Long-acting injectable 14 days formulations: Amoxycyline and Metronidazole
Treatments using dental implants to replace missing teeth are effective and predictable and show good long term success rates. However, with the ever-growing popularity of implant treatments and the increasing number performed in recent years, the incidence of short-term and long-term complications has increased. One of these complications, which may lead to loss of the implant in the long term, is peri-implantitis.
Peri-implant diseases present in two forms : peri-implant mucositis and peri-implantitis. Both of these are characterized by an inflammatory reaction in the tissues surrounding an implant Such therapies include mechanical debridement, the use of antiseptics, adjunctive administration of local and/or systemic antibiotics, access flap surgery with or without the use of bone regenerating procedures and supportive therapy.
One of the common adjunctive systemic antibiotic therapies, is metronidazole plus amoxicillin. The findings demonstrated that in patients with advanced periodontal disease, systemic administration of metronidazoie plus amoxicillin resulted in (i) an improvement of the periodontal conditions, (ij) elimination/suppression of putative periodontal pathogens such as A. aclinomycctemcomitans, P. gingivalis. P. intermedia and (iii) reduction of the size of the infiammatory lesion. Local delivery of antimicrobials has been investigated for the possibility of overcoming the limitations of conventional therapy. These products provide a long-term, effective treatment at the site of infection at much smaller doses.
Long-acting injectable 1 month formulations: Vancomycine
In antibiotic therapy, the antibiotic concentration must be higher than the minimum inhibitory concentration (MIC). Because of difficulty of delivering antibiotics to a target site in an effective concentration by the conventional routes of oral and parenteral, it is wise to use methods of local administration. One marketed approach for this purpose is to mix antibiotics with a carrier material that can then locally release the drug. Non-biodegradable polymethylmethacrylate bone cement and beads have been used extensively for osteomyelitis treatment, but they suffer from the disadvantages of non-absorbility and their need to removal from body after the therapeutic period by surgery. Because biodegradable carriers such as in situ forming delivery system do not need surgical removal, this is an important advantage. Furthermore, in situ forming delivery compared with other biodegradable implants has the advantage of injectability; thus, it does not need surgery for insertion into body. Vancomycin is a tricyclic glycopeptide antibiotic and the first choice for the prophylaxis and treatment of infections caused by gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) like osteomyelitis.
Long-acting injectable 1 month formulations: Octreotide 20 mg
Octreotide is the acetate salt of a cyclic octapeptide. It is a long-acting octapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. Octreotide has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and Vasoactive Intestinal Peptide (VIP) secreting adenomas (watery diarrhea). Octreotide substantially reduces and in many cases can normalize growth hormone and/or IGF-I (somatomedin C) levels in patients with acromegaly. The peptide drugs after oral and parental administration have poor bioavailability in the blood due to their short biological half-lives caused by their metabolic instability. So that these peptide drugs should be formulated by polymeric drug delivery systems such as microparticles or implants, which enabling their sustained release after a residence time in the polymer that protects the peptide against enzymatic and hydrolytic influences of biological media. Polymeric drug delivery systems are attractive alternatives to control the release of drug substances to obtain defined blood levels over a specified time. These delivery systems are limited by patient and physician acceptance related to ease of administration, reliable kinetic profiles, or product costs. In-situ implants are advantageous over the microspheres and implants.
Microspheres manufacturing process is often complex and difficult control. As a result, there are often questions involving costs and batch-to-batch product uniformity. In solid implants, they require surgical implantation or the use of large troches to administer the product so it is less patient and physician acceptance related to ease of administration. So that insitu implants have patient and physician acceptance related to ease of administration, reliable kinetic profiles, or product costs.
Long-acting injectable 3 month formulations: Triptoreline pamoate 11.25 mg
Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation. It is indicated for treatment of prostate cancer, endometriosis, uterine fibroids and precocious puberty. The sustained-release formulation of this molecule is advantageous in conditions requiring chronic hormone suppression.
Gonadotropin-releasing hormone (GnRH), also kwon as luteinizing hormone-releasing hormone (LHRH), a 10 amino acid peptide synthesized by gonadotropic cells of the hypothalamus naturally, is a central mediator of the human reproductive axis. It interacts with GnRH receptor localized on cells of anterior pituitary gland and stimulates the production and release of LH and FSH, which promote gonadal steroid synthesis and gametogenesis. The half-life of GnRH in the circulation is very short, about 8 minutes. Therefore efforts have been made to synthesize analogue of GnRH with higher half-life. Triptorelin, a decapeptide (pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2), is a synthetic GnRH agonist and existed in two salt forms of acetate and pamoate. By causing constant stimulation of the pituitary, it decreases pituitary secretion of LH and FSH. Like other GnRH agonists, triptorelin may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, precocious puberty, estrogen-dependent conditions (such as endometriosis or uterine fibroids), and in assisted reproduction.
Long-acting injectable 1 month formulations: Buprenorphine
Buprenorrphine, is a derivative of morphine alkaloid thebaine. It is a partial agonist opioid at the receptor and an opioid antagonist at the receptor. Buprenorphine exhibits special features, including (a) a ceiling on agonist activity that decreases the possibility of overdose and may limit abuse liability (b) opioid-antagonist activity that blocks the effects of exogenously administered opioids (c) a high affinity for the opioid receptor that decreases the magnitude of withdrawal signs and symptoms and (d) opioid-agonist activity that promotes treatment compliance.
Recently, sublingual tablets containing a fixed dose combination of buprenorphine hydrochloride and naloxone hydrochloride dehydrate have been approved by the FDA for treating opiate dependence. Buprenorphine also has long been viewed as an option for cancer pain. Because compared with morphine, it is 25 times stronger in analgesic effect and 10 times longer in effective duration. With the development of a transdermal formulation in 2001, Buprenorphine emerges as suitable choice for cancer pain.
To provide long-term constant buprenorphine delivery, researchers need to develop a sustained-release formulation that could be released the drug for approximately 1 month at relatively constant rates sufficient to treat addiction. The development of a subcutaneous buprenorphine sustained-release preparation would be beneficial to patients because buprenorphine is not known to cause any local irritation or tissue necrosis following subcutaneous injection.