Mucoadhesive polymeric systems for vaginal drug delivery: a systemic review / Sistemas poliméricos mucoadhesivos para la liberación vaginal de fármacos: revisión sistemática

ABSTRACT Intravaginal drug administration has many advantages in comparison to other delivery routes: its local and systemic effect, lower dosages, and easiness of administration. Furthermore, makes it a reliable and comfortable way of therapy. This route can be used to prevent and treat a wide range of conditions including, sexually transmitted infections (STIs), hormonal treatment, birth control, and cancer treatment. The dosage forms may vary from ovules, tablets, rings, gels, creams, films and many more; lately adding the mucoadhesiveness to the characteristics to reduce the waste of active molecules. This review focuses on the way mucoadhesive polymeric systems have been applied in vaginal delivery. This review presents a bibliographical compilation of results from various investigations published in scientific databases: Science Direct, SciELO, and PubMed Central. Results compiled demonstrate that the intravaginal drug administration can be an alternative form of medication for women with more stable and prolonged results than traditional routes requiring lower doses and avoiding the first-pass effect.

RESUMEN La administración de fármacos por vía intravaginal cuenta con múltiples ventajas a comparación de otras rutas, puede lograr un efecto tanto local como sistémico, las dosis requeridas son menores, facilidad de administración entre otras, hacen que esta forma de administración sea confiable y cómoda. Esta vía de administración puede ser empleada para prevenir y tratar diferentes trastornos, como enfermedades de transmisión sexual, desordenes hormonales, anticonceptivos y tratamiento contra el cáncer. La presentación de las dosis puede variar, desde óvulos, tabletas, anillos, geles, cremas, películas entre otros, agregando a esta, en los últimos tiempos, la característica de mucoadhesividad para reducir el desecho de moléculas activas. Este trabajo se enfoca en las aplicaciones que han tenido los sistemas poliméricos mucoadhesivos en la vía intravaginal. La bibliografía recolectada se obtuvo de bases de datos como Science direct, SciELO, y PubMed Central. Los resultados obtenidos demuestran que la administración de fármacos por vía intravaginal puede ser una forma alternativa para medicación en mujeres, con resultados más estables y prolongados que otras rutas, requiriendo menores dosis y evitando el efecto de primer paso.

Formulation and evaluation of Buccal mucoadhesive tablets of diclofenac sodium using 23 factorial designs

Buccal tablets

Diclofenac sodium

Drug release

Mucoadhesion

Mucoadhesive tablets

Release kinetics

Preparation of oxytocin liposomes modified by cell penetrating peptides and evaluation on brain targeting efficiency via intranasal delivery / 药学学报

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Design and evaluation of dental pastes Containing anti-inflammatory drugs

Abstract Periodontitis is an oral disease associated with inflammation and pain with swollen and bleeding gums. In the present study, dental pastes containing NSAIDs, namely, diclofenac sodium and nimesulide (1 % w/w) were prepared to treat periodontitis. Dental pastes of diclofenac sodium and nimesulide (1 % w/w) were prepared with/without mucoadhesive hydrocolloid polymers such as sodium carboxy methyl cellulose (NaCMC), hydroxyl ethyl cellulose (HEC) and methyl cellulose (MC) by conventional trituration method. The pH, drug content, viscosity, tube spreadability and tube extrudability of these prepared dental pastes were measured. These dental pastes of diclofenac sodium and nimesulide (1 % w/w) were characterized by FTIR analyses for drug-excipient compatibility. The in vitro drug releases from these dental pastes in 6.4 pH phosphate buffer solution displayed sustained release over longer period and the drug release rate was found to be decreased when the concentration of mucoadhesive polymer was increased. These dental pastes displayed good adhesion to the oral mucosa revealing more retention time in mouth when tested for ex vivo mucoadhesion using bovine cheek pouch. The stability study results reveal that the DC3 and NC3 dental paste formulations were found stable enough over a longer period in different storage conditions. The present study revealed that the prepared mucoadhesive dental pastes of diclofenac sodium and nimesulide (1 % w/w) had good adhesion with the oral mucosa to maintain consistent release of drugs over prolonged time.

Development, in-vitro and ex-vivo evaluation of muco-adhesive buccal tablets of hydralazine hydrochloride

Abstract Hydralazine hydrochloride is an anti-hypertensive drug. The drug has poor oral bioavailability (BA) of about 30- 50% due to extensive first-pass metabolism. Hence, the buccal delivery was used to enhance the BA of hydralazine hydrochloride. Buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M, sodium alginate and sodium carboxy methyl cellulose (NaCMC) as muco-adhesive polymers. Prepared formulations were evaluated for physico-chemical characterization, ex-vivo residence time and in-vitro release studies. The some of the parameters viz hardness, thickness, weight variation are showing the values within the pharmacopeial limits. However, the swelling and bio-adhesive strength were increased with increasing polymer concentrations. From the in-vitro release studies, F9 buccal tablets prepared with NaCMC exhibited better release (96.56%, 6 h) profile than all other formulations and considerd as optimized. The release mechanism from kinetic methods suggests that, the drug release follows zero-order kinetics with diffusion mechanism. Thus, the buccal tablets of hydralazine hydrochloride showed enhanced BA and were further confirmed by in-vivo studies.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Sodium alginate-guar gum and carbopol based methotrexate loaded mucoadhesive microparticles for colon delivery: An in vitro evaluation

Methotrexate (MTX) is famous for its therapeutic potential against different cancers including colorectal cancer. Goal of the present investigation was to formulate MTX loaded mucoadhesive microparticles for colon targeting. The optimized formulation (MTX-MS2) was composed of mucoadhesive polymers (sodium alginate, guar gum and carbopol 940) in an appropriate ratio. MTXMS2 was developed by ionic-gelation method. The suitable particle size and zeta potential were found to be 21.10 ± 0.18 µm and 3.01 ± 0.16 mV for MTX-MS2 respectively. The % yield (98.60 ± 2.12), % entrapment efficiency (97.98 ± 1.22) and % drug loading (1.04 ± 0.03) were estimated for MTXMS2. The swelling index (0.99 ± 0.04 θ) and mucoadhesion (97.29 ± 4.61%) were significantly (***P ˂ 0.01) achieved with MTX-MS2 as compared to other formulations. The optimum drug release (96.07 ± 4.52%) was significantly achieved with MTX-MS2 at simulated gastric fluid (pH 7.4) for 36 h in a sustained manner. This profile may be attributed towards excellent mucoadhesivness of the polymers used in the formulation. Therefore, the current investigation suggests that mucoadhesive carrier system could be promising approach for colon delivery. Thus, the proposed work would be helpful for the treatment of colorectal canc

Investigation of Corchorus olitorius mucilage as a potential mucoadhesive agent in developing in situ mucoadhesive nasal gel

The present study aimed to formulate a mucoadhesive in situ gel with mucilage extracted from Corchorus olitoriusfor the intranasal route. Propranolol HCl used as a model drug. For the comparative study, the mucoadhesive in situgels were prepared using two different concentration 0.4% and 0.5% of C. olitorius mucilage, Carbopol P-934 andhydroxypropyl methylcellulose. The prepared in situ gel was subjected to characterization test, such as pH, appearance,gelation temperature, spreadability, viscosity, mucoadhesive strength, and in vitro study. From the comparative study,0.5% mucilage containing in situ gel formulation can be considered as optimum formulation.

Formulation And Evaluation Of Racecadotril Mucoadhesive Microspheres

Objective: To develop and evaluate the mucoadhesive microsphere using combinations of natural polymers chitosan and xanthan gum for sustained release. Methods: In the present work mucoadhesive microspheres were prepared by using natural polymers like chitosan and xanthan gum by using the emulsion chemical cross-linking method. Chemical cross-linking was done by using glutaraldehyde. The 22 factorial design was employed to show the effect of cross-linking agent and processing factor-like stirring and speed. Prepared microspheres were evaluated for their particle size, surface morphology, drug entrapment efficiency, in vitro drug release, swelling index, and mucoadhesive strength. Results: The size of microspheres of factorial batches were in the range of 26-46 µm. The swelling index was showed in the range of 1.51-1.66 percentage. The equation of multiple regression revealed that there was significant interaction among factors. The glutaraldehyde concentration had a positive effect on % entrapment efficiency, % cumulative drug release and % mucoadhesion. Stirring speed showed a negative impact on % entrapment efficiency, % cumulative drug release and % mucoadhesion. The interactive effect of glutaraldehyde concentration and the stirring speed was found to be positive for % entrapment efficiency and % cumulative drug release. In vitro drug release study of optimized formulation F2 show 96 % of drug release with 6 h indicating sustained release behavior with diffusion mechanism. The SEM image of the optimized batch was spherical with a porous surface. Conclusion: The results obtained in this research work indicated that a promising potential of chitosan and xanthan gum combination for the preparation of the mucoadhesive microsphere of Racecadotril.

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

Poly (Methacrylic Acid)-Grafted-Okra Gum: Synthesis, Characterization And Evaluation As Mucoadhesive

Recently, worldwide extensive attention is being paid in exploration and exploitation of pharmaceutical excipients from natural resource. Various natural polysaccharides have been significantly reported as prospective drug delivery carriers. These natural gums are preferred over synthetic polymers because of their biocompatibility, low cost, free availability and biodegradability. But due to variable chemical composition, microbial load, microbial growth and change in viscosity upon aging, acceptability is low compared to commercial synthetic products. Tailoring or modification may be an approach to make them smart as drug carriers specially in order to modulate the site of drug release and it’s kinetic. The chemical modification of okra gum (OG) was the main objective of the present study in order to make it potential mucoadhesive for the application in mucoadhesive drug delivery. In this study, methacrylic acid was grafted onto okra gum. At first, okra gum has been isolated from the fruits of Hibiscus esculentus. Poly (methacrylic acid)-grafted-okra gum (PMAc-g-OG) was synthesised employing a microwave-promoted and redox-initiated method. Potassium persulphate was used as free- radical-initiator. Methacrylic acid was mixed to 1% solution of OG and then 30 ml of potassium persulphate aqueous solution was added to the previous mixture along with continuous stirring. The mixture was exposed to microwave in a domestic micro-oven. The mixture was kept overnight and the copolymer was collected and purified using acetone and aqueous methanol (30% v/v) subsequently. The copolymer was charateized by elemental analysis, FTIR, DSC-TGA, and 13C NMR study. Ex-vivo mucoadhesion test was performed using goat stomach. A highest % grafting of 448.32% was found in the synthetic procedure employed in the study. The characterization studies also substantiate the successful grafting. Ex-vivo mucoadhesion study also showed excellent mucoadhesive capacity over a period of 16 hours. The study exhibited that the method employed was very simple, less time consuming, one-pot and without N2 atmosphere. The copolymer also exhibited excellent mucoadhesivity which might be applied in different mucoadhesive drug delivery systems such as prolonged release gastroretentives, buccal gels, etc.

Design And Characterization Of Mucoadhesive Microspheres Of Etodolac

Mucoadhesive microspheres are drug delivery system intended for targeting a drug to particular region. Etodolac is a Non-steroidal anti-inflammatory drug. The objective of the present work was to develop sustain release of Etodolac loaded mucoadhesive microspheres due to relatively short residence time in the GIT tract before elimination. Mucoadhesive microspheres were prepared by non-aqueous solvent evaporation method using Carbopol 974P, HPMC K100M and HPMC K4M as the polymers. Central composite design was selected for the development of the formulation. Evaluation parameters like particle size, entrapment efficiency, shape and surface morphology, degree of swelling, drug content, in-vitro drug release study and in-vitro drug release study was done. Based on the results obtained from the preliminary formulations three optimized formulations were designed. The percentage mucoadhesion and swelling index of the optimized formulation was found in the range of 66-70 % and 82.50-83.84 % respectively. Optimized formulation releases 90.94% to 92.11% of drug at the end of 10 hours and follows zero order release kinetics.

Amphotericin-B and vancomycin-loaded chitosan nanofiber for antifungal and antibacterial application

In the present study, a mucoadhesive non-woven fiber mat (d= 116 nm) was fabricated by the electrospinning method using chitosan (80% Wt), polyethylene oxide (10% Wt), cysteine (4% Wt) and drugs (6% Wt), respectively. In addition, a comparative study was conducted to define effect of drugs and mucoadhesive agent on the nanofiber formation. FTIR, SEM, DSC and DMA were used to investigate the chemical and physical properties of the nanofibers. In vitro release of the drugs was assessed over a 48-hour period by the total immersion method. Release data were fitted to kinetic models, including the zero-order, first-order, Higuchi matrix, and Hixson-Crowell. Zone inhibition investigations were used to describe the inhibition content of vancomycin and amphotericin B loaded in the mats. The SEM images displayed a slight decrease in the fiber diameter with adding drugs and mucoadhesive agents. FTIR spectra confirmed that any undesirable reaction between VAN-AMB and CS-PEO was not observed. DSC test recognized the uniform distribution of drugs in the polymeric bead of the fiber without any crystal form. The elasticity modulus of the nanofiber was in an acceptable range for oral mucosa (approximately 5 Mpa). The results indicated that biodegradable mucoadhesive nanofibrous membranes released high concentrations of VAN in the first 24 hours, but the AMB release was affected in more controlled phenomena

Preparation and performance of pH-responsive nanocarriers for mucus penetration / 国际生物医学工程杂志

Objective To prepare pH-responsive osmotic nanocarriers (pMPPs),observe their distribution in the genital tract mucosa in mice,and evaluate their radiosensitizing effects in tumor cells.Methods Amphiphilic polymers containing pH-sensitive hydrazone bonds were synthesized and pMPPs were prepared by ultrasonic emulsification.At the same time,the hydrophobic polymer polylactic acid-glycolic acid copolymer (PLGA) and the amphiphilic polymer PLGA-polyethylene glycol without hydrazine bond were selected,and the mucoadhesive nanoparticles(MPs) and mucus-penetrating particles (MPPs) were prepared in the same way.Fluorescence microscopy was used to observe the distribution of three kinds of nanocarriers labeled with fluorescent dye Cy5.5 in the genital tract mucosa.The toxicity of nanocarriers to human cervical cancer cell line HeLa was tested by thiazolyl blue assay.The amphiphilic polymer containing pH-sensitive hydrazone bond was combined with oil-soluble gold nanoparticles to form a multi-encapsulated nanocarrier,and its radiotherapy sensitization effect in HeLa cells was evaluated by thiazole blue assay.Results The pMPPs were successfully prepared with relatively uniform particle size and good dispersion.Fluorescence microscopy showed that pMPPs not only had good mucus permeability,but also could improve the endocytosis efficiency of the nanocarriers in reproductive tract mucosa.The results of thiazolyl blue test showed that when the concentration of the carrier reached to 0.80 mg/ml,the survival rate of HeLa cells in the pMPPs group was higher than 90％ which was higher than that in the MPs and the MPPs groups,indicating that pMPPs had good biosafety.The HeLa cell survival rate of the CMNa group (0.80 mg/ml) was higher than that of the multi-package nanocarrier group under different doses of X-ray irradiation (4 Gy:82.90％ vs.61.79％;8 Gy:64.75 ％ vs.42.36％).This result indicated that compared with the CMNa,a commonly used clinical radiotherapy sensitizer,the multi-encapsulated nanocarriers can more effectively enhance the sensitivity of tumor cells to radiation therapy,thereby improving the lethality of radiation therapy on tumor cells.Conclusion This study solved the conflict between mucus permeation and endocytosis design of nanocarriers in mucosal tissue application,and provided new insight for the treatment of mucosal tissue diseases.

Oral Immunization of FMDV Vaccine Using pH-Sensitive and Mucoadhesive Thiolated Cellulose Acetate Phthalate Microparticles

Several barriers such as gastric pH, enzymatic degradation and rapid transit should be overcome to orally deliver antigens for taking up by epithelial microfold cells in Peyer's patches of small intestine. To solve the above mentioned problems, we designed pH-sensitive and mucoadhesive polymeric microparticles (MPs) prepared by double emulsion technique using cellulose acetate phthalate (CAP) to enhance immune response of foot-and-mouth disease (FMD) virus (FMDV) subunit vaccine. Thiolation of CAP improved mucoadhesive property of CAP to prolong the MPs transit time through the gastrointestinal tract. Thiolated CAP (T-CAP) also slowed down antigen release in acidic pH of stomach but released more antigens in neutral pH of small intestine due to the pH-sensitivity of the T-CAP. Oral immunization of a chimerical multi-epitope recombinant protein as the FMD subunit vaccine via T-CAP MPs effectively delivered the vaccine to Peyer's patches eliciting mucosal IgA response. It will make a step forward into a promising oral subunit vaccine development in livestock industry.

A smart approach for delivery of aripiprazole via oro-soft palatal mucosal route for improved therapeutic efficacy

Effective management of schizophrenia, acute mania, mixed episodes associated with bipolar disorders, and depression can be managed with aripiprazole moiety. In the present research work an attempt was made to minimize the dose related side effects thus improving the quality life of the patients. A novel biopolymer was isolated from the fruits of Trachyspermum ammi. Ten optimized nanosized aripiprazole loaded formulations were prepared in 1-5% concentration of biopolymer (FA1-FA5) and sodium CMC (FM1-FM5) by solvent casting technique. The formulated flexy films were evaluated for thickness, folding endurance, weight uniformity, surface pH, mucoadhesivity, In-vitro drug release studies, In-vivo pharmacodynamic study and stability studies. The isolated biopolymer showed inbuilt fimability and mucoadhesivity and consists of carbonyl, hydroxyl and thiocarbonyl functional groups. All formulations showed folding endurance from 153 to 170, mucoadhesion time in the range of 24-48hrs., and in-vitro drug release was performed using dynamic Franz Diffusion cell and analyzed using BIT-SOFTWARE. The experimental animals showed improved activity score on actophotometer. The formulated nanosized aripiprazole loaded bio-flexy films showed pharmacotherapeutic response. Conclusion can be drawn that optimized formulation showed effective Pharmacodynamic activity and can be used as for improving therapeutic efficacy of aripiprazole through this platform.

Decades of research in drug targeting using gastroretentive drug delivery systems for antihypertensive therapy

ABSTRACT The limitations in absorption of drugs with narrow absorption window, or those unstable in the intestinal pH or those exhibiting low solubility at high pH are primary candidates for gastroretentive drug delivery systems (GRDDS). The delivery system has been widely explored for its commercial potential for a wide variety of therapeutic agents. GRDDS offer clinical therapeutics for acute and chronic management. Hypertension is a chronic disease that requires long term treatment and its management by patient compliant dosage forms would be clinically useful. Antihypertensives belonging to different classes have proved good candidates for the formulation of GRDDS. The review aims to discuss various GRDDS researched for antihypertensive drugs to increase the gastric residing time, bioavailability, henceforth to reduce the dose of the drug, dosing frequency and increase patient compliance. It also explores various marketed products and the patents filed/granted for GRRDS of antihypertensives. The GRDDS investigated include effervescent and non-effervescent floating drug delivery systems, swelling and expanding systems and bio/mucoadhesive systems. Many other systems that provided research platforms include high density systems, raft forming systems and osmotic delivery systems. In clinical context, wherein combination of antihypertensives is indicated, dual release delivery systems may also be explored.

Non-Starch Plant Polysaccharides: Physicochemical Modifications and Pharmaceutical Applications.

Polysaccharides of natural, synthetic or semi-synthetic origin have been used from time immemorial in the development of drug delivery systems designed to achieve tailored and site-specific drug release. Starch-based polysaccharides derived from plants have been extensively studied in this regard. Natural polymeric excipients are preferred over their synthetic counterparts owing to their low cost, availability, biocompatibility, biodegradability and non-toxicity. The present review attempts to provide a new direction and a comprehensive insight on the physical properties, rheological behavior, toxicity profile, pharmaceutical applications, swelling behavior and drug diffusion kinetics from dosage forms based on non-starch polysaccharides of plant origin such as, psyllium, pectin, arabinoxylan, xyloglucan, guar gum galactomannan and konjac glucomannan. It has been observed from the current review that non-starch polysaccharides are safe for human consumption and can be successfully employed to deliver drugs specifically to stomach and colon in a sustained fashion. They have thus widened the scope of natural polymeric excipients and demand better industrial utilization on a commercial scale to minimize cost of production and to satisfy therapeutic needs in safe and effective manner.

Obtenção de gel mucoadesivo de nistatina para o tratamento da candidíase oral. Desenvolvimento e caracterização de dispersões sólidas de nistatina / Mucoadhesive gel obtaining nystatin for the treatment of oral candidiasis. Development and characterization of solid dispersions of nystatin

A nistatina (NYS) é o fármaco de primeira escolha no tratamento da candidíase oral, que frequentemente acomete mais os indivíduos imunocomprometidos e pacientes com outras desordens (diabetes não tratada, neoplasias, imunodeficiências). No mercado brasileiro, a NYS é encontrada na forma de suspensão oral aquosa, onde o procedimento para sua administração consiste em bochechar o medicamento. Apesar de haver a indicação de que se mantenha o contato direto entre fármaco e a mucosa oral, na qual se encontra a Candida spp., o que aumentaria expressivamente o sucesso terapêutico, a suspensão não apresenta tal propriedade. Assim, a NYS que é fármaco com ação efetiva contra a candidíase oral, é considerada pertencente à Classe IV do Sistema de Classificação Biofarmacêutica, ou seja, apresenta baixa solubilidade e baixa permeabilidade. A baixa solubilidade pode comprometer sua disponibilidade na cavidade oral, e consequentemente, sua ação farmacológica. Diante desse quadro, o objetivo do presente trabalho foi o desenvolvimento de dispersões sólidas de NYS para o tratamento da candidíase oral, e sua posterior incorporação em gel mucoadesivo oral, favorecendo a formulação no local de ação. As dispersões sólidas são sistemas farmacêuticos, onde um fármaco pouco solúvel em água encontra-se dispersado em um carreador, no estado sólido. Os carreadores normalmente são hidrofílicos, o que permite que esses sistemas sejam empregados para aumentar a solubilidade aquosa do fármaco. Assim, foram desenvolvidas as dispersões sólidas de NYS, pelo método de eliminação do solvente, empregando como carreadores, lactose, HPMC, poloxamer 407 e poloxamer 188. Essas foram submetidas à caracterização por análise térmica, usando os ensaios de calorimetria exploratória diferencial (DSC) e termogravimetria/termogravimetria derivada (TG/DTG). Dentre essas dispersões sólidas, aquelas que se mostraram com comportamento térmico sugerindo a formação de um novo "sistema", foram analisadas por meio de ensaio de solubilidade. Dessa forma, a formulação NYS DS G2 (49) se destacou, pois apresentou maior solubilidade em água (4,484 mg/mL); em pH 5,5 (4,249 mg/mL) e em pH 7,0 (4,293 mg/mL), ou seja, houve um aumento de 1,426 vezes em água; 4,227 vezes em pH 5,5; e 2,743 vezes em pH 7,0. Essa formulação foi, por fim avaliada por difração de raio-X e espectroscopia de infravermelho com transformada de Fourier, técnicas que corroboraram com a análise térmica quanto à indicação de formação da dispersão sólida. Por sua vez, essa dispersão sólida foi incorporada em 4 bases de géis mucoadesivos de carbopol ® 934 PNF, alterando apenas a concentração do polímero (0,5; 1,0; 1,5; 2,0 %p/p). Foi observado que a liberação de NYS DS G2 (49) foi superior, quando comparada à liberação de NYS MP a partir do gel, e através do ensaio de mucoadesão, percebeu-se que os géis desenvolvidos apresentaram propriedades mucoadesivas compatíveis com relatos na literatura, independentemente da quantidade de carbopol ® empregada. As características reológicas foram distintas, e foi observado que as formulações Gel A e Gel B, que possuem menor quantidade de polímero, tiverem um indicativo de comportamento de fluido newtoniano, diferente dos demais, o que pode não ser desejado para esse tipo de forma farmacêutica tópica e semi-sólida. Ao final desse trabalho, pode-se concluir que foi possível desenvolver um sistema farmacêutico na forma de dispersão sólida com maior solubilidade que a NYS pura, e sua incorporação em uma forma farmacêutica mucoadesiva, e que a liberação da NYS na forma DS foi muito superior que o fármaco na forma "convencional", o que permite que a NYS esteja mais disponível na cavidade oral, e também junto à mucosa bucal, o que levaria a efeito farmacológico mais efetivo do antifúngico

Nystatin (NYS) is the drug of first choice in the treatment of oral candidiasis that most often affect immunocompromised individuals, and patients with other disorders. In the Brazilian market, NYS is found in the form of aqueous oral suspension, a medication used in the form of mouthwash. Although there is an indication to maintain direct contact between the drug and the oral mucosa, where Candida spp. is found, as well as where therapeutic success would significantly be increased, the suspension has no such property. Thus, the NYS is an effective drug against oral candidiasis, and belongs to Class IV of the Biopharmaceutical Classification System, it has low solubility and low permeability. The low solubility can compromise its availability in the oral cavity, and consequently, its pharmacological action. Given this situation, the objective of this work was the development of solid dispersions of NYS for the treatment of oral candidiasis, and its subsequent incorporation into oral mucoadhesive gel, in order to facilitate its action. Solid dispersions are pharmaceutical systems, in which a solid drug poorly soluble in water is dispersed in a carrier. These carriers are usually hydrophilic, and this allows the systems to be employed in order to increase the aqueous solubility of the drug. Thus, the solid NYS dispersions were developed by the solvent evaporation method, employing lactose, HPMC, poloxamer 407 and poloxamer 188 as carrier. These samples were subjected to characterization by thermal analysis, using differential scanning calorimetry (DSC) and thermogravimetry / derivative thermogravimetry (TG / DTG). Among these solid dispersions, those samples which showed a specific thermal behavior suggesting the formation of new "system" were analyzed by solubility test. Thus, the NYS DS G2 formulation (49) stood out, once it showed greater solubility in water (4.484 mg/mL); at pH 5.5 (4.249 mg/mL) and pH 7.0 (4.293 mg/mL), in other words, an increase of 1,426 times in water; 4,227 times at pH 5.5; and 2,743 times at pH 7.0. This formulation was finally evaluated by X-ray diffraction, infrared spectroscopy with Fourier transform, techniques that corroborate the thermal analysis, indicating the formation of the solid dispersion. On the other hand, this solid dispersion was incorporated into 4 Carbopol ® 934 PNF mucoadhesive gels, with a variation of the polymer concentration. It was observed that NYS is improved of delivery from the gels, employing mucoadhesion test, and was also observed that the gels have mucoadhesive properties consistent with reports in the literature. However, the rheological characteristics are different, and it was observed that the Gel A and Gel B formulations, which has a lower amount of polymer behaved as a Newtonian fluid, which may not be desired for this type of topical gel. As conclusion, it was possible to develop a pharmaceutical system in the form of solid dispersion with greater solubility than the pure NYS, and their incorporation in a mucoadhesive dosage form and the release of NYS as DS was far superior wherein the drug in the "conventional" manner, which allows the NYS is longer available in the oral cavity, and also adjacent to the buccal mucosa, leading to more effective pharmacological effect of the antifungal agent