Controlled and sustained drug delivery has recently begun to make an impression in the area of treatment of dental diseases. Many researchers demonstrated that CRDDS of antimicrobial agents such as chlorhexidine, ofloxacin and metronidazole could effectively treat and prevent peridontitis.
The incidence of dental carries and formation of plaque can also be reduced by CRDDS of fluoride. Delivery systems used are film forming solutions, polymer inserts, implants and patches. Since dental diseases are usually chronic, sustained release of therapeutic agents in the oral cavity would obviously be desirable.
III) OCULAR SYSTEMS :
The eye is unique in its therapeutic challenges. An efficient mechanism, that of tears and tear drainage, which quickly eliminates drug solution, makes topical delivery to the eye somewhat different from most other areas of the body. Usually less than 10% of a topically applied dose is absorbed into the eye, leaving the rest of the dose to potentially absorb into the blood stream resulting in unwanted side effects.
The goal of most controlled delivery systems is to maintain the drug in the precorneal area and allow its diffusion across the cornea. Suspensions and ointments, although able to provide some sustaining effect, do not offer the amount of control desired. Polymeric matrices can often significantly reduce drainage but other newer methods of controlled drug delivery can also be used.
The application of ocular therapy generally includes drugs for glaucoma, artificial tears, and anticancer drugs for intraocular malignancies. The sustained release of artificial tears has been achieved by hydroxypropylcellulose polymer insert. However, the best-known application of diffusional therapy in the eye, Ocusert-Pilo. The device is a relatively simple structure with two rate-controlling membranes surrounding the drug reservoir containing pilocarpine.
Thus, a thin, flexible lamellar ellipse is created and serves as a model reservoir device. The unit is placed in the eye and resides in the lower cul-de-sac, just below the cornea. Since, the device itself remains in the eye, the drug is released into the tear film.
The advantage of such a device is that it can control intraocular pressure for up to a week. Further, control is achieved with less drug and hence fewer side effects, since the release of drug is close to zero order. The system is more convenient, since application is weekly as opposed to the four times a day dosing for pilocarpine solutions.
This greatly improves patient compliance and assures round-the-clock medication, which is of great importance for glaucoma treatment. The main disadvantage of the system is that it is often difficult to retain in the eye, and can cause some discomfort.
Another method of delivery of drug to the anterior segment of the eye, which has proved successful, is that of prodrug administration. Since the corneal surface presents an effective lipoidal barrier, especially to hydrophilic compounds, it seems reasonable that a prodrug that is more lipophilic than the parent drug will be more successful in penetrating this barrier.
Many drugs have been derivatized for prodrug ocular delivery e.g. timolol, nadolol, pilocarpine, prostaglandin F 2 a , terbulatine, aciclovir, vidarabine and idoxuridine.
New sustained release technologies are gaining importance in ocular delivery as in other routes. Liposomes as drug carriers have achieved enhanced ocular delivery of certain drugs; antibiotics and peptides. Biodegradable matrix drug delivery of pilocarpine can be achieved with a polymeric dispersion.
Implantation of polymers containing endotoxin for neovascularization, gancyclovir, 5-flurouracil and injections of doxorubicin have also resulted in sustained delivery. However, topical ocular delivery is preferred considerably over implants and injection.