Raman mapping of fentanyl transdermal delivery systems with off-label modifications.

Raman mapping is a powerful and emerging tool in characterization of pharmaceuticals and provides non-destructive chemical and structural identification with minimal sample preparation. One pharmaceutical form that is suitable but has not been studied in-depth with Raman mapping is transdermal delivery systems (TDS). TDS are dosage forms designed to deliver a therapeutically effective amount of active pharmaceutical ingredient (API) across a patient's skin.

Measurement of drug in small particles from aqueous nasal sprays by Andersen Cascade Impactor.

Purpose: To determine if cascade impactor (CI) measurement of drug in small particles from aqueous nasal sprays, described in FDA's 2003 draft Nasal Bioavailability/Bioequivalence Guidance, can be optimized to reduce measurement variability. To examine the influence of flow rate configurations and number of impactor stages on CI deposition and explore the importance of inlet volume.

Methods: A total of eight assemblies and manual vs.

Evaluating elevated release liner adhesion of a transdermal drug delivery system (TDDS): a study of Daytrana™ methylphenidate transdermal system.

Background: Complaints from healthcare providers that the adhesive on the Daytrana™ methylphenidate transdermal drug delivery system (TDDS) adhered to the release liner to such an extent that the release liner could not be removed prompted this study. Daytrana™ has a packaging system consisting of a moisture-permeable pouch contained within a sealed tray containing a desiccant; the tray is impermeable to ambient moisture. The objective of this project was to determine if the Daytrana™ packaging system influenced the difficulty in removing the release liner.

Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles.

Titanium dioxide (TiO(2)) is included in some sunscreen formulations to physically block ultraviolet radiation. A dermal penetration study was conducted in minipigs with three TiO(2) particles (uncoated submicron sized, uncoated nano-sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight in a sunscreen. These and control formulations were topically applied to minipigs at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks).

Release liner removal method for transdermal drug delivery systems (TDDS).

A release liner removal test is a valuable test for assessing the quality of a transdermal drug delivery system (i.e., TDDS, patch).

Transdermal delivery of fentanyl from matrix and reservoir systems: effect of heat and compromised skin.

The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the current research focuses on the in vitro characterization of fentanyl reservoir (Duragesic) and matrix (Mylan) systems with respect to drug release and skin permeation under conditions of elevated temperature and compromised skin. In addition, different synthetic membrane barriers were evaluated to identify the one that best simulates fentanyl skin transport, and thus may be useful as a model for these systems in future studies.

Reservoir based fentanyl transdermal drug delivery systems: effect of patch age on drug release and skin permeation.

Purpose: To understand and evaluate the stability and skin permeation profiles of fentanyl reservoir systems as a function of patch age.

Methods: Drug release and skin permeation studies were performed using a modified USP apparatus 5 with a novel sample preparation technique.

Results: The amount of fentanyl present in the EVA/adhesive layer (EAL) increased from about 17% of label claim (LC) at 5 months to 25% LC at 22 months.

Comparing methods for detecting and characterizing metal oxide nanoparticles in unmodified commercial sunscreens.

Aims: To determine if commercial sunscreens contain distinct nanoparticles and to evaluate analytical methods for their ability to detect and characterize nanoparticles in unmodified topical products using commercial sunscreens as a model.

Methods: A total of 20 methods were evaluated for their ability to detect and characterize nanoparticles in unmodified commercial sunscreens.

Results: Variable-pressure scanning-electron microscopy, atomic-force microscopy, laser-scanning confocal microscopy and X-ray diffraction were found to be viable and complementary methods for detecting and characterizing nanoparticles in sunscreens.

Evaluation of substrates for 90 degrees peel adhesion--a collaborative study. II. Transdermal drug delivery systems.

In a previous study on peel adhesion for medical tapes, it was shown that a stainless steel (SS) substrate better discriminated among medical tapes than a high-density polyethylene (HDPE) substrate. The objective of this study was to determine if a SS substrate would also better distinguish among transdermal drug delivery systems (TDDSs). Five TDDSs (Vivelle Dot, Climara, Catapres-TTS, Duragesic, and Mylan Fentanyl) were evaluated on three different substrates (SS, HDPE, and human cadaver skin).

Evaluation of substrates for 90 degrees peel adhesion--a collaborative study. I. Medical tapes.

As part of a method development for peel testing, an interlaboratory comparison among Food and Drug Administration-Center for Drug Evaluation and Research, Food and Drug Administration-Center for Devices and Radiological Health and Southwest Research Institute was conducted using medical tapes. The aim was to determine which readily available substrate [stainless steel (SS), high density polyethylene (HDPE) or Vitro-Skin(R)] would best distinguish among various medical tapes. Five medical tapes (3M 1523, 3M 1525L, 3M 1776, Mepiform(R) and Mediderm(R) 3505) were evaluated on four different substrates (SS, HDPE, Vitro-Skin, and human cadaver skin) using the following peel parameters: approximately 3 min dwell time, 90 degrees peel angle, and 300 mm/min peel rate.

Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute.

Transdermal drug delivery systems (TDDS), also known as "patches," are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. In the Drug Quality Reporting System (DQRS), the United States Food and Drug Administration (FDA) has received numerous reports of "adhesion lacking" for transdermal drug delivery systems.

Quality assessment of internet pharmaceutical products using traditional and non-traditional analytical techniques.

This work investigated the use of non-traditional analytical methods to evaluate the quality of a variety of pharmaceutical products purchased via internet sites from foreign sources and compared the results with those obtained from conventional quality assurance methods. Traditional analytical techniques employing HPLC for potency, content uniformity, chromatographic purity and drug release profiles were used to evaluate the quality of five selected drug products (fluoxetine hydrochloride, levothyroxine sodium, metformin hydrochloride, phenytoin sodium, and warfarin sodium). Non-traditional techniques, such as near infrared spectroscopy (NIR), NIR imaging and thermogravimetric analysis (TGA), were employed to verify the results and investigate their potential as alternative testing methods.