8 Polymers and macromolecules 8.1. Phormoceutcal polymers 274 8.5. Woterinsolible polymers and polymer 8.2 Wetersoluble polymers 281 membranes 303 8.3. Generel proper of polymer 8.5 Some opplications of polymeric systems solutions 282 in eg delivery 311 8.4 Some watersoluble polymers used in Summary 326 Pharmacy and medicine 293, References 327 This survey ofthe pharmaceutical aspects of polymers ond macromolecules emphasizes their vee in formulation. It stesses the key fectures of polymers ~ ther mlecular weight distibution and their versailily in terms of heir morphology, crysaliniy,solbilly ond performance. Wis convenient to think of polymeric systems as either wotersoluble or woterinsoluble, This division, while not rigid os some polymers ere waierlispersible, is useful in thal separates the ‘wo main ares of use which form the basis of his chapter. Wotersoluble materials are used to ‘modify the viscosity of aqueous solutions and lo maintain the stcbilly of suspensions to form tho basis of film coatings ond as the besis of wolorsoluble matrices (for example, the higher ‘molecular weight polyoxyethylene glycols as supposiory bases), Adhesives for use in the buccal mucota fbioadhesivet) are usually water soluble, while pressure sensitive adhesives for use in transdermal particles ‘end to be polyacrylates and polysiloxanes. Waterinscluble materials form mombranes and matrices. The fectors cHfocing the ranepott of drugs in the systems should bo understood: he thickness of the membrane, the solilily of the drug in the membrane and the relationship of his to ils lipophilicity gonerelly, copolymer ratios, poroity end holerogonsiy of the mix caused by filers or plstcisers. Wotecsoluble polymers con be crosslinked elecirosoticaly or covelently to give hydregels. Crossinked hydrogels absorb water but do no! dissolve. The dfferonces in release of drugs rom ‘watecinsoluble matrices and from swelling hydrogels should be opprecioted8.1 Pharmaceutical polyme: Polymers are used widely in pharmaceutical systems as suspending and emulsifying agents, occulating agents, adhesives, packaging and coating materials, and increasingly as com- ponents of contiolled and site-specific drug elivery systems (Scheme 8.1). The synthesis of polymers with specific properties (e.g. pH- dependent solubility or viscosity, blodegrad- ability, membrane-forming character) offers exciting possibilities, especially 28 #t holds out the hope of obtaining new polymers for drug delivery devices, so essential for the efficient use of many of today’s potent and toxic drugs. 1.1. Definitions Polymers are substances of high molecular weight made up of repeating monomer units. Substances isith short chains containing rela tively few monomers are called oligomers. Polymers owe their unique properties to theit size, their three-dimensional shape and some- times to their asymmetry. The chemical reac- ivity of polymers depends on the chemistry of thelr monomer units, but their properties depend to a large extent on the way the ‘monomers are put together; itis this fact that leads to the versatility of synthetic polymers. el esbres i Scheme 8.1 Ho Polymer molecules may be linear or branched, and separate linear or branched chains may be Joined by crosslinks, Extensive etosslinking leads toa thice-dimensional and often insolu- ble polymer netwoxk. Polymers im which all the monomeric units are identical are referred to as homopolymers; those formed ftom more than one monomer type are called copolymers. ‘Various arrangements of the monomers and Bin the copolymer molecules (Fig. 8.1) can be produced with consequent effects on the physical properties of the resulting polymer. Synthetic polymers may have their main Chains substituted in different ways, depend- ing on the conditions of the reaction, such that atactic (random), isotactic or syndiotactic forms are produced, as diagrammatically represented in Fig. 8.1. Copolymers may be described as alternating copolymers, block copolymers or graft copoly- mers. The molecular architecture of copolymers may, however, be more complicated than represented in Fig. 8.1. Homopolymers can be linear, sar or branched (Fig. 8.2), giving rise to so-called! star block copolymers defined by the umber of arms (7). Polymers that have fairly symmetrical chains and sirong interchain forces can be drawn into fibres, Pastics are polymers with lower degrees of crystallinity which can be moulded. Further down the rigidity scale are rubbers and elastomers, whose properties are well known. |ol tendon abe cep eto pane cdooscosoosoo$. obegebogeSe Feure 8.1. o} Vatotes of cope 5 melaclr srcutsateinabl though the pelymritetio a we dierent movers ‘proved by end 8 Feprrencionorendon coc, uabecte ce ytoacl copes It is apparent that polymer molecules will havea much wider range of physical properties than small chemical entities. Even when con- sidering one chemical type (for example, poly- ‘tinylene) the properties ofthe product may be altered by increasing or decreasing the moleeu- lar weight (Fig. 8.3). There sa possible degree of contiol over properties which there Is Rot with simple organic materials and, generally, {tis because of this that synthetic polymers have an advantage over many variable natural polymers. Naturat materials can be modified chemically, and this approach can lead to useful new products, as with those derived from cellulose or dextran. The structural for- mulae of some common macromolecules are sglven in Table 8.1. Dendvimers. ace highly branched polymer constructs formed from a central core which defines their intial geometry." Their branch- like structure (Fig. 8.4) leads to spheres which in higher generations appear to be the size of micelles and ultimately nanospheres of small dimensions. They can be functionalised and in this way ‘layerec” systems can be formed by using different monomers for succeedingFigo 82. the rong of seuctiras of homopolymacs ond Hr Hck, gr Bleck end mulblock cepaymer reactions (generations); such chemical archi- tecture has virtually no bounds. Dendrons ate partial dendrimers. 8.1.2 Poydispersiy Polymers and macromolecules with a range of molecular weights; exceptions to this ate proteins and natural polypeptides, each of which occurs 3s a substance with a single well-defined molecular weight, The ‘molecular weight of a polymer or macromol- cecular subtance is thus an average molecular ‘weight, which may be determined by cheml- cal analysis or by osmotic pressure or light- scattering measurements. When determined by chemical analysis or osmotic pressure meas- urement a mumber average molecular weight, My Is found, which in a mixture containing » moles of polymer with molecular Weights My, My My. spectively, is defined oy fiyMy tieMat nh r= BUM, My, Eat 9 Ts i, a) ‘The individual molecular weights M,, Ms cannot be determined separately ~the equa: tion merely explains the meaning of the value Mr. In light-scattering techniques, larger mol- ectiles produce greater scattering: thus the ‘weight (or more strictly the mass) rather than. the number of the molecules is important, siving a weight average molecular weight, My M, t:Mz+myMy+_ DhM? Neatly all synthetic polymers and naturally my imine EM cxcurring macromolecular substances exist 62) bbe ob coo go] tne tga 3 “he } ' i rey epson Cte soe ‘sid 0 eo tooo too00ea0 Male it Faure 8.2 Approxinterelaion between meleclor weigh, T, (glass payne properis jon lonpercirel, Ty reling pt Epptbeed toch ty, Thc Pp, 2d, Wi Ne Ya, 1971Phaimaceutcel polymeis 277° Nome ‘Chon rece ‘enone Polymers with @ corbon chain backbonet Pahalylene. Pohpropylne Polar Pelyringclei Polyetfecoetylene Pelycerlonicle Polyving obcbel) Polyvinocette) Potycrylanide Fely(rethy marie) Fohninypyclidone - Polymers with @ heterochain backbone: Polfohylene oxide) ~0- aya) Palyenepyane ed Calulose fpalyghcosid, #14)Polymers and macromolecules Figure 8.5 Rapretntoive peymerpolyrer phota bahoviour with diferent malacslr archteches Microphate separctan [a esls when hemodynomiealy ncompatble ineerhomopaiyme's ore mized. The covlet band between blocks ina diblock copolymer leads o microphase segregation (). A mead archictr finer homop}yners andthe comatponding block eepayer produces a urecertikedabitzed iermediciescale phate seperation So we a Figure 6. Repression ofthe aay oper nerpelagisnsliion and he gl or mcage sod oe. trasson he crforncion of plymer capes cr fern of payne-sakentiniachors end wile or ret he polymer choins associate to form micellar aggregates. Crystals of polymer and microcrystals con be prepared, and gels: Erte famed fom covauntyrcainad & pyser chars extoated by hycoger nding cr hyiophone fer: ‘Ser. lifed am he kena in whch nos paler cen be bcd: mantra, Rte, Comper, MSH MDE ‘pheres and microcapsules can olso feature, as discussed later in this chapter.The bulk viscosity of polymer solution is an important parameter also when polymers are being used as suspending agents to maintain solid particles in suspension by prevention of settling (see Chapter 7) and when they are used to modify the properties of liquid ‘medicines for oral and topical use. 83 General properties of polymer solutions 8.3.1 _Viseosty of polymer solutions The presence in solution of large macromol- ecular solutes may have an appreciable effect fon the viscosity of the solution. From a study of the concentration dependence of the viscosity it Is possible to gain information on the shape or hydration of these polymers in solution and also their average molecular weight. The assumption Is made in this section that the solution exhibits Newtonian flow characteristics, The viscosity of solutions of macromol- ecules is conveniently expressed by the relative viscosity, defined as the ratio of the viscosity of the solution, 1, to the viscosity of the pure solvent m ae (4) Another useful expression is the specific vise costy, ny, of the solution, defined by gts (85) For ideal solutions the ratio ny/¢ (called the reduced viscosity) is independent of solution concentration, In real solutions the reduced viscosity varies with concentration owing to molecular interactions and it Is usual. to extrapolate plots of no/e versus cto zero con- centration, The extrapolated value is called the intrinsic viscosity tl Einstein showed from hycrodynamic theory that for a dilute system of rigid, spherical particles neh 4259 (86) Polymers and macromolecules ie, li, ole!) =2.5 62) where pis the volume traction of the particles, defined as the volume of the particles divided by the total volume of the solution. ‘Departure ofthe limiting value of, fram the theoretical value of 25 may result from either hydration of the particles, or from particle asymmetry, o- from both as discussed In Box 8.1 Box 8.1 fect of shope ord hydration on vicosty Effect of particle shape A more geneicl form of equain (8.6) cloning for (parti esyrmaty i nan lany ee ‘where via shope factor rected che aid ratio oon ‘lipid nthe cote ofronhydraton spheres ede 0.25. The wolame i usally oploced by the weight concerti, « Fore macromelecule efhydedynanic ‘olune » ond molec weight 9) @.19 Hydration effects Comider a hyckated mocromclecle conbiing 0) ‘rams of solver per gram of cry rocrencleculor note ‘al. The specie velume vo (lune per gran) of the lenropped woter may ba tonsideraby diferent om thot of pure saben, v7. fv; i he evoroge spect solune of the macromoieclt materi, hon the Stal hrdiceamic vole ofthe patil is M wep crened en The otal lume Vofesluten conning 5, groms of sole ond grams of dry macromolctlas sles Vewolame ofsahin “volume of wate of hyceation + vlame of ree soe! 0% 64m (01~ 8 OE 14General properties. polymer solutions!) |) 283))) Troster, ) cist be 613 _Substotng fo sn equation 6.11} gives Ke nia 14) ‘Substating fr» in equation (8.10) aro) 1S) ihe patil can be cttumed obo ushydaied, ofthe ogee of hydition can be esimated wah extiny from ether experimeril techiques, equction @.15) ‘may be ated 19 doermina the asyrevey cf the pore. Abwretivay, fthe macrovalecuie nay be cssumed © bbe symneticl or fx otynmaty it Inown fon ober technique, fn ths equction may be used fo einate the exert ef hydration of fhe mocromoecle. ‘Shape and solvent As the shape of molecules is to a large extent the determinant of flow properties, change in shape due to changes in polymer-solvent interactions and the binding of small mol- cules with the polymer may lead to signifi ‘ant changes in solution viscosity. The nature Of the solvent is thus of prime importance in this regard. In so-called ‘good! solvents linear ‘macromolecules will be expanded as the polar _groups will be solvated. Tn a ‘poor’ solvent the intramolecular attraction between the seg. ments is greater than the segment-solvent affinity and the molecule will tend to coil up (Gee Fg. 8.6). The viscosity of tontsed macro. molecules. is complicated by charge inter: actions which vary with polymer concen: tratlon and additive concentration, Flextble ‘charged macromolecules will vary in shape with the degree of ionisation. At maximum ionisation they are stretched out owing to mutual charge repulsion and the viscosity inereases. On. addition of small counterions the effective charge Is reduced and the mol- ‘ecules contract; the viscosity falls as a result, Some of the effects ate illustrated later in ths ‘chapter in discussion of individual macro molecules, for example, gum Arabic (acacia). The viscosity of solutions of globular pro- teins (which are more or less rigid) Is only slightly affected by change in ionic strength. ‘The intrinsic viscosity of serum albumin varies only between 3.6 and 4.1 cm" g"! when the pH ls varied between 4.3 and 105 and the ionic strength between zero and 0.50. Viscosity in phormacoposiol specifications In cases where control of molecular weight is Important, for example in the use of dextran fractions as plasma expanders, a. viscosity method is specified, for example, in the BP monograph. Staudinger proposed that the reduced viscosity of solutions of linear high polymers is proportional to the molecular weight of the polymer or its degree of poly- merisation, p: 6.16) ‘This empirical law has been modified to ony eae 7 here isa constant nthe ange 0-2, which for most high polymers has.a value between 0.6 and 08, |n] is the intrinsic viscosity as denned previously, an Ate the moleala treght ofthe polymer. Fora given polymer John oper Rand care coodaat, Values of these constants may be determined fom mea emonts on a seer of factions of tnoven molecular weight and: hence the fuolecuat sweght of an unknown fraction can be deter mined by measurement of We ineste Ws: Cesly-THe vices vera nobecuarWelght cssetially 2 weight average since the Larger ‘macomolecls fluc Hs nore an the smaller ones ‘The Tense wscsty of Destran 40 BP is stated to be not less than 16cm*g” and not more than 20cm*g* at 37°C fle that of Deatran 110 snot ess than Dram’ gand ot more than 32cm §‘Srucure V Corrlex formation boween pletylensinine ond pobfacrc oid) (002 A, oxen ° ho. on icons 6008 or oF coe 0H on fe ‘Srucure VI Repeating soqvence of hyalton ecid,« hgh melee weigh ghyeoominogycan ase coo” Sirucure Vil Repeating sequence of heparin ‘The two types of chondroitin (chondroitin sulfate and 6-sulfate) differ from hyaluronic acid by replacement of the -acetylghico- samine with sulfated N-acetylgalactosamine. As with hyaluronic acid, helices of varying degrees of compactness are found. The chondroitin and dermatan sulfate chains are of lower molecular weight (about 500 000) than those of hyaluronate and occur int vivo covalently linked to a protein core. Some glycoproteins, particularly those with numerous, generally distributed, oligosaccha- ride side-chains, are able to form dispersions with ‘stringy’ characteristics, as in nasal mucus oo salivary discharges. The theological impll- cations of interactions between mucus and drugs have been studied. As yet there is no coherent view as to what the ideal mucolytic ‘Sucre Vit Calin complased in polysaccharides agent, for example, should achieve. Reduction in ‘viscosity’ fs too simple a concept to use for such complex systems, and parameters such as ‘consistency’ and dynamic viscosity have tobe studied. (see Chapter 7) 8.3.5. Binding of ions to macromolecules Calcium Is coordinated between certain ‘uronic acid-containing polysaccharides (VII, which can explain the tight binding of calcium and other multivalent ions in poly- saccharide stnictures, and also how bivalent tons can induce gel formation in acidic poly. saccharides such as alginic acid solutions. It has been found that such. Interactions have dietary significance. Dietary fibre from plants binds calcium in propertion to its turonic acid content. This binding by the oncellulosic fraction of bre reduces the availability of calcium for small-ntestinal absorption, although colonic digestion of tronic acids liberates the calcium,’ The pH ependence of the binding strongly suggests the involvement of carboxylic acd groups. Where daily fibre intakes vary between 50 and 150 g, with perhaps 39 10 110 mmol uronic acid, the binding capacity of fibre may exceed the fotal intake of ealcium, which may be less tian 20 mmol (800 mg) per day. 8.34 Ineraion of polymers wth sents incdng water Asa consequence of their size, polymers Inter act with solvents in a more complex fashionGevarl propris palmer oons 289 than do smaller crystalline solutes. A given polymer may have no saturation solubility it Usually either dissolves completely or is only swollen by a given liquid. If the polymer is ‘crosslinked, solution cannot occur and the polymer will only swell by imbibition of liquid to form a gel. Swelling decreases asthe degree ‘of crosslinking increases. Swelling is also a function of the solubility parameter of the liquid phase, and if the polymer is ionic, swelling will be dependent on the ionic strength of the solution as shown in Fig. 8.10, for crosslinked hyaluronicacid gels. Increasing, ionic strength decreases the repulsion between, the chains and allows the polymer to shrink. Highly polar polymers like poly(vinyl chlor- ide) and some cellulose derivatives require Dla liquid solvents, in which dipote inter- ‘actions or hydrogen bonding betwreen polymer and solvent molecules occur. However, sol: ation does not necessarily eed to solution because the liquid, if it isto act as a solvent, must dissolve the solvated polymer. ‘This process may be very slow because of the high viscosity of the partially solvated system, Swelling of hydrogels ond deug release ‘The relative mobility of a drug diffusing tn the swelling hydrogel is given by the swelling tebe sling (8 Interface munber, Sw defined as swe 8.18) where v is the velocity of the moving front, ‘(tis the thickness of the rubbery layer (the infiltration and gel layers represented in Fig. 8.7) at time 1, and D is the diffusion coefficient of the drug in the matrix.* When Sw> 1, Fickian drug diffusion predominates, whereas when Swe, zero-order release kinetics are observed. The amount of drug released from a thin slab is expressed as an exponential: Me in zene 6.19) nn varying from ~0.5 to>1.0 where M/M_Is the fraction of drug and k is a constant, It has been seen in Chapter 7 that the use of macromolecules as dispersion stabilisers depends in part on the osmotic forces arising from the interaction of solvated polymer chains as neighbouring particles approach (see Fig. 7.7). {tts thus important to know how factors such as temperature and additive affect this interaction. Flory has given the free energy of dilution (the opposite process to the concentration effect discussed in section 7.2) Figure 8.10 Relative swelling ofhyalren ecd hydrogel in dflerent concentrators of NeCl.ond No;S03 sition, oped Hon Tree) Cath Ble 38,1599Genesal propeies of polymer solions |) 291) eee ee bo ' - i Pa i { fn eh «ij “9 100 ee a a a a ee ib Figure 8.12 (2) Responsive swaling (@| ond welcse (il from PSSAlbaded HA hydrogls wen on slacic fal of 1OV em * was swiched of (Reproduced from R- Tome’ a! al, J Contol Relsse, 33, 405 (1995) (] The fic of n ‘ecm Feld on 0 paveecrolve network, The redabibston of ine casses singe of he gel ot the extoda ord ‘eportion othe once, than in the stomach or duodenum; that is, they should swell in neutral rather than acidic Or alkaline conditions. In artificial intestinal juice, psyllium seed gum increased in volume ‘5-14 times, locust bean gum 5-10 times and methylcellulose 16-30 times in 24 hours. fn vo evaluation of methyicellulose and carboxy methylcellulose suggests that they have two advantages over the natural gums. Methyl cellulose is more efficient as a bulk laxative because of its greater water-retentive capacity, whereas carboxymethylcellulose gives uniform distribution through the intestinal contents. 8.3.7 Adsorption of mocromolecules “The ability of some macromolecules to adsor at interfaces is made use of in suspension and emulsion stabilisation (see Chapter 7) Gelatin, acacia, poly(vinyl alcohol) and pro- teins adsomb at interfaces. Sometimes such adsorption is unwanted, as In the case of insulin adsocption onto glass infusion bottles and poly(vinyl chloride) infusion containers and tubing used In giving sets. Adsorption of insulin to glass botties and plastic iv. tubing at slow rates of infusion is well documented, Ititd te “dure Nomacel Sc m!} 8 234 6 mw welt) a macromolecules tom somo ‘ro 4 3 4 3 é 3 tod 100 — witis om» Te “ Figae 8.13. ] The yolemeatoined by 5 of Normocol Speci vrious slucrs ever 20h, The vlumes atined bof 59 of Nemocel Special gel ord Cele nestled water end font Benenden 285 5011979) ranged from 59% to 3.1% when 20and 40 units respectively were added to S00 cm? of isotonic sodium chloride solution, while plastic Lv. tubing adsorbed 30% of 20 units and 26% of 40 units added to the same Infusion bottles (Fig. 8.14). Adsorption occurs rapidly, within 15 seconds. Addition of albumin to prevent adsorption Is now common practice. The albumin adsorbs at the glass or plastic surface land presents a more polar surface to the solu- tion, thus reducing, but not always prevent- ing, adsorption of the insulin (Fig. 8.15). The binding is considered to be a nonspecific phenomenon which may occur on other inert ‘materials such as polyethylene and glass. The adsorption of macromolecules at inter faces may be the reason why molecules such as those of hyaluronic acid ean act as biological lubricants in joint fuids. In healthy joints ‘only 0.8 cm? of synovial fluid is required to provide almost perfect lubrication; in diseased joints there are sometimes faults in this system and some research has been almed at prod= cing synthetic substitutes for synovial fluid. Fgure 8.14 Anouts of inlin st by edorpion te glass bots and plese irraverausbieg ellwing ijecion of 30 wrt of ral. The potert receiver ony 6.38 unt ended ton 6 hy nee | Gon snes, 486Some water-soluble polymers used in|pharmaey ond cr Bp ware wie ae I osmancte 75 er? KH Peete rine Figure 8.15. Prevertion of insu los ve edsrpion by he ection of hurtn serum clburtn (HSA) or Fasmancte te 1600 cin” of Ringer's lactate) sobton ina gloss bot. Inslin (30 uns) wos injected and reasurd ct Snir. Value: represent means = SEM. AlIHSA ond Plasmorole voles were (@<0.001), cory cifleret fom Ringe lcete soliton cores Fens Fon Py ent Conch, Atm 0 (978 Polymer solutions provide one approach as thelr theological characteristics more closely approach those of the natural fluid, which is non-Neatonian. 8.4. Some woter-soluble polymers used in pharmacy and medic In this section the properties of some specific polymers used in pharmacy and medicine will be discussed. This cannot be an exhaustive treatment of the subject, 0 choice of the ‘macromolecular material for this section has bbeen based partly on the degree of use, but partly on the generally interesting features they display. The choice of a macromolecular ‘material for a particular pharmaceutical use is often difficult because of the diversity of properties exhibited by the materials avall- able, Figure 8.16 illustrates how the fleld can be narrowed to some extent by grouping the natural and synthetic materials of Interest to the formulator. This is, however, a very general guide, as the properties of individual macromolecules will often vary with pH, temperature, molecular weight and ionic strength. The most readily altered variable is, fof course, the concentration of the macro: molecule, whose effect on viscosity Is illus- trated for a range of compounds in Fig, 8.17. ‘The most viscous material shown here Is Carbopol 934. 8.4.1 Carboxypolymethylene Corbomer, Carbopel ‘This Is used as @ suspending agent in pharma. ‘ceutical preparations and asa binding agent in tablets, and it is used in the formulation of prolonged-action tablets. It is a high mol- ‘ecular weight polymer of acrylic acid, con- taining 2 high proportion of carboxyl groups. Its aqueous solutions are acidic; when new- tralised the solutions become very viscous with a maximum viscosity between pH 6 and 11. Electrolytes reduce the viscosity of the system and thus high concentrations of the polymer have to be employed in ‘wehicles here ionisable drugs are present.Etipliydroxyethylcelulose is an ether of cellulose with both ethyl and hydroxyethyl substituents attached via ether linkages to the anhydroglucose rings. It swells in water to form a clear viscous colloidal solution. Preparation of solutions of cellulose deriv atives requires hydration of the macro- molecules, the rate of which is a function of both temperature and pHl, as shown in the ‘example in Fig. 8.18. Eviplmethyiceutose contains ethyl and methyl groups, 2 4% solution having approxi mately the same viscosity as acacia mucilage. Hysroxyethleeltaae is soluble in hot and cold water but does not gel. It has been used in ‘ophthalmic solutions. More widely used for the latter, however, is Inudoxypropyimethplel- lulose (hypromeliose) which is a mixed ether (of cellulose containing 27-30% of OCH, soups and 4-7.5% of -OC,l1OH groups. It forms a viscous colloidal solution. There are various pharmaceutical grades. For example, hhypromellose 20 is a 2% solution which has a viscosity between 15 and 25 ¢S (centistokes) at 20°C; the viscosity of 3 2% hypromeliose 15.000 solution lies between 12.000 and 18.000 cS. Hypromeliose prolongs the action (of medicated eyedrops and is employed! as an atificial tear tui, Sodium carboxymetiyleltuese is soluble in water at all temperatures. Because of the » ae « 7° awe zo B 0 o 1fantares Wet Figore 8.18 fect of pH and perature on th hydction time of fxtcutoling grades of hydrosyotyleallown sulfone’ ln CaP ese Polymers and macromolecules carboxylate group its mucilages are_more sensitive to change in pH than are those of methylcellulose. The viscosity of a sodium carboxymethylcellulose mucilage ts decreased markedly below pHS or above pH 10, Addition of heavy metal ions (AI, Zn, Fe) causes changes in solution properties. 84.3. Noturol gums ond mucileges Guru arabic (acacia) has been used in phate macy as an emulsifier. It is a polyelectrolyte whose solutions are highly viscous owing to the branched structure of the macromolecular ‘chains; ts adhesive properties are also believed. to be due to, oF in some way related to, this branched structure. Molecular weights of between 200 000 and 250 000 (M,) have been determined by osmotic pressure, values between 250 000 and 3» 10° by sediment- ation and diffusion, and values of 10° by light scattering, which also points 10 the shape fof the molecules as shart stiff spirals with numerous side-chains. Arabic acid prepared from commercial gum arabic by precipitation is a moderately strong acid whose aqueous solutions have a pH of 2.2-2.7. It has a higher viscosity than its salts, but emulsions prepared with arable acid cream are not as stable as those made with its salts, Whereas most _gums are very viscous in aqueous solution, gum arabic is unusual in that, being extremely soluble, itcan form solu tions over a wide range of concentrations up to about 3796 at 25°C. The marked variation in viscosity means that the gum arabic molecules ‘must be flexible, with the ionic acid carboxyl {groups distributed along the chain, At low PH the carboxyl groups are unionised. On Increase of pH the carboxyl groups become progressively tonised and the folded chains expand owing to repulsion between the charged groups, causing an increase In vis cosity, On addition of NaOH to the system the viscosity falls again as the concentration of counterion (Na") increases and effectively shields the acidic groups, The molecule then folds on itself, Similar falls In viscosity are exhibited on addition of sodium chloride.