In situ gelling xyloglucan/alginate liquid formulation for oral sustained drug delivery to dysphagic patients.

BACKGROUND: The oral administration of liquid dosage forms of suitable consistency and with sustained release characteristics may provide a means of improving the compliance of geriatric patients who experience difficulties in swallowing conventional solid dosage forms. AIM: We have designed and evaluated liquid preparations for administration to dysphagic patients, composed of aqueous mixtures of xyloglucan, which has thermally reversible gelation characteristics, and sodium alginate, which has ion-responsive gelation characteristics. METHOD: The gelation and in vitro and in vivo release characteristics of liquid formulations containing appropriate concentrations of xyloglucan and sodium alginate with mannuronate/guluronate ratios of either 0.5 or 0.8 were assessed. RESULTS: Aqueous mixtures of 1.5% xyloglucan and 0.5% alginate had suitable viscosities for ease of swallowing and appropriate gelation temperatures (approximately 33 degrees C) to ensure in situ gelation following oral administration. The in vitro release of paracetamol at pH 5.0 from gels formed by these formulations and also by a 1.5% xyloglucan solution was diffusion-controlled. Plasma levels of paracetamol after oral administration to gastric-acidity controlled rats (pH 5) of a solution containing 1.5% xyloglucan/0.5% alginate showed that a more sustained release was achieved from the gels formed by the in situ gelation of this formulation compared with that of a 1.5% xyloglucan solution. Visual observation of the contents of the rat stomach after oral administration showed that the inclusion of alginate in the xyloglucan solutions was effective in reducing gel erosion, so sustaining drug release. CONCLUSIONS: Liquid formulations of xyloglucan and sodium alginate in appropriate proportions are of suitable consistency for ease of administration to dysphagic patients and form gels in situ in the rat stomach capable of sustaining the release of paracetamol over a 6-hour period.

The influence of gastric acidity and taste masking agent on in situ gelling pectin formulations for oral sustained delivery of acetaminophen.

Dilute solutions of pectin containing complexed calcium ions form gels when these ions are released in the acidic environment of the stomach. The aim of this study was to examine the influence of a variation of gastric pH and the addition of a taste masking agent on the gelation of the pectin solutions and on the in vitro and in vivo release of acetaminophen from the gels. Increase of pH above 2.5 and addition of 10% (w/v) D-sorbitol significantly affected the ability of 1.5% (w/v) pectin solutions to form coherent gels in vitro. Gelation of sorbitol-free formulations was observed at pH 1.2 and in vitro release of acetaminophen from the gels followed diffusion-controlled kinetics; in vitro gelation of these formulations, however, was incomplete at pH 3.0 resulting in poor sustained release characteristics. Inclusion of 10% (w/v) D-sorbitol in the formulations inhibited the in vitro gelation of the 1.5% (w/v) pectin sols and poor sustained release properties were noted from these formulations even at pH 1.2. The bioavailability of acetaminophen from gels formed in the stomach of gastric-acidity controlled rabbits following oral administration of the liquid formulations was not, however, significantly affected either by the inclusion of 10% (w/v) D-sorbitol or increase of pH to 3.6. Visual observation showed in situ gelation of 1.5% (w/v) pectin formulations containing D-sorbitol at pH 4.3 suggesting that normal variations of gastric acidity in the fasting state will have no effect on the bioavailability of acetaminophen when delivered using these formulations.

Successful management of supraventricular tachycardia in a fetus using fetal magnetocardiography.

We report a fetus at 33 weeks of gestation with supraventricular tachycardia, which was successfully managed by transplacental administration of an antiarrhythmic agent. Fetal magnetocardiography (fMCG) revealed supraventricular tachycardia of the long RP' tachycardia type. Transplacental administration of sotalol, instead of digoxin, was selected as the first-line drug, and it successfully converted supraventricular tachycardia to sinus rhythm. The diagnosis of the type of supraventricular tachycardia was confirmed by electrocardiography after birth. Sotalol was also effective after birth to maintain sinus rhythm. This case demonstrates that fMCG is potentially useful for prenatal differentiation of the type of supraventricular tachycardia and for prenatal treatment of fetal tachyarrhythmias.