Effect of Micronization on the Bioavailability and Pharmacologic Activity of Spironolactone

Abstract

The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of these tablets were identical. After 200-mg single doses, the bioavailability of micronized tablets was significantly higher than that of standard tablets. Furthermore, as assessed by 24-hour urine log10 10 Na/K ratio, the pharmacologic activity of micronized spironolactone was significantly greater than that of the standard formulation. The significant influence on renal antimineralocorticoid activity of raised plasma and urinary levels of canrenone, quantitatively the major active metabolite of spironolactone in man, emphasizes the clinical importance of the bioavailability of spironolactone preparations. Since this study, the process used in the manufacture of spironolactone (Aldactone) tablets has been under review.

Oil-In-Water Microemulsion Encapsulation of Antagonist Drugs Prevents Renal Ischemia-Reperfusion Injury in Rats

“…In fact, SP has poor availability due to low aqueous solubility. In order enhance SP bioavailability, different methods have been used including simultaneous administration of surface active agents, micronization of SP [50], complexation of SP with cyclodextrin [51,52] and utilization of microsomal carriers [23]. Indeed, it was demonstrated that drug delivery via liposomal carrier enhances the bioavailability of drugs, therefore improving longevity, target-ability, distribution characteristics and therapeutic efficacy [19].…”

Improving the dissolution properties of spironolactone using liquisolid technique

“…Percentages of drug released from the liquisolid tablets and conventional tablets in distilled water, error bars are standard error and rotational paddle speed was identical in all dissolution tests. Spereas et al showed similar results and inference in their study on enhancing the prednisolone dissolution properties by using liquisolid compacts (13,15,22,26,28). It seems that the kind of liquid vehicle used in preparing liquisolid compacts had some effects on drug dissolution properties (11).…”

“…Drug content (%) ± SD By increasing in Cs, the concentration gradient (Cs-C) will be increased, consequently increasing in dissolution rate according to Noyes-Whitney equation will occur. As it is shown in figure1 the dissolution rate of liquisolid compacts are higher than conventional direct compress tablets (13,22,26,27).…”

“…Spironolactone is a selective aldosterone antagonist which mostly use for treating edematous conditions (19,20). This drug has a low water solubility and dissolution rate which may reduce its bioavailability (21,22). To improve this undesirable property, in this project several formulations of spironolactone through liquisolid technique with different types of vehicle were prepared and studied.…”

In-vitroandin-vivostudy of amorphous spironolactone prepared by adsorption method using supercritical CO2

“…Many strategies have been employed to obtain the favorable bioavailability for SP, such as micronization 3 , nanoparticles 4 , nanocapsules 5 , liposomes 6 and cyclodextrin complexes 7 . However, the application was limited due to the potential problems, such as solvent residues, complicated operation and unfavorable drug stability.…”