Shane Burggraaf

Fertility regulation in cattle.

This paper reviews the physiological, endocrinological and pharmaceutical literature pertaining to the design, development and optimisation of subcutaneous and intravaginal progestogen-containing drug delivery systems used in the control of synchrony and ovulation in cattle.

Reengineering of a commercially available bovine intravaginal insert (CIDR insert) containing progesterone

The purpose of this study was to reengineer a commercially available intravaginal insert containing 1.9 g progesterone (CIDR intravaginal insert) for a 7-day insertion period in cattle. The reengineering process resulted in a reduced initial drug load (1.38 g) and a reduction in the residual drug load following insertion, while at the same time maintaining the biological performance of the insert. The in vitro and in vivo pharmaceutical properties of the commercially available CIDR intravaginal insert were characterized initially to gain a thorough understanding of the factors that affected progesterone release from the insert. The effect of changing a selection of formulation and physical variables of the insert was also investigated (including surface area, drug load, addition of pore forming materials, silicone shore hardness and drug particle size). The knowledge gained from these studies was used to define the characteristics of the reengineered insert which was then manufactured and shown to be bioequivalent and clinically equivalent to the commercially available insert.

Conceptual and commercially available intravaginal veterinary drug delivery systems

In the veterinary area the utilization of the vagina as a route for drug delivery has focused on the systemic delivery of hormonal steroids to control synchrony, ovulation and fertility in a variety of livestock. There are several reasons for administering drugs to modify the menstrual cycle in humans and the estrous cycle in animals and this paper provides a comparison of the objectives of drug intervention to control reproduction in humans and livestock. In addition, the types of hormones and their concentrations found during the menstrual cycle in humans and during the estrous cycle in animals are compared. The paper also reviews the intravaginal drug delivery systems developed for the control of the estrous cycle in livestock and both conceptual and commercially available intravaginal drug delivery systems that have been described in the literature are described. The history of some of the delivery systems is included and the future directions of this area of research are discussed.

Development of an injection molded poly(ϵ-caprolactone) intravaginal insert for the delivery of progesterone to cattle

Abstract This paper reports experiments conducted to research, develop and clinically evaluate an injection molded intravaginal insert manufactured from the biodegradable polyester poly(ϵ-caprolactone). The study demonstrated that it is possible to engineer poly(ϵ-caprolactone) into a shape that is well retained, and can be used as a platform for the controlled delivery of progesterone via the vagina of cows. Field evaluation showed that the poly(ϵ-caprolactone) intravaginal inserts containing 10% (w/w) progesterone were at least as effective clinically as the commercially available CIDR intravaginal insert.

Controlled release drug delivery systems for estrous control of domesticated livestock

Publisher Summary The need for controlled release drug delivery systems in the field of estrous control of domesticated livestock arises due to the physicochemical and pharmacokinetic characteristics of the drugs. The first use of controlled release drug delivery systems to control the estrous cycle of sheep and cattle dates back to the mid 1960s and mid 1970s, respectively. In spite of the long history associated with this area of drug delivery, the opportunity to develop and commercialize controlled release drug delivery systems to control the estrous cycle of domesticated species has never been greater. This is because of the rise in on-farm use of procedures such as embryo transfer and new assisted reproductive technologies. This chapter describes the controlled release drug delivery systems which are currently available or in development for the control of the estrous cycle in sheep, cattle, pigs, and horses. It describes some of the formulation considerations for such products and highlights recent advances in the field of estrous control in horses and pigs.

Design and development of controlled release intravaginal veterinary drug delivery systems

Publisher Summary The inception of intravaginal veterinary drug delivery dates back to the early 1960s when polyurethane sponges were investigated as a means to deliver synthetic progestagens to sheep and goats. In the 1990s, microchip technology was investigated as a means of delivering multiple drugs at different times and rates for the precise control of estrous synchrony and fertility. All the current intravaginal drug delivery systems used in animals have inherent pharmaceutical problems such as high residual drug loads. These limitations have not appeared to have affected their acceptability with the end-user. This chapter reviews the avenues of research taken by these innovative scientists with animal or plastic engineering backgrounds. The purpose of this chapter is to critically review the literature in order to glean the available information relating to the design and development of intravaginal veterinary drug delivery systems. This information provides the basis upon which to design and assess future intravaginal veterinary drug delivery systems.

In vitro drug release testing of controlled release veterinary drug products

Publisher Summary The purpose of this chapter is to discuss various aspects of in vitro drug release test method development, optimization, and validation. It discusses both compendia and non-compendia methods and provides suggestions to achieve sound, scientific development, and validation for such methods. A controlled release veterinary pharmaceutical is specifically designed to release its contents over an extended period at a predefined rate. The release characteristics of the product are dependent upon its formulation and the process conditions used during its manufacture. Manufacturers need some method that allows them to determine the effect of formulation and manufacturing variables on release rate. It is important to develop an inexpensive, rapid, and reproducible test that assesses the drug release characteristics of the product in vitro, but which provides assurances to manufacturers and regulatory bodies of the batch-to-batch in vivo performance of the product.

Stability testing of veterinary drug products

Publisher Summary Every step of the development process of a veterinary product results in an improvement of its quality, efficacy, and safety until the process of optimization is completed resulting in the final product. It is judicious to generate information on the stability of the product throughout the entire development and scale-up process. Three major stages in the development of a drug product can be identified from a stability viewpoint: the initial development stage, in which the stability studies are designed to provide an insight into potential stability issues relating to the product; the pilot batch stage, in which the stability studies confirm that the process can be operated on a large scale to manufacture batches within specification and with uniform properties; the final product full scale manufacture stage, in which the stability studies are designed to provide on-going information which supports the shelf. This chapter discuses the aspects of stability test programs for the assessment of drug product which falls within the latter two stages of product development.