Pharmacokinetics of a prototype formulation of sublingual testosterone and a buspirone tablet, versus an advanced combination tablet of testosterone and buspirone in healthy premenopausal women.
The study aimed to compare the kinetics of two novel combination drug products for Female Sexual Interest/Arousal Disorder (FSIAD). Thirteen women received testosterone via the sublingual route followed 2.5 hours later by a buspirone tablet, versus a single combination tablet swallowed at once. The first clinical prototype consisted of a sublingual solution containing testosterone (0.5 mg) complexed with cyclodextrin and a tablet containing 10 mg buspirone, in a gelatin capsule to ensure blinding during the clinical studies. The innovative fixed-combination tablet consists of an inner-core component of 10 mg buspirone coated with a polymeric time-delay coating and an outer polymeric coating containing testosterone with hydroxypropyl-beta cyclodextrin. We observed an immediate testosterone pulse absorption from both formulations. We also demonstrated that there was adequate absorption of buspirone (>80 % relative to the conventional tablet) and a time delay in release of buspirone of 3.3 hours, close to the 3.0 hours of the reference formulation that showed clinical efficacy in early proof-of-principle studies. The newly developed combination tablet fulfils its design criteria and is a convenient tablet for further clinical studies in FSIAD.
Emotional Brain B.V., Louis Armstrongweg 78, 1311 RL, Almere, The Netherlands, k.vanrooij@emotionalbrain.nl.
Kim
K
van Rooij
Leo
L
de Leede
Henderik W
HW
Frijlink
Jos
J
Bloemers
Saskia
S
Poels
Hans
H
Koppeschaar
Berend
B
Olivier
Adriaan
A
Tuiten
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002065:Buspirone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D017697:Premenopause; D013607:Tablets; D013739:Testosterone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D004338:Drug Combinations; D013607:Tablets; D013739:Testosterone; D002065:Buspirone