Pressure-controlled Drug Release

6 A Practical Approach in the Design of Colon-specific Drug Delivery Systems 

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Another strategy rehes on the strong peristaltic waves in the colon that lead to a temporarily increased luminal pressure (pressure-controlled drug release). Pressure-sensitive drug formulations release the drug as soon as a certain pressure limit is attained, i.e. destruction force is exceeded. 

Osmotic pressure can be used for controlled drug release. The osmostic pressure can pump out drug at a constant rate, as described below. An important consideration is that because the pumping principle is based on osmosis, pumping rate is unaffected by changes in experimental conditions. Hence, in vitro drag release rate is often consistent with the in vivo release profile. 

Comparative pharmacokinetic profiles of nifedipine delivered from Procardia XL, an osmotic pressure-controlled drug delivery system, once-a-day versus that from Procardia, an immediate-release dosage form, taken on time 0, 8 and 16 in human volunteers. Modified from Y.W. Chien. Oral drug delivery and delivery systems. Y.W.Chien (ed.) (1992) Novel Drug Delivery Systems. Marcel Dekker, Inc. New York, pp. 139-196... 

Ulman, K. L., and C-L. Lee. 1989c. Drug permeability of modified silicone polymers. III. Hydrophilic pressure-sensitive adhesives for transdermal controlled drug release applications. /. Contr. Rel. 10 273-281. 

The Rauwolfia alkaloid reserpine, due to its strong central component of activity, is excluded from this review, even though it has the peripheral effect of releasing norepinephrine from storage sites where it can be metabolized by monoamine oxidase. This results in neurotransmitter depletion and it appears that good blood pressure control would be achieved by a drug which has this peripheral mechanism but lacks the central component. The Mead-Johnson compound MJ-10459-2 (LXI) shows activity in... 

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

Pressure-controlled Disintegration of the drug release dosage form in the colon... 

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