Mucosal formulations

Over the next 5-10 years, additional growth drivers are also expected to become important, including the first successful outcomes to research into delivery systems for gene therapy, new targeting systems for anticancer therapies, and additional sectors including mucosal formulations. 

Exploitation of the cationic/hydrophobic effect for mucosal substrate use is a design principle that lends itself toward the investigation of a variety of structural analogues. However, the measure of success for any vehicle, combination of activities, and a final formulated product will be the demonstration of unequivocal efficacy in vivo. 

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. 

Interchangeability Do not use itraconazole capsules and oral solution interchangeably. Drug exposure is greater with the oral solution than with the capsules when the same dose of drug is given. Additionally, the topical effects of mucosal exposure may be different between the two formulations. 

Topical formulations of nystatin and of amphotericin B are useful in the management of Candida albicans infections of the skin. Both antibiotics are ineffective against dermatophytes. The use of nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow spectrum and its negligible absorption from the gastrointestinal tract. Hypersensitivity reactions are rare. It is not known whether topical nystatin can cause fetal harm when used by a pregnant woman. Amphotericin B has broader antifungal activity but its topical use is restricted to Candida. Topical use of amphotericin B has shown minimal absorption through the skin and is well tolerated. Limited human surveillance data do not indicate any harm to mother or fetus, but relative safety is still unknown. 

Cefuroxime is only poorly absorbed from the gastrointestinal tract and so was originally only an injectable product, but a commercially successful new orally-administered cerufoxime ester product has been developed which has created a new surge in sales. This acetoxyethyl pro-drag form of cefuroxime is rapidly hydrolysed in the brash-border mucosal epithehal cells of the duodenum and small intestine, but requires special formulation so as to ensure efficient dissolution following investigation. 

In a more recent study, Webster et al. (2006) report the expression and characterization of lettuce-derived measles vaccine. The MV-H protein expressed in lettuce was demonstrated to be immunogenic in mice following intraperitoneal injection in the absence of adjuvant in addition to intranasal inoculation in the presence of a mucosal adjuvant. The highest response was observed in mice primed first with MV-H DNA and then boosted with an oral formulation of freeze-dried MV-H lettuce in conjunction with a mucosal adjuvant. In addition to this, the type of immune response was found to depend largely on the manner in which MV-H is presented to the immune system. Secreted and soluble forms of MV-H were demonstrated to induce a Th2 type response, while membrane-bound MV-H protein was found to be associated with a Thl response. 

Lian, T., T. Bui, and R.J. Ho, Formulation of HFV-envelope protein with lipid vesicles expressing ganglioside GMl associated to cholera toxin B enhances mucosal immune responses. Vaccine, 1999. 18(7-8) 604-11. 

Pancreatic enzyme supplements are well tolerated. The capsules should be swallowed, not chewed, because pancreatic enzymes may cause oropharyngeal mucositis. Excessive doses may cause diarrhea and abdominal pain. The high purine content of pancreas extracts may lead to hyperuricosuria and renal stones. Several cases of colonic strictures were reported in patients with cystic fibrosis who received high doses of pancrelipase with high lipase activity. These high-dose formulations have since been removed from the market. 

The most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

An allergen preparation has been administered via direct ingestion (oral route) or by so-called mucosal routes nasal, sublingual or oromucosal. This implies that some local effects or local absorption were expected. As a matter of fact, a demonstration of the clinical efficacy of mucosal allergen immunotherapy has been provided, and some hypotheses about its mechanism of action have been formulated [15-19,24-32],... 

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

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