Effect of Polyunsaturated Fatty Acids and Some Conventional Penetration Enhancers on Transdermal Delivery of Atenolol

Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems.

Section: Nar Permeation From Tc:pbs (Ph 68) Systemssupporting

confidence: 93%

Section: Permeation From Single Solventsmentioning

confidence: 99%

Oral transmucosal delivery of naratriptan

Sattar

Lane

2016

“…Even though the mechanism by which TC interacts with the skin is not known, its potential to act as a penetration enhancer has been reported for a number of compounds (Lane, 2013). Puglia and Bonina (2008) PG is a hydrophilic solvent that has been used in topical formulations as a solvent for many actives (Lane, 2013;Haque et al, 2017b;Haque et al, 2018;Paz-Alvarez et al, 2018;Hossain et al, 2019;Iliopoulos et al, 2019;Zhang et al, 2019b). In the present work, 5 μL doses of 3 % (w/w) NIA in PG were applied to porcine skin and the percentage permeation after 24 h was 19.2 %.…”

Section: Permeation Studies Using Neat Solventsmentioning

confidence: 99%

Topical delivery of niacinamide: Influence of neat solvents

Iliopoulos¹,

Sil

Hossain³

et al. 2020

Niacinamide (NIA) has been widely used in cosmetic and personal care formulations for several skin conditions. Permeation of topical NIA has been confirmed in a number of studies under infinite dose conditions. However, there is limited information in the literature regarding permeation of NIA following application of topical formulations in amounts that reflect the real-life use of such products by consumers. The aim of the present work was therefore to investigate skin delivery of NIA from single solvent systems in porcine skin under finite dose conditions. A secondary aim was to probe the processes underlying the previously reported low recovery of NIA following in vitro permeation and mass balance studies. The solubility and stability of NIA in various single solvent systems was examined.The solvents investigated included Transcutol® P (TC), propylene glycol (PG), 1-2 hexanediol (HEX), 1-2 pentanediol (1-2P), 1-5 pentanediol (1-5P), 1-3 butanediol (1-3B), glycerol (GLY) and dimethyl isosorbide (DMI). Skin permeation and deposition of the molecule was investigated in full thickness porcine skin in vitro finite dose Franz-type diffusion experiments followed by mass balance studies. Stability of NIA for 72 h in the solvents was confirmed. The solubility of NIA in the solvents ranged from 82.9 ± 0.8 to 311.9 ± 4.5 mg/mL. TC delivered the highest percentage permeation of NIA at 24 h, 32.6 ± 12.1 % of the applied dose. Low total recovery of NIA after mass balance studies was observed for some vehicles, with values ranging from 55.2 ± 12.8 % to 106.3 ± 2.3 %. This reflected the formation of a number of NIA degradation by-products in the receptor phase during the permeation studies. Identification of other vehicles for synergistic enhancement of NIA skin delivery will be the subject of future work.

“…Harrison et al (1996) and Puglia and Bonina (2008) reported long-standing use in pharmaceutical and cosmetic products (Sullivan Jr. et al, 2014).…”

Section: P a G E | 15mentioning

confidence: 99%

Topical delivery of hexamidine

Parisi¹,

Paz-Alvarez²,

Matts

et al. 2016

Hexamidine diisethionate (HEX D) has been used for its biocidal actions in topical preparations since the 1950s. Recent data also suggest that it plays a beneficial role in skin homeostasis. To date, the extent to which this compound penetrates the epidermis has not been reported nor how its topical delivery may be where there are minor differences in molecular structures. We also believe that they underline the ongoing necessity for fundamental studies on the interaction of topical excipients with the skin.