Oral delivery systems limitations

Oral Delivery Systems. The oral route of drug administration has been the most popular one, however, it is not without problems and constrains. First of all, the total gastrointestinal residence time limits the time frame or "window" for oral absorption. The... 

Furthermore, by in vitro experiments, it has been verified that stereospecific activation of alprenoxime is organ-specific, occurring in the eye and not systemically. When administered locally to rabbits, marked decreases in intra-ocular pressure were observed, whereas oral administration elicited almost no cardiac effects. Such ketoximes represent promising chemical delivery systems in the treatment of glaucoma However, a major limitation is their poor stability in solution, seemingly due to hydrolysis of the oxime function. 

Drug-delivery systems are essentially specialized dosage forms developed to overcome the limitations of conventional dosage forms, such as simple tablets, capsules, injectable solutions, etc. Some of the reasons behind the development of oral DDSs are listed below ... 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

The use of therapeutic proteins is growing rapidly and it has been suggested that this class of drugs may soon represent a significant fraction of the pharmaceutical market [45]. There is an urgent need for the development of delivery systems for proteins because, so far, the use of therapeutic proteins is limited to their low oral and transdermal bioavailability. 

In many cases in drug development, the solubility of some leads is extremely low. Fast dissolution rate of many drug delivery systems, for example, particle size reduction, may not be translated into good Gl absorption. The oral absorption of these molecules is usually limited by solubility (VWIImann et al., 2004). In the case of solubility limited absorption, creating supersaturation in the Gl Luids for this type of insoluble drugs is very critical as supersaturation may provide great improvement of oral absorption (Tanno et al., 2004 Shanker, 2005). The techniques to create the so-called supersaturation in the Gl Luids may include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles, which can be found in some chapters in the book. 

In addition to their usefulness in the enhancement of oral bioavailability of lipophilic drugs, microemulsion formulations have found considerable application as potential delivery systems for peptides whose delivery is often limited by poor GI permeability. W/O microemulsions provide a convenient means of delivery of both permeability-enhancing lipids and water-soluble peptides. The GI permeability-enhancing effects of lipids and their use in the delivery of highly water-soluble compounds are reviewed elsewhere [18, 56, 59],... 

Parenteral delivery systems involve the use of needles. This is painful for the patient, as well as generally requiring the intervention of medical professionals. The oral route, which involves merely swallowing a tablet, liquid or capsule, thus represents a much more convenient and attractive route for drag delivery. Transdermal patches are also well accepted by patients and convenient. Some other dosage forms, for example nebulizers, pessaries and suppositories, may meet with more limited patient compliance. 

Ionization, pKa, and Aqueous Solubility Most drugs are weak acids or bases. It is important to note the relationship between the pKa of the compound and the absorptive environment. Delivery systems that are dependent on diffusion or dissolution will likewise be dependent on the solubility of drug in the aqueous media. Since drugs must be in solution before they can be absorbed, compounds with very low aqueous solubility usually have the oral bioavailability problems because of limited GI transit time of the undissolved drug particles and they are limited at the absorption site. Unfortunately, for many of the drugs and bioactive compounds, the site of maximum absorption occurs at the site where solubility of these compounds is least. 

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. 

Although routine oral delivery of proteins has not been realized, some protein formulations have been developed for pulmonary delivery. Pulmonary delivery can result in either parenteral or local administration of the drug and, like oral delivery, is considered non-invasive. As with other routes of delivery, the size of the protein may limit its ability to be delivered systemi-cally via the pulmonary route of administration. Pulmozyme , a DNase-based formulation approved for the treatment of cystic fibrosis (CF), is delivered to the lungs by a nebulizer to clear blockage of the airways in the CF patient.Formulations for insulin to be administered by inhalation for systemic delivery of... 

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