Bioadhesive force

The electronic theory is based on the assumption that the mucoadhesive hydrogel and the target biological tissue have different electronic structures. When two materials come into contact with each other, electron transfer occurs, causing the formation of a double layer of electrical charge at the bioadhesive-biological interface. The bioadhesive force is believed to be due to attractive forces across this electrical double layer. 

Tang, C., et al. 2005. New superporous hydrogels composites based on aqueous Carbopol solution (SPHCcs) synthesis, characterization and in vitro bioadhesive force studies. Eur Polym J 41 557. 

Yong et ah [175] developed an effective omeprazole buccal adhesive tablet with excellent bioadhesive force and good drug stability in human saliva. The omeprazole buccal adhesive tablets were prepared with various bioadhesive polymers, alkali materials, and croscarmellose sodium. Their physicochemical properties, such as bioadhesive force and drug stability in human saliva, were investigated. The release and bioavailability of omeprazole delivered by the buccal adhesive tablets were studied. As bioadhesive additives for omeprazole tablet, a mixture of sodium alginate and hydroxypropylmethyl cellulose was selected. The omeprazole tablets prepared with bioadhesive polymers alone had bioadhesive forces suitable for a buccal adhesive tablet, but the stability of omeprazole in human saliva was not satisfactory. Magnesium oxide is an alkali stabilizer for omeprazole buccal adhesive tablets. Croscarmellose sodium enhanced the release of omeprazole from the tablets but it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. 

Unfortunately, values of yd and yp for mucus and glycoproteins, the main components of the mucous layer, are not yet available, but from the fact that the best candidates for bioadhesion are hydroxyl- and carboxyl-containing polymers, one can infer that the polar component is the predominant factor. The experimental data relating cellulose derivatives (mostly by measuring bioadhesive force) generally only compare NaCMC to one or two nonionic derivatives and the former always proved to be superior to the latter, and equivalent to other carboxyl-containing polymers (see e.g. [85]). 

Bioadhesion to the vaginal substrate implies knowledge and demonstration of the mechanism of interaction. In the present case, mucoadhesion, bioadhesion, and substantivity can be used interchangeably when evaluating the mucosa as a substrate. Several forces may be active, such as electrostatic, hydrophobic, and hydrogen bonding, giving rise to surface interactions between the polymer and the mucosal substrate or diffusion into the mucus layer [48,49]. 

The adsorption theory states that the bioadhesive bond formed between an adhesive substrate and tissue or mucosae is due to van der Waals interactions, hydrogen bonds, and related forces. Alternatively, when mucus or saliva are interacting with a solid dosage form, the molecules of the liquid are adsorbed on the solid surface. This is an exothermic process. The free energy of adsorption is given by Eq. (1). 

The diffusion theory states that interpenetration and entanglement of polymer chains are additionally responsible for bioadhesion. The intimate contact of the two substrates is essential for diffusion to occur, that is, the driving force for the interdiffusion is the concentration gradient across the interface. The penetration of polymer chains into the mucus network, and vice versa, is dependent on concentration gradients and diffusion coefficients. It is believed that for an effective adhesion bond the interpenetration of the polymer chain should be in the range of 0.2-0.5 pm. It is possible to estimate the penetration depth (/) by Eq. (5),... 

According to Duchene et al. [17], when tensiometry is used to measure the maximum detachment force as a function of the displacement of the upper support (function of the joint elongation), the work of bioadhesion can be defined as in Eq. (7). 

Measurement of tensile or shear stress is the most commonly used in vitro method to determine bioadhesion. All in vitro measurements provide a rank order of bioadhesive strength for a series of candidate polymers. Measurement of tensile strength involves quantitating the force required to break the adhesive bond between the test polymer... 

The bioadhesive characteristics of tablets for oral use made from modified starch, poly(acrylic acid), polyethylene glycol) and sodium carboxymethyl cellulose were recently investigated [406]. In this work, the force and energy adhesion were determined in vitro, and maximum adhesion times were evaluated in vivo in humans [406], In the in vitro, studies, the poly(acrylic add) gave the best performance, however in vivo bioadhesion was not strongly correletated with... 

Buccoadhesive-controlled release tablets for delivery of nifedipine were prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer (CP) and compared to those prepared with PVP, PVA, HPMC, and acacia by a modified tensiometry method in vitro. It was found that the adhesion force was significantly affected by the mixing ratio of CP CMC in the tablets. CMC is necessary for controlling the release rate, whereas CP is important in providing bioadhesion. The tablets containing 15% CMC and 35% CP were found to have optimum drug release rate and bioadhesion [81]. 

A confirmation of the soundness of electronic theory was derived from a recent study, performed by Bogotaj et al. [46], They measured the zeta potential of different polymer dispersions and mucosal homogenates and found a correlation between such a parameter and the force necessary to detach a polymer dispersion from the biological substrate. The adsorption theory states that the bioadhesive bond is due to van der Waals interactions, hydrogen bonds, and other related weak interactions [44],... 

Various mechanical testing methods have been used to assess the bioadhesive properties of materials and formulations. Review of the literature reveals that the technique most commonly used is the tensile test [82,85]. This test provides the measure of the force needed to detach a layer of the tested material or formulation from a mucosal substrate as a function of the displacement occurring at the bioadhesive interface. Besides maximum force of detachment, another parameter provided by tensile test is the work of adhesion calculated as the area under the force versus displacement curve. Such a parameter gives more complete... 

Bioadhesion is an interfacial phenomenon in which a synthetic or natural polymer becomes attached to a biological substrate by means of interfacial forces. If it involves mucin or mucous-covered membrane, the narrow term mucoadhesion is employed. Bioadhesion has been used to enhance bioavailability of dmgs via various other routes including oral (Section 6.7.1), transmucosal (Section 1.123) and vaginal (Section 11.7.6). Bioadhesion may offer several unique features ... 

Mucoadhesive Polymers Bioadhesion refers to the attachment of a drug molecule or a delivery system to a specific biological tissue by means of interfacial forces. If the surface of the tissue is covered by a mucin film, as is the case for the external globe, it is more commonly referred to as mucoadhesion. 

Weyenberg, W., Vermeire, A., Remon, J. R, and Ludwig, A. (2003), Characterization and in vivo evaluation of ocular bioadhesive minitablets compressed at different forces, J. Controlled Release, 89(2), 329-340. 

The diffusion theory states that interpenetration and entanglement of polymer chains are additionally responsible for bioadhesion. The intimate contact of the two substrates is essential for diffusion to occur that is, the driving force for the interdiffusion is the... 

Fig. 19 Example of a force-deflection profile obtained from a butt bioadhesion experiment utilizing hot-melt extruded films in vivo using a Chatillon digital force gauge attached to a motorized test stand. (From Ref. l)...

In some cases, cell surface expression of certain species can be induced for example, interleukin-1 has been shown to induce the biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells [197]. Such materials may also be exploitable as candidates for bioadhesion studies. Millions of lives of patients with diabetes have been saved since the introduction of insulin therapy. However, several daily injections of insulin are required to maximize glucose control in diabetic patients. Insulin is administered by subcutaneous injection, but this route of administration has a slow onset and subsequent prolonged duration of action. These limitations show up more when higher doses of insulin are injected, which results in a long duration of action and forces the patients to consume additional amounts of food to limit the risk of hypoglycemia [198]. 

---