Influence of adsorbents in transdermal matrix patches on the release and the physical state of ethinyl estradiol and levonorgestrel.
The drug release from medium molecular weight polyisobutene patches containing adsorbates (drug content: 0.2% ethinyl estradiol, 1.0% levonorgestrel; adsorbent content: 20%, w/w) increased in the order of no adsorbent<titanium dioxide<MCC<crospovidone. This was attributed to differences in drug crystallinity which increased in the order of crospovidone (crystal free)<MCC<titanium dioxide<no adsorbent and the water uptake which increased in the order of no adsorbent (0.1%)=titanium dioxide (0.1%)<MCC (1.6%)<crospovidone (4.8%) at 90% rh. Patches containing adsorbates onto crospovidone were investigated in detail. Increasing the adsorbate's drug loading increased the drug release up to a crospovidone content of 15% (w/w). Patches were crystal free for crospovidone contents ≥ 10% (w/w), which corresponds to a drug loading of crospovidone of 12% (w/w). In conclusion, the incorporation of drug adsorbates onto crospovidone into patches based on polyisobutene significantly increased the drug release (approximately 9.1 times for ethinyl estradiol and 15.4 times for levonorgestrel) and prevented drug recrystallization.
College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Martin
M
Schulz
Bernhard
B
Fussnegger
Roland
R
Bodmeier
D000279:Administration, Cutaneous; D000327:Adsorption; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003460:Crystallization; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004967:Estrogens / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008970:Molecular Weight; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D057968:Transdermal Patch; D014867:Water
D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D004967:Estrogens; D014867:Water; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D011205:Povidone