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Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

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Excipient Applications in Formulation Design and Drug Delivery

Abstract

Moisture sensitivity of active pharmaceutical ingredients (APIs) presents a formidable challenge in the formulation of oral dosage forms. The interaction of moisture with APIs is crucial to an understanding of water-based processes, e.g. manufacturing or prediction of solid dosage form stability and shelf-life. Unwarranted moisture sorption by either APIs or excipients can result in unstable oral solid formulations. The appropriate selection of excipients for the core formulation and appropriate moisture barrier film coating helps to remedy the moisture-related issues with APIs and thus can improve the storage stability of the final formulations. In this chapter, we review the nature and extent of the moisture sensitivity and possible approaches taken to overcome it. Use of excipients that bind tightly with water reduce its potential interaction with the API. In addition, application of a barrier coating to reduce rate and extent of moisture ingress into the core of the solid dosage form during the storage (in original packaging or while in-use), are some of the many simple options that have been considered and described.

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Abbreviations

Alu:

Aluminum

API:

Active pharmaceutical ingredient

ASA:

Acetylsalicylic acid

CAM:

Controlled atmosphere microbalance

CCS:

Croscarmellose sodium

DCP:

Dibasic calcium phosphate

DVS:

Dynamic vapor sorption

EC:

Ethyl cellulose

ERH:

Equilibrium relative humidity

FBD:

Freezing bound water

FT:

Fourier transform

FW:

Free water

HDPE:

High density polyethylene

HPC:

Hydroxypropyl cellulose

HPMC:

hydroxypropylmethyl cellulose

DSC:

Differential scanning calorimetry

DVS:

Dynamic vapor sorption

ERH:

Equilibrium relative humidity

IMC:

Isothermal microcalorimetry

LOD:

Loss on drying

MCC:

Microcrystalline cellulose

MVTR:

Moisture vapor transmission rate

NIR:

Near infra-red spectroscopy

NMR:

Nuclear magnetic resonance

OWS:

Optical waveguide spectroscopy

PVA:

Polyvinyl alcohol

PVC:

Polyvinyl chloride

PVP:

Polyvinyl pyrrolidone

RH:

Relative humidity

SSG:

Sodium starch glycollate

TGA:

Thermogravimetric analysis

USP:

United states pharmacopeia

WVTR:

Water vapor transmission rate

References

  • Achanta AS, Adusumilli PS, James KW, Rhodes CT (2001a) Thermodynamic analysis of water interaction with excipient films. Drug Dev Ind Pharm 27(3):227–240

    Article  CAS  PubMed  Google Scholar 

  • Achanta AS, Adusumilli PS, James KW, Rhodes CT (2001b) Hot-melt coating: water sorption behavior of excipient films. Drug Dev Ind Pharm 27(3):241–250

    Article  CAS  PubMed  Google Scholar 

  • Agrawal AM, Manek RV, Kolling WM, Neau SH (2003a) Studies on the interaction of water with ethylcellulose: effect of polymer particle size. AAPS PharmSciTech 4(4):E60

    Article  PubMed  Google Scholar 

  • Agrawal AM, Manek RV, Kolling WM, Neau SH (2003b) Water distribution studies within microcrystalline cellulose and chitosan using differential scanning calorimetry and dynamic vapor sorption analysis. J Pharm Sci 93:1766–1779

    Article  CAS  Google Scholar 

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

    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 62:87–95

    Article  CAS  Google Scholar 

  • Airaksinen S, Luukkonen P, Jørgensen A, Karjalainen M, Rantanen J, Yliruusi J (2003) Effects of excipients on hydrate formation in wet masses containing theophylline. J Pharm Sci 92:516–528

    Article  CAS  PubMed  Google Scholar 

  • Airaksinen S, Karjalainen M, Shevchenko A, Westermarck S, Leppänen E, Rantanen J, Yliruusi J (2005a) Role of water in the physical stability of solid dosage formulations. J Pharm Sci 94(10):2147–2165

    Article  CAS  PubMed  Google Scholar 

  • Airaksinen S, Karjalainen M, Kivikero N, Westermarck S, Shevchenko A, Rantanen J, Yliruusi J (2005b) 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 

  • Angberg M (1995) Lactose and thermal analysis with special emphasis on microcalorimetry. Thermochim Acta 248:161

    Article  CAS  Google Scholar 

  • Angberg M, Nyström C, Castensson S (1988) Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies. I. Precision and accuracy for static experiments in glass vials. Acta Pharm Suec 25:307–320

    CAS  PubMed  Google Scholar 

  • Angberg M, Nyström C, Castensson S (1990) Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies. II. Methods to evaluate the microcalorimetric response. Int J Pharm 61:67–77

    Article  CAS  Google Scholar 

  • Angberg M, Nyström C, Castensson S (1991) Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies. III. Crystallographic changes due to water vapor uptake in anhydrous lactose powder. Int J Pharm 73:209–220

    Article  CAS  Google Scholar 

  • Angberg M, Nyström C, Castensson S (1992a) Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies. V. A new approach for continuous measurements in abundant water vapour. Int J Pharm 81:153–167

    Article  CAS  Google Scholar 

  • Angberg M, Nyström C, Castensson S (1992b) Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies. VI. Continuous monitoring of the interaction of watervapour with powders and powder mixtures at various relative humidities. Int J Pharm 83:11–23

    Article  CAS  Google Scholar 

  • Aso Y, Yoshioka S, Terao T (1994) Effect of binding of water to excipients as measured by 2 H-NMR relaxation time on cephalothin decomposition rate. Chem Pharm Bull 42:398–401

    Article  CAS  Google Scholar 

  • Aso Y, Sufang T, Yoshioka S, Kojima S (1997) Amount of mobile water estimated from 2 H spin–lattice relaxation time, and its effects on the stability of cephalothin in mixtures with pharmaceutical excipients. Drug Stab 1:237–42

    CAS  Google Scholar 

  • Aso Y, Yoshioka S, Kojima S (2001) Feasibility of using isothermal microcalorimetry to evaluate the physical stability of amorphous nifedipine and phenobarbital. Therm Acta 380:199–204

    Article  CAS  Google Scholar 

  • Aulton ME, Twitchell AM (1995) Film coat quality. In: Cole GC (ed) Pharmaceutical coating technology. Taylor & Francis, London, pp 363–408

    Google Scholar 

  • Badaway SIF, 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 223:1–13

    Article  Google Scholar 

  • Baert L, Remon JP (1993) Water vapour permeation of aqueous based ethylacrylatemethylmethacrylate copolymer films. Int J Pharm 99:181–187

    Article  CAS  Google Scholar 

  • Belder EG, Rutten HJJ, Perera DY (2001) Cure characterization of powder coatings. Prog Org Coat 42(3):142–149

    Article  CAS  Google Scholar 

  • Bell LN, Hageman MJ (1994) Differentiating between the effects of water activity and glass transition dependent mobility on a solid state chemical reaction: aspartame degradation. J Agric Food Sci 42:2398–2401

    Article  CAS  Google Scholar 

  • Bergren MS ( 1994) An automated controlled atmosphere microbalance for the measurement of moisture sorption. Int J Pharm 103:103–114

    Google Scholar 

  • Best R, Spingler E (1972) Messung von Adsorptions- und Desorptionisothermen mit einer vollautomatischen Apparatur. Chem-Ing-Techn 44:1222–1226

    Article  CAS  Google Scholar 

  • Bhaskar G, Ford JL, Hollingsbee DA (1998) Thermal analysis of the water uptake by hydrocolloids. Thermochim Acta 322:153–165

    Article  CAS  Google Scholar 

  • Bhutani H, Mariappan TT, Singh S (2003) Behaviour of uptake of moisture by drugs and excipients under accelerated conditions of temperature and humidity in the absence and the presence of light. Part II: packaged and unpackaged antituberculosis drug products. Pharm Tech 27(6):44–52

    Google Scholar 

  • Blair TC, Buckton G, Beezer AE, Bloomfield SF (1990) The interaction of various types of microcrystalline cellulose and starch with water. Int J Pharm 63:251–257

    Article  CAS  Google Scholar 

  • Bley O, Siepmann J, Bodmeier R (2009a) Protection of moisture-sensitive drugs with aqueous polymer coatings: importance of coating and curing conditions. Int J Pharm 378(1–2):59–65

    Article  CAS  PubMed  Google Scholar 

  • Bley O, Siepmann J, Bodmeier R (2009b) Importance of glassy-to-rubbery state transitions in moisture-protective polymer coatings. Eur J Pharm Biopharm 73:146–153

    Article  CAS  PubMed  Google Scholar 

  • Bley O, Siepmann J, Bodmeier R (2009c) Characterization of moisture-protective polymer coatings using differential scanning calorimetry and dynamic vapor sorption. J Pharm Sci 98(2):651–664

    Article  CAS  PubMed  Google Scholar 

  • Bodmeier R, McGinity JW (2005) Dry coating of solid substrates with polymeric powders. Drug Del Tech 5(9):70–73

    CAS  Google Scholar 

  • Buckton G (2000) Isothermal microcalorimetry water sorption experiments: calibration issues. Thermochim Acta 347:63–71

    Article  CAS  Google Scholar 

  • Buckton G, Beezer AE (1988) A microcalorimetric study of powder surface energetics. Int J Pharm 41:139–145

    Google Scholar 

  • Buckton G, Beezer AE (1991) A microcalorimetric study on the role of moisture in photolysis of nifedipine powder. Int J Pharm 72:181

    Google Scholar 

  • Buckton G, Choularton A, Beezer AE, Chatham SM (1988) The effect of comminution technique on the surface energy of a powder. Int J Pharm 47:121–128

    Google Scholar 

  • Bugay DE (1993) Solid-state nuclear magnetic resonance spectroscopy: theory and pharmaceutical applications. Pharm Res 10(3):317–327

    Google Scholar 

  • Burghart W, Burghart K, Raneburger J (2004) Solid formulation of levothyroxine and/or liothyronine salts containing controlled amount of water for stability. (Globopharm Pharmazeutische Produktions- und Handelsgesellschaft m.b.H., Austria). Patent Application.

    Google Scholar 

  • Carstensen JT (1980) Solid pharmaceutics: mechanical properties and rate phenomena. Academic, New York

    Google Scholar 

  • Carstensen JT (1988) Effect of moisture on the stability of solid dosage forms. Drug Dev Ind Pharm 14:1927–1969

    Google Scholar 

  • Carstensen JT, Li Wan Po A (1992) The state of water in drug decomposition in the moist solid state: description and modeling. Int J Pharm 83:87–94

    Google Scholar 

  • Carstensen JT, Van Scoik L (1990) Amorphous-to-crystalline transformation of sucrose. Pharm Res 7:1278–1281

    Google Scholar 

  • Cerea M, Zheng W, Young CR, McGinity JW (2004) A novel powder coating process for attaining taste masking and moisture protective films applied to tablets. Int J Pharm 279:127–139

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Chu L-Q, Mao H-Q, Knoll W (2006) In situ characterization of moisture sorption/desorption in thin polymer films using optical waveguide spectroscopy. Polymer 47(21):7406–7413

    Article  CAS  Google Scholar 

  • Collier JW, Shah RB, Gupta A, Sayeed V, Habib MJ, Khan MA (2010) Influence of formulation and processing factors on stability of levothyroxine sodium pentahydrate. AAPS PharmSciTech 11(2):818–825

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Craig DQM, Doherty C (1998) Characterisation of the glass transition of an amorphous drugusing modulated DSC. Pharm Res 15:1117–1121

    Article  PubMed  Google Scholar 

  • Craig DQM, Johnson FA (1995) Pharmaceutical applications of dynamic mechanical thermal analysis. Thermochim Acta 248:97–115

    Article  CAS  Google Scholar 

  • Creamer M (2010) Masterclass. Dehumidification. Part 54. ACR News. http://www.businessedgeltd.co.uk/master_class/mc54.pdf. Accessed 2 April 2015

  • Cunningham C (1999) Maize starch and superdisintegrants in a direct compression formulation. Pharm Manuf Rev 12:22–24

    Google Scholar 

  • Cunningham CR, Scattergood LK (2004) The effect of Starch 1500® on the stability of aspirin tablets stored under accelerated conditions. Poster presentation at the meeting of the American association of pharmaceutical scientists, Baltimore, MD, November 2004

    Google Scholar 

  • Cunningham CR, Kinsey BR, Scattergood LK (2001) Formulation of acetylsalicylic acid tablets for aqueous enteric film coating. Pharm Tech Eur. 13:38–43

    Google Scholar 

  • Cunningham C, Farrell T, Quiroga A (2005) The effect of coating process conditions and coating formula type on the quantity and location of water in film coated tablets. SAFyBI poster presentation, Buenos Aires, AR. 2005

    Google Scholar 

  • Delwiche SR, Pitt RE, Norris KN (1991) Examination of starch-water and cellulose-water interactions with near infrared (NIR) diffuse reflectance spectroscopy. Starch/Stärke 43(11):415–422

    Article  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 59:229–232

    Article  CAS  PubMed  Google Scholar 

  • Du J, Hoag SW (2001) The influence of excipients on the stability of the moisture sensitive drugs aspirin and niacinamide: comparison of tablets containing lactose monohydrate with tablets containing anhydrous lactose. Pharm Dev Technol 6(2):159–166

    Article  CAS  PubMed  Google Scholar 

  • Dürig T, Fassihi AR (1993) Identification of stabilizing and destabilizing effects of excipient-drug interactions in solid dosage form design. Int J Pharm 97(1–3):161–170

    Article  Google Scholar 

  • Eichie FE, Okor RS (2007) Application of a certain acrylatemethacrylate (water-insoluble) copolymer in protective coating of aspirin tablets. J Pharm Res 6(1):17–19

    CAS  Google Scholar 

  • Elder JP (1994) Thermophysical characterization studies of pharmaceutical hydrates. Thermochim Acta 234:153–164

    Article  CAS  Google Scholar 

  • Fegely K, Prusak B (2003) Correlation of free salicylic acid content to the water vapor transmission properties of aqueous film coating systems. Abstracts of posters. Meeting of the American association of pharmaceutical scientists, Salt Lake City, UT, October 2003

    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: 674–678

    Article  CAS  PubMed  Google Scholar 

  • Flemming A, Picker-Freyer KM (2008) Compaction of lactose drug mixtures: quantification of the extent of incompatibility by FT-Raman spectroscopy. Eur J Pharm Biopharm 68(3):802–810

    Article  CAS  PubMed  Google Scholar 

  • Ford JL (1999) Thermal analysis of hydroxypropylmethylcellulose and methylcellulose: powders, gels and matrix tablets. Int J Pharm 179:209–228

    Article  CAS  PubMed  Google Scholar 

  • Friend B, Jordan M, Turnbull N (2002) Characterisation of the water vapour permeability of pharmaceutical film coating polymers. Annual meeting of the American association of pharmaceutical scientists. Chicago. November, 2002

    Google Scholar 

  • Fukumori Y (1997) Coating of multiparticulates using polymeric dispersions. In: Ghebre-Sellassie I (ed) Multiparticulate oral drug delivery. Marcel Dekker, New York, pp 79–111

    Google Scholar 

  • Gaisford S, Buckton G (2001) Potential applications of microcalorimetry for the study of physical processes in pharmaceuticals. Therm Acta 380(2):185–198

    Article  CAS  Google Scholar 

  • Gal S (1967) Anleitungen für die chemische Laboratoriumpraxis, XI: Die methodic der wasserdampf-sorptionsmessungen. Springer, Berlin

    Book  Google Scholar 

  • Gal S (1975) Recent advances in techniques for the determination of adsorption isotherms. In: Duckworth RB (ed) Water relations of foods. Academic Press, London, pp 139–154

    Google Scholar 

  • Gal S (1981) Recent developments in techniques for obtaining complete sorption isotherms. In: Rockland LB, Stewart GF (eds) Water activity: influences on food quality. Academic, New York, pp 89–110

    Chapter  Google Scholar 

  • Gander P (1999) Barrier materials make more resistant blisters. Manuf Chem 70:31–32

    Google Scholar 

  • Gimbel J, To D, Prusak B, Teckoe J, Rajabi-Siahboomi AR (2014) Evaluation of a novel, PEG-free, immediate release Opadry aqueous moisture barrier film coating with high productivity. AAPS annual meeting and exposition, San Diego, USA

    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 68:197–202

    Article  CAS  PubMed  Google Scholar 

  • Gouda HW, Moustafa MA, Al-Shora HI (1984) Effect of storage on nitrofurantoin solid dosage forms. Int J Pharm 18:213–215

    Article  CAS  Google Scholar 

  • Gruber P, Spickermann D (2008) Stabilized solid pharmaceutical compositions containing moisture-sensitive active components. EP1902708A1 (Patent)

    Google Scholar 

  • Gurny PR (1976) Permeability of water vapor in polymers utilized for coating in the form of free films. Pharm Acta Helv 51(1):1–10

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Hancock BC, Zografi G (1997) Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 86:1–12

    Article  CAS  PubMed  Google Scholar 

  • Hansen LD (2000) Calorimetric measurement of the kinetics of slow reactions. Ind Eng Chem Res 39:3541–3549

    Article  CAS  Google Scholar 

  • Hansen LD, Crawford JW, Keiser DR, Wood RW (1996) Calorimetric method for rapid determination of critical water vapor pressure and kinetics of water sorption on hygroscopic compounds. Int J Pharm 137:1

    Article  CAS  Google Scholar 

  • Hatakeyama H, Hatakeyama T (1998) Interaction between water and hydrophilic polymers. Thermochim Acta 308:3–22

    Article  CAS  Google Scholar 

  • Hatakeyama T, Nakamura K, Hatakeyama H (2000) Vaporization of bound water associated with cellulose fibres. Thermochim Acta. 352/353:233–239

    Article  Google Scholar 

  • Heidarian M, Mihranyan A, Strømme M, Ek R (2006) Influence of water-cellulose binding energy on stability of acetylsalicylic acid. Int J Pharm 323:139–145

    Article  CAS  PubMed  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 moisture absorption properties on the stability of film-coated tablet formulations of a moisture sensitive active pharmaceutical ingredient. Annual meeting of the American association of pharmaceutical scientists, New Orleans, LA

    Google Scholar 

  • Heng PWS, Easterbrook M (2002) Tablet coating technology. Eur Pharm Rev 7(3):44–47

    Google Scholar 

  • Herman J, Visavarungroj N, Remon JP (1989) Instability of drug release from anhydrous theophylline-microcrystalline cellulose formulations. Int J Pharm 55:143–146

    Article  CAS  Google Scholar 

  • Hodge RM, Edward GH, Simon GP (1996) Water absorption and states of water in semicrystallinepoly(vinyl alcohol) films. Polymer 37:1371–1376

    Article  CAS  Google Scholar 

  • Hollenbeck RG, Peck GE, Kildsig DO (1978) Application of immersional calorimetry to the investigation of solid liquid interactions: microcrystalline cellulose-water system. J Pharm Sci 67(11):1599–1606

    Article  CAS  PubMed  Google Scholar 

  • Hughes K, Crake N, Farrell T, Do N, Yu F, Vautravers S (2006) Protection and processing of a highly hygroscopic herbal extract by drug layering and film coating. Abstracts of posters. Meeting of the American association of pharmaceutical scientists, San Antonio, TX, November 2006

    Google Scholar 

  • Islam SMA, Hossain A, Kabir ANMH, Kabir S, Hossain K (2008) Study of moisture absorption by ranitidine hydrochloride: effect of % RH, excipients, dosage forms and packing materials. Dhaka Univ J Pharm Sci 7(1):59–64

    Google Scholar 

  • Jain R, Railkar AS, Malick AW, Rhodes CT, Shah NH (1998) Stability of a hydrophobic drug in presence of hydrous and anhydrous lactose. Eur J Pharm Biopharm 46(2):177–182

    Article  CAS  PubMed  Google Scholar 

  • Jordan MP, Easterbrook MG, Hogan JE (1995) Investigations into the moisture barrier properties of polyvinylalcohol (PVA) tablet film coatings. In: Proceedings of first world meeting APGI/APV, Budapest, May 1995

    Google Scholar 

  • Jørgensen AC, Airaksinen S, Karjalainen M, Luukkonen P, Rantanen J, Yliruusi J (2004) Role of excipients in hydrate formation kinetics of theophylline in wet masses studied by near-infrared spectroscopy. Eur J Pharm Sci 23:99–104

    Article  PubMed  CAS  Google Scholar 

  • Joshi NH, Topp EM (1992) Hydration in hyaluronic acid and its esters using differential scanning calorimetry. Int J Pharm 80:213–225

    Article  CAS  Google Scholar 

  • Joshi NH, Wilson TD (1993) Calorimetric studies of dissolution of hydroxypropyl methylcellulose E5 (HPMC E5) in water. J Pharm Sci 82:1033–1038

    Article  CAS  PubMed  Google Scholar 

  • Kahela P, Aaltonen R, Lewing E, Anttila M, Kristoffersson E (1983) Pharmacokinetics and dissolution of two crystalline forms of carbamazepine. Int J Pharm 14(1):103–112

    Article  CAS  Google Scholar 

  • Khan K, Pilpel N (1987) An investigation of moisture sorption in microcrystalline cellulose using sorption isotherms and dielectric response. Powder Technol 50:237–241

    Article  CAS  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 63:226–233

    CAS  PubMed  Google Scholar 

  • Khankari RK, Grant DJW (1995) Pharmaceutical hydrates. Thermochim Acta 248:61–79

    Article  CAS  Google Scholar 

  • Khankari RK, Law D, Grant DJW (1992) Determination of water content in pharmaceutical hydrates by differential scanning calorimetry. Int J Pharm 82(1–2):117–127

    Article  CAS  Google Scholar 

  • Konno H, Taylor LS (2008) Ability of different polymers to inhibit the crystallization of amorphous felodipine in the presence of moisture. Pharm Res 25(4):969–978

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Kontny MJ, Conners JJ (2002) Encyclopedia of pharmaceutical technology. 2nd edn New York: Marcel Dekker, pp 2970–2987 (In: Swarbick J, Boylan JC (eds))

    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 

  • Kristajansson T (2007) A stable pharmaceutical formulation of olanzapine. WO2007/052164 A2 (Patent)

    Google Scholar 

  • Lane RA, Buckton G (2000) The novel combination of dynamic vapor sorption gravimetric analysis and near infra-red spectroscopy as a hyphenated technique. Int J Pharm 2007:49–56

    Article  Google Scholar 

  • Langmuir I (1917) The constitution and fundamental properties of solids and liquids. J Am Chem Soc 39 (9):1848–1906

    Google Scholar 

  • Lechuga-Ballesteros D, Bakri A, Miller DP (2003) Microcalorimetric measurement of the interaction between water vapor and amorphous pharmaceutical solids. Pharm Res 20(2):308–318

    Article  CAS  PubMed  Google Scholar 

  • Leeson LJ, Mattocks AM (1958) Decomposition of aspirin in the solid state. J Am Pharm Assoc 47(5):329–333

    Article  CAS  Google Scholar 

  • Levina M, Cunningham CR (2005) The effect of core design and formulation on the quality of film coated tablets. Pharm Tech Eur 4:29–37

    Google Scholar 

  • Levina M, Wan P (2004) The influence of core formulation, film coating level and storage conditions on stability of ranitidine tablets. Abstracts of posters. Meeting of the American association of pharmaceutical scientists, Baltimore, MD, November 2004

    Google Scholar 

  • Li Y, Sanzgiri YD, Chen Y (2003) A study on moisture isotherms of formulations: the use of polynomial equations to predict the moisture isotherms of tablet products. AAPS Pharm Sci Tech 4(4):E59

    Article  Google Scholar 

  • Luthra SA, Shalaev EY, Medek A, Hong J, Pikal MJ (2012) Chemical stability of amorphous materials: specific and general media effects in the role of water in the degradation of freeze-dried zoniporide. J Pharm Sci 101(9):3110–3123

    Article  CAS  PubMed  Google Scholar 

  • Luukkonen P, Rantanen J, Mäkelä K, Räsänen E, Tenhunen J, Yliruusi J (2001) Characterization of silicified microcrystalline cellulose and a-lactose monohydrate wet masses using near infrared spectroscopy. Pharm Dev Technol 6:1–9

    Article  CAS  PubMed  Google Scholar 

  • Marshall PV, York P (1989) Crystallisation solvent induced solid-state and particulate modifications of nitrofurantoin. Int J Pharm 55(2–3):257–263

    Article  CAS  Google Scholar 

  • Martinez H, Byrn SR, Pfeiffer RR (1990) Solid-state chemistry and crystal structure of cefaclordihydrate. Pharm Res 7(2):147–153

    Article  CAS  PubMed  Google Scholar 

  • McCrystal CB, Ford JL, Rajabi-Siahboomi AR (1997) A study on the interaction of water and cellulose ethers using differential scanning calorimetry. Thermochim Acta 294:91–98

    Article  CAS  Google Scholar 

  • McCrystal CB, Ford JL, Rajabi-Siahboomi AR (1999) Water distribution studies within cellulose ethers using differential scanning calorimetry. 1. Effect of polymer molecular weight and drug addition. J Pharm Sci 88(8):797–801

    Article  CAS  PubMed  Google Scholar 

  • McCrystal CB, Ford JL, He R, Craig DQ, Rajabi-Siahboomi AR (2002) Characterization of water behavior in cellulose ether polymers using low frequency dielectric spectroscopy. Int J Pharm 243:57–69

    Article  CAS  PubMed  Google Scholar 

  • McGinity JW (ed) (1997) Aqueous polymeric coatings for pharmaceutical dosage forms, 2nd edn. Marcel Dekker, New York

    Google Scholar 

  • McGinity JW (2005) Dry powder coating: a novel technique for film coating solid substrates. Yakuzaigaku 65(3):134–138

    CAS  Google Scholar 

  • Mihranyan A, Llagostera AP, Karmag R, Strømme M, Ek R (2004) Moisture sorption by cellulose powders of varying crystallinity. Int J Pharm 269:433–442

    Article  CAS  PubMed  Google Scholar 

  • Mihranyan A, Strømme M, Ek R (2006) Influence of cellulose powder structure on moisture-induced degradation of acetylsalicylic acid. Eur J Pharm Sci 27:220–225

    Article  CAS  PubMed  Google Scholar 

  • Mitrevej A, Hollenbeck RG (1983) Influence of hydrophilic excipients on the interaction of aspirin and water. Int J Pharm 14:243–250

    Article  CAS  Google Scholar 

  • Monkhouse DC, Van Campen L (1984) Solid state reactions—theoretical and experimental aspects. Drug Dev Ind Pharm 10:1175–1276

    Article  CAS  Google Scholar 

  • Moribe K, Sekiya N, Fujito T, Yamamoto M, Higashi K, Yokohama C, Tozuka Y, Yamamoto K (2007) Stabilization mechanism of limaprost in solid dosage form. Int J Pharm 338(1–2):1–6

    Article  CAS  PubMed  Google Scholar 

  • Morris T, Carstensen JT (1990) Effect of single to multilayer moisture coverage on stability of indomethacin in the solid state. Pharm Res 7:S195

    Article  Google Scholar 

  • Morris KR, Rodriguez-Hornedo NH (1993) Encyclopedia of pharmaceutical technology. Marcel Dekker: New York, pp 393–440 (In: Swarbrick J, Boylan JC (eds))

    Google Scholar 

  • Mwesigwa E, Buckton G, Basit AW (2005) The hygroscopicity of moisture barrier film coatings. Drug Dev Ind Pharm 31:959–968

    Article  CAS  PubMed  Google Scholar 

  • Mwesigwa E, Basit AW, Buckton G (2008) Moisture sorption and permeability characteristics of polymer films: implications for their use as barrier coatings for solid dosage forms containing hydrolyzable drug substances. J Pharm Sci 97(10):4433–4445

    Article  CAS  PubMed  Google Scholar 

  • Nakamura K, Hatakeyama T, Hatakeyama H (1983) Relationship between hydrogen bonding and bound water in polyhydroxystyrene derivatives. Polymer 24:871–876

    Article  CAS  Google Scholar 

  • Narang AS, Desai D, Badawy S (2012) Impact of excipient interactions on solid dosage form stability. Pharm Res 29(10):2660–2683

    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 

  • Nokhodchi A, Ford JL, Rubinstein MH (1997) Studies on the interaction between water and (hydroxypropyl)methylcellulose. J Pharm Sci 86(5):608–615

    Article  CAS  PubMed  Google Scholar 

  • Obara S, Maruyama N, Nishiyama Y, Kokubo H (1999) Dry coating: an innovative enteric coating method using a cellulose derivative. Eur J Pharm Biopharm 47:51–59

    Article  CAS  PubMed  Google Scholar 

  • Okhamafe AO, York P (1983) Analysis of the permeation and mechanical characteristics of some aqueous-based film coating systems. J Pharm Pharmacol 35:409–415

    Article  CAS  PubMed  Google Scholar 

  • Osawa T, Kamat MS, DeLuca PP (1988) Hydrscopicity of cefazolin sodium: application to evaluate the crystallinity of freeze-dried products. Pharm Res 5:421–425

    Article  CAS  PubMed  Google Scholar 

  • Otsuka M, Teraoka R, Matsuda Y (1991) Physicochemical stability of nitrofurantoin anhydrate and monohydrate under various temperature and humidity conditions. Pharm Res 8(8):1066–1068

    Article  CAS  PubMed  Google Scholar 

  • Otsuka T, Yoshioka S, Aso Y, Kojima S (1995) Water mobility in aqueous solutions of macromolecular pharmaceutical excipients measured by oxygen-17 nuclear magnetic resonance. Chem Pharm Bull 43:1221–1223

    Article  CAS  Google Scholar 

  • Otsuka M, Hasegawa H, Matsuda Y (1997) Effect of polymorphic transformation during the extrusion granulation process on the pharmaceutical properties of carbamazepine granules. Chem Pharm Bull 45:894–898

    Article  CAS  Google Scholar 

  • Otsuka M, Ohfusa T, Matsuda Y (2000) Effect of binders on polymorphic transformation kinetics of carbamazepine in aqueous solution. Colloids Surf B Biointerfaces 17:145–152

    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 

  • Pearnchob N, Bodmeier R (2003) Dry polymer powder coating and comparison with conventional liquid-based coatings for Eudragit RS, ethylcellulose and shellac. Eur J Pharm Biopharm 56:363–369

    Article  CAS  PubMed  Google Scholar 

  • Pearnchob N, Siepmann J, Bodmeier R (2003) Pharmaceutical applications of shellac: moisture-protective and taste-masking coatings and extended-release matrix tablets. Drug Dev Ind Pharm 29:925–938

    Article  CAS  PubMed  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 72:1072–1074

    Article  CAS  PubMed  Google Scholar 

  • Phipps MA, Mackin LA (2000) Application of isothermal microcalorimetry in solid state drug development. Pharm Sci Tech Today 3(1):9–17

    Article  CAS  Google Scholar 

  • Pikal MJ, Dellerman M (1989) International stability testing of pharmaceuticals by high-sensitivity isothermal calorimetry at 25 °C: cephalosporins in the solid and aqueous solution states. IntJ Pharm 50:233–252

    Article  CAS  Google Scholar 

  • Pikal MJ, Lukes AL, Lang JE (1977) Thermal decomposition of amorphous beta-lactam antibacterials. J Pharm Sci 66(9):1312–1316

    Article  CAS  PubMed  Google Scholar 

  • Plaizier-Vercammen JA, De Neve RE (1993) Evaluation of water and organic coating formulations for the protection of tablets against humidity. Pharmazie 48(6):441–446

    CAS  Google Scholar 

  • Poole JW, Owen G, Silverio J, Freyhof JN, Rosenman SB (1968) Physiochemical factors influencing the absorption of the anhydrous and trihydrate forms of ampicillin. Curr Ther Res Clin Exp 10(6):292–303

    CAS  PubMed  Google Scholar 

  • Porter SC (2007) Coating of tablets and multiparticulates. In: Aulton ME (ed) Aulton’s pharmaceutics. The design and manufacture of medicines. Elsevier, Hungary, pp 500–514

    Google Scholar 

  • Porter SC, Saraceni K (1988) Opportunities for cost containment in aqueous film coating. Pharm Tech 9:62–76

    Google Scholar 

  • Prinderre P, Cauture E, Piccerelle P, Kalantzis G, Kaloustian J, Joachim J (1997) Evaluation of some protective agents on stability and controlled release of oral pharmaceutical forms by fluid bed technique. Drug Dev Ind Pharm 23:817–826

    Article  CAS  Google Scholar 

  • Pudipeddi M, Sokoloski TD, Duddu SP, Carstensen JT (1996) Quantitative characterization of adsorption isotherms using isothermal microcalorimetry. J Pharm Sci 85(4):381–386

    Article  CAS  PubMed  Google Scholar 

  • Rajabi-Siahboomi AR, Farrell T (2008) The applications of formulated systems for the aqueous film coating of pharmaceutical oral solid dosage forms. In: McGinity JW, Felton LA (eds) Aqueous polymeric coatings for pharmaceutical dosage forms. Informa Healthcare, New York, pp 323–343

    Google Scholar 

  • Rasmussen MD, Akinc M (1983) Microcomputer-controlled gravimetric adsorption apparatus. Rev SciInstrum 54:1558–1564

    Article  CAS  Google Scholar 

  • Remuñán-López C, Bodmeier R (1997) Mechanical, water uptake and permeability properties of crosslinked chitosan glutamate and alginate films. J Contr Rel 44:215–225

    Article  Google Scholar 

  • Rosenberg JM, Schilit S, Nathan JP (2008) Clinical Q & A: which oral solid medications should be protected from light and/or moisture? Drug topics. .http://drugtopics.modernmedicine.com/drugtopics/Pharmacy/Clinical-Q-amp-A-Which-oral-solid-medications-shou/ArticleStandard/Article/detail/515477. Accessed 2 April 2015

  • Roskar R, Kmetec V (2005) Evaluation of the moisture sorption behavior of several excipients by BET, GAB and microcalorimetric approaches. Chem Pharm Bull 53:662–665

    Article  CAS  PubMed  Google Scholar 

  • Rouquerol F, Rouquerol J, Sing K (1999) Adsorption by powders and porous solids: principles, methodology and applications. Academic, London

    Google Scholar 

  • Royall PG, Craig DQ, Doherty C (1999) Characterisation of moisture uptake effects on the glass transitional behaviour of an amorphous drug using modulated temperature DSC. Int J Pharm 192(1):39–46

    Article  CAS  PubMed  Google Scholar 

  • Schepky G (1976) Pressed articles containing moisture-sensitive contents, stabilized against moisture. DE2512247 (Patent)

    Google Scholar 

  • Schoneker DR (2005) More than just a pretty color. Pharm Exec

    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 

  • Sing KSW (1998) Adsorption methods for the characterization of porous materials. Adv Colloid Interface Sci 76–77:3–11

    Article  Google Scholar 

  • Sing KSW, Everett DH, Haul RAW, Moscou L, Pierotti RA, Rouquerol J, Siemieniewska T (1985) Reporting physisorption data for gas/solid systems with special reference to the determination of surface area and porosity (recommendations). Pure Appl Chem 57:603–619

    Article  CAS  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 Tech 31:56–71

    CAS  Google Scholar 

  • Stamm AJ, Hansen LA (1937) The bonding force of cellulosic materials for water (from specific volume and thermal data). J Phys Chem 41:1007–1016

    Article  CAS  Google Scholar 

  • Sun CC (2008) Mechanism of moisture induced variations in true density and compaction properties of microcrystalline cellulose. Int J Pharm 346:93–101

    Article  CAS  PubMed  Google Scholar 

  • Suryanarayanan R, Wiedmann TS (1990) Quantitation of the relative amounts of anhydrous carbamazepine (C15H12N2O) and carbamazepine dihydrate (C15H12N2O·2H2O) in a mixture by solid state NMR. Pharm Res 7:184–187

    Article  CAS  PubMed  Google Scholar 

  • Suzuki N, Kawasaki T (2005) Evaluation of solid state form of troglitazone by solid state NMR spectroscopy. J Pharm Biomed Anal 37(1):177–181

    Article  CAS  PubMed  Google Scholar 

  • Szakonyi G, Zelkó R (2012) The effect of water on the solid state characteristics of pharmaceutical excipients: molecular mechanisms, measurement techniques, and quality aspects of final dosage form. Int J Pharm Investig 2(1):18–25

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Taylor LS, Langkilde FW, Zografi G (2001) Fourier transform Raman spectroscopic study of the interaction of water vapor with amorphous polymers. J Pharm Sci 90(7):888–901

    Article  CAS  PubMed  Google Scholar 

  • Teckoe J, Farrell F (2010) Novel immediate release coating offering excellent coating productivity, moisture barrier and drug release. AAPS Annual Meeting and Exposition, New Orleans, Louisiana, USA

    Google Scholar 

  • Teng DC, Zarrintan MH, Groves MJ (1991) Water vapor adsorption and desorption isotherms of biologically active proteins. Pharm Res 8:191–195

    Article  CAS  PubMed  Google Scholar 

  • Thembalath R, Bansal YK, Singh V (2004) Stabilized paroxetine hydrochloride formulation. US20040208932 (Patent)

    Google Scholar 

  • Vadas EB, Toma P, Zografi G (1991) Solid-state phase transitions initiated by water vapor sorption of crystalline L-660,711, a leukotriene D4 receptor antagonist. Pharm Res 8:148–155

    Article  CAS  PubMed  Google Scholar 

  • Vromans H, Schalks EJM (1994) Comparative and predictive evaluation of the stability of different freeze-dried formulations containing an amorphous moisture-sensitive ingredient. Drug Dev Ind Pharm 20(5):757–768

    Article  CAS  Google Scholar 

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

    Article  CAS  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 (2002) Hydrolysis in pharmaceutical formulations. Pharm Dev Tech 7(2):113–146

    Article  CAS  Google Scholar 

  • Whiteman M (1995) Evaluation the performance of tablet coatings. Manuf Chem 66:24–27

    Google Scholar 

  • Whiteman M, Jordan MP, Buckton G (1998) Performance of moisture barrier film coatings. In: Proceedings of 2nd world meeting APGI/APV, Paris, pp 367–368

    Google Scholar 

  • Yamamoto R, Takahashi T (1956) Studies on hygroscopicity of medicine. J Pharm Soc Jpn 76:7–10

    CAS  Google Scholar 

  • Yamauchi T, Murakami K (1991) Differential scanning calorimetry as an aid for investigating the wet state of pulp. J Pulp Pap Sci 17:J223–J226

    Google Scholar 

  • York P (1981) Analysis of moisture sorption hysteresis in hard gelatin capsules, maize starch and maize starch: drug powder mixtures. J Pharm Pharmacol 33:269–273

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka S, Aso Y (2007) Correlations between molecular mobility chemical stability during storage of amorphous pharmaceuticals. J Pharm Sci 96(5):960–981

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka S, Aso Y, Otsuka T, Kojima S (1995) Water mobility in poly(ethylene glycol)-, poly(vinylpyrrolidone), and gelatin-water systems, as indicated by dielectric relaxation time, spin-lattice relaxation time, and water activity. J Pharm Sci 84:1072–1077

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, Luo Y, Ma YL, Zhang H (2011) Direct coating of solid dosage forms using powdered materials. USA Patent, 7,862,848, B2

    Google Scholar 

  • Zografi G (1988) States of water associated with solids. Drug Dev Ind Pharm 14:1905–1926

    Article  CAS  Google Scholar 

  • Zografi G, Hancock BC (1994) Water-solid interactions in pharmaceutical systems. In: Crommelin DJA, Midha KK, Nagai T (eds) Topics in pharmaceutical sciences. Medpharm Scientific Publishers, Stuttgart, pp 405–419

    Google Scholar 

  • Zografi G, Kontny MJ (1986) The interactions of water with cellulose and starch-derived pharmaceutical excipients. Pharm Res 3(4):187–194

    Article  CAS  PubMed  Google Scholar 

  • Zografi G, Kontny MJ, Yang AYS, Brenner GS (1984) Surface area and water vapor sorption of microcrystalline cellulose. Int J Pharm 18:99–116

    Article  CAS  Google Scholar 

  • Zografi G, Grandolfi GP, Kontny MJ, Mendenhall DW (1988) Prediction of moisture transfer in mixtures of solids: transfer via the vapor phase. Int J Pharm 42:77–88

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Colorcon Inc., 275 Ruth Road, 19438, Harleysville, PA, USA

    Ali R. Rajabi-Siahboomi & Jason Teckoe

  2. GSK, Ware, UK

    Marina Levina

  3. Catalent, Somerfield, NJ, USA

    Sampada B. Upadhye

Authors
  1. Ali R. Rajabi-Siahboomi
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  2. Marina Levina
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  3. Sampada B. Upadhye
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  4. Jason Teckoe
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Correspondence to Ali R. Rajabi-Siahboomi .

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  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

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Rajabi-Siahboomi, A., Levina, M., Upadhye, S., Teckoe, J. (2015). Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs. 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_13

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