Formulation and biopharmaceutical evaluation of a transdermal patch containing letrozole

Abstract

The purpose of this study was to formulate a drug-in-adhesive (DIA) transdermal patch containing letrozole, a third generation aromatase inhibitor for the treatment of breast cancer, using pressure-sensitive-adhesives (PSAs) and to evaluate the percutaneous penetration and pharmacokinetics of letrozole after transdermal administration, compared with that for the oral route. The formulation factors for such a patch, including the PSAs, enhancers and amount of drug loaded were investigated. Among the tested preparations, the formulation with DURO-TAK 87-4098, Azone and propylene glycol showed the highest letrozole permeation. The pharmacokinetic characteristics of an optimized DIA patch containing letrozole were determined using rats, while orally administered letrozole in solution was used as a control. The pharmacokinetic parameter, such as the mean residence time (MRT) was significantly (p<0.05) different following transdermal administration compared with oral administration. The in vivo results observed with the patches in rats were in good agreement with the plasma concentrations predicted from the in vitro penetration data. As a patient-friendly, convenient, high local drug concentration and sustained dosing therapeutic system, the transdermal patches incorporating letrozole provide a useful strategy for the prevention and treatment of breast cancer.

<p>Development Of Saquinavir Mesylate Nanoemulsion-Loaded Transdermal Films: Two-Step Optimization Of Permeation Parameters, Characterization, And Ex Vivo And In Vivo Evaluation</p>

“…To completely evaporate any water, the dishes were placed in a hot air oven at 40°C. The backing membrane was used to cover the films and cut into specific dimensions of 202 ± 24 mm with uniform thickness and stored in a desiccator 45. The same amount of SQR was used to prepare pure SQR-loaded transdermal films using the same protocol described earlier.…”

Transdermal Delivery of Chemotherapeutics: Strategies, Requirements, and Opportunities

“…Moreover, the low systemic levels of letrozole from the patch could decrease the incidence of the aforementioned adverse effects [ 54 ]. Li et al [ 55 ] optimized the delivery from the transdermal patch of letrozole by using various adhesives, permeation enhancers, and different letrozole concentrations. The permeation of letrozole through excised rat skin was significantly higher through the patch with adhesive DURO-TAK ® 87-4098, which lacks a carboxyl group, compared to DURO-TAK ® 87-2677 and 87-2852, the adhesives with a carboxyl group.…”

“…The permeation of letrozole through excised rat skin was significantly higher through the patch with adhesive DURO-TAK ® 87-4098, which lacks a carboxyl group, compared to DURO-TAK ® 87-2677 and 87-2852, the adhesives with a carboxyl group. It was speculated that the triazole group of letrozole could interact with the carboxyl group to form hydrogen bonds [ 55 ], which could impede the release of the drug from the adhesive with carboxylic groups. Conventional chemical enhancers were used to optimize the permeation, and the results indicated that a combination of azone (10%) with propylene glycol (5%), containing 1.5% of letrozole, was optimal for the adhesive patch [ 55 ].…”

“…It was speculated that the triazole group of letrozole could interact with the carboxyl group to form hydrogen bonds [ 55 ], which could impede the release of the drug from the adhesive with carboxylic groups. Conventional chemical enhancers were used to optimize the permeation, and the results indicated that a combination of azone (10%) with propylene glycol (5%), containing 1.5% of letrozole, was optimal for the adhesive patch [ 55 ]. Maniyar et al [ 56 ] formulated spray-dried letrozole (SPD-LET) as a liposomal dispersion in cream for topical delivery to breast cancer tumors.…”

Complex Drug Delivery Systems: Controlling Transdermal Permeation Rates with Multiple Active Pharmaceutical Ingredients

“…Over the past few decades, transdermal drug delivery system (TDDS) designs have moved from the conventional reservoir design to the drug-in-adhesive (DIA) matrix design. This DIA design has several advantages including a lightweight and thin presentation providing patients with a more flexible patch while also eliminating the potential for drug leakage (6)(7)(8). The DIA's relatively simple design appearance belies the relatively complex and critical role of the pressuresensitive adhesive (PSA) that must maintain proper adhesive and cohesive properties while concurrently acting as a carrier for the drug substance (9,10).…”