Superior bioavailability of digoxin solution in capsules

Abstract

The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers. Digoxin tablets that were 97% dissolved in 1 hr in vitro were not significantly better absorbed than tablets with a dissolution rate of 78%. A solution given in capsule form had greater bioavailability than tablets of 97% dissolution rate; serum and urinary glycoside levels after 0.4 mg doses of the encapsulated solution were similar to those attained after 0.5 mg doses of tablets with dissolution rates of 78% and 97%. The bioavailability of the solution in capsule form exceeded that of equal doses of the same solution given as a liquid or that of a standard elixir. No increase in gastrointestinal or cardiac toxicity was detected. Inter- and intrasubject variation in bioavailability was not decreased. Above a certain level, dissolution rate is no longer the limiting factor in digoxin absorption. The mechanism of the enhanced bioavailability of concentrated liquid digoxin in capsule form remains to be determined. Such a preparation deserves further consideration as a possible replacement for digoxin tablets.

Soft Gelatin Capsules (Softgels)

“…[55][56][57] The extent of diffusion of a polyethylene glycol from the fill into the shell decreases with an increase in its molecular weight. [61][62][63][64][65][66][67] However, while polyethylene glycols often may have high solubilizing power for some poorly water soluble compounds, the high affinity of these vehicles for water can potentially lead to the precipitation of dissolved compounds when the formulation comes into contact with an aqueous environment in vitro or in vivo. 54,[58][59][60] individual variability in the absorption have been shown to provide exceptionally high bioavailability and reduced inter-subject variability in plasma concentrations when dosed as solutions or suspensions in polyethylene glycols.…”

Isomerisierung und biologische Verf�gbarkeit von ?- und ?-Acetyldigoxin

“…Hingegen ergibt der Vergleich der Glykosidkonzentrationen im Plasma und der kumulativen Glykosidausscheidung im Harn nach einmaliger und repetierter oraler Applikation von Novodigal® und Dioxanin ® eine relative biologische Verffigbarkeit von Dioxanin von etwa 70%. Eine weitere Steigerung der Resorptionsquote kann durch Bildung eines Copr/izipitates von Digoxin und Polyvinylpyrrolidon, durch Inkorporierung yon Digoxin in eine Aerosilmatrix als Tr/igersubstanz [13] und ferner durch L6sungsvermittlung von Digoxin in Poly/ithylenglycol und Propylenglykol [2,9] erzielt werden, wobei letztere Zubereitung in Form yon Weichgelatinekapseln verabfolgt werden kann. Bei Anwendung fester Arzneiformen yon Digitalisglykosiden mul3 das wenig polare Glykosid erst in L6sung gehen, bevor es aufgenommen werden kann.…”

Influence of soft gelatin on digoxin absorption.

“…It has been shown that the bioavailability of digoxin is greater from soft gelatin capsules containing a solution of digoxin in polyethylene glycol than from either an aqueous solution of digoxin or from tablets of rapid dissolution rate (Mallis, Schmidt & Lindenbaum, 1975;Johnson, Bye, Jones & Sabey, 1976). It has been suggested that digoxin absorption might be facilitated by the solvent or by a factor in the capsule wall or that encapsulation might protect digoxin from inactivation by gastric acid or increase the local concentration at the intestinal absorption site (Mallis et al, 1975;Johnson et a., 1976).…”

“…It has been suggested that digoxin absorption might be facilitated by the solvent or by a factor in the capsule wall or that encapsulation might protect digoxin from inactivation by gastric acid or increase the local concentration at the intestinal absorption site (Mallis et al, 1975;Johnson et a., 1976).…”