Omar Sarheed

Development of an optimised application protocol for sonophoretic transdermal delivery of a model hydrophilic drug.

It has now been known for over a decade that low frequency ultrasound can be used to effectively enhance transdermal drug penetration - an approach termed sonophoresis. Mechanistically, acoustic cavitation results in the creation of defects in the stratum corneum that allow accelerated absorption of topically applied molecules. The aim of this study was to develop an optimised sonophoresis protocol for studying transdermal drug delivery in vitro. To this end, caffeine was selected as a model hydrophilic drug while porcine skin was used as a model barrier. Following acoustic validation, 20kHz ultrasound was applied for different durations (range: 5 s to 10 min) using three different modes (10%, 33% or 100% duty cycles) and two distinct sonication procedures (either before or concurrent with drug deposition). Each ultrasonic protocol was assessed in terms of its heating and caffeine flux-enhancing effects. It was found that the best regimen was a concurrent 5 min, pulsed (10% duty cycle) beam of SATA intensity 0.37 W/cm2. A key insight was that in the case of pulsed beams of 10% duty cycle, sonication concurrent with drug deposition was superior to sonication prior to drug deposition and potential mechanisms for this are discussed.

Design and evaluation of a bioadhesive film for transdermal delivery of propranolol hydrochloride

Design and evaluation of a bioadhesive film for transdermal delivery of propranolol hydrochloride The objective of the study was to develop a suitable trans-dermal delivery system for propranolol hydrochloride (PPL) via employing chitosan as a film former. Drug concentration uniformity, thickness, moisture uptake capacity and skin bioadhesion of the films were characterized. The effects of chitosan and PPL concentration and different penetration enhancers on the release and permeation profiles from the films were investigated. Skin irritation of the candidate film was evaluated. Chitosan film (PPL 2 mg cm-2, chitosan 2 %, m/m, cineol 10 %, m/m) was found nonirritant and achieved 88.2 % release after 8 hours in phosphate buffer. Significant high (p < 0.001) permeation of PPL through rat skin was obtained using this film compared to the film without enhancer (about 8 times enhancement factor), making it a promising trans-dermal delivery system for PPL. Dizajniranje i vrednovanje bioadhezijskog filma za transdermalnu isporuku propranolol hidroklorida Cilj rada bio je razvoj pogodnog transdermalnog sustava na bazi kitozana za isporuku propranolol hidroklorida (PPL). Svim pripravcima ispitana je jednoličnost udjela lijeka, debljina, sposobnost vlaženja i bioadhezivnost na kožu. Ispitivan je i utjecaj kitozana, koncentracije PPL-a i sredstva za povećanje permeacije na oslobađanje i permeacijski profil, te potencijalni iritacijski učinak na kožu. Iz kitozanskog filma (PPL 2 mg cm 2, 2 %, m/m, kitozana i 10 %, m/m, cineola), koji nije djelovao iritabilno, postignuto je 88,2 % oslobađanja nakon 8 sati u fosfatnom puferu. S ovim pripravkom postignuta je i vrlo značajna (p < 0,001) permeacija PPL kroz kožu štakora, oko osam puta veća u usporedbi s filmom bez sredstva za povećanje permeacije. Pripravak bi se mogao upotrijebiti za transdermalnu isporuku PPL.

An Investigation and Characterization on Alginate Hydogel Dressing Loaded with Metronidazole Prepared by Combined Inotropic Gelation and Freeze-Thawing Cycles for Controlled Release

The purpose of this study was to investigate the effect of combined Ca2+ cross-linking and freeze-thawing cycle method on metronidazole (model drug) drug release and prepare a wound film dressing with improved swelling property. The hydrogel films were prepared with sodium alginate (SA) using the freeze-thawing method alone or in combination with ionotropic gelation with CaCl2. The gel properties such as morphology, swelling, film thickness, and content uniformity and in vitro dissolution profiles using Franz diffusion cell were investigated. The cross-linking process was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. In vitro protein adsorption test, in vivo wound-healing test, and histopathology were also performed. The hydrogel (F2) composed of 6% sodium alginate and 1% metronidazole prepared by combined Ca2+ cross-linking and freeze-thawing cycles showed good swelling. This will help to provide moist environment at the wound site. With the in vivo wound-healing and histological studies, F2 was found to improve the wound-healing effect compared with the hydrogel without the drug, and the conventional product.