T

Surface skin layer OFF

Drug release ON

Surface skin layer OFF

A G1 is therefore zero at the theta temperature when deviations from ideality vanish, that is, there are no polymer-polymer or polymersolvent interactions. When T = 0 there can thus be no stabilisation as molecules will interpenetrate without net interaction and will exert no forces on each other.

Not only do most linear polysaccharides tend to form spirals in solution, but in their tendency to associate they may form double helices, as does carrageenan, for instance. Under certain conditions of concentration and temperature the double helices may associate, forming gels. Possibilities exist for complex gel formation as with carrageenan, or of xanthan gum with locust bean gum. The locust bean gum molecule can associate over part of its length with the helix of xanthan, for example, while the other part of the molecule associates with another xanthan molecule, thereby acting as a bridging agent.

The firmness or strength of gels produced by such interactions will depend on the degree of interaction of the complex with water and the properties of the bridging units.

The ability to change the swelling characteristics of a polymer gel by heat, pH or application of electric current can be valuable in specialised delivery systems, as exemplified in

Figure 8.11 On-off switching mechanism for drug release.

Reproduced from R. Yoshida et al., Adv. Drug Del. Rev., 11, 85 (1993).

Fig. 8.11, which shows the effect of temperature change on the swelling and deswelling of a hydrogel, resulting in an on-off 'switching' mechanism.

The relationship between swelling and release in an electrically responsive hydrogel is shown in Fig. 8.12. The mechanism of the current-induced change in volume of the gel is shown as an insert to the figure.

Hydrophilic polymers as bulk laxatives

The ability of carbohydrates and other macro-molecules to imbibe large quantities of water is put to use both medicinally and industrially; for example in absorbent paper and sanitary towels, incontinence pads and surgical dressings. Medically, use is made of the swelling properties in the treatment of constipation and in appetite suppression. Three properties are of importance in the in vitro evaluation of bulk laxatives:

• The volume of water absorbed in the various media

• The viscosity and texture of the gel formed

• The ability of the gel to retain water

The swelling properties of a sterculia-based preparation (Normacol) in various aqueous media and a comparison of Normacol with two other agents are shown in Fig. 8.13. It is desirable that colloidal bulk laxatives swell in the lower part of the small intestine and in the large intestine to cause reflex peristalsis, rather

Negative charge

Stress

Negative charge

Stress

Figure 8.12 (a) Responsive swelling (•) and release (■) from PSSA-loaded HA hydrogels when an electric field of 10 V cm01 was switched off. (Reproduced from R. Tomer et al., J. Control. Release, 33, 405 (1995).) (b) The effect of an electric field on a polyelectrolyte network. The redistribution of ions causes shrinkage of the gel at the cathode and expansion at the anode.

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. In vivo evaluation of methylcellulose 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 macromolecules

The ability of some macromolecules to adsorb at interfaces is made use of in suspension and emulsion stabilisation (see Chapter 7). Gelatin, acacia, poly(vinyl alcohol) and proteins adsorb at interfaces. Sometimes such adsorption is unwanted, as in the case of insulin adsorption onto glass infusion bottles and poly(vinyl chloride) infusion containers and tubing used in giving sets. Adsorption of insulin to glass bottles and plastic i.v. tubing at slow rates of infusion is well documented. It

Figure 8.13 (a) The volume attained by 5 g of Normacol Special in various solutions over 30 h. (b) The volumes attained by 5 g of Normacol Special, Isogel and Celevac in distilled water.

Reproduced from J. D. Ireson and G. B. Leslie, Pharm. J.,205, 540 (1970).

Figure 8.13 (a) The volume attained by 5 g of Normacol Special in various solutions over 30 h. (b) The volumes attained by 5 g of Normacol Special, Isogel and Celevac in distilled water.

Reproduced from J. D. Ireson and G. B. Leslie, Pharm. J.,205, 540 (1970).

ranged from 5% to 3.1% when 20 and 40 units respectively were added to 500 cm3 of isotonic sodium chloride solution, while plastic i.v. 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 and presents a more polar surface to the solution, thus reducing, but not always preventing, 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 interfaces may be the reason why molecules such as those of hyaluronic acid can act as biological lubricants in joint fluids. In healthy joints only 0.5 cm3 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 aimed at producing synthetic substitutes for synovial fluid.

Figure 8.14 Amounts of insulin lost by adsorption to glass bottles and plastic intravenous tubing, following injection of 30 units of insulin. The patient receives only 6.36 units.

Reproduced from C. Petty and N. L. Cunningham, Anaesthesiology, 40, 400 (1974).

Figure 8.14 Amounts of insulin lost by adsorption to glass bottles and plastic intravenous tubing, following injection of 30 units of insulin. The patient receives only 6.36 units.

Reproduced from C. Petty and N. L. Cunningham, Anaesthesiology, 40, 400 (1974).

RL gla

HSA 1 cm3

HSA 2 cm3

Plasmanate 60 cm3

Plasmanate 75 cm3

30 40

Percentage insulin loss

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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