DATA & REVIEW

An Overview of the
Effect of Moisture on
Compaction and Compression
Ali Nokhodchi

T
he identification and quantification of the numerous pa-
rameters that affect the compaction process are vital for
product uniformity. For example, moisture adsorption
plays an important role in physical and chemical stabil-
ity, in the properties of solid dosage forms and excipients, and
in polymers for sustained-release formulations.
The vapor pressure of water in the atmosphere is quantified
PHOTODISC, INC.

by the percent relative humidity (% RH). The moisture con-
tent at which a solid material produces a water vapor pressure
equal to that of the surrounding environment is defined as the
equilibrium moisture content (EMC). The solid’s resultant
weight gain at a specified temperature and % RH is expressed
The effects of moisture on the as a percentage of its initial dry weight. For a drug known to
flow properties, tensile strength, undergo hydrolysis in the presence of moisture, it is important
to study EMC and hygroscopicity.
Heckel plot (particle
In terms of powders’ hygroscopic behavior, studies find that
rearrangement, yield pressure), five factors determine the moisture adsorbance rate: (a) the
energies involved in compaction pressure gradient between the vapor pressure of water in the
(gross, plastic, and elastic atmosphere over the sorbed moisture layer of the drug sub-
energies), and elastic recovery stance, (b) temperature, (c) the surface area of solid drug ex-
are reviewed. posed to the water vapor, (d) the velocity of moist air’s move-
ment, and (e) a reaction constant that is characteristic of the
solid. Mikuliniskii and Rubinshtein studied the kinetics of mag-
nesium sulfate’s moisture uptake (1). They concluded that the
kinetics depended on: (a) surface adsorption, occurring at a
rate proportional to the difference between the partial pressure
of water vapor in the atmosphere and that of the saturated salt
solution, and (b) water diffusion into the crystal at a rate de-
pendent on the product of the diffusion coefficient and the con-
centration gradient of water.
The effect of moisture on tablets’ chemical and physical sta-
bility is outside the scope of this article.
Ali Nokhodchi is a lecturer in
pharmaceutics, Department of
States of water in a powder
Pharmacy, School of Health and The moisture adsorption of solid dosage forms and excipients
Life Sciences, King’s College provides information for selecting excipients (e.g., disintegrating
London, 150 Stamford Street, agents) and direct-compression carriers and binders, and for de-
Franklin-Wilkins Building, London termining the humidity control required during production and
SE1 9NN, UK, tel. 144 2 7848
storage. The amount of moisture adsorbed by drugs and excipi-
4787, fax 144 2 7848 480, ali.
nokhodchi@kcl.ac.uk. ents effects the flow, compression characteristics, and hardness of
granules and tablets. In addition, moisture transmission through
46 Pharmaceutical Technology JANUARY 2005 www.phar mtech.com

ars or salts (4. polymers capable of hydrogen bond. alginic acid. On the basis of this study. bulk density and tapped density measurements plification of the interaction that occurs between water in the are much more widely used than angles of repose to assess pow- moist air and a solid (7). The contributing factors are interfacial tension and deliquescence and its EMC increased only slightly at higher tem. starch) (4. The connections temperatures (3). At most. of solid dosage forms.com . more-open structure than if the particles were noncohesive. the solid’s mole. Chan Coelho and Harnby studied the effect of humidity on the form and Pilpel reported that a moisture uptake of . leaving little or no moisture on the particle surfaces. even at 50 8C and 100% RH (4). 18). how- sation occurs at the contact points and generates liquid bridges.25–0. therefore. which sometimes is denoted as monolayer ad. An expansion in the number of solid bridges peratures. Coelhi and Harnby can result in increased cohesion and aggregation and. the thick. water can soluble powders exposed to a high RH. Zografi. Their presence reduced interpar- acteristic of the solid and is the point above which the adsorbed ticulate cohesion by decreasing the number of liquid bridges within water assumes the character of a bulk solution or condensate (6. surface area. Caking is the state in which the ride had higher EMCs compared with coarse particles of these powder cannot be moved by vigorously shaking or tapping the materials (5). nesium oxide to the starch. RH and stops completely at 70% RH (13). A transition region be- ing. Free moisture exists ical affinity for the solid and the number of available sites of in. of contacting powder particles of identical material. the moisture associated with a powder’s face properties (19). indicated that high levels of moisture absorption by sodium cromoglycate particles caused the crystal structure to expand Effect of moisture on powder flow reversibly (20). 9). the frictional force liquid bridges which kept them further apart and produced a that opposes the relative motion of the particles is reduced. the formation of a hard cake. may adsorb on the surface and influence the surface energy. plate-shaped magnesium oxide par- cules can dissolve in the water and may cause its deliquescence. The caking process. the deposition of solid bridges between particles (15). (22) and Peleg and Moreyra (23) studied the ef- the resistance exerted by one particle against the motion of an. Lactose. The fine. The adsorbed mois.80% RH). Cox. organic sugars. Several researchers multilayer adsorption occurs and the water becomes more move. They other particle at the points of contact. and crystalline hydrates have high EMCs. Waals and electrostatic forces. a small reduction in Powder properties such as flow will be affected by the surface bulk density would be expected from increasing the moisture condition of the constituent particles. noted that fine particle size fractions of sucrose and sodium chlo. effect also produced greater compressibility for moist powders 48 Pharmaceutical Technology JANUARY 2005 www. This observation was thought to be caused particles is adsorbed water vapor. In a fairly dry atmos. and (c) it may condense in the a major factor in the formulation. and Such materials as nonporous talc and kaolin have low EMCs. the caking material (4. fect of moisture content on food powders’ bulk density. Thus. which often occurs in water- If water adsorption onto the material is excluded. The reduction in pow- ture film lubricates the particles and possibly prevents. In contrast. der cohesion and flow properties. and performance capillary regions contiguous to the true area of contact (12). in which liquid bridges occur between individual particles. At present. ness of the adsorbed layer also enlarges until eventually. used powder excipients (e. ever. ture content on the flow properties of some pharmaceutical ex- Cohesion is the mutual attraction and resistance to separation cipients is listed in Table I (21). (b) Water interacts with pharmaceutical solids at virtually all it may alter the surface conductivity and.. in the beds of bulk solids in at least two states: a pendular state teraction. has pointed out that this model is a sim. a capillary state in which all the pores of the bed are filled with conversely. The phere.DATA & REVIEW polymers and free films may help characterize the possible effects teraction between solid particles in at least three ways: (a) it on the dissolution and transport of drugs from dosage forms. Using such methods. higher temperature caused hydrates of the liquid bridges depend on the water content and its dis- to form and dissolve at lower RHs. This Hiestand found that moisture may influence the force of in. by the absorption of moisture into the interior of the particles.phar mtech. the water will be relatively tightly bound as a nonfreely subsequent moisture evaporation causes recrystallization and movable layer.. however. They sodium cromoglycate particles produced no effect on their sur- suggested that at low RH. did not show tribution. however. or 1% magnesium oxide to the sug- comes “solvent like”) (8). the cold welding of asperities. but remained unaffected by increased also involve solid bridges between particles. and nature of the material (2). Cohesion in moist powders involves liquid bridges and may creased as RH increased. 17).e.5% mag- able and may be denoted as condensed water (i. capillary pressure. The amount of water associated with a Schepky showed that granules’ flowability falls sharply at 60% solid at a particular RH and temperature depends on its chem. ture forms a saturated solution on the particles’ surfaces. Therefore. ultimately. 17). ders upon increasing moisture content.15% w/w by of water retained in nonporous and insoluble powders (11). observed that caking was suppressed by adding 0. container (2). liquid concave menisci at the pore ends. 10). the electro- stages of manufacture. 16. to some der bulk density was attributed to the presence of interparticle degree. Shotton and Harb tween these two states also has been suggested (14). At higher RH (.g. water–powder interaction is static charging of the particles. ticles adhered to the surfaces of the caking material by van der The critical humidity (RH0) at which this takes place is a char. sorbed moisture (8) or water vapor adsorption. When this occurs. observed that the EMCs of starch. and tragacanth in. Frictional forces act at a observed reduced bulk density and caking of water-soluble pow- tangent to the surface of the contact point. is caused when mois- interact with solids in two ways (5–7). 2–3 Caking has been observed at high RHs with several commonly vapor layers will be adsorbed (7. The effect of mois- forces that can affect powder flow are cohesion and friction. Friction is Peleg et al. processing. The two fundamental content of sodium cromoglycate powder. As the RH increases. conden. the water be.

moisture content rose.21 451 compacts decreased with increasing mois- hesive fractions increased to a plateau as the 1. whereas their cohesive behavior was similar at higher water crystallization prevented the formation of tablet materi- moisture contents. This effect was at. standardized conditions before compression (30). 25).63 748 properties of procaine penicillin powders effect powder bed tensile strengths include Fast-flow 0. however. solvents (e.4%) because of the hydrates such as a-lactose monohydrate. an increase duced tablet hardness and greater pressure was required to in moisture content decreases the powder flow of nonporous achieve specified hardness values (32). which allows tensile strength because of weakening pendular bonds (25).pression of b-cyclodextrin and found that samples lost their hesive powders (e.13 — Effect of moisture on powder compaction mension of liquid pendular bonds. have found that at a constant state of pack.54 510 the tensile strength of the procaine penicillin ing.32 749 der (2). An . Beyond a certain moisture content (.4% moisture). 25). moisture content. possessed inherent ten. Table I: Effect of moisture on flow creases and becomes insignificant. static effects and allowed the powder samples to equilibrate under As an example of a nonporous and noncohesive powder. and noncohesive materials.68 237 by crystal hydrates that compress well and to funicular bonds (18. when dry. Factors that 0. Thermal dehydration or desiccation by means of organic moisture). *corn starch flows very poorly and no do not form strong tablets when water crys- Eaves and Jones observed that increas. nonco.and by recrystallization. When the powder mass’s water content was als which normally compact by direct compression (28).ture content appeared to be optimum for maximum com- lar for fine and coarse sodium chloride particles.24 505 and showed that the attraction forces be- the nature of material. Jaffe and Foss reported that the removal of . and material packing density. Shukla and Price eval- more powerful than those at near-contact points. particle lactose 0.1% w/w ical means before compaction resulted in greater tablet strength moisture) and eventually at near-contact points (at 4% w/w (31).Emcompress 0. Lerk et al. 1. Absorbed water also de- PH-101” microcrystalline cellulose (MCC.27 554 tween particles decreased as the moisture size. FMC BioPolymer. 29).DATA & REVIEW than for dry powders at low-compression pressures. Lowering the surface tension of the liquid reduced was ascribed to the lubrication of the die wall.04 — The need for optimal moisture content in moisture content and packing densities. advantageous pressing magnesium carbonate immediately after drying.der bed. high beta-content. Thus. Maltodextrin 2. ing on whether the material. the ten- sile strength exponentially decreases to a low A powder bed’s tensile strength with a rate of excipients.com . Studies 0.Corn starch* 6.g. Moisture increases the solids beds at a fixed state of packing resulted in greater tensile compact strength by increasing the tensile strength of the pow- strength which either remained constant or decreased depend. by thermal and chem- additional liquid bridges initially at contact points (0. 24) tensile strength increased ported that the removal of water crystallization from organic as moisture content increased (as high as .14% mois- ber and strength of the liquid bridges’ attractive forces are simi. espe- 50 Pharmaceutical Technology JANUARY 2005 www. thus demonstrating than with coarse particles (24). At higher 12. Train lubrication by the liquid occurred. re- sodium chloride’s (32–75 mm) (18.g. more of the applied force to be transmitted through the com- The effect of moisture on the cohesive properties of “Avicel pact onto the lower punch (R value). the tensile strengths of coarse. tablets’ adhesion to the die wall. methanol) converted crystals of a-lactose mono- the number of liquid bridges of both types remained constant. creases particles’ surface energy and subsequently decreases Philadelphia. hydrate into a stable anhydrous product with much increased The liquid bridges’ attraction force at actual contact points are binding capacity and excellent flowability.g. When high enough to cover much of the particle surface.phar mtech. anhydrous a plateau. At moisture levels .6%.40 739 effects of moisture content on the tensile ders also has been quantified. ferrous sulfate ing the liquid content of nonporous bulk heptahydrate) (28). was more cohesive than Emcocel MCC at moisture contents of Tensile strength. PA) and “Emcocel” MCC (JRS Pharma. the particle–particle interaction de.Emedex 0.flow rate could be obtained.30% w/w. promoting the flow of the obtained anomalous results which were attributed to electro- particulate material with significantly reduced frictional forces. however. An increase in the lactose’s moisture content re- and dimension of liquid pendular bonds. This effect is attributed to a growth in the number lactose (32). The combined effects of the num. Avicel PH-101 MCC compaction also functions as a low-viscosity lubricant (28. Rees showed that moisture improved consolidation. moisture. an increase in shear cell (which can be obtained from Moisture Flow rate moisture cannot be expected to improve the measurements of the packed powder bed’s Excipient content (%) (g/min) flow properties of an already cohesive pow- shear strength) and the influence of mois.3.42 548 content increased.32 mm]) compactibility upon the removal of water.. Therefore.97 241 the formation of strong tablets is indicated liquid bridges may progress from pendular 7. With higher pactibility of the samples studied. plateau value (18. 10. fine sodium chloride particles [. Patterson. Pande and Shangraw studied the role of moisture in the com- More potential sites of contact exist with nonporous and co. As moisture uated the effect of moisture content on the compression prop- content increased further. The reduction tablet density variation sile strength. 0. by decreasing the density variation within the tablet.that moisture is essential for compression (33)..46 460 ture content. tallization is removed (e. Walton and Pilpel (27) studied the ture content on the flow properties of pow. 24.13 — tributed to a growth in the number and di.. the tensile strength reached erties of directly compressible. (26). Any water expressed during NY) were evaluated by Staniford et al.

ited interparticulate shear forces and thus reduced the amount ing between two anhydroglucose units. also the flow and compression properties of phenacetin. in shear force with water content varied. nificant difference in compression behavior. Substances produced with MCC that contained 7. Among the direct compression sugars examined. Cedar was responsible for tablet lamination because the yield force Rapids. Higher press tablets to the same relative density decreased with increas- moisture concentrations resulted in the formation of pendular ing moisture content. sodium evaluated under various conditions of humidity. Despite the low viscosity of the liquid film. Armstrong and Griffiths re. Khan et al. and disintegration times water adsorbed at particle surfaces has a very limited effect on were studied. Li and Peck found that compacts produced by amounts (37). ture content. Further moisture content increases resulted in de- came harder as the moisture content increased (38). The lubricant effect ing of one water molecule to each anhydroglucose unit. Despite the sig- MCC is an important excipient that has been extensively in. Finally. compaction. The strongest compacts were strength on drying were in the same order as solubility. Although the materials varied. were studied (45). and dextrose monohydrate (49).60% RH. high RHs decreased tablet strength in most cases. paracetamol. any increase in moisture content generated by expo- content. Condensation of water vapor at whereas sorbitol and sucrose absorbed large amounts. of moisture during compaction of sodium chloride cannot be sorption of more-loosely bound water will occur as described attributed simply to hydrodynamic properties (36). Ahlneck characteristics of tablets prepared by direct compression (37).9% produced a marked reduction in both into the cellulose structure (41). influence the tablet strength indirectly by affecting the volume Sangekar et al. A marked reduction in Avicel tablet tensile strength and tablet toughness. of bonding that occurred at high pressure. Armstrong and Patel examined moisture’s bonds on the particle surfaces. Shukla and Price studied the effect of moisture content on tent increased and as the compression force increased until the the compression properties of two dextrose-based. cles in compacts prepared at low pressure from samples with The effect of water on the rheological and mechanical prop. lubrication inhib- Several steps are involved. moisture uptake. tablets containing MCC became harder as the moisture con. which typically affect to the com. with low water solubility would show little. The ex- RH within 48 h. creased tensile strength of compacts. moisture rapidly at . studied the effect of moisture on the physical reduction of the powder mass during compression. increase in cohesiveness for both samples. For dextrose mono- MCC tablet tensile strength was observed at . erties of commercial Avicel PH-101 and Emcocel MCC also ported some effects of moisture on granules’ compaction prop. This latter structure increases the mo.3% w/w. (52) and Shotton and Rees (51) found that mixtures of MCC-PVP also has been investigated (43). It has been shown that . They related the increase in both strength parameters (tablet crushing strength changes in mechanical properties of MCC and the tensile and tablet toughness) because of recrystallization. unrestricted form (42). increase in The powder mass’s moisture content before compression may compact strength caused by the loss of moisture on drying. and Alderborn studied the role of adsorbed water in volume Twenty-four formulations of placebo tablets—made from eight reduction as well as on the tensile strengths of tablets for some direct compression excipients and three disintegrants—were crystalline materials (e. present in the powder mass.. if any.com . anhydrous lactose. although the change respond in many respects with those of Rees and Shotton (36). hardness. examined the effect of MCC’s moisture content on the com- and dextrose monohydrate without the addition of an excipient pression properties of formulations containing paracetamol (35). followed by the bind.phar mtech. and tensile strength. Sorbitol.DATA & REVIEW cially at low applied pressure (34). Pilpel 10% moisture in sodium chloride exerted a hydrodynamic re- and Ingham’s work and other studies support the conclusion sistance to consolidation that counteracted the lubricant effects. when directly compressed. Teng et al. The samples’ cohesive- Armstrong and Griffiths also studied the effect of moisture on ness did not vary when more water was added. effect on the compressional properties of anhydrous dextrose pact strength. their conclusions cor. The addition of water caused an . noted that. Tablets containing soy protein be. ception was when a fairly large amount of condensed water was and lactose beadlets absorbed minimal amounts of moisture.3% moisture. The volume citrate. The pressures required to com- moisture is internally chemisorbed by the particles (40). Shotton and by Khan and Pilpel (44). sodium chloride. Both diluents sorbed and elastic recovery increases. however. This effect may be attributed to hydrostatic resistance sure to elevated humidity reduced both tensile strength and to consolidation caused by the presence of water in a relatively toughness. Lack of moisture pressible diluents.9% increase in the an- Pilpel and Ingham studied the effect of MCC’s moisture on hydrous dextrose’s moisture content produced a corresponding density.g. IA) and “Sweetrex” (Mendell) (48). 10% moisture (52). did not exhibit noticeable differences in crystallinity (47). including one water molecule bind. Dibasic calcium phosphate. The results showed that of tablets. A 0–8. directly com- true density of the material was reached (39). the five maltodextrins vestigated. The effect of moisture on the binary Strickland et al. that moisture is sorbed into the amorphous part of Avicel MCC.8% w/w water hydrate.8. dextrose. “Emdex” (Penwest Pharmaceuticals.4% moisture at 100% the volume reduction behavior of a particulate solid. It was observed that compacts prepared in 52 Pharmaceutical Technology JANUARY 2005 www. Their results suggested that the increases in compacts’ and potassium phenethicillin (45). and monocalcium phosphate absorbed intermediate In addition. maltodextrins with a lower degree of polymerization exhibited mannitol exhibited the least sensitivity to moisture and the a greater tensile strength for a given pressure at a .8% mois- smallest changes in volume. Any mois- strength of its compacts to the way in which water is sorbed ture increase .20–30% erties (35). or acetylsalicylic acid) (46). Emcompress. Every formulation gained . Ganderton examined fractured surfaces of hexamine and found lecular mobility of MCC and may explain why water could act that the failure had almost entirely occurred around the parti- as a plasticizer of the amorphous part of MCC.

reached a maximum at . The effect of moisture content on a polymer’s compaction prop- ture can change below RH0. For example. as the moisture content of pharma. at least part of the in. (specifically at low moisture contents). 66). compact strength decreased with also have been reported for MCC (41. moisture content further increased from 2. obtained moisture sorption and desorption then decreases (specifically at higher moisture content).. the increase or decrease in tensile strength with moisture accord- structuring of the tablets’ surface (10. the ten. an of various powders (53. tion forces and thereby reduce tablet strength (55.e. and Malamataris et al. 45–125-mm fraction of HPMC K4M increased as the RH in- and (b) adsorbed layers can touch or penetrate each other. increase the tensile strength of HPMC K4M tablets with in- 54 Pharmaceutical Technology JANUARY 2005 www. These theories were applied to increases in tensile strength externally adsorbed water. (55). 62. compact strengths were a water multilayers or the presence of free water at the surfaces.5-. when moisture content was approximately double that correspon- sorbed water assumes the character of a bulk solution or con. ding to a tightly bound monomolecular layer. Similarly. tensile strength reached a maximum value and then decreased is a characteristic of the solid and is the point above which ad.5 Mpa 2. 61). light liquid paraffin). the range and served when HPMC K4M was compressed at various forces (5–20 magnitude of the van der Waals’ forces between the particles. Water molecules initially adsorbed tween the particle surfaces (60). For all sam- is expected to occur at fairly low RHs (i. function of the compact’s state of consolidation. 61. First. for variations in the materials’ tableting performance and the thus increasing the amount of solid bridges (55). ing to the type of moisture associated with polymers. kN) in the presence of moisture. and then decreased as the and capping pressure (53). water. 63–68). (64).DATA & REVIEW the presence of moisture and subsequently dried showed an in.9) by applying linear cles’ surface molecular structure (44. A similar trend was ob. thus creased (see Table II). the tensile strengths of HPMC to 14. tion and/or melting of powder particles should control the ten- creased tablet tensile strengths probably increase the contact be. at a compression force of 10 kN (60). increased from 23 to 75%. duced tablets with optimal crushing strength. Many re- Another possible explanation for increasing tensile strength is searchers have found that the presence of moisture in varying that immobile water layers sorbed at particle surfaces can en. Because the thicknesses of HPMC and the development of additional bonds by plastic deforma- K4M tablets also decreased with moisture. showed that when the moisture K4M tablets concomitantly increased.2 or 4% w/w water They explained that the subsequent reduction in ibuprofen formed stronger tablets than those without moisture (54). it does not exclude the possibility that the particle surface struc. the tensile strength exhibited an Rees and Hersey investigated the role of liquids in the com. sile strength of the tablets. on the surfaces may form a monomolecular layer and increase To eliminate the effects of particle packing on tensile strength the van der Waals forces. The changes in the densate (6). regarded the parts of the particles that reduce interparticular sur.g. monolayer-bound water can be regarded as part of the parti- sile strength at a fixed packing fraction (0.3-fold increases in internally absorbed water. 4. Such an effect physicochemical properties of the resulting tablets. At a packing fraction of 0. the tensile strengths increased from sile strength of HPMC K4M tablets increased from 5. showed that the crushing strength of ibupro- during consolidation and that a 6% w/w moisture content pro.com . initial plateau as high as 6% w/w moisture content. relative density.5 to 10% w/w (63). Their conflicting findings can adsorbed water vapor layer can contribute to the interactions’ be ascribed to the fact that moisture can be present in powders in strength in two ways: (a) tightly bound water vapor layers can be three varying physical states (see Figure 1). data for direct-compression excipients and calculated the fraction An increase in tensile strength with increasing moisture con. The distribution of moisture in various forms could account adsorbed water could function as a surface-restructuring medium.9. RH0 ples. and monolayer-adsorbed water. below the RH0). and 2. an increase in erties has been reviewed briefly (65.54 Mpa (see Table II). reduced interparticulate bond strength. of moisture corresponding to various forms of water in powder tent or RH has been explained by two possible mechanisms.6 to 8. The distribution of moisture in a material.phar mtech. In the presence of non. as the RH content of HPMC K4M increased from 10 to 15% w/w. Similar results were obtained by Garr and Rubinstein for ceutical substances increases. etamol powder was strongly determined by moisture present Nokhodchi et al. etamol–cellulose mixtures containing . An increase in RH from 23 to 75% caused increasing the attraction forces between neighboring particles 7. tion of tablets compressed at increasing pressure (10–100 MPa) crease in strength because of interparticulate recrystallization. (57–59).9% (60). fen tablets initially increased with increasing moisture content.8-. Similar observations compacts containing moisture. Such water may then disturb or reduce intermolecular attrac- Garr and Rubinstein found that the compressibility of parac. of moisture on the interparticle and intermolecular forces. For decreased as the moisture content increased. 63). This Karidas determined the overall interparticle bonding force as ten. thereby smoothing out the surface mi- and to evaluate the effect of bonding strength. Bangudu and Pilpel stated that parac.. Nokhodchi et al. 48. Nokhodchi et al. Malamataris and croirregularities and reducing interparticle separation (24). The internally absorbed and externally adsorbed water in the face distances and increase intermolecular attraction forces (5). A decrease in tensile strength is a result of the formation of solvents (e.5% w/w. 56). tablets’ crushing strength could be caused by the presence of free According to the literature. the tablets’ tensile strength increases nonhygroscopic paracetamol tablets (53). quantities could either increase or reduce the mechanical strengths hance particle–particle interaction.2. According to this theory. These effects would regression analysis between log tensile strength and packing frac. explained tensile strength with RH has been suggested to be a result of a re. Although it is normally assumed that this point must mechanical characteristics were explained by the combined effect be reached before adsorbed water can begin to dissolve a solid. tensile strength paction of sodium chloride that contained moisture (29). re- of HPMC K4M tablets with increasing moisture content from 0 spectively (see Table II).15 to 8. For sodium chloride. reaches a maximum. 70).

40 properties of binary mixtures also has been 43 (5.8) 1. HPMC tablets with increasing RH or moisture content. moisture pure HPMC and pure ibuprofen in the mation and more solid bonds may form presence of various moisture contents.2. it can be concluded that the reverse effect of the compres- tilayer adsorption increased. The Tg of amorphous materials such as HPMC E5 ordered state of the amorphous solid makes it possible for water (73) or PVP (73. Because HPMC has a primarily amorphous structure and An alternative explanation for the effects of moisture on the ibuprofen has a crystalline structure. Although the amount of mul.ture were not affected by the compression force (76). when the decreases in mean yield pressure. the plasticizing effect of hydrogen bonding between adjoining molecules of the solid water was related to Tg (73. content. 23 (2. 75). 58 (9. internally absorbed moisture.ticizer to greatly increase the solid’s free volume by reducing tic properties of polymers.3 3. Table II: Moisture distribution. It was shown tion (12).11 Moisture’s effect on the compaction 33 (3.fore. An increase found that increasing the moisture con- Monomolecular in the monolayer of water in HPMC adsorption tent from 0 to 13. one must pressure. 74) reduces as the moisture content increases. moisture may transfer into force had no significant effect on tablets’ the material (8.2 8.6) 2.05).2 1. At a certain moisture content with a corresponding reduction in its glass transition temper- above the level consistent with the transition from the glassy to ature (77–79). Similar explanations account tensile strength of compacts decreased with moisture content for the decreases in mean yield pressure and elastic recovery of .15 53. and externally adsorbed moisture contents.1 3. 71–72).5% (63).tion between the drug and HPMC (80). At higher moisture.tablets.phar mtech.02 compaction properties of binary mixtures * figures in parentheses are the moisture content (% w/w) of HPMC K4M–Ibuprofen (50:50).2 8. Externally compact’s tensile strength. the effect of moisture on tablet tensile strength is the this moisture content is the reason for the identical tensile result of the balance between the amount of monolayer-adsorbed strengths of the mixture at various compression forces. however.DATA & REVIEW creasing moisture content.12 6. a compression force increase resulted in increased ten- It has been suggested that water adsorption reduced tablet ten. There- ternally adsorbed moisture values.sile strength of HPMC.6 5.on HPMC tablets’ tensile strength (61). Therefore.9) 1. The water sorbed by amorphous solids is deter.6 2.ture (68).21 stein studied the effect of moisture on the 75 (14. Water’s effect on solid properties is attributed to the mined by the water’s chemical affinity for the polymer and the fact that water dissolved in an amorphous solid can act as a plas- water’s role as a plasticizer (73. they compact poorly. tensile strength at 10 kN.1 3. Water uptake by the crystalline ibupro- Hancock and Zografi showed that the Tg of HPMC E5 reduced fen would occur in no more than two or so molecular layers at from 428 to 345 K as the moisture content increased from 0 to the highest RH relative to absorption into the amorphous struc- .9) 2. any water sorbed by the compaction properties of HPMC involves the glass transition tem.2) 1. which moisture content increased from 0 to 15. indicate greater plasticity of the HPMC (see Table II) and ac.1 2. In the case of HPMC K4M. humidity (%)* adsorption adsorption adsorption (Mpa) (Mpa) recovery (%) thus leading to lower tablet porosities (70). At a higher absorbed As more water molecules adhere to moisture moisture content (13.5 5. and compressional Low-moisture starches are not applicable parameters (mean yield pressure and elastic recovery) for HPMC K4M at as direct-compression materials because various relative humidities. (44). 74). Water is needed to Moisture distribution (%) Tensile Mean yield enhance the compressibility and facilitate Relative Monolayer External Internal strength pressure Elastic the plastic deformation of glassy starches.15% w/w (73). sion force on the tensile strengths of the mixture components at Therefore. These effects could account for the Figure 1: Various states of moisture.mixture is almost entirely associated with the HPMC. whereas the tensile strengths of the mix- sile strength (53) because of condensation and multilayer adsorp.05% increased the K4M occurs (see Table II). the area of contact between the Internally consider the compaction properties of absorbed particles will increase with plastic defor.5% increases compact strength. Increasing the moisture sorbed moisture dominate the compaction properties of HPMC. At temperatures exceeding Tg.the tablet tensile strength increased (60). as assessed by tensile strength values.9 3.5 1.02 50. and higher forces lower that crushing strength (63).6 36.18 8.54 31. The dis- perature (Tg). tensile strength did not decrease.45 44. At a higher moisture count for the tablets’ increased tensile strength.4 4. content of pure ibuprofen to . The monolayer adsorbed moisture and internally ab.8 7. This effect may tensile strengths.14 17. The extent of multilayer adsorption in Table II can be that 10 kN is the maximum compression force for ibuprofen estimated by subtracting the monolayer adsorption from the ex. under high To explain this observation. Sorbed water located at the points of physical the rubbery state.3. poly. Nokhodchi and Rubin. to dissolve in HPMC. Water changes the viscoelas. significant changes occur in the mechanical contact between drug and excipient can facilitate an interac- properties of the polymer.18 11.08 13.62 investigated (76). Such interactions might mers exhibit highly increased chain mo- bility and elasticity. They 56 Pharmaceutical Technology JANUARY 2005 www. soften the particles’ surfaces. the moisture has a negative effect moisture. compression the surface.3 2. which will have major consequences for compaction properties.com .

pressing of diluents were linear for all moisture contents (32).3 and 70.48% w/w for compression forces pharmaceutical powders to identify the Compression pressure (Mpa) of 12. both under compression and after be characterized by Heckel plots (see Fig. A 0–14.tion for each of five maltodextrins evaluated (47). and the changes in the relative densities attributed to ture contents greater than that of the original diluent. the extrapolated densities from the linear portions of the Heckel Yield pressures (calculated from Heckel plots) increased at mois- plots (Da). A 0–2.ues as a result of the two humidity conditions. Materials with a high mean was greater for the maltodextrins with lower degrees of poly- yield pressure are classified as brittle-fracturing or fragmentary. JRS Pharma. Mollan and Çelik stated that the low humidity con- low pressures and improved compressibility as the materials’ ditions caused the materials to exhibit the most brittle behav- moisture contents increased. a change in the glass transi.tent on the consolidation and compaction properties of parac- tional forces. The values indicate that moisture may act as a lubricant by Garr and Rubinstein investigated the effect of moisture con- smoothing out the surface microirregularities. The magnitude of this equation [1]. They compared the mean yield pressures of Increased moisture content yields lower mean yield pressures— various pharmaceutical excipients at 11.com . Em- the measure of the plasticity of a compressed material (i.of compression are measured using energy analysis on force–dis- tributed to the assumption that water facilitates the deformation placement plots. was obtained. 18. Shukla and Price stated that Heckel plots obtained from com- Nokhodchi et al.e. The net work of ever (87). with an increased moisture load attractive forces and the compression behavior of oxytetracycline from storage under high humidity conditions causing an in- formulations. The increase in moisture contents increased the crease in the plasticity of the powder. ln[14(1 – D)] and produce significant changes in its NY) (88). fragmentation. moisture content resulted in reduced mean yield pressures.80 to 31. The maltodextrins all and Pilpel (85) investigated moisture’s effect on the interparticle behaved similarly to each other. reducing the fric. Energy analysis (plastic and elastic energies). as was expected terial)—and lower plastic energy during compaction. with increasing RH. studied the effect of sorbed moisture on affected by the moisture content. compression (21). 7.13% moisture content (see Table III) (86). the applied compression force in that it sure (P). The mean yield pressures de- speed of 15 mm/s (86). increasing moisture content as high as 9. Mollan and Çelik also studied the effects of humid- and materials with low mean yield pressures are classified as plas. slope–1 5 mean yield pressure ship between porosity and water con- tion temperature would be expected to tent of dicalcium phosphate tablets affect the molecular mobility of the solid (Emcompress. K is propor. The mean yield moisture content because of moisture’s overall plasticizing effect.9% w/w increase in mois. They ture content caused a marked reduction in the mean yield pres.5% w/w increase in ibuprofen tablets’ creased as the RH increased from 33 to 75%. ticles. The yield forces and porosity gen.the compression behavior of HPMC polymers (89). the extent of densification during compaction a function of the initial porosity. Armstrong et al. as sures of HPMC tablets from 58. the relative density (D) is and particle rearrangement. respectively. They showed that increasing viscoelastic and mechanical properties. Plastic energy is energy that is permanently im- of particles in combination with reduced interparticle friction. 84). decreased as compression force increased. whereas increasing the moisture load caused the materials erated under compression for anhydrous dextrose decreased with to deform plastically to a much greater extent (21). and 24 kN. A Da the moisture content of Emcompress Heckel analysis (yield pressure).90% RHs. and facilitating particle rearrangement and slippage etamol (53). showed that the added water was bound as the crys- to densification caused by the slippage and rearrangement of par. This effect continued with crit- ure 2) (81. Several researchers have ical water contents as high as 8.phar mtech. elastic energy is energy that is de- 58 Pharmaceutical Technology JANUARY 2005 www. The mean yield pressure decreased with increasing during the densification phase of compaction. how. In the Heckel Figure 2: Heckel plot of plasticity. studied the relation- In addition.DATA & REVIEW alter the system’s mechanical properties.5% w/w.ity and storage time on the behavior of maltodextrins for direct tic or elastic deforming substances. Esezobo from an insoluble fragmenting material. showed that the initial relative densities (D0).talline hydrate.53. mean compression (plastic energy) and expansion work (elastic energy) yield pressures increased. greater compress showed only a slight change in its yield pressure val- mean yield pressure indicated a lower degree of plasticity of ma.2% (48). 82).22 Mpa at a compression expected. shown by decreases in yield Heckel plot slope. As the moisture content increased . performed on the diluent with 5. ln[1 4 (1 – D)] = KP 1 A [1] Li and Peck showed that an increase in the powder moisture content reduced the yield pressure and improved the densifica- (1 – D) represents the pore fraction or porosity. parted to the tableted material. The tablets increased apparent tablet den- compression behavior of powders may Db 5 Da – Do sity.2. merization.38.showed that particle slippage and rearrangement increases. critical water content was dependent on related to the applied compression pres.ior. Patterson. Increased mean yield pressures were at.. indicating a greater degree of densification at pressures. Da is a parameter relating moisture. be- types of mechanisms occurring during yond which a reduction in densification compression (83. successfully applied Heckel’s equation to and 6. Do ejection. pressures of HPMC K4M (86) and ibuprofen (87) tablets were Malamataris et al. At equivalent tional to the reciprocal of the mean yield pressure (Py) and A is moisture levels. Differen- particle rearrangement (Db) could be affected by the presence of tial scanning calorimetry.

1% w/w) yielded considerably lower tablet cles and the binding forces between them. The calculated net work was small. The stress relaxation ratio (ER–SR). nificantly decreased the plastic energy.of the compacts (53). that contribute to the tensile strength Ragnarsson and Sjogren showed that as the moisture con. For a paracetamol and MCC mixtures (54).9 and 4. thus supporting the theory that may be explained by reduced friction caused by the formation of moisture may induce plasticity into the brittle Emcompress par.4% w/w) decreased the elastic recovery– ted against the upper punch force.9% were presented by Khan and Pilpel (40). the ratio only increased. because at these levels. compression force. sure level. to achieve a constant ten.frictional forces responsible for interparticle attraction. done or energy (J). Increased moisture content in powders and granules can affect the frictional properties of the probably affects the plastic energy by a combined effect of re. the elastic recov- fer much from those of the dried material at the highest pres. thus reducing the under curve CBD corresponds to the decompression or elastic en. For example. The plastic and elas.DATA & REVIEW livered by the compact back to the punch ture on the plasto-elasticity and tableting of B during the decompression phase.the small volume of liquid.4% w/w).moisture film acting as a lubricant at the die wall. To achieve a constant strength. With Avicel MCC.02 or 0. They stated that in the presence tent affects the elasticity of Emcompress compressed at 20 kN of 0. while the area particles’ surface. the water probably plastic and elastic energy measurements. For HPMC K4M. force. Bangudu and Pilpel studied the effects of mois. in- w/w) throughout the pressure range. Consequently.86 J moisture in the compaction process by using an ideal particulate at moisture contents of 0. the liquid reduced the by a combined effect of reducing particle resistance and enhanc.2 MPa.force.2% water) were satisfactory at low pres. The amount of moisture present needed for the dried material (91). various measurements of tablet friction have been used. to obtain tablets with a tensile strength Force lost to the die wall. B is the force at the minimum the tablets’ tensile strength then decreased Figure 3: Force–punch separation plot for punch separation (D).elastic recoveries reduced. an increased sodium chloride punch force (88). The elastic work lessened at high moisture crease in ER–SR ratio (and consequent increase in tensile levels because of retarded tablet expansion. adding small amounts of water bile. (.used by Shotton and Rees (51). respectively. This result explained why samples con- tent increased.5%. reduced inter.provided less die-wall lubrication at all values of applied force tents. They stated 60 Pharmaceutical Technology JANUARY 2005 www. thus reducing interparticle friction be. Avicel MCC with a low mois. because sufficient void space remained to accommodate sile strength.9%. The force lost ticles. respectively. and 14. If plastic energy is plotted and Rees showed that a lower moisture content (0.16%) as a function of tablet tensile strength for various moisture con. the sure. Elastic recovery. R-value or punch force (transmission) ratio was increased bonding. tween cellulose particles. in contact with the die wall increased.decahydronaphthalene.com .9. a higher net work was Lubrication effect of moisture. At higher water content. but were less affected by pressure increase and did not dif. The net compaction or plastic energy was determined from Liquid water also tends to rupture the hydrogen bond be- the difference between areas ABD and CBD. 5. Malamataris et al. Rees and Shotton investigated the role of of . Shotton cause of moisture’s lubrication effects. They showed that as the RH increased.pact decreased. a moisture content increase sig.tic recovery (88).eries were 8. 4. a significant increase in elastic to the die wall increased with applied force as the compact area energy or decompression work was generated. and 2. the ratio increased. a higher plastic energy for the dried material was needed to (51). Moisture content increases an increase in applied force caused liquid expulsion to form a con- probably affected the net compaction energies (plastic energies) tinuous film at the die wall. The area under the was beginning to form multilayers on the curve ABD yields the gross energy (total energy). the void spaces became filled with liquid. A reduction in elastic energy occurs upon increasing the ratio (R) at low applied force will caused compaction. Liquid did not migrate to the die wall even at high applied achieve a specific tablet strength. the mixtures. Thus. Armstrong and Patel showed that water con. in which A is the The researchers explained that the ER–SR punch separation at the first measurable Punch separation (mm) values increased when more water was added.taining 75% w/w or more of cellulose exhibited virtually no de- als decreased (90). the punch separation may be plot.55% moisture. at higher Compression force (kN) area under this curve will be the work amounts (. ture content. tic energies of compaction of the poly.friction coefficient between particles and the die wall.fect. In studies covering this aspect of moisture ef- duced resistance to deformation of the particles.stricted movement of the solid in contact with the die. Figure 3 illustrates a typical force– lar bonds that hold the particles together.compact formed. For all system in which both punches are mo. at 33 and 52% RH.06. system of crystalline sodium chloride and three liquids: water. particle friction caused by the lubricating effect of water. and also re- ing particle deformation. and light liquid paraffin (36). ergy. The bonding properties vestigated the effect of moisture content on HPMC tablets’ elas- of the moist sample (8. the net work required to compress the materi. The effect on the strength) when as much as 2% w/w of water was added. As the porosity of the com- For a given compression force. This effect water content from 0 to 6.phar mtech. Then. and Punch force ratio. the plastic energy needed was 7. Similar results also strength than the one with a normal moisture content (4.65. D C A punch separation plot. These layers act as a lubricant. The initial decrease in values of ER–SR in mer tablets are measured using energy the mixtures was caused presumably by the analysis on the force–punch separation development of surface tension and pendu- plot.9%. a lower plastic energy is needed with increasing mois. and C is the de.addition of moisture increased the surface energy of the parti- ture content (1.

090 on the Equilibrium Moisture Content of Powders. 342–348 (1972). Theoretical Considerations of Heat Transport Control. “Tensile Strength of Granules Materials. J.407 0. “Velocity of Moisture Absorp- (% w/w) D0 Da Db D0 Da Db tion by MgSO4” J. the proportion of the 11. it Sci.547 0. T. Sci.463 0. the application of lubricant to Forms.616 0. The lowest ejection forces were associated with 26. 18.C.435 0. “An Approach to the ciably less than with light liquid paraffin or decahydronaphtha.7% w/w (91).141 0. M.” J. C.D. scured the moisture’s effect on phenacetin and lactose behavior.2. 15 (10).DATA & REVIEW The critical moisture content in MCC to optimize tensile Table III: Values of D0. Harb.345 0.” Nature. W.M.” Drug Dev.” J. Good transmission of radial force implied 24. 22. 9.5% w/w. Zografi. (1937). and G.551 0. 15. 25. “The Effect of Humidity and Temperature on tion usually has little effect on die-wall friction compared with a the Cohesion of Powders. Lubrication of both the die wall and in. 17 (8).” J. 4. 217 the die is more effective than the addition of lubricant to a pow. der before compression. Pharm. Mikuliniskii and R. Pharm. or both together produced paraceta. 61 (2). T. “Powders: Particle–Particle Interactions. 72 (12).” J. (13). E.I. J.2 0. 16. Jones. Pharmacol. Ind.G. Burak. friction because reducing the coefficient of interparticulate fric.137 0. Da is extrapolated densities from the 5.401 0. 736–737 (1968).M. Hiestand.416 0. D. Pharm. York. of Beds of Moist Bulk Solids.1π30 Humid Conditions. and W.N. Harb. P.N. 504–508 (1965). Passy. 10 (2). Shotton and N. Peleg. During particulate material compaction. “The Effect of Humidity and Temperature 5. They have been criticized that 19.“Effect of Surface Tension on the Tensile Strength ing phenacetin and starch and concluded that the optimal mois.” J. Pharm. glycate and Mixtures of Sodium Cromoglycate and Lactose. “The Effect of Humidity on the Form of Water Retention in a Powder. the die wall. In the presence of moisture. 197–200 applied force transmitted to the die wall is affected by several fac. wall (Fd) and to consecutive compression increases were appre. 1465–1468 (1971).9 0. Pharm.B. Eaves and T. tors including: (a) the radial component of the applied force. “Effect of Moisture on Tensile Strength of Hydrolyzed gelatin. 136T–144T (1958). Van Campen. Sodium Chloride and Effect of Particle Size. the force lost to the die sules. S. Zografi. the additives present. Jones.. “Chemicals for Improving the Flow Properties of Powders. 477–481 (1983). “Absorption of Moisture by Sodium Cromo- the granulation contained a high proportion of starch. 201–205 (1978).” Powder Technol.J. Moisture Compression speed (mm/s) References content 15 500 1. The behavior of paraceta. High 5 (1). 537–545 (1972). 2. lene. that although differences in the three liquids’ behavior could be 7. N. M. 959–963 (1973). 1905–1926 (1988). 35 (8).567 0. Craik and B. G. Shotton and N. “Solid State Chem- istry of Cromolyn Sodium (Disidium Cromoglycate). Evaluation of Hygroscopicity for Pharmaceutical Solids. Amidon. Dawoodbahai and C.” terparticulate junctions produces a net decrease in the die-wall Chem. 844–846 (1966).085 Ind. “Effect of Addition of Water on the Rheological compacts produced from MCC containing 5% w/w moisture.191 0. G.” J.321 0. 10 (2).” J.421 0. 38 (6).M. 33 (5). “Moisture Bonding in Powders. Seth and Munzel studied a lactose-based granulation contain.J. Sci.088 3. Pilpel. 14 (14). Jones.” Int. 73–78 (1958). Pharmacol. Fine Particle Size Materials with Varying Inherent Co- mol and phenacetin mixtures with satisfactory compression herence. Moreyra. Food Sci.” Drug Dev.514 0.T. Mollan and M. “Mechanisms of Hardness of Aged Com- of applied force by interparticulate lubrication. E.146 0. Bulk Solids: II. D0 is initial relative densities. Pharm. L. Manheim.com . and moisture on the compression characteristics of on the Behavior of Maltodextins for Direct Compression. and (c) the coefficient of friction at 55 (12).F. S. and Maize Starch:Drug Powder Mixtures.” J. water. 2. “The Effect of Moisture on Powder 0 0. strength and ejection force is .137 0. 729–752 (1984).410 0. McCrone.” Pharm. 23–32 (1995).401 0. L. “Effect of Moisture on Tensile Strength of Bulk Solids: I.” J.” Powder Technol.phar mtech.542 0. 1577–1600 (1989). 23 (2). Pharm.” J. 17. “Preformulation: The Role of Moisture in Solid Dosage ratio of radial stress to axial stress. D. Pharm. Pharm. Lordi and P. M. Shiromani. Harnby. and Db is changes in relative Technol. ture content was . Phys. water apparently Pharm. Eaves and T. 15 (10). Pietsch. or water was similar to a Mohr body. densities attributed to particle rearrangement.H. M.425 0. Eaves and T. 277–279 (1979). 269–273 (1981). Pharmacol.Y.414 0. Pharm. Pharmacol. 10 (5). 62 Pharmaceutical Technology JANUARY 2005 www.” Drug Dev. E. Because interparticulate lubrication increases the 13. Maize Starch. 6.145 0. the die wall pressure was 23. 1–18 (1980). and J. R.9 0. 3. Pharm. 47 (8). 20.” J. J. 21. 20 (3). “States of Water Associated with Solids. Ind. Pharm. J. pacts. G. Coelho and N. S. did not indicate that the tablet formed was physically stable. and Db at low. 14.100 macol. Schepky. Chem. Zografi.J. Fd values were attributed to an increase in the radial component 10. Craik. exerted a boundary lubrication in addition to hydrodynamic 8.421 0. “The Flow Properties of Powders Under 14. but alone. 1325–1344 (1966). Sci. Woodward. “Flow Properties of Some Food mol or phenacetin and their mixtures with gelatin hydrolysate Powders.“Effect of Moisture on the Stress Relaxation affected by the particle size of the material compressed and by Pattern of Compacted Powders. Chan and N. T. paracetamol and phenacetin (92).” J. 256–261 (1972). (b) 12. Phar- 9.6 0. M.552 0.333 0. G. Da.” Drug Dev. “Analysis of Moisture Sorption Hysteresis in Hard Gelatin Cap- properties. Carstensen. Rubinshtein.S. Sci. N. Pharm. that the material could be consolidated initially. 114 (1). E. Pharm. Pharm. and Ind. and N. 9 (431). Çelik. Coelho and N. the effective area of contact.331 0. Harnby.080 Flow and on Compaction and Physical Stability of Tablets. 1715–1741 (1989).363 0.C. Miller. Cox. 1381–1388 (1983). Pharmacol. decrease in the coefficient of friction at the die wall. Peleg and M. both of which had a negligible die wall lubricant effect.8 0. Van Campen.” Powder linear portions of the Heckel plot. Ind.” Int. characteristics. 61 (3). “The Effects of Humidity and Storage Time gelatin.C. 175–178 (1966). Acta Helv. Staniforth et al. “Moisture Sorption Ki- netics for Water-Soluble Substances: I. Pharm. hydrolyzed 21. attributed partly to the differences in viscosity. Ejection force 60 (8).and high. Obiorah and Shotton investigated the effect of waxes.T. compression speeds at various moisture contents. (1978). which ob.384 0. 18 (3). Rhodes. “The Flow Properties of Starch Powders and Mixtures. 20 (3).L.

macol. J. pp. Turner and M. Rees and E. Pharm. Shukla and J.A. (3). Amer.J. G. 34. “Zugfestigkeit von Presslingen Mitvorwiegen- ing. 121–127 (1974). D. butions to the Tensile Strength of Weak Particulate Masses. H. Stubberud et al. 71.B. Res. W. 28. 36 (4). Sangekar. Effect of Moisture Ibuprofen Tablets. “The Effect of Moisture Content on the Com. Sci. Rubinstein. 68 (5). “The Compressional Properties of Dex.C. 60 (11). N.” Powder Technol. Sci. Rees. Young and G. Groves.A. 22 (3). Shangraw. and M. “The Effects of Moisture on the Humidity During Storage of Tablets of Three Crystalline Materials. 13 (Suppl.” Int.” Int. A. 245–246 (1970). J.M. 70. Jaffe and N. tablets: III. J. Tablets of Sodium Chloride. 35 (11).” Drug Dev.” S. “Effect of Moisture Content on Compres. “Studies on the Interac- Crystalline Materials.H. 45 (1). Nokhodchi.DATA & REVIEW and Mechanical Properties of Microcrystalline Cellulose.E. 10 (Oct. 47. G.L. 608–615 (1997).T. I. 37 (5).A. Phar- ture. Paracetamol and Int. 115–123 pactibility of a-Cyclodextrin. “An Investigation of Moisture Sorption in Mi. F. 8 (10). Rumpf. Pharmacol. 104 (1). 59. Pharmacol. J. 48 (11).” Int. 379–418. and J.” Int.” J.P. Microcrystalline Cellulose Mixtures.phar mtech. Res. tion Between Water and HPMC. Malamataris and T.).” Int. P.). Pharm. 191–197 (1995). C. 1992.” J.). “Moisture Adsorption and Tableting: Behavior. 1962). Pharm. Shotton and J.J.. Pharm. Ind. Pharm. E. tion and Moisture on the Crushing Strength of Sodium Chloride Com- ticulate Material. (4). G. 76P (1988). 18 (Suppl. 144T–151T (1961). S. P. 45 (11). 50. A. cipients. C. damental Aspects of Tablet Lubrication. The Role of Moisture in the Com. Pharm. E. “The Strength of Granules and Agglomerates. Pande and R.com . Goidas.“The Effect of Adsorbed Water Adsorptionsschichten. Reier and R. Alkan.. Balasubramanian. Khan. 53. Pilpel. Holm. J. S. Pharmacol. “Tensile Strength and Compression of sion Properties of Two Dextrose-Based Directly Compressible Dilu.G. Conf. Sci.H.” J. Warr. Pharm. Bonding and Capping in 29.C.” ride in Presence of Moisture. Malamataris. 235–243 (1972). Sci. Pharm. Pharm. Fun. 145–150 (1986). Tsiri.” Powder Technol. Sci.A. Rees. 27. 48 (1). Nokhodchi. 60. Rubinstein. 38.E. 51. Patel.” J. M. Goidas.F. Kristensen. Shangraw. Aspirin and Hexamine. V. “Characterisation of a-Cyclodextrin for Moisture on the Tensile Strength of Some Tableted Hydroxypropyl- Direct Compression Tableting: II. 86 (5). Rumpf. 237–241 (1987).H.” 6th Int. “The Interactions of Water with Cellu- trose Monohydrate and Anhydrous Dextrose of Varying Water Con. “The Effect of Moisture Pharma Sci.E. Effect on Volume Reduction Properties and Tablet Strength for Some 67. Pharmacol. 11 (3). Li and G. Pilpel. Com. Foss.” Powder Pharm. 54 (3). Garr and M. Price. Shotton and D. J. 1704–1708 (1971). Alderborn.” Pyrrolidone. Pharm. Ahlneck and G.S. N.. 55. 68. ferent Size Fractions of Some Direct Compression Excipients and Ten- nol. Pharm. A. 49.). 2208).R.” Flow Properties and Compression of Phenacetine. Pilpel. A. A. J. 79–88 (1996). J. 64.E. “Effect of Particle Size and Sorbed 33. Pharm. Pharm. Pharmacol. 42. C. 41 (3). “Sorption of Moisture in Dif- Tensile Strength of Microcrystalline Cellulose Powder. 1885–1901 (1986). Acta. Coated Pharmaceutical Powders: Tablets.” J.. Ganderton. 227–237 (1985). 1–6 (1983). F. 46. 3 tent. A.N. Shotton. methylcellulose (HPMC) Polymers. J. Musikabhumma.F. A. Turba and H. Rajabi-Siahboomi. Most Agglomerates in Relation to Granulation Mechanisms: Part.H. L. Khan and N. 160S–167S (1966). A. (1985). Kontny. “Increased Binding Capacity and Flowability of a. J. 2325–2336 (1986).” Pharm. Ind. 63. “The Com- ties of Some Formulations. “The Tensile Strength of Compressed Pharm. Rubinstein. Ind. 66. “An Investigation into the Compaction of Powders. Pharm.” Acta Pharm. on Compaction Properties and the Dissolution of Quinacrine Hy. Pharm.” Pharm. J. Price. II. Sorption and Glass Transition Temperature on Compactibility of Mi. E. Rubinstein.“The Compaction Properties of Sodium Chlo- ture Content on the Tensile Properties of Procaine Penicillin Powders. 12 (11–13). 2067–2081 (1991). “The Use of Compression Modulus to Describe Compaction 56. Down and J. eration. 131–141 (1989). Pharmacol. 69.E. 12 (11–13). Schaefer. Sheth.” J.” Powder Technol. Technol. Lactose Monoydrate after Dehydration. Ed.H. 61 (6). 30. Hersey. Moisture and 747–748 (1983).” Pharm. Armstrong and A. P. 56 (1). 35 ents. lose and Starch-Derived Pharmaceutical Excipients. M. Walton and N. 51–55 (1956). Ing. Technol. pacts.A. 52.P.A. 42–48 (1998).“The Effect of Particle Size.” J. W. Pharm. Ind. S. 939–944 (1972). Nokhodchi and M. Pilpel and S. 745–760 (1956). Tech- 41. Zografi and M. “Moisture Adsorption and Tableting: I. Dimitriou. 692–700 (1970). Properties of Hydroxypropylmethylcellulose and Ethylcellulose. Pharm. Armstrong and R. 1116–1121 (1996). Deformability of Moist Densified Agglomerates. Ingham. 58. J. J.” Drug Dev.” J. Pilpel. Shape and Mois. Nokhodchi et al. 81 (2–3). G. The Relation of Particle Size. “An Overview on the Effect of crocrystalline Cellulose Using Sorption Isotherms and Dielectric Re. “The Effect of Interparticulate Fric- 36.” Powder 62. L. 40 (Suppl. 24 (Suppl. Malamataris and N. “Mechanical Properties of Technol. Fassihi. 54. solidation and Compaction Properties of Paracetamol. “Effect of Moisture Content on Compres. 231–239 (1995). Shukla and J.” J.” Powder Tech.” Int.” J. Pharm.H.C.” Drug Dev.” J.F. (1). 10 (3). 10P–16P (1972). and P. Pharmacol. 42 (2). 37.H. G. and M. Strickland et al. Karidas.A. Amer. Peck. “The Effect of Moisture on the Density. “The Influence of Moisture Content on the Con- pression Properties of Maltodextrins. Ass. N.” J.A. Materials and Process Variables on the Compaction and Compression sponse. A. Train. Griffiths. 187–194 (1986). and A. 48. Moisture Con.” J.E. Helv. Alderborn. 195–202 (2001) Contents of Microcrystalline Cellulose on the Compressional Proper. paction Behavior of Hydrophilic Cellulose Ether Polymers. Khan and N.D. “The Influence of Moisture on Con- Pharmacol. “Effects of Composition. 65. and P. 525–528 (1981). “The Effect of Particle Size and Moisture on the 61. Dextrose Monohydrate. 510–514 (1966).” in Agglom- cal Characteristics of Tablets Prepared from Direct Compression Ex. Pharmacol.A. Teng. Pharmacol. 231–236 (1988). “Compression of Crystalline Substances. S. (1994). J.” J.” Pharm.R. Pilpel. 161–164 (1988). K. McMullen.. Rees and J. S. New York. Int. 289–293 sion Properties of Directly Compressible High Beta-Content Anhy.” Int. Ed. 195–204. 48 (1). “Water–Solid Interactions: II. 187–192 (1992). paction and Tensile Strength of Microcrystalline Cellulose. 134 (1–2).V. “Microcrystalline Cellulose in Tablet. sile Strength of Corresponding Tablets. J. 57. 55 (5). nol. Pharm. The Effect on Tensile Strength and Air Permeability of the Relative 35. 143–150 (1989). drous Lactose. Nokhodchi et al.J.” J. Knepper. Sarli. A. 45. J. 118 (2). 230–240 (1964). Pharm. and M. 54 (2).S. Bangudu and N. H. Pharm. Pharm.). Helv. C.” Chem. Pharm. 51–60 (1991). Pharm. 31. Pharm.R. 40. Malamataris. der Bindung Durch van der Waals-Krafte Undihre Beeinflussung Durch 39. “Moisture Sorption and crocrystalline Cellulose Alone or in Binary Mixtures with Polyvinyl Tensile Strength of Some Tableted Direct Compression Excipients. Technol. 169–174 (1985). Nelson. “The Effect of Moisture on the Properties of 43. Ed. Pharm.E. “The Strength of Compacts Containing Mois. C. Sci. K. Pharm. (John Wiley and Sons. 42 (4). 8 (3). 44 tent and Tensile Strength of Microcrystalline Cellulose Compacts. “Effects of Moisture in Compaction of Par. 47 (3). “Investigations of the Contri- drochloride from Compacted Matrices by Soy Protein. NY. Pharm. 336–340 (1991). Lerk et al.B. Paris.” Drug Dev. “Effect of Moisture on Physi. “The Physics of Tablet Compression: IX. “Theory of Hysteresis Between Sorption 64 Pharmaceutical Technology JANUARY 2005 www. 17 (15). and T. “Interrelationships Between Yield Pressure. Stearic Acid on the Plasto-Elasticity and Tableting of Paracetamol- 32.J. 44.” J. Ahlneck and G. 124 (2). 7 (5). Ass. 50 (3). Pharm. 26–29 (1959). solidation Properties of Hydroxypropylmethylcellulose K4M (HPMC 272–275 (1990). Ford. J.

” in Water Science Reviews. Ahlneck and G. Water. 84. Rubinstein.. Eng.T. Levine and L. Pharm. 62 (2–3). Obiorah and E. and P. Pharmacol. Soc. Roberts and R. F. 60 (12). 7 (Plenum Press. Slade and H.” Trans. 654–657 (1990). 73. 245–254 (2001). Rowe. Pharmacol. Pharm. 1001–1008 (1961). “Effect of Particle Size and Sorbed Moisture on the Compression Behavior of Some Hydroxy- propylmethylcellulose. Nokhodchi et al. Pharma Sci. “The Effect of Moisture on the Compaction Properties of the Binary Mixture of HPMC K4M/Ibupro- fen. 48 (11). 9–13 (1959). 207–215 (1985). Karidas. N.H. Pharmacol. Goidas. Franks. 11 (4). 74. “Non-equilibrium Behavior of Small Carbohydrate/Water Systems.P. circle a number: 339 Very useful and informative 340 Somewhat useful and informative 341 Not useful or informative Your feedback is important to us. Sci. 205–215 (1994). 80.” S. NY. 1987). Patel. 671–675 (1961).” Int. Res. “The Effect of Moisture Content on the Energies Involved in the Compaction of Ibuprofen. PT Please rate this article. Metall.“Water as a Plasticizer: Physicochemical Aspects of Low Moisture Polymeric Systems. Frijlink. Pharm. Heckel. A. Lerk. Pharm. 120 (1). New York. 179–185. Seth and K. Pharm. Munzel. 66 Pharmaceutical Technology JANUARY 2005 www. AIME 222 (5). J. 83. J.P.F.com .T. “The Effect of Waxes.” Pure Appl. H. R.” J. Agric. Sjogren. “The Molecular Basis of Moisture Effects on the Physical and Chemical Stability of Drugs in Solid-State. L.M. and C. 88. Soc. Hancock and G. Ind. 173–177 (1988). pp. Pharmacol. 78. pp. Phar- macol. Esezobo and N.” Eur. S.” J. 629–632 (1976).“The Relationship Between the Glass Tran- sition Temperature and Water Vapor Absorption of Polyvinylpyrroli- done. Ragnarsson and J.” Trans. 13–20 (1995).phar mtech. 76. 14 (3).” J. Am. 7 (6).” Pharm. Nokhodchi and M. Jones. “Moisture and Gelatin Effects on the Inter- particle Attractive Forces and Compression Behavior of Oxytetracy- cline Formulations. C. Zografi.” Trans. F. 89. Pharm. 756–761 (1967). 81. H. 10 (5). Hydrolyzed Gelatin and Moisture on the Compression Characteristics of Paracetamol and Phenacetin. 79.C.” J. 77. A. “Research of Hysteresis Between Sorp- tion and Desorption Isotherms of Wheat. Pharm. Shotton. On the Reader Service Card. Zografi. Armstrong. “An Analysis of Powder Compaction Phenomena. Pharm. 37 (6). Zografi.” Int. “Plasticisation of Amylodex- trin by Moisture: Consequences for Compaction Behavior and Tablet Properties. 92. Pharm. X. Franks Ed.W. (Cambridge University Press.A. Pharm. 215–338. UK. R. Eng. 86. “Der Einfluss des Feuchtigkeitsgehaltes Eines Granulates auf die Press Barkeit und die Eigenschaften der Tabletten. A Comprehensive Transite: Vol.A. Carstensen. Oksanen and G.J. 10 (5). 260–263 (1967). J. Nelson. S. 90. T.” Int..A.” Pharm. 1121–1127 (1996). Metall.H. 85. J. 72. Chem. Pharm. G. “Density–Pressure Relationship in Powder Compaction. B. 28 (8). 1982). J. Levine. J. Am.W.L. 377–384 (1985). Steendam.” Trans. 25 (2). Young and G. Nokhodchi et al.” Int. A. 21 (1).W. 75. P. R.H. 37 (3). 8 (6). 87–95 (1990). Hou and J. 1841–1864 (1988).“Relationship Between Poros- ity and Water Content of Dicalcium Phosphate Tablets. 75–81 (1976). B.C. and T. and Desorption Isotherms in Biological Materials. “Force-Displacement Measurement in Tableting. 145–150 (1985). 28 (2). AIME 222 (4). 82.” Int. 471–477 (1994). J. Agric.” J. Malamataris. 87. “The Effect of Moisture on the Heckel and En- ergy Analyses of Hydroxypropylmethylcellulose 2208. “The Effect of Punch Velocity on the Com- paction of Variety of Materials. “Compression Characteristics of Basic Tricalcium Phosphate. R.” Pharm. 349–356 (1998). Pilpel. Slade. 48 (1–3). 91. C.“The Relationship Between the Glass Tran- sition Temperature and Water Vapor Absorption by Poly(vinylpyrroli- done). Heckel. Cambridge. 103 (3). Res. A.