Mucoadhesion

The release of locally acting drugs can be targeted using mucoadhesive platform. Natural biodegradable polymers are considered as suitable contenders as mucoadhesive polymers. The aim of current research was to evaluate mucoadhesive role of agarose (AG) by preparing directly compressible tablets. AG was aided by carbopol ® (CP) for simultaneous release of benzocaine (BZN) and tibezonium iodide (TIB) from mucoadhesive tablets. In order to prepare tablets, ingredients were mixed geometrically and compressed using a ZP35 rotary tablet machine. The prepared tablets were characterized for physical, ex vivo mucoadhesive time (ET) and mucoadhesive strength (MS), swellability, erosion and in vitro drugs release. The solid state studies revealed that no unusual peak in the physical mixture of ingredients through FTIR and DSC analysis. Values of weight variation and friability tests of the tablet formulations complied with USP specifications which showed that variation in the polymers did not affect physical parameters of the tablets. The highest ET (24.3 h) and MS (22.6 g) values were associated with formulation T9. Maximum erosion was observed in T1 formulation with lowest concentration of AG (10%) used in the study. Similarly, higher SI was observed with T2 (74.02%) at 6 h. The optimized tablet formulation T2 showed complete drug release after 6 h with better swelling. In addition, when polymers were used alone, AG exhibited poor MS and ET values compared to CP whereas polymers used in combination (AG-CP) exhibited much better properties. Therefore, it was concluded that AG when combined with a mucoadhesive agent like CP have much improved potential to effectively deliver drugs. RESUMEN. RESUMEN. La liberación de fármacos de acción local puede orientarse utilizando una plataforma mucoadhesiva. Los polímeros biodegradables naturales se consideran contendientes adecuados como polímeros mucoadhesivos. El objetivo de la investigación actual fue evaluar el papel mucoadhesivo de la agarosa (AG) mediante la preparación de tabletas comprimibles directamente. AG fue asistido por carbopol® (CP) para la liberación simultánea de benzocaína (BZN) y yoduro de tibezonio (TIB) de tabletas mucoadhesivas. Para preparar las tabletas, los ingredientes se mezclaron geométricamente y se comprimieron utilizando una máquina rotatoria de tabletas ZP35. Los comprimidos preparados se caracterizaron por el tiempo mucoadhesivo (ET) físico y ex vivo y la fuerza mucoadhesiva (MS), capacidad de hinchamiento, erosión y liberación de fármacos in vitro. Los estudios de estado sóli do revelaron que no hubo un pico inusual en la mezcla física de ingredientes a través del análisis FTIR y DSC. Los valores de las pruebas de variación de peso y friabilidad de las formulaciones de las tabletas cumplieron con las especificaciones de la USP que mostraron que la variación en los polímeros no afectó los parámetros físicos de

Buccal delivery involves the administration of the desired drug through the buccal mucosal membrane lining of the oral cavity. The objective of this article is to review buccal drug delivery by discussing the structure and environment of the oral mucosa and highlighting the mechanisms of drug permeation and methodology in evaluating buccal formulations. This review also highlights a brief description of advantages, limitations of buccal drug delivery and theories involved in mucoadhesion along with method of preparation mucoadhesive system, mucoadhesive polymer, and classification of buccal system.

Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different dosage forms were developed based on this principle. This study aims to prepare bucco-adhesive tablets of anti-migraine drug zolmitriptan as a suitable candidate for improving its oral bioavailability and therapeutic efficacy and to evaluate them for many pre/post-formulation parameters in-vitro/exvivo. The bucco-adhesive tablets containing 2.5 mg zolmitriptan were prepared using carbopol 934LR as a primary polymer alone or in combination with chitosan or xanthan gum as secondary polymers by direct compression. Drug-excipients compatibility and micromeritics study were carried out. Tablets were evaluated for physico-chemical parameters, surface pH, ex-vivo residence time, in-vitro swelling study, ex-vivo mucoadhesive strength, in-vitro drug release study, ex-vivo permeation study and physical stability in human saliva. No interactions were found between drug and excipients. Tablets had good physico-chemical characters. Formulation containing carbopol 934LR and chitosan in a ratio of 1: 3 approximately was the optimum one. It swelled by only 37.67±0.65% after 5 h and showed a nearly neutral surface pH. Ex-vivo residence time was long enough for delivery of the drug for more than 8 h. Ex-vivo mucoadhesive strength was 32.7±2.1 g. Drug release was 86.93±3.73 % after 7 h following zero order kinetics and permeation flux was 0.045 mg/cm 2 h. Tablets were physically stable W WO OR RL LD D J JO OU UR RN NA AL L O OF F P PH HA AR RM MA AC CY Y A AN ND D P PH HA AR RM MA AC CE EU UT TI IC CA AL L S SC CI IE EN NC CE ES S V Vo ol lu um me e 2 2, , I Is ss su ue e 6 6, , 4 42 22 25 5--4 42 24 48 8. . R Re es se ea ar rc ch h A Ar rt ti ic cl le e I

In the present context the buccal route ranks with oral treatment as the successful innovative research area in the drug delivery. However the success of a drug to be used for systemic delivery via buccal route depends mainly on the ability of the drug to permeate through buccal mucosa in sufficient quantities which can be achieved with the help of penetration enhancers. Metoprolol tartrate is the preferred drug because it has plasma half life of 3-4 hrs and has low bioavailability which is an essential condition for formulation of buccal patches. In this study, hydrophilic polymers like Gelatin, Na alginate were used in different concentrations. The result of present investigation stated that the Sod. Gelatin and Na Alginate have good matrix/film forming characteristics which was confirmed by the visual and physiological characterization of the patches. In-vitro and exvivo studies indicated that successful buccal patches of Metoprolol Tartrate could be prepared using hydrophilic polymers viz. Gelatin and Na Alginate employing solvent casting technique.

The aim of the study was to design and evaluate mucoadhesive buccal patches of naproxen for local treatment of pain and inflammations of the oral cavity. Buccal patches were fabricated by solvent casting technique using hydroxypropylmethylcellulose E4M, Eudragit RLPO, ethyl cellulose, polyvinylpyrrolidone, methyl cellulose, hydroxypropylcellulose and chitosan either alone or as mixtures. Ten formulations were subjected to various evaluation parameters. Based on the evaluation of the results, it was concluded that Formula-2 (F-2) containing 1% HPMC and 0.5% Eudragit RLPO showed good mucoadhesive strength (47.07 g), promising controlled and complete drug release within 210 min, highest residence time (120 min in vivo and 125 min in vitro), acceptable elasticity (13.834%mm -2), swelling index (85.4% in 15 min) and surface pH (65). Accordingly, F-2 could be selected as the best formula among the formulations studied and was subject to further in vivo study. The obtained in vivo results indicate that the concentration of naproxen in the oral cavity was maintained above 4 μg/mL for a period of 120 min, which was within and higher than the reported range of the IC 50 of naproxen. A significant in vitro/in vivo correlation was obtained (R 2 = 0.9787). The results indicate that the mucoadhesive buccal patches of naproxen may be a good choice to bypass the undesirable systemic side effects and can be proposed as a new therapeutic tool against dental and buccal inflammatory diseases and disturbs.

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The current article focuses on polymers used in mucosal delivery of therapeutic agents. The mucoadhesive drug delivery system is a popular novel drug delivery method because mucous membranes are relatively permeable, allowing for the rapid uptake of a drug into the systemic circulation and avoiding the first pass metabolism. Mucoadhesive polymers have been utilized in many different dosage forms in efforts to achieve systemic delivery of drugs through the different mucosa. These dosage forms include tablets, patches, tapes, films, semisolids and powders. The objective of this review is to study about novel mucoadhesive polymers and to design improved drug delivery systems.

This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral bioavailability, the mechanism of each additive.

Background : The delivery of drugs through the buccal mucosa has received a great deal of attention over the last two decades, and yet there are not many buccal delivery products available on the market. Objective : This review outlines the advantages and disadvantages of buccal drug delivery, provides a historical perspective and discusses representative developmental and marketed drugs. Methods : The structure of the oral mucosa is briefly described to preface a description of the pathways for drug absorption and a critical discussion of permeation experiments. A brief historical perspective followed by a description of some of the currently marketed products provides a picture of where we are today. An indication is given of likely progress in this area and of the attributes of a successful business entity of the future. Conclusion : The authors provide an assessment of the future potential of buccal and sublingual drugs.

The primary goal of bioadhesive controlled drug delivery is to localize a delivery device within the body to enhance the drug absorption process in a site-specific manner. Bioadhesion is affected by the synergistic action of the biological environment, the proprties of the polymeric controlled release device, and the presence of the drug itself. The delivery site and the device design are dictated by the drug's molecular structure and its pharmacological behaviour. This review addresses several issues which clarify the central goals of bioadhesive drug delivery research. Subsequently, a brief review of a wide variety of techniques which have been used to characterize bioadhesives is presented. This is followed by an overview of several proposed mechanisms of adhesion. The primary mechanisms for polymer systems, adsorption and diffusion, are examined in more detail. 0 1996 Elsevier Science Limited

The current study aimed at development and validation of a simple, accurate, precise, sensitive, robust and specific high performance liquid chromatography (HPLC) method for simultaneous estimation of benzocaine (BZN) with tibezonium iodide (TIB) from combined dosage form as well as from human saliva. Instrumental conditions were developed on an auto-sampler Agilent® 1260 Infinity series RP-HPLC machine. The method was validated in accordance with ICH harmonized guidelines Q2 (R1) by using acetonitrile and phosphate buffer as mobile phase in a volumetric proportion of 70:30 which was flowing through C 18 Agilent® column. Flow of mobile phase was maintained at 1 mL/min at 35 °C and elute was detected 318 nm. The peaks for BZN and TIB were separated at 2.29 and 4.15 min, respectively. Linearity range for such were 0.24-20.16 and 0.14-10.08 μg/mL, respectively. Linear coefficient of regression (R2) for BZN and TIB were 0.9987 and 0.9993, respectively. The relative standard deviation (RSD) values for both drugs were less than 2.0% indicating the accuracy and precision. The limit of detection (LOD) and limit of quantification (LOQ) outcomes for BZN were 56 and 187 ng/mL, respectively. For TIB, it were 38 and 127 ng/mL, respectively. The drugs separation against placebo justified the specificity of the method. It was concluded that the developed and validated method could be potentially for in vitro as well as in human salivary extracts of formulated dosage forms.

In the present study, an attempt was made to formulate mucoadhesive buccal patches of antidepressant drug Sertraline hydrochloride inorder to bypass the first pass metabolism. Buccal patches were prepared by solvent casting technique using polymers like Eudragit and HPMC E15LV.The prepared patches were evaluated for their weight variation, thickness, folding endurance, surface pH, swelling index, moisture uptake study, moisture absorbance study, drug content uniformity and in-vitro drug release and FTIR studies were conducted for Drug -Excipient compatibility testing. The optimized patches showed that the drug release indicates non-fickian release kinetics and diffusion as chain relaxation mechanism. Formulation F3 showed the highest release rate of 83.412% and concluded that all the prepared patches were effective and showed excellent sustained drug release.

Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field. This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs. The synthesis...

Plants gums are complex mixtures of different polysaccharides with a variety of biological activities and pharmaceutical applications. Few studies have focused on physicochemical and biological properties of gums obtained from different plants. This study was designed to determine potential pharmaceutical and pharmacological values of the gum exudates and its isolated biopolymers obtained from Astragalus myriacanthus Boiss [syn. Astracantha myriacantha (Boiss.) Podlech] (Fabaceae). The physicochemical, rheological, and mucoadhesion properties of the gum and its fractions was measured at 7, 27, and 37 °C with and without the presence of NaCl (1%). Also, the structural and immunomodulatory properties of several water soluble biopolymers isolated using ion exchange and size exclusion chromatographic methods were investigated on Jurkat cells at concentrations of 31.25, 62.5, 125, 250, 500 and 1000 μg/mL. The consistency and shear-thinning property of the gum and its fractions decreased as temperature increased. In the presence of NaCl, the consistency increased but no regular pattern was observed regarding to shear-thinning behavior. The mucoadhesion strength was 40.66 ± 2.08 g/cm 2 which is suitable for use as a formulary mucoadhesive polymer. The isolated biopolymers had proteo-arabinoglycan structure. Their molecular weight was calculated to be 1.67-667 kDa. One biopolymer had a proliferative effect and others had dose dependent cytotoxic/proliferative properties. The crude gum and its insoluble fraction showed suitable mucoadhesion, swellability and rheological properties which makes them suitable for designing drug delivery systems. The gum proteo-arabinoglycans with different molecular weight and structures had different immunomodulatory properties.

This study examined the rheological and mucoadhesive properties of polymeric systems composed of the bioadhesive copolymer poly(methylvinylether-co-maleic anhydride), PMVE/MA and poly(vinylpyrrolidone, PVP) as candidate platforms for improved drug delivery to the oral cavity. Aqueous, neutral formulations were prepared containing PMVE/MA (10 or 15% w/w) and PVP (0-9% w/w). The rheological properties were examined at 20 AE 0.18C using both oscillatory rheometry (0.01 to 1.0 Hz at a constant strain of 1.0 Â 10 À3 rad) and controlled stress flow rheometry using a Carri-Med CSL 2-100 rheometer. The mechanical properties were examined using texture profile analysis (15-mm depth of insertion, 9 mm s À1 rate of insertion, 15 s delay period between the end of the first and beginning of the second compressions). The interaction of the various formulations with mucin was examined using oscillatory rheometry. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of each polymeric component increased the zero-rate viscosity (calculated using the Cross model), hardness, compressibility, the storage (G 0) and loss (G 00) moduli, and decreased the loss tangent. These observations may be due to greater polymeric entanglement between adjacent polymer chains. Specifically, rheological synergy was observed between PMVE/MA and PVP, evidence of complexation between these two polymers. From the relationship between the viscoelastic properties and oscillatory frequency, and the mathematical comparison of steady and oscillatory shear response of formulations using the Cox-Merz equation, it may be concluded that formulations containing 15% w/w PMVE/MA and either 6 or 9% w/w PVP exhibited rheological properties that were consistent with gel behavior. All other formulations exhibited rheological properties that resembled polymeric liquids. Increasing the concentrations of PMVE/MA and PVP significantly increased the interaction with mucin, the rheological synergy between the polymeric formulations and mucin and, in addition, the adhesiveness of the formulations. This is evidence of the muco/bioadhesive properties of the formulations. Conversely, the time of contact between each formulation and mucin did not affect their resultant interaction. In conclusion, this study has uniquely described the rheological and mucoadhesive properties of aqueous systems composed of PMVE/MA and PVP. In particular, the concentrations required for gel formation have been defined and the interaction between these two polymeric components illustrated using rheological methods. Furthermore, the simultaneous analysis of rheological, mechanical, and mucoadhesive

Safe and effective manipulation of soft tissue during laparoscopic procedures can be achieved by the use of mucoadhesive polymer films. A series of novel adhesive polymer films were formulated in house based on either Carbopol or Chitosan modified systems. The mechanical properties of the polymers and their adherence to bowel were evaluated using ex-vivo pig bowel immersed in 37°C water bath and connected to an Instron tensiometer. Young's modulus was 300 kPa for the Carbopol-polymer and 5 kPa for the Chitosan-polymer. The Chitosan-polymer exhibited much larger shear adhesion than its tensile adhesion: 3.4 N vs. 1.2. Both tensile and shear adhesions contributed to the large retraction force (2.6 N) obtained during l polymer-bowel retraction testing. Work of adhesion at the polymer/serosa interface, defined as the area under the force curve, was 64 mJ, which is appreciably larger than that reported with existing polymers. In conclusion, adhesive polymers can stick to the serosal ...

Buccal mucosa can be used for local drug delivery as in for periodontitis, dental caries or for oral mucosal drug delivery as for analgesia or transmucosal systemic effect or delivery of biotechnological products like proteins and peptides. This review article is an overview of buccal drug delivery systems encompassing a review of oral mucosa, formulation considerations, theories and mechanism of mucoadhesion, different mucoadhesive formulations for buccal drug delivery and active ingredients delivered via the buccal route. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity.

Computer-aided drug discovery is a growing frontier in science. It covers different sub areas like chemoinformatics and chemogenomics. Chemogenomics is one of the emerging inter-disciplinary approaches in drug discovery, which combines conventional ligand based approach with biological information of drug targets. The main goal of this review is to check effective application of chemogenomics in understanding interactions between all possible ligands and their potential drug targets at molecular level. Recent studies revealed that increased expression of sFRP1an inhibitor of Wnt signalling pathway, seems to be responsible for Elevated Intracellular Pressure (IOP) in glaucoma patients. Glaucoma is a worldwide spread disease. Here, secreted frizzled-related protein-1 (sFRP1) has been used as a target protein. An important role of sFRP1, an antagonist of Wnt signalling pathway, has been found in regulating IOP. Wnt3a ligand protein and a natural compound from marine source Mycaperoxide H -have been used as ligands. In-silico docking of these ligands with sFRP family implies answers to many intricate queries in drug development field. Using above mentioned ligand-protein model in this study, application of chemogenomics has tried to explore the interaction of active site of proteins with the novel ligands. Henceforth, the present review will focus on predictive in-silico chemogenomic approaches with computer aided drug design could be used in drug design domain in identifying new targets in various diseases, in time and cost effective manner. Glaucoma [25] is one of the major causes of visual impairment and blindness [26] throughout the world. A

Objective: Buccal mucosa is a potential site for the delivery of drugs to the systemic circulation, a drug administered through the buccal mucosa enters directly to the systemic circulation, thereby which bypass the drug from the first-pass hepatic metabolism and adverse gastrointestinal effect. Duloxetine hydrochloride (DLX HCL) is a selective serotonin and noradrenaline reuptake inhibitor (SSNRI). It is used in the treatment of depression, diabetic peripheral neuropathic pain and in moderate to severe stress urinary incontinence in women.However, it undergoes extensive first-pass metabolism, and it is susceptible to undergo degradation in the acidic environment of the stomach, which results in the poor bioavailability. The objective of the present investigation is to design and evaluate the mucoadhesive buccal patches of DLX HCL with a goal of to increase the bioavailability and improve the patient compliance.Methods: Mucoadhesive buccal patches were prepared by solvent casting tec...

Safe and effective manipulation of soft tissue during laparoscopic procedures can be achieved by the use of mucoadhesive polymer films. A series of novel adhesive polymer films were formulated in house based on either Carbopol or Chitosan modified systems. The mechanical properties of the polymers and their adherence to bowel were evaluated using ex-vivo pig bowel immersed in 37°C water bath and connected to an Instron tensiometer. Young's modulus was 300 kPa for the Carbopol-polymer and 5 kPa for the Chitosan-polymer. The Chitosan-polymer exhibited much larger shear adhesion than its tensile adhesion: 3.4 N vs. 1.2. Both tensile and shear adhesions contributed to the large retraction force (2.6 N) obtained during l polymer-bowel retraction testing. Work of adhesion at the polymer/serosa interface, defined as the area under the force curve, was 64 mJ, which is appreciably larger than that reported with existing polymers. In conclusion, adhesive polymers can stick to the serosal ...

Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different dosage forms were developed based on this principle. This study aims to prepare bucco-adhesive tablets of anti-migraine drug zolmitriptan as a suitable candidate for improving its oral bioavailability and therapeutic efficacy and to evaluate them for many pre/post-formulation parameters in-vitro/ex-vivo. The bucco-adhesive tablets containing 2.5 mg zolmitriptan were prepared using carbopol 934LR as a primary polymer alone or in combination with chitosan or xanthan gum as secondary polymers by direct compression. Drug-excipients compatibility and micromeritics study were carried out. Tablets were evaluated for physico-chemical parameters, surface pH, ex-vivo residence time, in-vitro swelling study, ex-vivo mucoadhesive strength, in-vitro drug release study, ex-vivo permeation study and physical stability in human saliva. No interactions were found between drug and excipients. Tablets had ...

The aim of this work was to investigate the role of mucoadhesion in the insulin uptake of nanocomplexes (NC) based of trimethyl chitosan (TMC) and poly(ethylene glycol) (PEG)-graft-TMC copolymers. Self-assembled insulin NC were prepared by polyelectrolyte complexation. The effects of PEGylation and positive charge density on mucoadhesion were assessed using a mucin assay and mucus-secreting HT29-MTX-E12 (E12) monolayers. The behaviors of corresponding insulin NC after adhesion to E12 were also established. All PEGylated TMC copolymers showed significantly higher levels of adhesion to mucus than unmodified TMC. The copolymer composed of 298 PEG chains per TMC macromolecules exhibited the highest level of mucoadhesion, being 3.4 times higher than TMC. The higher mucoadhesive properties of PEGylated TMC copolymers resulted from the synergistic effects of interpenetration of PEG chains into the mucus and electrostatic interaction between positive charged TMC and anionic glycoproteins present in the mucus layer. Compared to TMC, insulin NC based on PEGylated TMC copolymers demonstrated no evidence of insulin uptake improvement due to complete release of insulin from NC after adhering to mucus. CLSM revealed the localization of TMC and its corresponding insulin NC at cell surface membranes of E12.

Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different dosage forms were developed based on this principle. This study aims to prepare bucco-adhesive tablets of anti-migraine drug zolmitriptan as a suitable candidate for improving its oral bioavailability and therapeutic efficacy and to evaluate them for many pre/post-formulation parameters in-vitro/exvivo. The bucco-adhesive tablets containing 2.5 mg zolmitriptan were prepared using carbopol 934LR as a primary polymer alone or in combination with chitosan or xanthan gum as secondary polymers by direct compression. Drug-excipients compatibility and micromeritics study were carried out. Tablets were evaluated for physico-chemical parameters, surface pH, ex-vivo residence time, in-vitro swelling study, ex-vivo mucoadhesive strength, in-vitro drug release study, ex-vivo permeation study and physical stability in human saliva. No interactions were found between drug and excipients. Tablets had g...

Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field. This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs. The synthesis...

ANDRADE, Jenny Patricia et al. Preformulation study for the development of a polymer-based gel with mucoadhesive propierties for its use in allelopathy assays in marine invertebrates. Acta biol. Colomb.[online]. 2010, vol. 15, n. 1, pp. 87-104. ISSN 0120-548X.