Patrick S. L. Wong

Nifedipine gastrointestinal therapeutic system

Convenient once-a-day dosage regimens are highly desirable in general, and especially for the treatment of asymptomatic diseases such as essential hypertension. Nifedipine is an insoluble, short-acting calcium channel blocker that presents a difficult technical challenge for formulation in a constant 24-hour delivery dosage form. Once-a-day dosage forms have been developed based on the gastrointestinal therapeutic system (GITS) push-pull osmotic pump configuration in three strengths with different drug delivery rates (mg/hour) per dose (mg), as 1.7/30, 3.4/60, and 5.1/90. The delivery rates of drug from these systems are controlled by their drug loading, composition of osmotic components, membrane properties, and dimensions. The release rates are independent of pH in the range from gastric pH = 1.2 to intestinal pH = 7.5. The release rates are independent of stirring rate and therefore unlikely to be influenced by motility in the gastrointestinal tract. The drug release rate from the nifedipine GITS dosage form in vivo in the gastrointestinal tract of dogs has been found to be equal to the release rate in vitro, indicating that the in vitro test is predictive of in vivo delivery. Following administration of the nifedipine GITS dosage forms to human subjects, absorption rates, calculated from resulting plasma concentrations, indicate that the cumulative amount of drug absorbed in humans over 24 hours is proportional to the amounts of drug delivered in vitro. Plasma concentrations are therefore predictable and remain relatively constant throughout the 24-hour dosing interval.

Pulsed drug delivery

Modern drug delivery aims to develop drug delivery systems that are able to meet specific therapeutic requirements. Whereas sustained drug release aims to maintain a constant drug level within the body, pulsed drug delivery intends to release the drug rapidly within a short period of time, as a result of a biological or external trigger, after a specific lag time. This editorial highlights some of the recent advances in new concepts for pulsed drug delivery and proposes some future strategies.

Enhanced ileal absorption of a hydrophilic macromolecule, pentosan polysulfate sodium (PPS)

An in situ gelling, bioadhesive liquid formulation was developed to enhance the bioavailbility (BA) of a polysaccharide, pentosan polysulfate sodium (PPS). The formulation was tested to determine its bioavailability enhancement in a non-flush/non-ligated rat ileal model. A potent synergistic effect was found with a gelling agent Cremophor and a permeation enhancer sodium salicylate. The absolute bioavailabilities were 1.9%, 4.6%, 6.3% and 46.4%, respectively, for the PPS solution in saline, sodium salicylate/PPS, Cremophor/PPS and Cremophor/sodium salicylate/PPS. Therefore, we successfully demonstrated the approach of utilizing an in situ gelling/bioadhesive liquid carrier to enhancing the bioavailability of a hydrophilic macromolecule at the distal small intestine.