Emulsions, ocular drug delivery

It has to be clear that, once diluted and injected (or administered in ocular and other routes), the emulsion stability and fate are determined by three measurable parameters. The first is the partition coefficient of each emulsion component (including added drugs and agents) between the emulsion assembly and the medium. To some extent this partition coefficient is related to oil-water and/or octanol-water partition coefficients. For example, it was well demonstrated that per component of which logP is lower than 8, the stability upon intravenous (IV) injection is questionable [42,138], The other two parameters are kQff, a kinetic parameter which describes the desorption rate of an emulsion component from the assembly, and kc, the rate of clearance of the emulsion from the site of administration. This approach is useful to decide if and what application a drug delivery system will have a chance to perform well [89],... 

TABLE 5 Selected List of o/w Nanosized Emulsions for Ocular Topical Drug Delivery... 

Over the last decade, o/w nanosized emulsions containing either anionic or cationic droplets have been recognized as interesting and promising ocular topical delivery vehicles for lipophilic drugs. Complete details are available elsewhere [117]. As an overview of this topic, important results on emulsion-based ocular topical drug delivery are covered below and are listed in Table 5. 

The use of ttaditional disperse systems, e.g., macroemulsions, in the pharmaceutical industry has been limited due to manufacturing complexity and stability problems [117]. The characteristic properties of nano-emulsions (kinetic stability, small and controlled droplet size, etc.) make them interesting systems for pharmaceutical applications. Indeed, nano-emulsions are used as drug delivery systems for administration through various systemic routes. There are numerous publications on nano-emulsions as drug delivery systems for parenteral [17,18,28,29,118-124], oral [25,125-129], and topical administration, which includes the administration of formulations to the external surfaces of the body skin [32,130,131] and to the body cavities nasal [30,132] as weU as ocular administration [31,133-136]. Moreover, many patents concerning pharmaceutical applications of nano-emulsions have been registered [17,18,25,137-145]. An application of nano-emulsions in this field has been in the development of vaccines [33,146-147]. 

Emulsions have been used for centuries for the oral administration of medical oils and vitamins and as dermatological vehicles. Recently, their application has been extended as drug carriers in the delivery and targeting of ophthalmic drags. An indomethacin emulsion has been reported to increase ocular bioavailability and efficacy compared to commercially available formulation in rabbits. 0.4% indomethacin emulsion showed 2.2 fold increase in the area under the anterior aqueous drag concentration/time curve compared to a 1% indomethacin suspension. The emulsion formulation also reduced ocular surface irritation caused by indomethacin Similar advantages have been shown for a pilocarpine emulsion which produced a prolonged therapeutic effect in comparison with pilocarpine hydrochloride eyedrops in man. It can be administered only twice a day, rather than four times daily for conventional formulation. 

New sustained technologies are also gaining much interest in ocular delivery, as in other routes. Liposomes as drug carriers have achieved enhanced ocular delivery of certain drugs, antibiotics, and peptides. Prolonged delivery of pilocarpine can be achieved with a polymeric dispersion or submicrometer emulsions [79]. 

It has been shown in a number of studies that the incorporation of drug in o/w nanosized emulsions significantly increased the absorption of the drug when compared with the equivalent aqueous solution administered orally [132-135], However, the use of emulsions for oral application is limited since other attractive alternatives, such as self-emulsifying oil delivery systems, which are much less sensitive and easy to manufacture, are available [136,137], Thus the potential of nanosized emulsions after administration with parenteral and traditional nonparenteral topical routes such as ocular, percutaneous, and nasal is covered in this section. 

Tamilvanan, S., and Benita, S. (2004),The potential of lipid emulsion for ocular delivery of lipophilic drugs, Eur. J. Pharm. Biopharm., 58, 357-368. 

Oil-in-water microemulsion has been widely studied and used for transdermal delivery of the drugs. Apart from its advantages as topical formulation, oil-in-water emulsion also offers numerous advantages such as bioavailability enhancement via transdermal, oral, ocular, and vaginal routes. 

There are several oil-based formulations for the delivery of hydrophilic and lipophilic drugs, which maj orly include emulsions and gels (Figure 58.2). Apart from these, various other novel formulations may also be named under this category such as micelles, reverse micelles, solid lipid nanoparticles, and liposomes. - Based on the physicochemical properties of the drug and patient requirements, the vegetable oil-based formulations may be delivered by various routes like oral, parenteral, topical, transdermal, pulmonary, or ocular, etc., - ... 

Drugs are normally applied to the eye as solutions (eye drops) and more rarely as suspensions or as ointments. However, the loss of drug either by tear flow or by drainage into the nasolacrimal duct as well as the impairment of vision by viscous ophthalmic ointments are major drawbacks for optimum delivery. As a submicron emulsion is biologically compatible, stable, and sterilizable, it appeared to be of imere.st as an ocular vehicle. Emulsion formulations have some advantages in providing a reservoir for slow release of drug in a nonviscous medium. 

Muchtar et at. (35) have demonstrated that submicron emulsions can also be used as an ocular delivery system for the lipophilic antiglaucoma drug. A"-tetrahydrocannabinol. They showed that the emulsion was able to achieve a long-lasting antidepressant effect on the intraocular pressure of rabbits following a single Instillation. 

To enhance encapsulation efficiency, a spray-drying method could be proposed. Thus, this technique provides a significant improvement of betamethasone encapsulation efficacy into PLGA microparticles, namely, 90% encapsulation efficacy compared with 15% for Wi/o/ W2 double emulsion process [28]. An emulsification/spray-drying technique has also been proposed as an alternative to the double emulsion method for encapsulation of peptide drug, vancomycin into microspheres for the topical ocular delivery (encapsulation efficacy 84-99%) [29]. 

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