Laser irradiation of ocular tissues to enhance drug delivery.

Scleral and corneal membranes represent substantial barriers against drug delivery to the eye. Conventional hypodermic needles-based intraocular injections are clinically employed to overcome these barriers. This study, for the first time, investigated a non-invasive alternative to intraocular injections by laser irradiation of ocular tissues. The P.L.E.A.S.E.® laser device was applied on excised porcine scleral and corneal tissues, which showed linear relationships between depths of laser-created micropores and laser fluences at range 8.9-444.4 J/cm2. Deeper and wider micropores were observed in scleral relative to corneal tissues. The permeation of rhodamine B and fluorescein isothiocyanate (FITC)-dextran were investigated through ocular tissues at different laser parameters (laser fluences 0-44.4 J/cm2 and micropore densities 7.5 and 15%). Both molecules showed enhanced permeation through ocular tissues on laser irradiation. Maximum transscleral permeation of the molecules was attained at laser fluence 8.9 J/cm2 and micropore density 15%. Transcorneal permeation of rhodamine B increased with increasing either laser fluence or micropore density, while that of FITC-dextran was not affected by either parameter. The transscleral water loss increased significantly after laser irradiation then returned to the baseline values within 24 h, indicating healing of the laser-created micropores. Laser irradiation is a promising technique to enhance intraocular delivery of both small and large molecule drugs.

A Novel Eutectic-Based Transdermal Delivery System for Risperidone.

This paper reports for the first time the possible formation of a novel room temperature therapeutic deep eutectic solvent (THEDES) of risperidone (RIS) with some fatty acids, namely capric acid (C10; CA), lauric acid (C12; LA), and myristic acid (C14; MA). All mixtures of RIS and MA yielded a solid or pasty-like solid and were readily discarded. Some of the prepared THEDESs from RIS and CA or LA have spontaneously transformed into a transparent liquid, without any precipitate at room temperature by simple physical mixing of the components. From the DSC thermograms, phase diagrams of the eutectic systems were constructed and the lowest obtained melting point for a RIS:CA mixture was 17°C at 40:60% w/w ratio. While 22°C was recorded as the lowest melting point for RIS:LA at a ratio of 30:70% w/w, solubility improvement of RIS was up to 70,000-fold compared with water. Freeze-drying microscopy provided valuable information regarding the phase change and transitions the drug undergoes as a function of temperature and it clarifies the interpretation of the DSC results and provides valuable evidence of drug crystals co-melting within the fatty acid base. The presence of natural fatty acid as one component of THEDES and the depression in the melting point significantly (P < 0.05) enhanced RIS skin permeation. Rheological studies showed a viscosity temperature dependency of the DES and well fitted to the Arrhenius equation. Application of the obtained THEDES on the shaved skin of rats revealed the absence of any irritation or edema effects.

Glyceryl monooleate-based otic delivery system of ofloxacin: release profile and bactericidal activity.

This study investigated the preparation and characterization of glyceryl monooleate- (GMO) based drug delivery system containing ofloxacin for the treatment of otitis externa. Acetate buffer (pH 4.5) containing dissolved ofloxacin was added to molten GMO as an aqueous phase, this resulted in the formation of a cubic and a reverse hexagonal phases. The release behavior of ofloxacin from the drug delivery system was studied using three different methods. The mechanism of drug release using paddles/dissolution apparatus and Franz diffusion cells followed Higuchi and Fickian diffusion models; whereas intrinsic release rate method showed zero-order kinetics. The intrinsic release rate was estimated and found to be 187.2 µg/cm(2)/h. The release mechanisms were similar irrespective of the loaded ofloxacin amount, however, the higher drug load displayed higher release rate. The drug delivery system was proven to be microbiologically effective by using agar diffusion method, against Staphylococcus aureus, and Pseudomonas aeruginosa. The GMO/ofloxacin formulation was stable for 6 months after preparation at room temperature as measured with respect to phase stability and antibacterial activity.