Pharm Sci 105: 2545-2555.
Desai PM, Liew CV and Heng PWS (2012). Understanding disintegrant action by visualization. J Pharm Sci 101: 2155-2164.
Di Martino P, Martelli S and Wehrlé P (2005). Evaluation of different fast melting disintegrants by means of a central composite design. Drug Dev Ind Pharm 31: 109-121.
Ekmekciyan N, Tuglu T, El-Saleh F, Muehlenfeld C, Stoyanov E and Quodbach J (2018). Competing for water: a new approach to understand disintegrant performance. Int J Pharm 548: 491-499.
Faroongsarng D and Peck GE (2008). The swelling and water uptake of tablets III: moisture sorption behavior of tablet disintegrants. Drug Dev Ind Pharm 1994; 20: 779-798.
Fransén N, Morin M, Björk E and Edsman K (2008). Physicochemical interactions between drugs and super-disintegrants. J Pharm Pharmacol 60: 1583-1589.
Gordon MS, Chalterjee B and Chowhan ZT (1990). Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability. J Pharm Sci 79: 43-47.
Gordon MS, Rudraraju VS, Dani K and Chowhan ZT (1993a). Effect of the mode of superdisintegrant incorporation on dissolution in wet granulated tablets. J Pharm Sci 82: 220-226.
Gordon MS, Rudraraju VS, Rhie JK and Chowhan ZT (1993b). The effect of aging on the dissolution of wet granulated tablets containing super disintegrants. Int J Pharm 9: 119-131.
Gould PL and Tan SB (1985). The effect of recompression on disintegrant efficiency in tablets prepared by wet granulation. Drug Dev Ind Pharm 11: 441-460.
Guest RT (2009). Croscarmellose Sodium. In Handbook of Pharmaceutical Excipients (Rowe RC, Sheskey PJ, and Quinn ME eds), Pharmaceutical Press, London, pp 206-208.
Hiew TN, Johan NAB, Desai PM, Chua SM, Loh ZH and Heng PWS (2016). Effect of moisture sorption on the performance of crospovidone. Int J Pharm 514: 322-331.
Hollenbeck RG (1988). Bioavailability of phenylpropanolamine HCl from tablet dosage forms containing croscarmellose sodium. Int J Pharm 47: 89-93.
Johnson JR, Wang LH, Gordon MS and Chowhan ZT (1991). Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution. J Pharm Sci 80: 469-471.
Khattab I, Menon A and Sakr A (1993). Effect of mode of incorporation of disintegrants on the characteristics of fluid-bed wet-granulated tablets. J Pharm Pharmacol 45: 687-691.
Kibbe AH (2009). Crospovidone. In Handbook of Pharmaceutical Excipients (Rowe RC, Sheskey PJ, and Quinn ME eds), Pharmaceutical Press, London, pp 208-210.
Kottke MK and Rudnic EM (2002). Tablet Dosage Forms. In Modern Pharmaceutics (Banker GS and Rhodes CT eds), Marcel Dekker, New York, pp 292-338.
Marais AF, Song M and de Villiers MM (2003). Effect of compression force, humidity and disintegrant concentration on the disintegration and dissolution of directly compressed furosemide tablets using croscarmellose sodium as disintegrant. Trop J Pharm Res 2: 125-135.
Markl D and Zeitler JA (2017). A review of disintegration mechanisms and measurement techniques. Pharm Res 34: 890-917.
Moreton RC (2008). Disintegrants in Tablets. In Pharmaceutical Dosage Forms: Tablets Rational Design and Formulation (Augsburger LL and Hoag SW eds), Informa Healthcare, New York, pp 217-250.
Nazmi M, Islam SMA, Bhuiyan MA and Reza S (2013). Effect of superdisintegrants and their mode of incorporation on disintegration time and release profile of carbamazepine from immediate release tablet. J App Pharm Sci 3: 80-84.
Palmieri A (2009). Polacrilin Potassium. In Handbook of Pharmaceutical Excipients (Rowe RC, Sheskey PJ, and Quinn ME eds), Pharmaceutical Press, London, pp 504-506.
Preetha B, Pandit JK, Rao VU, Bindu K, Rajesh YV and Balasubramaniam J (2008). Comparative evaluation of mode of incorporation of superdisintegrants on dissolution of model drugs from wet granulated tablets. Acta Pharm Sin 50: 229-236.
Quodbach J and Kleinebudde P (2016). A critical review on tablet disintegration. Pharm Dev Technol 21: 763-774.
Quodbach J and Kleinebudde P (2015). Performance of tablet disintegrants: impact of storage conditions and relative tablet density. Pharm Dev Technol 20: 762-768.
Quodbach J and Kleinebudde P (2014). Systematic classification of tablet disintegrants by water uptake and force development kinetics. J Pharm Pharmacol 66: 1429-1438.
Quodbach J, Moussavi A, Tammer R, Frahm J and Kleinebudde P (2014). Tablet disintegration studied by high-resolution real-time magnetic resonance imaging. J Pharm Sci 103: 249-255.
Rahman M, Roy S, Hasan S, Alam A, Jha MK, Ahsan Q and Ferdaus J (2011). Effect of mode of addition of disintegrants on dissolution of model drug from wet granulation tablets. Int J Pharm Sci Res 2: 84-92.
Rudnic EM, Kanig JL and Rhodes CT (1985). Effect of molecular structure variation on the disintegrant action of sodium starch glycolate. J Pharm Sci 74: 647-650.
Rudnic EM, Lausier JM, Chilamkurti RN and Rhodes CT (1980). Studies of the utility of cross linked polyvinylpolypyrrolidine as a tablet disintegrant. Drug Dev Ind Pharm 6: 291-309.
Rudnic EM, Kanig JL and Rhodes CT (1983). The effect of molecular structure on the function of sodium starch glycolate in wet granulated systems. Drug Dev Ind Pharm 9: 303-320.
Sacchetti M, Teerakapibal R, Kim K and Elder EJ Jr (2017). Role of water sorption in tablet crushing strength, disintegration, and dissolution. AAPS Pharm Sci Tech 18: 2214-2226.
Sarisuta N and Parrott EL (1988). Effects of temperature, humidity, and aging on the disintegration and dissolution of acetaminophen tablets. Drug Dev Ind Pharm 14: 1877-1881.
Shah S and Augsburger L (2001). Evaluation of the functional equivalence of crospovidone NF from different sources. I. physical characterization. Pharm Dev Technol 6: 39-51.
Sheen PC and Kim SI (1989). Comparative study of disintegrating agents in tiaramid hydrochloride tablets. Drug Dev Ind Pharm 15: 401-414.
Shotton E and Leonard GS (1976). Effect of intragranular and extragranular disintegrating agents on particle size of disintegrated tablets. J Pharm Sci 65: 1170-1174.
Smallenbroek AJ, Bolhuis GK and Lerk CF (1981). The effect of particle size of disintegrants on the disintegration of tablets. Pharm Weekbl Sci 3: 172-175.
Van Kamp HV, Bolhuis GK and Lerk CF (1983). Improvement by superdisintegrants of the properties of tablets containing lactose, prepared by wet granulation. Pharmaceutisch Week blad 5: 165-171.
Wren SAC, Alhusban F, Barry AR and Hughes LP (2017). Mechanistic understanding of the link between sodium starch glycolate properties and the performance of tablets made by wet granulation. Int J Pharm 529: 319-328.
Zarmpi P, Flanagan T, Meehan E, Mann J and Fotaki N (2017). Biopharmaceutical aspects and implications of excipient variability in drug product performance. Eur J Pharm Biopharm 111: 1-5.
Zhao N and Augsburger LL (2006a). The influence of product brand-to-brand variability on superdisintegrant performance a case study with croscarmellose sodium. Pharm Dev Technol 11: 179-185.
Zhao N and Augsburger LL (2006b). The influence of granulation on superdisintegrant performance. Pharm Dev Technol 11: 47-53.
Zhao N and Augsburger LL (2005). The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharm Sci Tech 6: E120-E126.
