Capsular-shaped systems

Krogel, I., and Bodmeier, R. (1999), Evaluation of an enzyme-containing capsular shaped pulsatile drug dehvery system, Pharm. Res., 16,1424-1429. 

Among newly developed colon-specific drug delivery systems, pressure-controlled delivery capsules (PCDCs) [161] can be mentioned. Their mechanism of action is based on the relatively strong peristaltic waves taking place in the colon and leading to an increased luminal pressure. They consist of a capsular-shaped suppositories coated with a water-insoluble polymer (ethyl cellulose). Once taken orally, PCDCs behave like an ethyl cellulose balloon, because the suppository base liquefies at body temperature. In the upper GI tract, PCDCs are not directly subjected to the luminal pressures since sufficient fluid is present in the stomach and small intestine. The reabsorption of water in the colon provokes an increase of the luminal content viscosity. As a result, increased intestinal pressures directly affect the system via colonic peristalsis. Consequently, PCDCs mpture and drug release in the colon take place. 

Fig. 9 Capsular-shaped pulsatile drug delivery system, consisting of an impermeable capsule body and (A) a swellable, insoluble coated plug and (B) an erodible plug. (From Ref. l)...

In the Chronset system (Fig. 11), the driving force for the drug release was an osmotically active layer in the semipermeable vessel, which pushed the cap out off the impermeable vessel after a predetermined time interval.f The complete release of the drug, often problematic in capsular-shaped dosage forms, was ensured by an expanding layer at the bottom of the capsule body. 

Very recently it was shown that Ga-K- and Ga-Zn-MONCs encapsulating T1 can be prepared [60b], In addition to the capsular MONC systems of different shapes it was found that these systems can form tubular and bilayer structures. To appreciate the wealth of possibilities of MONCs, the reader is advised to consult recent reviews oti the subject [29, 60b]. 

Table 2 indicates that the most suitable capsular membranes comprised semi-or non-transparent systems. Generally, the multicomponent blending resulted in smooth capsules with the exception of the alginate/spermine-polymethylene-co-guanidine systems which were either irregularly shaped or mosaic. There was no correlation observed between the capsule turbidity and permeability. 

Coordination interactions are not the only way to use self-assembly to produce closed, capsular systems capable of binding guest species in solution. Work by Julius Rebek Jr (Scripps, USA)43 has shown that multiple hydrogen-bonding interactions, because of their relatively weak, but directional, nature, are ideal for the strict self-assembly of closed spherical molecules and capsules. For example, component 10.49 consists of two intrinsically curved diphenylglycoluril units linked by a durene-based (1,2,4,5-tetramethyl benzene-based) spacer. In both solution and in the solid state, 10.49 self-assembles spontaneously to produce the tennis ball-shaped dimer (10.49)2 shown in Figure 10.43. The formation of the dimer has been observed by ... 

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