In today’s pharmaceutical arena, it is estimated that more than 40% of new chemical entities produced during drug discovery efforts exhibit poor solubility characteristics. However, over the last decade hot-melt extrusion (HME) has emerged as a powerful processing technology for drug delivery and has opened the door to a host of such molecules previously considered unviable as drugs. HME is considered to be an efficient technique in developing solid molecular dispersions and has been demonstrated to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. This article reviews the myriad of HME applications for pharmaceutical dosage forms such as tablets, capsules, films and implants for drug delivery through oral, transdermal, transmucosal, transungual, as well as other routes of administration. Interest in HME as a pharmaceutical process continues to grow and the potential of automation and reduction of capital investment and labor costs have made this technique worthy of consideration as a drug delivery solution.

Purpose-Hesperidin holds potential in treating age-related macular degeneration, cataract and diabetic retinopathy. The aim of this study, constituting the first step towards efficient ocular delivery of hesperidin, was to determine its physicochemical properties and in vitro ocular tissue permeability.Methods-pH dependent aqueous solubility and stability were investigated following standard protocols. Permeability of hesperidin across excised rabbit cornea, sclera, and sclera plus retinal pigmented epithelium (RPE) was determined using a side-bi-side diffusion apparatus.Results-Hesperidin demonstrated poor, pH independent, aqueous solubility. Solubility improved dramatically in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) and the results supported 1:1 complex formation. Solutions were stable in the pH and temperature (25, 40°C) conditions tested, except for samples stored at pH 9. Transcorneal permeability in the apical-basal and basal-apical directions was 1.11±0.86×10 −6 and 1.16±0.05×10 −6 cm/s, respectively. The scleral tissue was more permeable (10.2±2.1×10 −6 cm/s). However, permeability across sclera/choroid/RPE in the sclera to retina and retina to sclera direction was 0.82±0.69×10 −6 , 1.52±0.78×10 −6 cm/s, respectively, demonstrating the barrier properties of the RPE.Conclusion-Our results suggest that stable ophthalmic solutions of hesperidin can be prepared and that hesperidin can efficiently permeate across the corneal tissue. Further investigation into its penetration into the back-of-the eye ocular tissues is warranted.

Objectives Flavonoids are a common group of plant polyphenols that give color and flavor to fruits and vegetables. In recent years, flavonoids have gained importance in the pharmaceutical field through their beneficial effects on human health and are widely available as nutritional supplements. Several pharmacological activities of the bioflavonoids may be useful in the prevention or treatment of ocular diseases responsible for vision loss such as diabetic retinopathy, macular degeneration, and cataract. This review summarizes potential therapeutic applications of various bioflavonoids in different ocular diseases and also discusses delivery of these agents to the ocular tissues. Key findings It is apparent that the flavonoids are capable of acting on various mecha- nisms or aetiological factors responsible for the development of different sight threatening ocular diseases. From a drug delivery perspective, ocular bioavailability depends on the physicochemical and biopharmaceutical characteristics of the selected flavonoids and very importantly the route of administration. Summary The potential therapeutic applications of various bioflavonoids in ocular dis- eases is reviewed and the delivery of these agents to the ocular tissues is discussed. Whereas oral administration of bioflavonoids may demonstrate some pharmacological activity in the outer sections of the posterior ocular segment, protection of the retinal ganglionic cells in vivo may be limited by this delivery route. Systemic or local administration of these agents may yield much higher and effective concentrations of the parent bioflavonoids in the ocular tissues and at much lower doses.

Purpose-The aim of this study was to evaluate the contribution of amino acid transporters in the transcorneal permeation of the aspartate (Asp) ester acyclovir (ACV) prodrug.Methods-Physicochemical characterization, solubility and stability of acyclovir L-aspartate (LAsp-ACV) and acyclovir D-aspartate (D-Asp-ACV) were studied. Transcorneal permeability was evaluated across excised rabbit cornea.Results-Solubility of L-Asp-ACV and D-Asp-ACV were about 2-fold higher than that of ACV. The prodrugs demonstrated greater stability under acidic conditions. Calculated pK a and logP values for both prodrugs were identical. Transcorneal permeability of L-Asp-ACV (12.1±1.48×10 −6 cm/s) was 4-fold higher than D-Asp-ACV (3.12±0.36×10 −6 cm/s) and ACV (3.25±0.56×10 −6 cm/s). ACV generation during the transport process was minimal. L-Asp-ACV transport was sodium and energy dependent but was not inhibited by glutamic acid. Addition of BCH, a specific B o,+ and L amino acid transporter inhibitor, decreased transcorneal L-Asp-ACV permeability to 2.66±0.21×10 −6 cm/ s. L-Asp-ACV and D-Asp-ACV did not demonstrate significant difference in stability in ocular tissue homogenates.Conclusion-The results demonstrate that enhanced transport of L-Asp-ACV is as a result of corneal transporter involvement (probably amino acid transporter B 0,+ ) and not as a result of changes in physicochemical properties due to prodrug derivatization (permeability of D-Asp-ACV and ACV were not significantly different).