Michael J. Rathbone

Current status and the future of buccal drug delivery systems.

Background: The delivery of drugs through the buccal mucosa has received a great deal of attention over the last two decades, and yet there are not many buccal delivery products available on the market. Objective: This review outlines the advantages and disadvantages of buccal drug delivery, provides a historical perspective and discusses representative developmental and marketed drugs. Methods: The structure of the oral mucosa is briefly described to preface a description of the pathways for drug absorption and a critical discussion of permeation experiments. A brief historical perspective followed by a description of some of the currently marketed products provides a picture of where we are today. An indication is given of likely progress in this area and of the attributes of a successful business entity of the future. Conclusion: The authors provide an assessment of the future potential of buccal and sublingual drugs.

Recent developments in buccal and sublingual delivery systems

Introduction: There have been several advances in the delivery of drugs through the buccal mucosa over the last 5 years, which have resulted in a number of new buccal delivery products appearing on the market. Areas covered: This review discusses the most recent developments in the area of buccal and sublingual drug delivery, with a focus on marketed drugs. Likely future directions are also considered and reported. Expert opinion: The future potential of buccal and sublingual delivery systems looks favorable. It is envisaged that in the future, buccal and sublingual delivery technologies will provide a platform for the successful delivery of vaccines and antigens. It is also foreseen that physical means of enhancing drug uptake (e.g., sonophoresis, iontophoresis and electroporation) will be commercialized for buccal delivery, thereby expanding the current drug candidate list for this area. The formulation of delivery systems for photosensitizers in photodynamic therapy is a potential emerging area, while buccal and sublingual delivery, in general, is attractive for the development of intellectual property.

Vaginal drug delivery: Strategies and concerns in polymeric nanoparticle development

Introduction: Vaginal infection is widespread and > 80% of females encounter such infections during their lives. Topical treatment and prevention of vaginal infection allows direct therapeutic action, reduced drug doses and adverse effects, convenient administration and improved compliance. The advent of nanotechnology results in the use of nanoparticulate vehicle to control drug release, to enhance dosage form mucoadhesive properties and vaginal retention, and to promote mucus and epithelium permeation for both extracellular and intracellular drug delivery. Areas covered: This review discusses the conflicting formulation requirements on polymeric nanoparticles in order to have them mucoadhesive and retentive in vaginal tract, while able to penetrate through mucus to reach adherent mucus layer or epithelium surfaces to prolong extracellular drug release, or facilitate mucosal permeation and intracellular drug delivery. Expert opinion: Nanoscale systems are potentially useful in topical vaginal drug delivery. A thorough understanding of their mucus penetration and retention behavior as a function of their formulation, size and surface properties, biorecognition, pH, temperature or other stimuli responsiveness is essential for design of therapeutically effective nanomatrices.

Controlled Release Drug Delivery in Farmed Animals: Commercial Challenges and Academic Opportunities

Currently there is a lack of new active pharmaceutical ingredients (APIs) appearing on the veterinary market. In the short term this problem can be offset by developing controlled release drug delivery technologies to extend the commercial life of existing drugs. However, such a commercial opportunity does not come without its challenges. These generally revolve around financial factors, which include limited budgets assigned to conduct veterinary R&D, the cost-competitive amount that can be charged for the finished product and the expensive time-consuming registration process. In addition, the gap between the perceived and actual market needs makes the return on investment hard to defend. It is not surprising therefore that few controlled release products appear on the market for farmed animals, despite their potential advantages to that sector. The landscape for an academic veterinary pharmaceutical scientist is quite different from that of the industrial one. When you remove the commercial requirement associated with product development, there are numerous fundamental and applied research opportunities, with the outcome of demonstrating the potential worth, or otherwise, of an approach being sufficient to achieve the major goal of academics, publication in peer-reviewed journals. A further opportunity arises when controlled release dosage forms are used as research tools to forward knowledge in the area of animal science. The aim of this review is to provide a perspective of the current animal health industry through examination of the commercial challenges per se, along with the potential for academic collaboration that lie within this demanding area of pharmaceutical science.

Oral Mucosal Drug Delivery and Therapy

This volume provides a comprehensive overview of the current issues facing scientists working on delivering drugs locally and systemically via the membranes that line the mouth. The book describes the anatomical and physiological challenges of this route for drug delivery and how they impact the design of oral mucosal drug delivery systems. It also provides a detailed description of current oral mucosal drug delivery technologies that overcome these challenges alongside research, development and assessment methods. In 11 authoritative chapters, the book affords an in-depth evaluation of the major issues associated with this route of administration, namely the retention of the drug/product at the site of administration and increasing drug permeability through the oral mucosa. The book provides insights into the in vitro and in vivo methods available to assess drug permeability and retention, offers solutions on how to improve the permeation of the drugs through the oral mucosa, and explores approaches to prolong drug/product retention at the site of administration. It also indicates future directions in research and product development. Oral Mucosal Drug Delivery and Therapy is a key resource for those wishing to extend their knowledge of this field

Long acting animal health drug products

Animal Health Markets and Opportunities - Farmed Animal Landscape.- Animal Health Markets and Opportunities - Companion Animal Landscape.- Anatomy and Physiology of the Farmed Animal.- Oral Anatomy and Physiology in the Companion Animal.- Physicochemical Principles of Controlled Release Veterinary Pharmaceuticals.- Biopharmaceutics and Veterinary Drug Delivery.- Quality by Design.- Final Product Testing and Specification Setting of Veterinary Pharmaceuticals.- In Vitro Drug Release Testing of Veterinary Pharmaceuticals.- Long Acting Rumen Drug Delivery Systems.- Controlled Release Intravaginal Veterinary Drug Delivery.- Veterinary Long Acting Injections and Implants.- Intramammary Delivery Technologies for Cattle Mastitis Treatment.- Veterinary Vaccines.- Delivery Systems for Wildlife.- Human: Veterinary Technology Cross Over.

In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing

Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 μg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 μg/mL. An inxa0vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 μg/mL phenytoin concentration resulted in 75%-82% scratch closure after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.

Evaluation of biosourced alkyd nanoemulsions as drug carriers

Novel oil-in-water (O/W) nanoemulsions were formulated using short, medium, and long oil length alkyds synthesized from palm kernel oil by a two-stage alcoholysis-polyesterification reaction. Alkyd/surfactant/water ternary phase diagrams identified a composition of 1% alkyd, 9% Tween 80, and 90% water where spontaneous production of nanoemulsions occurred. The pH, droplet size, and zeta potential of all formulations were in the range of 6.4-6.6, 11-14 nm, and -6mV to -8mV, respectively. Rheological studies showed that the nanoemulsions displayed non-Newtonian shear thinning behavior at low shear rates up to 20 s-1 with conversion to Newtonian behavior above this shear rate. All nanoemulsions were found to be stable against phase separation on storage at 4°C and 25°C for three months. Short oil length alkyd nanoemulsions exhibited significantly higher stability compared with medium and long oil length alkyd nanoemulsions, as demonstrated by an absence of phase separation and only minor changes of droplet size on storage at an elevated temperature of 45°C for 3 months. The drug carrying capacity and storage stability of the nanoemulsions were assessed using phenytoin. The entrapment efficiency of alkyd nanoemulsions was in excess of 90% and loss of phenytoin content was restricted to less than 4% during storage of the nanoemulsions for three months at 4°C, 25°C, and 45°C. Taken together, these findings indicate that nanoemulsions prepared from palm kernel oil-based alkyds offer potential as nanocarriers for drug delivery applications.

Vaginal Drug Delivery

While the human vagina has great potential as an administration route for drug delivery, several challenges remain due to its variable nature and innate barriers. In this chapter, the distinctive barriers resulting from the anatomy and physiology of the vagina are presented. We then discuss strategies to rationally design vaginal drug delivery systems to maximize the efficacy and control the kinetics of drug delivery across the vaginal mucosa. The physical, rheological, and retentive properties of current vaginal dosage forms are compared as well as pharmacological considerations for vaginal delivery. Emerging nanomaterial strategies for vaginal drug delivery including nanoparticles and electrospun fibers are reviewed in depth, with a specific focus on HIV microbicide applications. The underlying principles for designing vaginal drug delivery systems that are discussed here have relevance for many reproductive health and mucosal delivery applications.

Overview of Oral Mucosal Delivery

This chapter explores the reasons for developing oral mucosal drug delivery systems, and identifies the key considerations in their design and development. In addition, it describes some of the delivery systems that have been successfully developed for use in this area.