The effect of formulation excipients on the penetration and lateral diffusion of ibuprofen on and within the stratum corneum following topical application to humans.

Distribution profiles of topically applied drugs can be influenced by the presence of excipients. This study investigated the effect of common topical excipients on the simultaneous lateral diffusion and stratum corneum (SC) penetration of a model compound, ibuprofen (IBU) in humans. IBU solutions with and without propylene glycol (PG), polyethylene glycol 200 (PEG 200), and/or octisalate (OS) were dosed onto the forearm of participants.

The buccal mucosa as an alternative route for the systemic delivery of risperidone.

The purpose of this study was to investigate the potential of the buccal mucosa for the systemic delivery of risperidone (RISP), and to determine the impact of Azone® (AZ) on the transport of RISP via this route. The permeability of RISP through porcine buccal mucosa was assessed in modified Ussing chambers at various concentrations to determine the mechanisms involved in transport across the tissue. The effect of AZ was assessed by administering AZ 5% (w/w) to the tissue as a pretreatment or together with RISP in solution or in a mucoadhesive gel formulation.

A novel flow through diffusion cell for assessing drug transport across the buccal mucosa in vitro.

A novel flow through (FT) diffusion cell for assessing the permeability of compounds across the buccal mucosa was designed. Porcine buccal mucosa was mounted between two chambers with flow through capacity in both the donor and receptor chambers. The permeability of caffeine (CAF), triamcinolone acetonide (TAC), and estradiol (E(2)) was determined over 4 h and flux values were compared to those obtained using a modified Ussing chamber (MUC).

Mechanisms of action of novel skin penetration enhancers: phospholipid versus skin lipid liposomes.

Employing thermal analysis, we investigated the mechanism of action of novel enhancers and probed phospholipid (PL) versus stratum corneum lipid (SCL) liposomes as model membranes. The enhancers included octyl salicylate (OS), padimate O (PADO) and 2-(1-nonyl)-1,3-dioxolane (ND). The negative controls were the empty liposomes.

Enhancing the buccal mucosal uptake and retention of triamcinolone acetonide.

In this study, the buccal mucosal uptake and retention of triamcinolone acetonide (TAC) were assessed in the presence of the skin penetration enhancer, Azone (AZ). Porcine buccal mucosa was excised, mounted in modified Ussing chambers, and pretreated with ethanolic solutions of AZ. After 2 h, the rate of TAC disappearance from the donor chamber and TAC appearance in the receptor chamber was monitored, and the mucosal retention of TAC was determined at the completion of the experiment.

Buccal penetration enhancers--how do they really work?

Certain agents that increase drug delivery through the skin, including surfactants, bile salts, and fatty acids, have been shown to exert a similar effect on the buccal mucosa. These agents enhance skin permeability by interacting with and disrupting the ordered intercellular lipid lamellae within the keratinized stratum corneum, and it has been assumed that a similar mechanism of action occurs in the nonkeratinized buccal mucosa. However, the chemical and structural nature of the lipids present within the intercellular regions of the buccal mucosa is quite different to that found within the stratum corneum, and so extrapolation of results between these two tissues may be misleading.

Synergistic enhancement of testosterone transdermal delivery.

In this study, the effects of occlusion, octisalate (OS), and propylene glycol (PG) on the in vitro skin permeability of testosterone (TES) have been investigated. TES (either alone or with OS 5% w/v) was applied as a finite dose to full-thickness neonatal porcine skin mounted in flow-through diffusion cells and the amount of TES appearing in the receptor solution (20% v/v ethanol) was determined over 24 h. The skin was occluded with a microscope glass cover slip and to determine the effect of PG, 400 microl of PG/water mixtures (of varying PG concentration) was applied.

Enhanced buccal mucosal retention and reduced buccal permeability of estradiol in the presence of padimate O and Azone: a mechanistic study.

In previous experiments, it was suggested that the reduction in estradiol (E2) buccal permeability after pretreatment with some skin penetration enhancers was attributed to enhanced membrane storage. To verify this, further in vitro permeability experiments were performed and the kinetics of E2 buccal mucosal uptake and permeability was assessed. Porcine buccal mucosa was pretreated with the skin penetration enhancers octisalate, padimate O (PO), or Azone (AZ) and placed in modified Ussing chambers.

The transdermal revolution.

Historically, developments in transdermal drug delivery have been incremental, focusing on overcoming problems associated with the barrier properties of the skin, reducing skin irritation rates and improving the aesthetics associated with passive patch systems. More-recent advances have concentrated on the development of non-passive systems to aid delivery of larger drug molecules, such as proteins and nucleotides, as the trend for discovering and designing biopharmaceuticals continues. Fundamentally, improvements in transdermal delivery will remain incremental until there is wider acceptance of this route of administration within the pharmaceutical industry.

Modification of buccal drug delivery following pretreatment with skin penetration enhancers.

The effect of the lipophilic skin penetration enhancers octisalate (OS), padimate O (PO), and Azone (AZ) on in vitro buccal permeability was assessed using caffeine (CAF), estradiol (E2), and triamcinolone acetonide (TAC) as model permeants. Buccal permeability was assessed in modified Ussing chambers, through both untreated porcine buccal mucosa and mucosa pretreated with an enhancer (5% w/v in 95% v/v ethanol) or ethanol alone. To ensure sink conditions were present, E2 permeability experiments were also performed with bovine serum albumin (BSA) 4% in the receptor solution.

Assessment of the effects of sodium dodecyl sulfate on the buccal permeability of caffeine and estradiol.

The concentration-dependent effects of sodium dodecyl sulfate (SDS) on the in vitro permeability of the buccal mucosa were assessed using caffeine (CAF) and estradiol (E(2)) as model hydrophilic and lipophilic markers, respectively. The permeability of CAF and E(2) through porcine buccal mucosa was determined in modified Ussing chambers, with and without exposure to different concentrations of SDS (0.01, 0.

The effect of various in vitro conditions on the permeability characteristics of the buccal mucosa.

The effect of various in vitro conditions on the permeability characteristics of the buccal mucosa was assessed using caffeine (CAF) and estradiol (E(2)) as model hydrophilic and lipophilic markers, respectively. The permeation of CAF and E(2) through porcine buccal mucosa was determined in modified Ussing chambers at 37 degrees C over 4 h. Comparative permeation studies were performed through full thickness and epithelial tissues, fresh and frozen tissues, and intact and intentionally damaged tissues.