With the advancement in development and technology, number of new-drug therapies have been invented, but maintaining steady therapeutic drug concentration levels, in vivo, has been a major problem. When using intermittent IV or oral-drug administration, the potential disadvantages of such drug therapies include: high plasma concentrations of drugs that may lead to toxicity or low drugs levels that cause to sub-therapeutic blood levels, and, potentially, cause drug resistance in some instances. In the past, the only way to eliminate the peak and trough plasma levels of drug therapy was by Before the initiation of implantation, however, both embryo and endometrium should embark on an elaborated process in a time- and location-specific manner. The crosstalk between a receptive uterus and a competent blastocyst can only occur during a limited time span, known as the “win of implantation” continuously IV infusing a patient at a constant rate based on the The idea of hormonal implantation in animals became standard practice in the 1950s and has been shown to increase the growth and feed efficiency of cattle [7]. This discovery sparked an interest in the area of implants leading to further studies and discoveries that have continued to the present time. It is anticipated that the demand for parenteral and implantable systems will increase 14% per year, through 1998, to $5.9 billion annually pmacokinetics of the drug.

Preconditions for implantation:

To achieve successful implantation, the uterus should undergo structural and functional remodeling. Estrogen and progesterone are the master hormones mediating these Change Estrogen and progesterone bind to their respective nuclear receptors. The progesterone receptor exists in two isoforms, PR-A and PR-B, and the estrogen receptor also exists in two isoforms, as ER? and ER?. Progesterone plays a pivotal role in implantation that allows the uterus to support the development of the embryo. The advent of advanced omics technologies provides unique insight of embryo implantation using targeted proteomics by identifying endometrial epithelial cellular and secreted protein changes in response to ovarian steroid hormones. Implantation begins with the loss of the zona pellucida known as hatching about 1-3 days after the morula enters the uterine cavity in preparation for attachment. Theactive blastocyst undergoes structure changes such that a more irregular surface with more microvilli is observed with accumulation of glycogen granules in the cytoplasm.

Implantation:

Implantation consists of three stages: (a) the blastocyst contacts the implantation site of the endometrium (apposition); (b) trophoblast cells of the blastocyst attach to the receptive endometrial epithelium (adhesion); and (c) invasive trophoblast cells cross the endometrial epithelial basement membrane and invade the endometrial stroma

METHODS OF PREPARATION OF IMPLANTS

There are mainly three methods for the preparation of implants that are discussed below:

Extrusion method

Firstly selected drug is dissolved in a suitable solvent system to produce a solution. After that polymer is added into the solution slowly and allowed to stand for 10-15 minutes for soaking purposes. The swollen material developed had been blended uniformly till it forms a dough-like material. The dough was transferred into the extruder cylinder and had been extruded in the form of long rods by the help nozzle. Implants dried the whole night at room temperature, and then cut into the optimum size and dried at 40oC

Compression Method

The polymer and drug were dissolved to develop the solution. The produced solution was subjected to freezedrying to produce a uniform cake. The cake was subjected to compression for the development of the implant. Implants have been developed by utilizing a Carver hydraulic press at a pressure of 1 metric ton, utilizing a stainless steel system developed for this objective, comprised of a 1mm diameter cylindrical punches set.

Molding Method

solution of polymer and the drug was firstly prepared in a suitable solvent system and then subjected for the lyophilization and converted to a uniform cake after that before the prepared cake was molded into rods through a Teflon sheet heated on a hot plate at a temperature about 100-120o C.

ADVANTAGES:

1.Localized delivery Drug(s) are released in immediate vicinity of implant. Action may Put be diffusion, limited to the specific location of implantation.

 2. Improved patient Compliance Patient does not need to comply with repeated and timely intake of medication throughout the implantation period. Compliance is limited to one-time implantation (and potential removal in the case of non-biodegradable implants).

3. Minimized systemic side effects Controlled release for extended periods of time and localized dosing possible with at site of action; adverse effects away from site of action are minimized; peaks and valleys in plasma drug concentration from repeated intermediate release dosing are avoided

4. Lower dose Localized implantation of site specific drugs can avoid first pass hepatic effects, thereby reducing dose required to ensure systemic bioavailability

5. Improved drug stability Protection of drug undergoing rapid degradation in the gastrointestinal and hepatobiliary system

Disadvantages:

1.Invasive For the insertion of the implants patient has to face either a major or a minor surgical procedure.

2.Termination non-biodegradable polymeric implants can be terminated from the body also with the help of a surgical method at the end of the treatment.

3.Danger of device failure If due to some reason the device fails to operate properly during the treatment then again surgical steps should be taken for removal of the devicefrom the patient’s body.

Current Therapeutic Applications

1.Implantable drug delivery devices have the potential to be used for a wide variety of clinical applications in areas including, but not limited to: women’s health, oncology, ocular disease, pain management, infectious disease and central nervous system disorders.

2.Women’s health is one area where implantable drug delivery devices have had a large impact, particularly in their use for contraception.

ZOLADEX [ Goserelin]

What is Zoladex? Zoladex is a man-made form of a hormone that regulates many processes in the body. Goserelin overstimulates the body's own production of certain hormones, which causes that production to shut down temporarily. Zoladex implants are used to treat symptoms of prostate cancer in men. Zoladex implant is used in women to treat breast cancer or endometriosis. Zoladex is also used in women to prepare the lining of the uterus for endometrial ablation (a surgery to correct abnormal uterine bleeding).

Molar mass: 1,269.41 g/mol

CAS ID: 65807-02-5

Boiling point: 1,696 °C

ChEMBL Id: 1201247

ChemSpider ID: 4470656

Other names: D-Ser (But)6Azgly10-GnRH

Protein binding: 27.3

Brand

Zoladex is the trade name for goserelin. In some cases, health care professionals may use the trade name zoladex when referring to the generic drug name goserelin. Drug type: Goserelin is a hormone therapy. It is classified as an "LHRH agonist.

What are the possible side effects of Zoladex?

Zoladex may cause serious side effects including:

1. difficulty breathing,
2. swelling of your face,
3. lips, tongue, or throat,
4. painful or difficult urination,
5. pain, bruising, swelling, redness, oozing, or bleeding where the implant was injected, increased urination, hunger, dry mouth,
6. drowsiness, dry skin, blurred vision, weight loss, nausea, vomiting, constipation, muscle pain, weakness, bone pain, confusion, tiredness, restlessness,
7. chest pain or pressure, sweating, back pain, muscle weakness,
8. problems with balance or coor.

Summary

Goserelin is a synthetic analog of luteinizing hormone-releasing hormone used to treat breast cancer and prostate cancer by reducing secretion of gonadotropins from the pituitary

Background

Goserelin is a synthetic hormone. In men, it stops the production of the hormone testosterone, which may stimulate the growth of cancer cells. In women, goserelin decreases the production of the hormone estradiol (which may stimulate the growth of cancer cells) to levels similar to a postmenopausal state. When the medication is stopped, hormone levels return to normal.

CONCLUSION