Fast Dissolving Research Articles

Functional maturation of hypothalamic GABAergic neurones; evidence for the emergence of a GABA A-receptor mediated inhibition of GABA secretion

Thiocolchicoside, a muscle-relaxant agent, is administered by the oral, intra-muscular and topical route. After oral administration the extent of bioavailability compared with intra-muscular administration is low, due to a first pass effect. In this paper, the delivery of thiocolchicoside through oral mucosa is studied to improve the bioavailability. Thiocolchicoside in vitro permeation through porcine oral mucosa and in vivo buccal transport in humans were investigated. Two dosage forms, a bioadhesive disc and a fast dissolving disc for buccal and sublingual administration of thiocolchicoside, respectively, were designed. The in vitro permeation of thiocolchicoside through porcine buccal mucosa from these dosage forms was evaluated and compared with in vivo absorption. Results from in vitro studies demonstrated that thiocolchicoside is quite permeable across porcine buccal mucosa and that permeation enhancers, such as sodium taurocholate and sodium taurodeoxycholate, were not able to increase its flux. The in vivo thiocolchicoside absorption experiments, in which the drug loss from oral cavity was measured, indicated that both formulations could be useful for therapeutic application. The fast dissolving (sublingual) form resulted in a quick uptake of 0.5 mg of thiocolchicoside within 15 min whereas with the adhesive buccal form the same dose can be absorbed over an extended period of time.

Pharmacodynamic Profile of Verapamil in Relation to Absolute Bioavailability

The absolute bioavailability F and response (prolongation of the PR interval) of verapamil after single doses of the same oral formulation administered on two different days were investigated in 16 male subjects with an 80 mg fast dissolving and a 240 mg controlled-release preparation and compared with a bolus injection of 5 mg of verapamil. The absolute bioavailability was 23% in both investigations for the 80 mg preparation and 32% in both investigations for the 240 mg dosage form. The individual values obtained for tmax, cmax, F, and AUC0-alpha showed a wide intersubject variability; therefore, no significant differences could be observed between the two trials for each dosage, but significant differences existed between the investigations of the two preparations. After intravenous administration, concentration-effect curves were about twofold left shifted when compared with the 80 mg tablet and about threefold left shifted when compared with the 240 mg tablet. Estimation of the drug input rate showed significantly (p less than 0.05) smaller values when the controlled-release tablet was given (80 mg tablet: 95.1 and 107.7 mg/h; 240 mg tablet; 55.8 and 46.3 mg/h). Thus, the effect and bioavailability of verapamil show sufficient intersubject reproducibility if the same formulation is given. The differences between the responses and the bioavailability after administration of different preparations may be related as well to the drug absorption rate and the stereoselective first pass of verapamil as to saturation of first-pass metabolism.

Correlation between dissolution rate and bioavailability of different commercial mefenamic acid capsules

A dissolution test was performed with five brands of 250 mg mefenamic acid capsule products available on the market. Three of them, the fast dissolving A and the slow dissolving D and E were subjected to a bioavailability study using a commercially available suspension as the reference. The products were administered orally in a cross-over design to 6 healthy men, and then parameters for the bioavailability were calculated from the plasma concentration-time curve. Analysis of variance indicated several significant differences among the products with respect to C max, T max and AUC. The relative availabilities of A, D and E were 86, 81 and 28%, respectively, with the AUC value (0-7 h) for the suspension as 100%. No correlation was observed between the in vitro dissolution rate of the drug from the capsules and the in vivo data, because the dispersing behavior of the capsule exerted a marked influence on its in vitro dissolution rate. To eliminate the influence of the capsule disintegrating process, a dissolution test was done on the contents of the capsules. A good correlation was found between the bioavailability and the dissolution rate of the drug from the capsule contents. Product E with the lowest bioavailability was passed through a 200-mesh sieve, placed in a new capsule, and tested for its bioavailabilky in humans. The AUC value was greater than that of the original product and the bioavailability was about equal to that of the suspension. The in vitro dissolution rate of the drug from the pulverized product E was also markedly increased.

Effect of Microcrystalline Cellulose on Liquid Penetration in and Disintegration of Directly Compressed Tablets

The penetration of isooctane and water into tablets of microcrystalline cellulose, dibasic calcium phosphate dihydrate, spray-crystallized maltose–dextrose, and blends of microcrystalline cellulose with one of the other excipients were studied. The isooctane penetrations occurred according to the Washburn equation and were not affected by the presence of 0.5 or 1.0% magnesium stearate. The inhibition of aqueous penetration into tablets resulting from hydrophobic magnesium stearate was less pronounced for vehicles like dibasic calcium phosphate, which exhibited extensive brittle fracture under compression. Microcrystalline cellulose tablets, both with and without magnesium stearate, exhibited extremely fast aqueous penetration even at low porosities, caused by breaking of the hydrogen bonds and subsequent widening of the pores. Ratios between water uptake and original pore volume up to 20 were obtained for microcrystalline cellulose tablets. This unique property was, however, suppressed by the presence of fast dissolving and highly soluble excipients like dextrose, resulting in an antagonistic disintegration behavior of tablets compressed at pressures over 10,000N/cm2. Improved disintegration properties were obtained by blending microcrystalline cellulose with an insoluble vehicle such as dibasic calcium phosphate dihydrate.

Thomas Wilson and the Tudor Commonwealth: An Essay in Civic Humanism

11fTOLSEY's fall marked more than the passing of a man: it symVAV bolized the end of an era in the evolution of statecraft. The cardinal's successor as chancellor was the layman Thomas More; henceforth, during that Reformation century the Tudor sovereigns were generally to prefer lay humanists to learned or ambitious clerics for administering the body politic of the realm. The humanists of Tudor England were seldom impractical academicians given to cloudy idealism; they were men versed in the ways of the world. If in their conservatism they envisioned and fought for an improved society cloaked in Platonic and Ciceronian finery, they meant to achieve it slowly by retaining much of that organic and hierarchical society in which they lived but which was fast dissolving. Hardheaded and ruthless when occasion demanded, they often displayed no less facility in racking a traitor than in discoursing on the classics. They served their masters and mistresses well, for in the throne they saw the only substantial bulwark against the new assault on custom. Their significance is best understood by reviewing the achievements of the civilians, diplomats, and secretaries-versatile men all -whose breadth of wisdom saw their commonwealth through so many storms. Thomas Wilson, a member of that second generation of English humanists which flourished at Cambridge during the 1540's, was one such scholar who left the hallowed atmosphere of the university for the more lucrative career promised by the civil law and royal preferment.1 Remembered for his humanist treatises on logic, rhetoric, and Demosthenes, he established for himself as well a reputation as an economist and commonwealth man by his lengthy essay condemning usury.2 In public affairs Wilson served his queen