Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems - Pharmaceutical Technology

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Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems
Novel hydrophobic bioadhesive polymers and dosage designs are now available to effectively achieve tailored release kinetics of a broad range of drugs to meet the clinical needs.

Pharmaceutical Technology
Volume 32, Issue 11, pp. 100-121

Another prerequisite for an ideal bioadhesive delivery system is that the bioadhesive and drug-release functions are independent of each other. Often, the bioadhesive polymer used in the dosage form is also used to regulate the release of drug. Generally, these formulations are made by mixing bioadhesive polymer and drug or by coating drug-loaded beads or tablets with the bioadhesive polymer. These approaches of using bioadhesive polymers to achieve both bioadhesion and drug-release functions have compromised results.

An effective bioadhesive formulation must not cause local tissue irritation or long-term tissue toxicity as a result of the bioadhesive polymer or other absorption enhancers used to promote drug absorption. Also, if encapsulated bioadhesive nanoparticles or multiparticulates beads are used as the delivery system, the particles may have a tendency to form agglomerates because of the charge or hydration within the capsule. Accordingly, measures should be taken to keep these structures monodisperse to allow maximum interaction with the mucosal surface upon release from the capsule. Other desirable characteristics of a bioadhesive dosage include high drug loading, complete drug release, and convenient administration.

Although the prerequisites described above apply to bioadhesive dosage forms, the potential impact of formulation excipients on the adhesive behavior of bioadhesive drug delivery systems and mucosal surfaces also should be carefully taken into account. For example, excipients containing hydroxyl groups could form hydrogen bonds with the hydrophilic functional group of bioadhesive polymers and, as a result, prevent their interaction with the mucosal surface (20). In addition, hydrophobic lubricants (e.g., magnesium stearate and talc) tend to hinder the formation of strong bioadhesive bonds and thus reduce the bioadhesive strength significantly (21). Structural breakdown of mucin has been observed by the addition of surfactants. A number of agents (e.g., tetracycline and progesterone) may alter the viscosity of mucus by altering its molecular composition. Integrity of mucin layers is also disrupted in some disease states (e.g., inflammation and ulceration). Therefore, in developing a bioadhesive dosage form, drug and excipient characteristics as well as the presence of disease states need to be taken into account.

Oral bioadhesive dosage forms targeting the GIT

Bioadhesive systems have been targeted to many sites within the GIT to increase the residence time available for absorption and thereby increase the overall bioavailability. Although bioadhesive polymers have been successfully used for oromucosal (buccal and sublingual) drug delivery (22), delivery to other GI sites has been a challenging task. The following sections review the drug delivery to various GI sites using bioadhesive formulations and discuss the degree of success.

Targeting to the esophagus. The esophagus is lined with stratified squamous epithelium and is continuously lubricated and coated by the swallowed saliva containing mucin. Bioadhesive materials have been used in various liquid dosage forms to specifically target the esophageal mucosa (23, 24). However, because the esophagus is associated with poor blood supply, drug delivery for systemic absorption through this site is not feasible.

Because of a relatively short esophageal transit time of dosage forms in supine subjects (10–15 s), liquid bioadhesive formulations have been explored as a vehicle for localized delivery to the esophageal mucosa or to provide a protective bandage for the underlying esophageal lining from gastric reflux (25). One study investigated the incorporation of antifungal agents into an oral formulation that coated the esophagus and provided drugs at the target site for localized delivery to treat esophageal candidiasis (26). Drug delivery to the esophagus was achieved in rabbits using magnetic particles in conjunction with hydroxypropyl cellulose and carboxyvinyl polymer as bioadhesive excipients. However, retention of the formulation (using bleomycin in hydroxypropyl cellulose:Carbopol) was insufficient for effective therapy. It was concluded that a stronger bioadhesive may help retain particles at the desired site of action (27).

Sodium alginate in a range of water-miscible vehicles was evaluated as a bioadhesive liquid for targeting the esophageal mucosa for the treatment of gastro-esophageal reflux disease (GERD). The study showed that vehicle composition had a considerable impact on the initial contact and retention of suspended alginate; however, the rate of detachment of the adhered layer was similar for each vehicle. Thus, the ability to modulate the mucosal retention of an alginate suspension as a function of hydration offers a novel strategy for the future development of formulations with tailored bioadhesive properties (28).

Localized delivery of hexylaminolevulinate to the Barrett's esophagus was achieved in human volunteers using poloxamer, chitosan, and sodium carboxymethylcellulose polymers as bioadhesive excipients. This study measured the esophageal transit time by endoscopic examination and suggested that a topical formulation delivered orally to treat adenocarcinoma of esophagus is feasible (29).


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