Skip to main content
SpringerLink
Log in

Impact of Excipient Interactions on Solid Dosage Form Stability

  • Chapter
  • First Online:
Excipient Applications in Formulation Design and Drug Delivery

Abstract

Drug-excipient interactions in solid dosage forms can affect drug product stability in physical aspects such as organoleptic changes and dissolution slowdown, or chemically by causing drug degradation. Recent research has allowed the distinction in chemical instability resulting from direct drug-excipient interactions and from drug interactions with excipient impurities. A review of chemical instability in solid dosage forms highlights common mechanistic themes applicable to multiple degradation pathways. These common themes include the role of water and microenvironmental pH. In addition, special aspects of solid-state reactions with excipients and/or excipient impurities add to the complexity in understanding and modeling reaction pathways. This paper discusses mechanistic basis of known drug-excipient interactions with case studies and provides an overview of common underlying themes. Recent developments in the understanding of degradation pathways further impact methodologies used in the pharmaceutical industry for prospective stability assessment. This paper discusses these emerging aspects in terms of limitations of drug-excipient compatibility studies, emerging paradigms in accelerated stability testing, and application of mathematical modeling for prediction of drug product stability.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Alu:

Aluminum

API:

Active pharmaceutical ingredient

ARP:

Amadori rearrangement product

BHA:

Butylated hydroxyanisole

BHT:

Butylated hydroxytoluene

GC:

Gas chromatography

HCl:

Hydrochloride

HCTZ:

Hydrochlorothiazide

HDPE:

High density polyethylene

HPLC:

High performance liquid chromatography

HPMC:

Hydroxypropyl methylcellulose

HPO:

Hydroperoxide

ICH:

International conference on harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

LC/MS:

Liquid chromatography tandem with mass spectroscopy

MVTR:

Moisture vapor transmission rate

NF:

National Formulary

NMR:

Nuclear magnetic resonance (spectroscopy)

PEG:

Polyethylene glycol

pHmax :

pH of maximum solubility

PVA:

Polyvinyl alcohol

PVP:

Polyvinyl pyrrolidone (povidone)

PhEur:

European Pharmacopeia

PVP-VA:

Polyvinylpyrrolidone-vinyl acetate copolymer

PXRD:

Powder X-ray diffraction

SDMT:

Sorption desorption moisture transfer

ssNMR:

Solid state NMR

USP:

United States Pharmacopeia

References

  • Abdoh A, Al-Omari MM, Badwan AA, Jaber AM (2004) Amlodipine besylate-excipients interaction in solid dosage form. Pharm Dev Technol 9(1):15–24

    Article  CAS  PubMed  Google Scholar 

  • Ahlneck C, Alderborn G (1988) Solid state stability of acetylsalicylic acid in binary mixtures with microcrystalline and microfine cellulose. Acta Pharm Suec 25(1):41–52

    CAS  PubMed  Google Scholar 

  • Ahlneck C, Zografi G (1990) The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. Int J Pharm 62(2–3):87–95

    Article  CAS  Google Scholar 

  • Ahlneck C, Waltersson J-O, Lundgren P (1987) Difference in effect of powdered and granular magnesium stearate on the solid state stability of acetylsalicylic acid. Acta Pharmaceutica Technologica 33(1):21–26

    CAS  Google Scholar 

  • Airaksinen S, Karjalainen M, Kivikero N, Westermarck S, Shevchenko A, Rantanen J, Yliruusi J (2005) Excipient selection can significantly affect solid-state phase transformation in formulation during wet granulation. AAPS PharmSciTech 6(2):E311–E322

    Article  PubMed Central  PubMed  Google Scholar 

  • Akiyama Y, Yoshioka M, Horibe H, Hirai S, Kitamori N, Toguchi H (1994) pH-independent controlled-release microspheres using polyglycerol esters of fatty acids. J Pharm Sci 83(11):1600–1607

    Article  CAS  PubMed  Google Scholar 

  • Al-Nimry SS, Assaf SM, Jalal IM, Najib NM (1997) Adsorption of ketotifen onto some pharmaceutical excipients. Int J Pharm 149(1):115–121

    Article  CAS  Google Scholar 

  • Antipas AS, Landis MS (2005) Solid-state excipient compatibility testing. In: Antipas AS, Landis MS (eds) Drugs and the pharmaceutical sciences, vol 153. Taylor and Francis Group, LLC, pp 419–458

    Google Scholar 

  • Ashraf-Khorassani M, Taylor LT, Waterman KC, Narayan P, Brannegan DR, Reid GL (2005) Purification of pharmaceutical excipients with supercritical fluid extraction. Pharm Dev Technol 10(4):507–516

    Article  CAS  PubMed  Google Scholar 

  • Aso Y, Sufang T, Yoshioka S, Kojima S (1997) Amount of mobile water estimated from 2H spin-lattice relaxation time, and its effects on the stability of cephalothin in mixtures with pharmaceutical excipients. Drug Stab 1(4):237–242

    CAS  Google Scholar 

  • Badawy SI (2001) Effect of salt form on chemical stability of an ester prodrug of a glycoprotein IIb/IIIa receptor antagonist in solid dosage forms. Int J Pharm 223(1–2):81–87

    Article  CAS  PubMed  Google Scholar 

  • Badawy SI, Hussain MA (2007) Microenvironmental pH modulation in solid dosage forms. J Pharm Sci 96(5):948–959

    Article  CAS  PubMed  Google Scholar 

  • Badawy SI, Williams RC, Gilbert DL (1999) Effect of different acids on solid-state stability of an ester prodrug of a IIb/IIIa glycoprotein receptor antagonist. Pharm Dev Technol 4(3):325–331

    Article  CAS  PubMed  Google Scholar 

  • Badawy SI, Gawronski AJ, Alvarez FJ (2001) Application of sorption-desorption moisture transfer modeling to the study of chemical stability of a moisture sensitive drug product in different packaging configurations. Int J Pharm 223(1–2):1–13

    Article  CAS  PubMed  Google Scholar 

  • Badawy S, Vickery R, Shah K, Hussain M (2004) Effect of processing and formulation variables on the stability of a salt of a weakly basic drug candidate. Pharm Dev Technol 9(3):239–245

    Article  CAS  PubMed  Google Scholar 

  • Badawy SI, Gray DB, Zhao F, Sun D, Schuster AE, Hussain MA (2006) Formulation of solid dosage forms to overcome gastric pH interaction of the factor Xa inhibitor, BMS-561389. Pharm Res 23(5):989–996

    Article  CAS  PubMed  Google Scholar 

  • Ballard JM, Zhu L, Nelson ED, Seburg RA (2007) Degradation of vitamin D3 in a stressed formulation: the identification of esters of vitamin D3 formed by a transesterification with triglycerides. J Pharm Biomed Anal 43(1):142–150

    Article  CAS  PubMed  Google Scholar 

  • Bharate SS, Bharate SB, Bajaj AN (2010) Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J Excip Food Chem 1(3):3–26

    CAS  Google Scholar 

  • Bindra DS, Williams TD, Stella VJ (1994) Degradation of O6-benzylguanine in aqueous polyethylene glycol 400 (PEG 400) solutions: concerns with formaldehyde in PEG 400. Pharm Res 11(7):1060–1064

    Article  CAS  PubMed  Google Scholar 

  • Blaug SM, Wesolowski JW (1959) The stability of acetylsalicylic acid in suspension. J Am Pharm Assoc 48:691–694

    Article  CAS  Google Scholar 

  • Bonfilio R, Pires SA, Ferreira LMB, de Almeida AE, Doriguetto AC, de Araujo MB, Salgado HRN (2012) A discriminating dissolution method for glimepiride polymorphs. J Pharm Sci 101(2): 794–804

    Google Scholar 

  • Botha SA, Lotter AP (1990) Compatibility study between naproxen and tablet excipients using differential scanning calorimetry. Drug Dev Ind Pharm 16:673–683

    Article  CAS  Google Scholar 

  • Bruce LD, Shah NH, Waseem Malick A, Infeld MH, McGinity JW (2005) Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid. Eur J Pharm Biopharm 59(1):85–97

    Article  CAS  PubMed  Google Scholar 

  • Buhler V (2008) Kollidon: polyvinylpyrrolidone excipients for the pharmaceuticals. Springer, Germany

    Google Scholar 

  • Buhler V, Filges U, Schneider T (2000) Stabilized polyvinylpyrrolidone formulation. WO Patent 2000059478

    Google Scholar 

  • Bundgaard H, Larsen C (1978) Kinetics and mechanism of the sucrose-accelerated degradation of penicillins in aqueous solution. Int J Pharm 1(2):95–104

    Article  CAS  Google Scholar 

  • Bundgaard H, Larsen C (1979) Piperazinedione formation from reaction of ampicillin with carbohydrates and alcohols in aqueous solution. Int J Pharm 3(1):1–11

    Article  CAS  Google Scholar 

  • Bundgaard H, Larsen C (1983) The influence of carbohydrates and polyhydric alcohols on the stability of cephalosporins in aqueous solution. Int J Pharm 16(3):319–325

    Article  CAS  Google Scholar 

  • Burghart W, Burghart K, Raneburger J (2004) Solid formulation of levothyroxine and/or liothyronine salts containing controlled amount of water for stability

    Google Scholar 

  • Carstensen JT, Attarchi F (1988) Decomposition of aspirin in the solid state in the presence of limited amounts of moisture II: kinetics and salting-in of aspirin in aqueous acetic acid solutions. J Pharm Sci 77(4):314–317

    Article  CAS  PubMed  Google Scholar 

  • Carstensen JT, Kothari RC (1980) Decarboxylation kinetics of 5-(tetradecyloxy)-2-furoic acid. J Pharm Sci 69(1):123–124

    Article  CAS  PubMed  Google Scholar 

  • Carstensen JT, Musa MN (1972) Decomposition of benzoic acid derivatives in solid state. J Pharm Sci 61(7):1112–1118

    Article  CAS  PubMed  Google Scholar 

  • Carstensen JT, Osadca M, Rubin SH (1969) Degradation mechanisms for water-soluble drugs in solid dosage forms. J Pharm Sci 58(5):549–553

    Article  CAS  PubMed  Google Scholar 

  • Carvalho T, Rao V, Levons J, Wu J, Narang A, Paruchuri S, Stamato H, Varia S, Hemenway J (2011) Formation of reactive impurities in PEG 400 and effects of antioxidants and oxidation inducers on the reaction rates. Paper presented at the American Association of Pharmaceutical Sciences Annual Meeting, Washington, DC

    Google Scholar 

  • Chen Y, Li Y (2003) A new model for predicting moisture uptake by packaged solid pharmaceuticals. Int J Pharm 255(1–2):217–225

    Article  CAS  PubMed  Google Scholar 

  • Chien YW, Van Nostrand P, Hurwitz AR, Shami EG (1981) Drug-disintegrant interactions: binding of oxymorphone derivatives. J Pharm Sci 70(6):709–710

    Article  CAS  PubMed  Google Scholar 

  • Claudius JS, Neau SH (1998) The solution stability of vancomycin in the presence and absence of sodium carboxymethyl starch. Int J Pharm 168(1):41–48

    Article  CAS  Google Scholar 

  • Cory W, Field K, Wu-Linhares D (2004) Is it the method or the process-separating the causes of low recovery. Drug Dev Ind Pharm 30(8):891–899

    Article  CAS  PubMed  Google Scholar 

  • Crowley P, Martini L (2001) Drug-excipient interactions. Pharm Technol Europe 13(3):26–28, 30–32, 34

    Google Scholar 

  • D’Souza AJ, Schowen RL, Borchardt RT, Salsbury JS, Munson EJ, Topp EM (2003) Reaction of a peptide with polyvinylpyrrolidone in the solid state. J Pharm Sci 92(3):585–593

    Article  PubMed  CAS  Google Scholar 

  • De Ritter E, Magid L, Osadca M, Rubin SH (1970) Effect of silica gel on stability and biological availability of ascorbic acid. J Pharm Sci 59(2):229–232

    Article  PubMed  Google Scholar 

  • del Barrio MA, Hu J, Zhou P, Cauchon N (2006) Simultaneous determination of formic acid and formaldehyde in pharmaceutical excipients using headspace GC/MS. J Pharm Biomed Anal 41(3):738–743

    Article  PubMed  CAS  Google Scholar 

  • Desai DS, Rubitski BA, Bergum JS, Varia SA (1994a) Effects of different types of lactose and disintegrant on dissolution stability of hydrochlorothiazide capsule formulations. Int J Pharm 110(3):257–265

    Article  CAS  Google Scholar 

  • Desai DS, Rubitski BA, Bergum JS, Varia SA (1994b) Effects of different types of lactose and disintegrant on dissolution stability of hydrochlorothiazide capsule formulations. Int J Pharm 110(3):257–265

    Article  CAS  Google Scholar 

  • Desai DS, Rubitski BA, Varia SA, Huang MH (1994c) Effect of formaldehyde formation on dissolution stability of hydrochlorothiazide bead formulations. Int J Pharm 107(2):141–147

    Article  CAS  Google Scholar 

  • Desai DS, Ranadive SA, Lozano R, Varia SA (1996) Dissolution instability of encapsulated marketed tablets. Int J Pharm 144(2):153–158

    Article  CAS  Google Scholar 

  • Desai SR, Shaikh MM, Dharwadkar SR (2003) Preformulation compatibility studies of etamsylate and fluconazole drugs with lactose by DSC. J Therm Anal Calorim 71(2):651–658

    Article  CAS  Google Scholar 

  • Desai D, Rao V, Guo H, Li D, Bolgar M (2007) Stability of low concentrations of guanine-based antivirals in sucrose or maltitol solutions. Int J Pharm 342(1–2):87–94

    Article  CAS  PubMed  Google Scholar 

  • Devani MB, Shishoo CJ, Doshi KJ, Patel HB (1985) Kinetic studies of the interaction between isoniazid and reducing sugars. J Pharm Sci 74(4):427–432

    Article  CAS  PubMed  Google Scholar 

  • Dey M, Enever R, Kraml M, Prue DG, Smith D, Weierstall R (1993) The dissolution and bioavailability of etodolac from capsules exposed to conditions of high relative humidity and temperatures. Pharm Res 10(9):1295–1300

    Article  CAS  PubMed  Google Scholar 

  • Dickinson CF, Heal GR (1999) Solid-liquid diffusion controlled rate equations. Thermochim Acta 340–341:89–103

    Article  Google Scholar 

  • Digenis GA, Gold TB, Shah VP (1994a) Cross-linking of gelatin capsules and its relevance to their in vitro-in vivo performance. J Pharm Sci 83(7):915–921

    Article  CAS  PubMed  Google Scholar 

  • Digenis GA, Gold TB, Shah VP (1994b) Cross-linking of gelatin capsules and its relevance to their in vitro-in vivo performance. J Pharm Sci 83(7):915–921

    Article  CAS  PubMed  Google Scholar 

  • Digenis GA, Sandefer EP, Page RC, Doll WJ, Gold TB, Darwazeh NB (2000) Bioequivalence study of stressed and nonstressed hard gelatin capsules using amoxicillin as a drug marker and gamma scintigraphy to confirm time and GI location of in vivo capsule rupture. Pharm Res 17(5):572–582

    Article  CAS  PubMed  Google Scholar 

  • Doherty C, York P (1989) The in-vitro pH-dissolution dependence and in-vivo bioavailability of frusemide-PVP solid dispersions. J Pharm Pharmacol 41(2):73–78

    Article  CAS  PubMed  Google Scholar 

  • Dubost DC, Kaufman MJ, Zimmerman JA, Bogusky MJ, Coddington AB, Pitzenberger SM (1996) Characterization of a solid state reaction product from a lyophilized formulation of a cyclic heptapeptide. A novel example of an excipient-induced oxidation. Pharm Res 13(12):1811–1814

    Article  CAS  PubMed  Google Scholar 

  • Durig T, Fassihi AR (1993) Identification of stabilizing and destabilizing effects of excipient-drug interactions in solid-dosage form design. Int J Pharm 97:161–170

    Article  CAS  Google Scholar 

  • EMEAguidance (2008) EMEA Guide line on the specification limits for residues of metal catalysts or metal reagents Doc. Ref. EMEA/CHMP/SWP/4446/2000. London

    Google Scholar 

  • Fereira PJ, Desjardin MA, Rohloff CM, Berry SA, Zlatkova-Karaslavova ES (2005) Non-aqueous formulations containing biodegradable polymers and methionine and solvents for removing peroxides and reducing the oxidative degradation of drugs. US Patent 2005276856

    Google Scholar 

  • Fielden KE, Newton JM, O’Brien P, Rowe RC (1988) Thermal studies on the interaction of water and microcrystalline cellulose. J Pharm Pharmacol 40(10):674–678

    Article  CAS  PubMed  Google Scholar 

  • Fitzpatrick S, McCabe JF, Petts CR, Booth SW (2002) Effect of moisture on polyvinylpyrrolidone in accelerated stability testing. Int J Pharm 246(1–2):143–151

    Article  CAS  PubMed  Google Scholar 

  • Forni F, Coppi G, Iannuccelli V, Vandelli MA, Cameroni R (1988) The grinding of the polymorphic forms of chloramphenicol stearic ester in the presence of colloidal silica. Acta Pharmaceutica Suecica 25(3):173–180

    CAS  Google Scholar 

  • Fukuyama S, Kihara N, Naksashima K, Morokoshi N, Koda S, Yasuda T (1994) Mechanism of optical isomerization of (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxopyrrolo[3,2,1-jk][1,4]-benzodiazepine-3-yl]-1H-indole-2-carboxamide (FK480) in soft capsules containing polyethylene glycol 400 and glycerol. Pharm Res 11(12):1704–1706

    Article  CAS  PubMed  Google Scholar 

  • Fukuyama S, Kihara N, Nakashima K, Morokoshi N, Koda S, Yasuda T (1996) Mechanism and suppression of optical isomerization of FK 480 in soft capsules containing polyethylene glycol 400 and glycerol. Drug Stab 1(2):128–131

    CAS  Google Scholar 

  • Gabr KE (1992) Effect of organic acids on the release patterns of weakly basic drugs from inert sustained-release matrix tablets. Eur J Pharm Biopharm 38(6):199–202

    CAS  Google Scholar 

  • George RC (1994) Investigation into the yellowing on aging of Sabril tablet cores. Drug Dev Ind Pharm 20(19):3023–3032

    Article  CAS  Google Scholar 

  • Glastrup J (1996) Degradation of polyethylene glycol. A study of the reaction mechanism in a model molecule: tetraethylene glycol. Polym Degrad Stab 52(3):217–222

    Article  CAS  Google Scholar 

  • Glombitza BW, Oelkrug D, Schmidt PC (1994) Surface acidity of solid pharmaceutical excipients. Part 1. Determination of the surface acidity. Eur J Pharm Biopharm 40(5):289–293

    CAS  Google Scholar 

  • Gordon MS, Rudraraju VS, Rhie JK, Chowhan ZT (1993) The effect of aging on the dissolution of wet granulated tablets containing super disintegrants. Int J Pharm 97(1–3):119–131

    Article  CAS  Google Scholar 

  • Gore AY, Banker GS (1979) Surface chemistry of colloidal silica and a possible application to stabilize aspirin in solid matrixes. J Pharm Sci 68(2):197–202

    Article  CAS  PubMed  Google Scholar 

  • Gu L, Strickley RG, Chi LH, Chowhan ZT (1990) Drug-excipient incompatibility studies of the dipeptide angiotensin-converting enzyme inhibitor, moexipril hydrochloride: dry powder vs wet granulation. Pharm Res 7(4):379–383

    Article  CAS  PubMed  Google Scholar 

  • Guerrieri P, Taylor LS (2009) Role of salt and excipient properties on disproportionation in the solid-state. Pharm Res 26(8):2015–2026

    Article  CAS  PubMed  Google Scholar 

  • Hancock BC, Zografi G (1994) The relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids. Pharm Res 11(4):471–477

    Article  CAS  PubMed  Google Scholar 

  • Hartauer KJ, Arbuthnot GN, Baertschi SW, Johnson RA, Luke WD, Pearson NG, Rickard EC, Tingle CA, Tsang PK, Wiens RE (2000a) Influence of peroxide impurities in povidone and crospovidone on the stability of raloxifene hydrochloride in tablets: identification and control of an oxidative degradation product. Pharm Dev Technol 5(3):303–310

    Article  CAS  PubMed  Google Scholar 

  • Hartauer KJ, Arbuthnot GN, Baertschi SW, Johnson RA, Luke WD, Pearson NG, Rickard EC, Tingle CA, Tsang PK, Wiens RE (2000b) Influence of peroxide impurities in povidone and crospovidone on the stability of raloxifene hydrochloride in tablets: identification and control of an oxidative degradation product. Pharm Dev Technol 5(3):303–310

    Article  CAS  PubMed  Google Scholar 

  • Hartley RF, Huang Y, Cassidy M, Razler TM, Qian F, Hussain MA (2011) The degradation kinetics and mechanism of an oxadiazole derivative, a g-secretase inhibitor drug candidate. J Pharm Sci (Submitted)

    Google Scholar 

  • Hasegawa J, Hanano M, Awazu S (1975) Decomposition of acetylsalicylic acid and its derivatives in solid state. Chem Pharm Bull (Tokyo) 23:86–97

    Article  CAS  Google Scholar 

  • Heidemann DR, Jarosz PJ (1991) Preformulation studies involving moisture uptake in solid dosage forms. Pharm Res 8(3):292–297

    Article  CAS  PubMed  Google Scholar 

  • Hemenway J, Kirby S, Narang A, Rao V, Paruchuri S, Derbin G, Stamato H (2010) Effect of water activity and water absorption properties on the stability of film-coated tablet formulations of a moisture sensitive active pharmaceutical ingredient. Paper presented at the American Association of Pharmaceutical Scientists Annual Meeting, New Orleans, LA

    Google Scholar 

  • Hickey MB, Peterson ML, Manas ES, Alvarez J, Haeffner F, Almarsson O (2007) Hydrates and solid-state reactivity: a survey of b-lactam antibiotics. J Pharm Sci 96(5):1090–1099

    Article  CAS  PubMed  Google Scholar 

  • Hong J, Lee E, Carter JC, Masse JA, Oksanen DA (2004) Antioxidant-accelerated oxidative degradation: a case study of transition metal ion catalyzed oxidation in formulation. Pharm Dev Technol 9(2):171–179

    Article  CAS  PubMed  Google Scholar 

  • Huffman RW, Donzel A, Bruice TC (1967) Aminolysis of esters. VII. The reaction of lysine with phenyl acetate and triacetin. J Org Chem 32(6):1973–1976

    Article  CAS  PubMed  Google Scholar 

  • ICH Q3A: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2000a) Draft revised guidance on impurities in new drug products. Q3B(R). http://www.ich.org/products/guidelines/quality/quality-single/article/impurities-in-new-drug-products.html. Accessed July 2015

  • ICHQ3B: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2000b) Draft revised guidance on impurities in new drug substances. Q3A. http://www.ich.org/products/guidelines/quality/quality-single/article/impurities-in-new-drug-products.html. Accessed July 2015

  • ICH Q3C: International Conferences on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (1997) Impurities: guidelines for residual solvents. Q3C. http://www.ich.org/products/guidelines/quality/quality-single/article/impurities-guideline-for-residual-solvents.html. Accessed July 2015

  • ICH Q1E: International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2004) Guidance for industry: Q1E evaluation of stability data. http://www.ich.org/products/guidelines/quality/quality-single/article/evaluation-of-stability-data.html. Accessed July 2015

  • Irwin WJ, Iqbal M (1991) Solid-state stability: the effect of grinding solvated excipients. Int J Pharm 75(2–3):211–218

    Article  CAS  Google Scholar 

  • Jander W (1927) Reaction in the solid state at high temperature. I. Rate of reaction for an endothermic change. Zeitschrift fuer Anorganische und Allgemeine Chemie 163:1–30

    Google Scholar 

  • Janicki CA, Almond HR Jr (1974) Reaction of haloperidol with 5-(hydroxymethyl)-2-furfuraldehyde, an impurity in anhydrous lactose. J Pharm Sci 63(1):41–43

    Article  CAS  PubMed  Google Scholar 

  • Johansen H, Moller N (1977) Solvent deposition of drugs on excipients II: interpretation of dissolution, adsorption, and absorption charcteristics of drugs. Arch Pharm Chem (Sci) 5:33–42

    Google Scholar 

  • Kararli TT, Needham TE, Seul CJ, Finnegan PM (1989) Solid-state interaction of magnesium oxide and ibuprofen to form a salt. Pharm Res 6(9):804–808

    Article  CAS  PubMed  Google Scholar 

  • Khan S, Giradkar P, Yeole P (2009) Formulation design of ranitidine hydrochloride to reduce its moisture absorption characteristics. PDA J Pharm Sci Technol 63(3):226–233

    CAS  PubMed  Google Scholar 

  • Khawam A, Flanagan DR (2005) Complementary use of model-free and modelistic methods in the analysis of solid-state kinetics. J Phys Chem B 109(20):10073–10080

    Article  CAS  PubMed  Google Scholar 

  • Khawam A, Flanagan DR (2006) Basics and applications of solid-state kinetics: a pharmaceutical perspective. J Pharm Sci 95(3):472–498

    Article  CAS  PubMed  Google Scholar 

  • Killion RB Jr, Stella VJ (1990a) The nucleophilicity of dextrose, sucrose, sorbitol, and mannitol with p-nitrophenyl esters in aqueous solution. Int J Pharm 66(1–3):149–155

    Article  CAS  Google Scholar 

  • Killion RB, Stella VJ (1990b) The nucleophilicity of dextrose, sucrose, sorbitol, and mannitol with p-nitrophenyl esters in aqueous solution. Int J Pharm 66(1–3):149–155

    Article  CAS  Google Scholar 

  • Kitamura S, Miyamae A, Koda S, Morimoto Y (1989) Effect of grinding on the solid-state stability of cefixime trihydrate. Int J Pharm 56(2):125–134

    Article  CAS  Google Scholar 

  • Konishi M, Hirai K, Mori Y (1982) Kinetics and mechanism of the equilibrium reaction of triazolam in aqueous solution. J Pharm Sci 71(12):1328–1334

    Article  CAS  PubMed  Google Scholar 

  • Kontny MJ (1988) Distribution of water in solid pharmaceutical systems. Drug Dev Ind Pharm 14(14):1991–2027

    Article  CAS  Google Scholar 

  • Kontny MJ, Koppenol S, Graham ET (1992) Use of the sorption-desorption moisture transfer model to assess the utility of a desiccant in a solid product. Int J Pharm 84(3):261–271

    Article  CAS  Google Scholar 

  • Kornblum SS, Sciarrone BJ (1964) Decarboxylation of P-aminosalicylic acid in the solid state. J Pharm Sci 53:935–941

    Article  CAS  PubMed  Google Scholar 

  • Kothari S, Paruchuri S, Rao V, Desai D (2006) Peroxide scavenging property of croscarmellose sodium and its potential to reduce N-oxidation of piperazine ring containing compounds. Paper presented at the American Association of Pharmaceutical Scientists, San Antonio, TX

    Google Scholar 

  • Ku MS, Lu Q, Li W, Chen Y (2011) Performance qualification of a new hypromellose capsule: part II. Disintegration and dissolution comparison between two types of hypromellose capsules. Int J Pharm 416(1):16–24

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Kalonia Devendra S (2006) Removal of peroxides in polyethylene glycols by vacuum drying: implications in the stability of biotech and pharmaceutical formulations. AAPS PharmSciTech 7(3):62

    Article  PubMed  Google Scholar 

  • Larsen J, Cornett C, Jaroszewski JW, Hansen SH (2009) Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state. J Pharm Biomed Anal 49(1):11–17

    Article  CAS  PubMed  Google Scholar 

  • Lessen T, Zhao DC (1996) Interactions between drug substances and excipients. 1. Fluorescence and HPLC studies of triazolophthalazine derivatives from hydralazine hydrochloride and starch. J Pharm Sci 85(3):326–329

    Article  CAS  PubMed  Google Scholar 

  • Li S, Patapoff TW, Overcashier D, Hsu C, Nguyen TH, Borchardt RT (1996) Effects of reducing sugars on the chemical stability of human relaxin in the lyophilized state. J Pharm Sci 85(8):873–877

    Article  CAS  PubMed  Google Scholar 

  • Mahato RI, Narang AS (2011) Pharmaceutical dosage forms and drug delivery, 2nd edn. CRC Press, Boca Raton

    Google Scholar 

  • March J (1992) Advanced organic chemistry: reactions, mechanisms, and structure, 4th edn, ­Wiley, New York

    Google Scholar 

  • Mauger JW, Paruta AN, Gerraughty RJ (1969) Consecutive first-order kinetic consideration of hydrocortisone hemisuccinate. J Pharm Sci 58(5):574–578

    Article  CAS  PubMed  Google Scholar 

  • Meyer MC, Straughn AB, Mhatre RM, Hussain A, Shah VP, Bottom CB, Cole ET, Lesko LL, Mallinowski H, Williams RL (2000) The effect of gelatin cross-linking on the bioequivalence of hard and soft gelatin acetaminophen capsules. Pharm Res 17(8):962–966

    Article  CAS  PubMed  Google Scholar 

  • Mollica J, Rehm C, Smith J (1969) Hydrolysis of hydrochlorotiazide. J Pharm Sci 58:1380–1384

    Article  Google Scholar 

  • Monajjemzadeh F, Hassanzadeh D, Valizadeh H, Siahi-Shadbad MR, Mojarrad JS, Robertson T, Roberts MS (2009a) Assessment of feasibility of Maillard reaction between baclofen and lactose by liquid chromatography and tandem mass spectrometry, application to pre formulation studies. AAPS PharmSciTech 10(2):649–659

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Monajjemzadeh F, Hassanzadeh D, Valizadeh H, Siahi-Shadbad MR, Mojarrad JS, Robertson TA, Roberts MS (2009b) Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets. Eur J Pharm Biopharm 73(3):404–413

    Article  CAS  PubMed  Google Scholar 

  • Murthy KS, Ghebre-Sellassie I (1993) Current perspectives on the dissolution stability of solid oral dosage forms. J Pharm Sci 82(2):113–126

    Article  CAS  PubMed  Google Scholar 

  • Murugesan R, Kaimulankara G, Pillai SRS (2007) A novel pharmaceutical composition. IN Patent 2005-CH990

    Google Scholar 

  • Mutalik S, Naha A, Usha AN, Ranjith AK, Musmade P, Manoj K, Anju P, Prasanna S (2007) Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac. Arch Pharm Res 30(2):222–234

    Article  CAS  PubMed  Google Scholar 

  • Narang AS, Rao VM, Raghavan K (2009) Excipient compatibility. In: Qiu Y, Chen Y, Zhang GGZ, Liu L, Porter W (eds) Developing solid oral dosage forms: pharmaceutical theory and practice. Elsevier, Burlington, pp 125–146

    Chapter  Google Scholar 

  • Narang AS, Lin J, Varia SA, Badawy S (2010a) Modeling drug degradation in a tablet. Paper presented at the American Association of Pharmaceutical Sciences Annual Meeting, New Orleans, LA

    Google Scholar 

  • Narang AS, Rao V, Farrell T, Ferrizzi D, Castoro J, Corredor C, Jain N, Varia S, Desai D (2010b) Stability implications of prolonged storage of PVA and PEG-based coating suspension. Paper presented at the American Association of Pharmaceutical Sciences Annual Meeting, New Orleans, LA

    Google Scholar 

  • Narang A, Kanthasamy M, Castoro J, Varia S, Desai D (2011) Effect of pro- and anti-oxidants on the formation of formyl species in PVA- and PEG-based tablet coating material. Paper presented at the American Association of Pharmaceutical Sciences Annual Meeting, Washington, DC

    Google Scholar 

  • Narang AS, Rao VM, Desai DS (2012) Effect of antioxidants and silicates on peroxides in povidone. J Pharm Sci 101(1):127–139

    Article  CAS  PubMed  Google Scholar 

  • Nassar MN, Nesarikar VN, Lozano R, Parker WL, Huang Y, Palaniswamy V, Xu W, Khaselev N (2004) Influence of formaldehyde impurity in polysorbate 80 and PEG-300 on the stability of a parenteral formulation of BMS-204352: identification and control of the degradation product. Pharm Dev Technol 9(2):189–195

    Article  CAS  PubMed  Google Scholar 

  • Naversnik K, Bohanec S (2008) Predicting drug hydrolysis based on moisture uptake in various packaging designs. Eur J Pharm Sci 35(5):447–456

    Article  CAS  PubMed  Google Scholar 

  • Nishikawa M, Fujii K (1991) Effect of autoxidation of hydrogenated castor oil containing 60 oxyethylene groups on degradation of miconazole. Chem Pharm Bull 39(9):2408–2411

    Article  CAS  Google Scholar 

  • Patel NK, Patel IJ, Cutie AJ, Wadke DA, Monkhouse DC, Reier GE (1988) The effect of selected direct compression excipients on the stability of aspirin as a model hydrolyzable drug. Drug Dev Ind Pharm 14(1):77–98

    Article  CAS  Google Scholar 

  • Perrier PR, Kesselring UW (1983) Quantitative assessment of the effect of some excipients on nitrazepam stability in binary powder mixtures. J Pharm Sci 72(9):1072–1074

    Article  CAS  PubMed  Google Scholar 

  • Phadnis NV, Suryanarayanan R (1997) Polymorphism in anhydrous theophylline-implications on the dissolution rate of theophylline tablets. J Pharm Sci 86(11):1256–1263

    Article  CAS  PubMed  Google Scholar 

  • Plackett RL, Burman JP (1946) The design of optimum multifactorial experiments. Biometrika 33:305–325

    Article  Google Scholar 

  • Podczeck F, Jones BE (2002) The in vitro dissolution of theophylline from different types of hard shell capsules. Drug Dev Ind Pharm 28(9):1163–1169

    Article  CAS  PubMed  Google Scholar 

  • Qiu Z, Stowell JG, Cao W, Morris KR, Byrn SR, Carvajal MT (2005) Effect of milling and compression on the solid-state Maillard reaction. J Pharm Sci 94(11):2568–2580

    Article  CAS  PubMed  Google Scholar 

  • Reed RA, Harmon P, Manas D, Wasylaschuk W, Galli C, Biddell R, Bergquist PA, Hunke W, Templeton AC, Ip D (2003) The role of excipients and package components in the photostability of liquid formulations. PDA J Pharm Sci Technol 57(5):351–368

    CAS  PubMed  Google Scholar 

  • Rivera SL, Ghodbane S (1994) In vitro adsorption-desorption of famotidine on microcrystalline cellulose. Int J Pharm 108(1):31–38

    Article  CAS  Google Scholar 

  • Rohrs BR, Thamann TJ, Gao P, Stelzer DJ, Bergren MS, Chao RS (1999) Tablet dissolution affected by a moisture mediated solid-state interaction between drug and disintegrant. Pharm Res 16(12):1850–1856

    Article  CAS  PubMed  Google Scholar 

  • Rowe RC, Forse SF (1983) Pitting: a defect on film coated tablets. Int J Pharm 17(2–3):347–349

    Article  CAS  Google Scholar 

  • Rowe RC, Sheskey PJ, Weller PJ, Rowe R, Sheskey P, Weller P (2003) Handbook of pharmaceutical excipients, 4th edn. APhA Publications, Pharmaceutical Press, London, UK

    Google Scholar 

  • Roy J (2002) Pharmaceutical impurities—a mini review. AAPS PharmSciTech 3(2):1–8

    Article  PubMed Central  Google Scholar 

  • Sakharov AM, Mazaletskaya LI, Skibida IP (2001) Catalytic oxidative deformylation of polyethylene glycols with the participation of molecular oxygen. Kinet Catal 42(5):662–668

    Article  CAS  Google Scholar 

  • Santos AFO, Basilio ID Jr, Souza FS, Medeiros AFD, Ferraz Pinto M, Santana DP, Macedo RO (2008) Application of thermal analysis in study of binary mixtures with metformin. J Therm Anal Calorim 93(2):361–364

    Article  CAS  Google Scholar 

  • Sarisuta N, Lawanprasert P, Puttipipatkhachorn S, Srikummoon K (2006) The influence of drug-excipient and drug-polymer interactions on butt adhesive strength of ranitidine hydrochloride film-coated tablets. Drug Dev Ind Pharm 32(4):463–471

    Article  CAS  PubMed  Google Scholar 

  • Schildcrout SA, Risley DS, Kleemann RL (1993) Drug-excipient interactions of seproxetine maleate hemihydrate: isothermal stress methods. Drug Dev Ind Pharm 19(10):1113–1130

    Article  CAS  Google Scholar 

  • Senderoff RI, Mahjour M, Radebaugh GW (1982) Characterization of adsorption behavior by solid dosage form excipients in formulation development. Int J Pharm 83(1–3):65–72

    Google Scholar 

  • Shalaev EY, Zografi G (1996) How does residual water affect the solid-state degradation of drugs in the amorphous state? J Pharm Sci 85(11):1137–1141

    Article  CAS  PubMed  Google Scholar 

  • Sherry Ku M, Li W, Dulin W, Donahue F, Cade D, Benameur H, Hutchison K (2010) Performance qualification of a new hypromellose capsule: part I. Comparative evaluation of physical, mechanical and processability quality attributes of Vcaps Plus, Quali-V and gelatin capsules. Int J Pharm 386(1–2):30–41

    Article  CAS  PubMed  Google Scholar 

  • Siepmann JI, Martin MG, Chen B, Stubbs JM, Potoff JJ (2000) Monte Carlo simulations of supercritical fluid extraction systems. Abstracts of Papers, 220th ACS National Meeting, Washington, DC, United States, August 20–24, 2000 FIELD Full Journal Title: Abstracts of Papers, 220th ACS National Meeting, Washington, DC, United States, August 20–24, 2000:COMP-143

    Google Scholar 

  • Sinclair W, Leane M, Clarke G, Dennis A, Tobyn M, Timmins P (2011) Physical stability and recrystallization kinetics of amorphous ibipinabant drug product by fourier transform Raman spectroscopy. J Pharm Sci 100(11):4687–4699

    Article  CAS  PubMed  Google Scholar 

  • Snider B, Liang P, Pearson N (2007) Implementation of water-activity testing to replace Karl Fischer water testing for solid oral-dosage forms. Pharm Technol 31(2):56, 58, 60, 62, 64–66, 68, 70–71

    Google Scholar 

  • Stanisz B (2005) The influence of pharmaceutical excipients on quinapril hydrochloride stability. Acta Pol Pharm 62(3):189–193

    CAS  PubMed  Google Scholar 

  • Stephenson GA, Aburub A, Woods TA (2011) Physical stability of salts of weak bases in the solid-state. J Pharm Sci 100(5):1607–1617

    Article  CAS  PubMed  Google Scholar 

  • Streubel A, Siepmann J, Dashevsky A, Bodmeier R (2000) pH-independent release of a weakly basic drug from water-insoluble and -soluble matrix tablets. J Control Release 67(1):101–110

    Article  CAS  PubMed  Google Scholar 

  • Swaminathan V, Kildsig DO (2001) An examination of the moisture sorption characteristics of commercial magnesium stearate. AAPS PharmSciTech 2(4):28

    Article  CAS  PubMed  Google Scholar 

  • Tallon MA, Malawer EG, Machnicki NI, Brush PJ, Wu CS, Cullen JP (2008) The effect of crosslinker structure upon the rate of hydroperoxide formation in dried, crosslinked poly(vinylpyrrolidone). J Appl Polym Sci 107(5):2776–2785

    Article  CAS  Google Scholar 

  • Tantry JS, Tank J, Suryanarayanan R (2007) Processing-induced phase transitions of theophylline-implications on the dissolution of theophylline tablets. J Pharm Sci 96(5):1434–1444

    Article  CAS  PubMed  Google Scholar 

  • Tardif R (1965) Reliability of accelerated storage tests to predict stability of vitamins (A, B-1, C) in tablets. J Pharm Sci 54:281–284

    Article  CAS  PubMed  Google Scholar 

  • Tatavarti AS, Mehta KA, Augsburger LL, Hoag SW (2004) Influence of methacrylic and acrylic acid polymers on the release performance of weakly basic drugs from sustained release hydrophilic matrices. J Pharm Sci 93(9):2319–2331

    Article  CAS  PubMed  Google Scholar 

  • Thakur AB, Morris K, Grosso JA, Himes K, Thottathil JK, Jerzewski RL, Wadke DA, Carstensen JT (1993) Mechanism and kinetics of metal ion-mediated degradation of fosinopril sodium. Pharm Res 10(6):800–809

    Article  CAS  PubMed  Google Scholar 

  • Tischinger-Wagner H, Endres W, Rupprecht H, Weingart A (1987) [Oxidative degradation of linoleic acid methyl ester in suspensions of inorganic excipients. 1. Auto-oxidation in the presence of silicic acid products and aluminum oxide]. Pharmazie 42(5):320–324

    CAS  PubMed  Google Scholar 

  • Tong P, Zografi G (2004) Effects of water vapor absorption on the physical and chemical stability of amorphous sodium indomethacin. AAPS PharmSciTech 5(2):No pp given

    Google Scholar 

  • Tuleu C, Khela MK, Evans DF, Jones BE, Nagata S, Basit AW (2007) A scintigraphic investigation of the disintegration behaviour of capsules in fasting subjects: a comparison of hypromellose capsules containing carrageenan as a gelling agent and standard gelatin capsules. Eur J Pharm Sci 30(3–4):251–255

    Article  CAS  PubMed  Google Scholar 

  • Vyazovkin S, Wight CA (1997) Kinetics in solids. Annu Rev Phys Chem 48:125–149

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Fiske JD, Jennings SP, Tomasella FP, Palaniswamy VA, Ray KL (2008) Identification and control of a degradation product in Avapro film-coated tablet: low dose formulation. Pharm Dev Technol 13(5):393–399

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Wen H, Desai D (2010) Lubrications in tablet formulations. Eur J Pharm Biopharm 75:1–15

    Article  PubMed  CAS  Google Scholar 

  • Wasylaschuk WR, Harmon PA, Wagner G, Harman AB, Templeton AC, Xu H, Reed RA (2007a) Evaluation of hydroperoxides in common pharmaceutical excipients. J Pharm Sci 96(1):106–116

    Article  CAS  PubMed  Google Scholar 

  • Wasylaschuk WR, Harmon PA, Wagner R, Wagner G, Harman AB, Tempelton AC, Xu H, Reed RA (2007b) Evaluation of hydroperoxides in common pharmaceutical excipients. J Pharm Sci 96(1):106–116

    Article  CAS  PubMed  Google Scholar 

  • Waterman KC, Adami RC (2005) Accelerated aging: prediction of chemical stability of pharmaceuticals. Int J Pharm 293(1–2):101–125

    Article  CAS  PubMed  Google Scholar 

  • Waterman KC, Macdonald BC (2010) Package selection for moisture protection for solid oral drug products. J Pharm Sci 99(11):4437–4452

    Article  CAS  PubMed  Google Scholar 

  • Waterman KC, Adami RC, Alsante KM, Antipas AS, Arenson DR, Carrier R, Hong J, Landis MS, Lombardo F, Shah JC, Shalaev E, Smith SW, Wang H (2002a) Hydrolysis in pharmaceutical formulations. Pharm Dev Technol 7(2):113–146

    Article  CAS  PubMed  Google Scholar 

  • Waterman KC, Adami RC, Alsante KM, Hong J, Landis MS, Lombardo F, Roberts CJ (2002b) Stabilization of pharmaceuticals to oxidative degradation. Pharm Dev Technol 7(1):1–32

    Article  CAS  PubMed  Google Scholar 

  • Waterman KC, Arikpo WB, Fergione MB, Graul TW, Johnson BA, Macdonald BC, Roy MC, Timpano RJ (2008a) N-methylation and N-formylation of a secondary amine drug (varenicline) in an osmotic tablet. J Pharm Sci 97(4):1499–1507

    Article  CAS  PubMed  Google Scholar 

  • Waterman KC, Gerst P, Macdonald BC (2011) Relative humidity hysteresis in solid-state chemical reactivity: a pharmaceutical case study. J Pharm Sci 101(2):610–615

    Google Scholar 

  • Wirth DD, Baertschi SW, Johnson RA, Maple SR, Miller MS, Hallenbeck DK, Gregg SM (1998) Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine. J Pharm Sci 87(1):31–39

    Article  CAS  PubMed  Google Scholar 

  • Wong J, Wiseman L, Al-Mamoon S, Cooper T, Zhang LK, Chan TM (2006) Major degradation product identified in several pharmaceutical formulations against the common cold. Anal Chem 78(22):7891–7895

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Dali M, Gupta A, Raghavan K (2009) Understanding drug-excipient compatibility: oxidation of compound A in a solid dosage form. Pharm Dev Technol 14(5):556–564

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Levons J, Narang AS, Raghavan K, Rao VM (2011a) Reactive impurities in excipients: profiling, identification and mitigation of drug-excipient incompatibility. AAPS PharmSciTech 12(4):1248–1263

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu Y, Levons J, Narang AS, Raghavan K, Rao VM (2011b) Reactive impurities in excipients: profiling, identification and mitigation of drug-excipient incompatibility. AAPS PharmSciTech (September)

    Google Scholar 

  • Wyttenbach N, Birringer C, Alsenz J, Kuentz M (2005) Drug-excipient compatibility testing using a high-throughput approach and statistical design. Pharm Dev Technol 10(4):499–505

    Article  CAS  PubMed  Google Scholar 

  • Yarkala S, Amaravadi S, Rao VU, Vijaykumar V, Navalgund SG, Jagdish B (2009) Role of excipients on N-oxide raloxifene generation from raloxifene-excipients binary mixtures. Chem Pharm Bull 57(10):1174–1177

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka S, Stella VJ (2000) Stability of drugs and dosage forms. Kluwer, New York

    Google Scholar 

  • Yoshioka S, Uchiyama M (1986) Kinetics and mechanism of the solid-state decomposition of propantheline bromide. J Pharm Sci 75(1):92–96

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka S, Ogata H, Shibazaki T, Ejima A (1979) Stability of sulpyrine. V. Oxidation with molecular oxygen in the solid state. Chem Pharm Bull (Tokyo) 27:2363–2371

    Article  CAS  Google Scholar 

  • Yoshioka S, Shibazaki T, Eijima A (1983) Stability of solid dosage forms. II. Hydrolysis of meclofenoxate hydrochloride in commercial tablets. Chem Pharm Bull (Tokyo) 31:2513–2517

    Article  CAS  Google Scholar 

  • Yoshioka S, Aso Y, Shibazaki T, Uchiyama M (1986) Stability of pilocarpine ophthalmic formulations. Chem Pharm Bull (Tokyo) 34(10):4280–4286

    Article  CAS  Google Scholar 

  • Yoshioka S, Aso Y, Terao T (1992) Effect of water mobility on drug hydrolysis rates in gelatin gels. Pharm Res 9(5):607–612

    Article  CAS  PubMed  Google Scholar 

  • Yu H, Cornett C, Larsen J, Hansen SH (2010) Reaction between drug substances and pharmaceutical excipients: formation of esters between cetirizine and polyols. J Pharm Biomed Anal 53(3):745–750

    Article  CAS  PubMed  Google Scholar 

  • Yuan LC, Dahl TC, Oliyai R (2000) Effect of carbonate salts on the kinetics of acid-catalyzed dimerization of adefovir dipivoxil. Pharm Res 17(9):1098–1103

    Article  CAS  PubMed  Google Scholar 

  • Zannou EA, Ji Q, Joshi YM, Serajuddin AT (2007) Stabilization of the maleate salt of a basic drug by adjustment of microenvironmental pH in solid dosage form. Int J Pharm 337(1–2):210–218

    Article  CAS  PubMed  Google Scholar 

  • Zhou D, Schmitt EA, Zhang GG, Law D, Wight CA, Vyazovkin S, Grant DJ (2003) Model-free treatment of the dehydration kinetics of nedocromil sodium trihydrate. J Pharm Sci 92(7):1367–1376

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The majority of this chapter and illustrations are reprinted from Pharmaaceutical Research, Vol. 29 (© 2012) pp 2660–2683, with permission from Springer.

Author information

Authors and Affiliations

  1. Drug Product Science and Technology, Bristol-Myers Squibb, Co., One Squibb Dr., 08903, New Brunswick, NJ, USA

    Ajit S. Narang Ph.D., Divyakant Desai & Sherif Badawy

Authors
  1. Ajit S. Narang Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Divyakant Desai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sherif Badawy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ajit S. Narang Ph.D. .

Editor information

Editors and Affiliations

  1. Bristol-Myers Squibb, Co., New Brunswick, New Jersey, USA

    Ajit S Narang

  2. Division of Industrial Pharmacy, Department of Pharmacy Practice, The University of Toledo, TOLEDO, Ohio, USA

    Sai H S. Boddu

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Narang, A., Desai, D., Badawy, S. (2015). Impact of Excipient Interactions on Solid Dosage Form Stability. In: Narang, A., Boddu, S. (eds) Excipient Applications in Formulation Design and Drug Delivery. Springer, Cham. https://doi.org/10.1007/978-3-319-20206-8_5

Download citation

Publish with us

Policies and ethics

Search

Navigation