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Mucuna gum extracted from the seeds of the tropical plant, Mucuna flagillepes was assessed for the bioadhesive delivery of theophylline. Theophylline containing granules were formulated by wet granulation, and thereafter, subjected to a bioadhesive test using adhesion on porcine jejunum. The bioadhesive properties of the gum dispersions were also assessed using coated glass beads and a tensiometer. Also, the physical properties of the film formulated from the gum were evaluated. Sodium carboxymethylcellulose (SCMC) and acacia gum were used as standard bioadhesive polymers. Results obtained indicated that mucuna gum is much more bioadhesive than acacia gum, but less bioadhesive than SCMC at equivalent concentration with respect to coated glass beads test; however, mucuna gum was more bioadhesive with respect to the tensiometric evaluation of the bioadhesive strength. The bioadhesive force recorded for mucuna gum may probably be high enough for the bioadhesive delivery of theophylline as the release study results show. SCMC had better film-forming properties than either mucuna gum or acacia gum. Ex vivo study showed that theophylline could be released from the granules.
A volume of attention is currently being drawn to the potentials inherent in African tropical plants as sources of bioactive substances and drug carriers as well as adjuncts in the formulation of drug delivery systems. One group of such carriers or adjuvants consists of polymeric plant metabolites, which can hydrate into gels or mucilages. These are generally known as plant gums. Although gums obtained from African tropical plants have been known for a very long time, their extraction, purification and utilization in pharmaceutical formulations are still at rudimentary stages. There appears to be greater industrial preference for synthetic or semi-synthetic hydrogels as vehicles, carriers and excipients in pharmaceutical, cosmetic or food products. But because of the naturalness of biopolymers of plant origin, with associated inertness and safety, more interest has to be shown, particularly by the pharmaceutical industry, towards the employment of plant gums as drug carriers, or adjuncts, in drug dosage forms. This article seeks to draw attention to some African tropical plant gums, obtained from different plant species, which have been shown, via laboratory studies, to exhibit potential applicability in the development of drug delivery systems.
This paper describes the determination of the glass transition temperature and the amorphicity of some natural gums. These two parameters are very important in pharmaceutical material science. Standard instrumental procedures were used in the determination. Results obtained were used to further characterize these functional polysaccharides that have been investigated in the formulation of some dosage forms, without to date adequately describing their thermal and crystal properties. Knowledge of the thermal and crystal properties will widen the horizon of usage of these emerging functional pharmaceutical excipients.
Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation
An investigation into the suitability of mucuna gum microspheres for oral delivery of glibenclamide is presented. Mucuna gum microspheres were formulated under different conditions of polymer concentration and crosslinking time at constant speed. The formulated microspheres were thereafter loaded with glibenclamide by the remote loading process. The microspheres were evaluated according to particle size, yield, loading efficiency and swelling. In vitro release of glibenclamide from the microspheres was studied in simulated intestinal fluid (SIF, pH 7.4). The release data was fitted into two release models to investigate the mechanism of glibenclamide release from the microspheres. All the microspheres showed good swelling characteristics in distilled water. The investigation revealed that the microspheres produced with 5% ( m/V ) mucuna gum with a crosslinking time of 5 h had the optimum prolonged release pattern. The microspheres produced using 10% ( m/V ) mucuna gum with a crosslinking time of 1 h had the highest delayed release of the incorporated drug, whereas those without crosslinking had the fastest release. The Ritger-Peppas case I transport model appeared to have adequately described the release process as about 54% of the batches of microspheres conformed to this model. This implies that a formulation of glibenclamide-loaded mucuna gum microspheres is likely to offer a reliable means of delivering glibenclamide by the oral route.
The present paper, Part 1, reviews surface and interfacial phenomena, including mechanisms of adhesion, which are relevant to the adhesive joining of materials with the aim of outlining the current philosophies, and relating them, where possible, to the practice of adhesive bonding. Part 2 will examine the mechanics of adhesive joint fracture and the effects of various operating environments on joint performance.
Admixtures containing Carbopols 940, 941 and sodium carboxymethylcellulose (SCMC) were assessed for bioadhesive delivery of metronidazole. The bioadhesive properties of the admixtures were estimated by using the adhesion of polymer coated glass beads on a biological tissue and the modified Lecomte Du Nouy tensiometer. The rheological behaviours of the polymers and their admixtures were studied as well. The bioadhesive, swelling and release characteristics of tablet compacts formulated with the polymers and their admixtures, which contained metronidazole, were also determined. Results obtained indicated that although all single polymers and their admixtures had high bioadhesive potentials, Carbopol 940 and 941 admixture (2:1) showed the best performance and SCMC/Carbopol 940 admixture (2:1) exhibited the least bioadhesive strength.
One proposed mechanism of mucoadhesion involves the interpenetration of the mucus/mucoadhesive molecules followed by the formation of non-covalent interactions. Mucus glycoproteins are believed to be the major structure forming component of mucus, giving rise to the cohesive and the viscoelastic nature of the mucus gel. The addition of a known mucoadhesive, the polyacrylic acid Carbopol 934P (paa), to purified mucus glycoprotein resulted in the formation of a strengthened gel network. This was indicated on visual examination, and also on rheological examination using mechanical spectroscopy. A large mean G' (the storage modulus, found between 10 and 0.1 Hz) was obtained for the glycoprotein/paa mix in comparison to when the glycoprotein and paa gels were tested separately at the same concentration. Similar results were obtained with crude and homogenised mucus samples. This gel strengthening phenomena was optimum at pH values around the pKa of paa. It was concluded that it is the glycoprotein component of mucus which interacts with paa to produce gel strengthening, and this may increase the cohesive nature of the weakest component of a mucoadhesive joint, thus allowing prolonged mucosal adhesion. A rheological investigation of a pH 6.2 glycoprotein/paa mix between 10 and 0.002 Hz indicated that this gel strengthening effect resulted from both chain entanglement and the formation of secondary chemical bonds.
Interfacial phenomena related to the adhesive properties of synthetic polymers, hydrocolloids and related systems in contact with soft, natural tissues are discussed. The nature of the adhesive interface, the surface roughness, the chemical structure of the bioadhesive-candidate material, the swelling (hydration) at the adhesive interface, and the dynamic development of the bioadhesive bond strength are analyzed in terms of molecular and surface theories. Available in vitro testing techniques for bioadhesion provide an indication of the efficiency of proposed polymers as bioadhesives. These theoretical analyses and experimental results are used to establish general guidelines for the development of bioadhesive controlled release systems of bioactive agents for buccal, nasal, gastric, intestinal, urinary and rectal uses.
To overcome the relatively short gastrointestinal time and improve localization for oral-controlled or sustained-release drug delivery systems, it is suggested that bioadhesive polymers which adhere to the mucin/epithelial surface will be effective and lead to significant improvements in oral drug delivery. Improvements would also be expected for other mucus-covered sites of drug administration.To examine a large number of polymers as to their bioadhesive potential and to derive meaningful information on the structural requirements for bioadhesion a new, simple experimental technique that can quantitatively measure bioadhesive properties of various polymers has been developed. The technique consists of labeling the lipid bilayer of cultured human conjunctival epithelial cells with the fluorescent probe pyrene. Addition of polymers to this substrate surface compresses the lipid bilayer causing a change in fluorescence as compared to control cells. The fluorescent probe, pyrene, provides information on membrane viscosity, which is proportional to polymer binding. In addition to the use of pyrene, membrane proteins were labeled with fluorescein isothiocyanate, and depolarization of probelabeled proteins was measured before and after polymer treatment. By using these fluorescent probes, it was possible to compare charge sign, charge type and density, and backbone structure as to their influence on polymer adhesion. Preliminary comments on structural features for polymer binding are that highly charged carboxylated polyanions are good potential bioadhesives for drug delivery.
The emulsifying and suspending properties of a new polysaccharide gum derived from an edible bean, Mucuna flagillepes have been investigated. The stability of the emulsion prepared with the gum was compared with that of emulsions prepared with acacia or tragacanth. Sherman's equations for concentrated emulsions were applied to determine the rate of coalescence k, and changes in mean cube globule diameter. Suspensions of sulphdimidine or zinc oxide prepared with tragacanth gum were compared with those prepared with mucuna gum. The final sedimentation height, Hu for each suspension was predicted using a biexponential relationship in the sedimentation pattern. The indication is that mucuna gum can be usefully employed as both an emulsifying and a suspending agent.
Prosopis gum (PG) extracted from Prosopis africana was investigated for bioadhesive delivery of theophylline (TPL). Bioadhesive granules containing TPL were formulated and the bioadhesive properties evaluated using adhesion of the granules onto a porcine intestinal mucus surface. The bioadhesion of the gum dispersion was also evaluated using coated glass beads and the strength of the films formulated from the gums was also determined. The release properties of the TPL-containing granules were assessed by diffusion of TPL from the granules through porcine intestinal wall into a sink solution. Sodium carboxymethylcellulose (SCMC) was used as the standard bioadhesive polymer. Results indicated that PG is highly bioadhesive compared to SCMC. The result of the release studies also showed that PG could be used to deliver TPL in a bioadhesive dosage form.