Simultaneous estradiol and levonorgestrel transdermal delivery from a 7-day patch: in vitro and in vivo drug deliveries of three formulations.

A new drug-in-adhesive transdermal patch was developed to deliver both estradiol and levonorgestrel through the skin over a 7-day period, but at different rates. This report elucidates the in vitro and in vivo biopharmaceutical studies that were necessary during the development of this product. Three test patches had to be manufactured, all delivering estradiol at the same rate, but delivering levonorgestrel at three different rates so that a levonorgestrel dose response could be studied in the clinic.

Novel poloxamer-based nanoemulsions to enhance the intestinal absorption of active compounds.

On the basis of Pluronic P104 as primary emulsifier and Lauroglycol 90 as amphiphilic oil phase, two nanoemulsion systems were developed with Pluronic((R)) L62 or L81 as secondary emulsifiers. The possible nanoemulsion region of combinations of these excipients was described in ternary phase diagrams. Three formulations were selected from the nanoemulsion region and their potential impact on oral absorption was examined in the Caco-2 monolayer model of the small intestine.

Comparison of permeation enhancing strategies for an oral factor Xa inhibitor using the Caco-2 cell monolayer model.

FXai, a direct inhibitor of the clotting factor Xa, provides high water solubility but poor membrane permeability due to multiple sites of ionization and a molecular weight exceeding 500 Da, making it a Class III drug according to the Biopharmaceutics Classification System. To overcome the ionization problem and increase the transcellular permeability, various ester and hydroxyamidine prodrugs exhibiting a reduced number of ionization sites were studied in the Caco-2 monolayer model for intestinal permeation. Alternatively, the potential transcellular permeation enhancement of Imwitor 742 and the potential paracellular enhancement of three chitosan formulations were investigated in the same model.

Evaluation of the transdermal permeation behavior of Proterguride from drug in adhesive matrix patches through hairless mouse skin.

The transdermal in vitro permeation behavior of the highly potent dopamine agonist Proterguride was investigated using hairless mouse skin as a model membrane. Drug in adhesive matrix formulations based on different types of pressure-sensitive adhesives (Eudragit E 100 and Gelva7883 as acrylates, Oppanol B 15 SFN as polyisobutylene, and BioPSA 7-4202 as silicone) with a drug load of 3% by weight were manufactured. All patches were examined for drug crystallization by polarized microscopy immediately after the manufacturing process and after storage for 30 days in sealed aluminium laminate bags at ambient temperature and at 40 degrees C, respectively.

In-vitro release and transdermal fluxes of a highly lipophilic drug and of enhancers from matrix TDS.

Transdermal systems (TDS) are a well-known application form for small, moderately lipophilic molecules. The aim of this study was to investigate the possibility of applying a highly lipophilic drug, the antiestrogen AE (log P=5.82) transdermally by polyacrylate-based matrix TDS.

Transdermal delivery of highly lipophilic drugs: in vitro fluxes of antiestrogens, permeation enhancers, and solvents from liquid formulations.

Purpose: Highly lipophilic basic drugs, the antiestrogens AE 1 (log P = 5.82) and AE 2 (log P = 7.8) shall be delivered transdermally.