Supersaturating drug delivery systems: effect of hydrophilic cyclodextrins and other excipients on the formation and stabilization of supersaturated drug solutions.
Supersaturating drug delivery systems (SDDS) utilize two important design elements in their preparation including converting the drug of interest into a high energy state or other rapidly dissolving form to facilitate the formation of supersaturated drug solutions and providing a means for stabilizing the formed supersaturated solution such that significant drug absorption is possible from the gastrointestinal tract. This has been referred to as a "spring" and "parachute" approach. The current effort is designed to assess materials which may affect properties in SDDS. To this end, a series of excipients was tested in a co-solvent/solvent quench method to assess their ability to attain and maintain supersaturation for a group of 14 drug development candidates. The approach focussed on hydrophilic cyclodextrins including hydroxypropyl-beta-cyclodextrin (HPbetaCD) and sulfobutyl-beta-cyclodextrin (SBEbetaCD). Various rheological polymers and surfactants were also included in the study. Consistent with previous investigations, the pharmaceutical polymers, as a class, had minimal effects on the extent of supersaturation but tended to be good stabilizers while the surfactants tended to provide for the greatest degree of supersaturation but the formed systems were poorly stable. This study found that hydrophilic cyclodextrins, especially SBEbetaCD, gave superior results in terms of attaining and maintaining supersaturation. A knowledge of the behavior and performance of excipients in this context can be useful in designing solid oral dosage forms for difficult-to-formulate drugs and drug candidates.
Brewster
M E
ME
Pharmaceutical Sciences, Johnson & Johnson Pharmaceutical Research and Development, a Division of Janssen Pharmaceutica, Beerse, Belgium. mbrewste@prdbe.jnj.com
Vandecruys
R
R
Verreck
G
G
Peeters
J
J
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012212:Rheology; D012997:Solvents; D013329:Structure-Activity Relationship
D003505:Cyclodextrins; D005079:Excipients; D019999:Pharmaceutical Solutions; D011108:Polymers; D012997:Solvents