Download - Bentham Science

74 Smart Nanomaterials for Sensor Application, 2012, 74-81
Songjun Li, Yi Ge and He Li (Eds)
All rights reserved - © 2012 Bentham Science Publishers
CHAPTER 4
Thermo Sensitive Polymers for Prolong Delivery of Contraceptive
Hormones in Women
Priyanka Singh 1* and Sibao Chen 2
1 2
1919 Elm Street, Fargo, ND 58102 and Purdue Pharmaceuticals L.P. 4701 Purdue Drive, Wilson, NC
27893
Abstract: This review discusses the various available controlled release products for contraception in
women as well as elaborates about the thermosensitive polymers, their characterization and application
for controlled delivery of contraceptive hormones. The thermosensitive polymers are free flowing
solutions in water at room temperature and turn into gel at body temperature and deliver the
incorporated hormones at controlled rate for longer duration after a single subcutaneous injection.
These polymers are biodegradable, biocompatible, and hold a great promise for prolonged delivery of
contraceptive hormones.
Keywords: Thermosensitive polymers; controlled release; contraceptive hormones.
INTRODUCTION
The Population Council began researching subdermal contraceptive implants in 1966 [1]. The idea of using
subdermal capsules using silicon polymers for contraceptive hormone evolved from the fact that these polymers
could form a reservoir for the prolonged release of a variety of lipophilic drugs. Currently available subdermal
implant, levonorgestrel, is contained in six flexible, closed capsules made of silicon polymer. Each capsule
contains 36 mg of the drug, levonorgestrel. Each capsule is 34 mm long and 2.4 mm in diameter [2].
Levonorgestrel implants are also available in rods (two rods, each contains 75mg of the levonorgestrel).
Although silicon based subdermal implants can control the release of incorporated hormone, however, the
removal of the implants after drug release can be challenging. One of the studies evaluated 1,253 removal
procedures at 15 clinical settings. The removal usually took 30 min [3]. However, about 19% of removals lasted
for more than 1h. A few patients had to return for a second removal procedure. About one-quarter of the
women reported substantial pain. In addition to the above difficulties, pruritis (generally transient), infection at
implant site, removal difficulties as well as damage to capsules were reported.
A retrospective analysis of 3,416 subdermal implant removals was performed, including women from 11
countries who participated in clinical trials [4]. Some of these women experienced difficult or complicated
removals. Most complicated removals were due to the implants being broken during the removal procedure;
embedding or displacement of the implants also led to difficult removals. Subdermal implants have become
the target of litigation. Law suits claimed that implants caused a variety of problems in users. Subdermal
implant litigation patterns have paralleled those relating to silicone breast implants [5, 6].
Injectables using microspheres or microcapsules containing one or more contraceptive hormones have been
investigated [7]. A sterile solution suspends the time-released spheres. The microspheres contain a polymer
commonly used in a biodegradable suture, poly-dl-lactide-co-glycolide. However, burst release from
microspheres is a problem. Also, microspheres pose a significant manufacturing challenges requiring 5 to 6
major processing steps. In addition, microspheres may cause an acute tissue reaction (e.g. nodule) and,
possible, transient irritation resulting in the presence of particles. In contrast, smart polymer based
injectable solution is simple to prepare and forms an implant upon injection. Smart polymers are widely
explored as potential drug-delivery systems [8-10]. Biodegradable, biocompatible, thermosensitive smart
*Address correspondence to Priyanka Singh: University of North Dakota, College of Medicine and Health Sciences, 1919 Elm
Street, Fargo, ND 58102; E-mail: psingh@medicine.nodak.edu