Influence of additives on swelling and mucoadhesion properties of glyceryl monooleate liquid crystals

Abstract Liquid crystalline systems of glyceryl monooleate/water are used as drug delivery systems due to their complex structure that controls drug diffusion. Mucoadhesive properties of glyceryl monooleate suggest it can be used for buccal delivery. Using additives is a strategy to modify physical and chemical properties of liquid crystalline systems and optimize their performance as a drug delivery system. However, the presence of additives can significantly alter properties such as phase behavior, swelling and mucoadhesion. Our aim is to investigate the influence of additives on swelling and mucoadhesion of glyceryl monooleate-based liquid crystals, intending them to be used as buccal drug delivery systems. The systems were characterized regarding their mesophases, swelling rate, and mucoadhesion. All the systems studied were able to absorb water and presented mucoadhesion, which is interesting for the development of buccal drug delivery systems. Additives induced phase transitions and affected the swelling performance, while mucoadhesive properties were poorly affected. Propylene glycol increased water uptake, while oleic acid induced the phase transition to the hexagonal phase and reduced the swelling rate. The association of oleic acid (5%) and propylene glycol (10%) resulted in a cubic phase system with strong mucoadhesive properties that can be a potential drug carrier for buccal delivery.

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.

Designing the new generation of intelligent biocompatible carriers for protein and peptide delivery

Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties, therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal (GI) tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drug delivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.

Insulin-loaded polymeric mucoadhesive nanoparticles: development, characterization and cytotoxicity evaluation

Abstract Mucoadhesive nanoparticles are particularly interesting for delivery through nasal or pulmonary routes, as an approach to overcome the mucociliary clearance. Moreover, these nanoparticles are attractive for peptide and protein delivery, particularly for insulin to treat diabetes, as an alternative to conventional parenteral administration. Thus, chitosan, a cationic mucoadhesive polysaccharide found in shells of crustaceans, and the negatively-charged dextran sulfate are able to form nanoparticles through ionic condensation, representing a potential insulin carrier. Herein, chitosan/dextran sulfate nanoparticles at various ratios were prepared for insulin loading. Formulations were characterized for particle size, zeta potential, encapsulation efficiency, scanning electron microscopy, differential scanning calorimetry, and in vitro drug release. Moreover, the interaction with mucin and the cytotoxicity against a lung cell line were studied, which altogether have not been addressed before. Results evidenced that a proper selection of polyelectrolytes is necessary for smaller particle size formation and also the composition and zeta potential impact encapsulation efficiency, which is benefited by the positive charge of chitosan. Insulin remained stable after encapsulation as evidenced by calorimetric assays, and was released in a sustained manner in the first 10 h. Positively-charged nanoparticles based on chitosan/dextran-sulfate at the ratio of 6:4 successfully interacted with mucin, which is a prerequisite for delivery to mucus-containing tissues. Finally, insulin-loaded nanoparticles displayed no cytotoxicity effect against lung cells at tested concentrations, suggesting the potential for further in vivo studies.

Mucoadhesive buccal films of tramadol for effective pain management / Filmes bucais mucoadesivos de tramadol para o controle eficaz da dor

Abstract Background and objectives: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. Methods: Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). Results: All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12 hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action.

Resumo Justificativa e objetivos: O cloridrato de tramadol é um analgésico opioide de ação central que se liga a receptores opioides específicos. É usado no tratamento de dor crônica e recomendado como fármaco de primeira linha para o tratamento no pós-operatório ou em dor aguda induzida por lesão ortopédica. O presente estudo visa a preparar e avaliar o filme bucal mucoadesivo de cloridrato de tramadol como uma nova forma de analgesia prolongada para pacientes com lesões ortopédicas. Método: Filmes bucais de cloridrato de tramadol foram preparados pelo método de evaporação de solvente. Os filmes preparados foram avaliados para os vários parâmetros de avaliação, como espessura, pH da superfície, uniformidade do peso, uniformidade do conteúdo, resistência a dobras, índice de intumescimento, estudo de liberação da droga in vitro, teste in vitro para mucoadesão e estudos in vivo (teste de irritação da mucosa primária e atividade analgésica). Resultados: Todas as formulações apresentaram bons resultados para caracterizações físico-químicas. Em estudo de libertação de droga in vitro, os filmes exibiram liberação controlada por mais de 12 horas. A formulação de BFT2 (com quitosana e PVP K-90) não mostrou efeito irritante sobre a mucosa bucal e provocou uma atividade analgésica significativa in vivo com 57,14% de analgesia versus a do padrão (61,04%). Concluiu-se que os filmes mucoadesivos de cloridrato de tramadol podem ser usados eficazmente para aliviar a dor intensa de lesões ortopédicas com início rápido e ação prolongada.

Bio-adhesive drug delivery system and its application in traditional Chinese medicine / 中国中药杂志

Bio-adhesive drug delivery system (BDDS) is a novel drug delivery system, which can prolong the retention time of the preparation, improve the stability of the drug, and improve the mucosa absorption and the targeting of the drug. With the development of polymer materials over the past 30 years, BDDS made a great progress. This paper reviews the muco-adhesion theory, adhesive materials, and methods to evaluate muco-adhesive properties and applications in traditional Chinese medicine according to domestic and foreign literatures, in order to provide new ideas for further studies.

Desenvolvimento e caracterização de filmes e comprimidos bucais a base de pectina e goma gelana para liberação tópica de triancinolona / Development and characterization of films and buccal tablets based on pectin and gellan gum for the topical release of triamcinolone

O tratamento farmacológico de patologias bucais é conduzido, geralmente, por via de adminis-tração local. No entanto, devido ao pouco tempo de permanência do fármaco no local de ação, esse tratamento pode ser bastante comprometido. Assim, este trabalho teve por objetivo o de-senvolvimento de formas farmacêuticas que proporcionem a liberação local de triancinolona na cavidade oral. Foram produzidos filmes e comprimidos mucoadesivos a partir de polímeros naturais como gelana e pectina. Os filmes bucais foram preparados por meio de evaporação do solvente (solvent casting) utilizando diferentes quantidades de polímeros. As matérias-primas e os filmes foram caracterizados fisico quimicamente utilizando espectroscopia vibracional (in-fravermelho com transformada de Fourier e Raman) e difração de raios X. As propiedades físicas e mecânicas dos filmes também foram avaliadas. Além disso, realizou-se os ensaios de mucoadesividade e de dissolução do fármaco. Os comprimidos foram preparados por com-pressão direta usando como base os polímeros naturais. Diferentes parâmetros em relação as misturas e as formulações foram avaliados tais como as propriedades de fluxo dos pós consti-tuintes, peso médio, dureza, friabilidade e desintegração. Em relação aos filmes bucais, estes foram obtidos com sucesso através de um método simples, sem a utilização de agentes reticu-lantes, ácidos ou solventes orgânicos. Todos apresentaram bons resultados nas propriedades avaliadas, no entanto as formulações com quantidades intermediarias de polímeros foram as melhores. Dentre as formulações de comprimidos preparadas, apenas 4 apresentaram boas ca-racterísticas, no entanto, os resultados dos ensaios de dissolução mostraram que estas formula-ções têm capacidade de agir como sistema de liberação controlada de fármacos.

Pharmacological treatment of oral pathologies is usually conducted by local administration. However, due to the short time the drug stays in the site of action, this treatment can be quite compromised. Thus, the objective of this work was to develop pharmaceutical forms that pro-vide the local release of triamcinolone in the oral cavity. Mucoadhesive films and tablets were made from natural polymers such as gellan and pectin. The buccal films were prepared by sol-vent casting using different amounts of polymers. The raw materials and films were characte-rized physically chemically using vibrational spectroscopy (FTIR and Raman) and X-ray diffraction. The physical and mechanical properties of the films were also evaluated. In addi-tion, the mucoadhesive and drug dissolution tests were performed. The tablets were prepared by direct pressing with the natural polymers. Different parameters in relation to mixtures and formulations were evaluated such as the flow properties of the constituent powders, average weight, hardness, friability and disintegration. In relation to oral films, these were successfully obtained by a simple method, without the use of crosslinking agents, acids or organic solvents. All presented good results in the evaluated properties, however the formulations with interme-diate amounts of polymers were the best. Among the tablet formulations prepared, only 4 sho-wed good characteristics, however, the dissolution test results showed that these formulations have the ability to act as a controlled drug delivery system.

Desenvolvimento e caracterização de filmes e comprimidos bucais a base de pectina e goma gelana para liberação tópica de triancinolona / Development and characterization of films and buccal tablets based on pectin and gellan gum for the topical release of triamcinolone

O tratamento farmacológico de patologias bucais é conduzido, geralmente, por via de administração local. No entanto, devido ao pouco tempo de permanência do fármaco no local de ação, esse tratamento pode ser bastante comprometido. Assim, este trabalho teve por objetivo o desenvolvimento de formas farmacêuticas que proporcionem a liberação local de triancinolona na cavidade oral. Foram produzidos filmes e comprimidos mucoadesivos a partir de polímeros naturais como gelana e pectina. Os filmes bucais foram preparados por meio de evaporação do solvente (solvent casting) utilizando diferentes quantidades de polímeros. As matérias-primas e os filmes foram caracterizados fisico quimicamente utilizando espectroscopia vibracional (in-infravermelho com transformada de Fourier e Raman) e difração de raios X. As propriedades físicas e mecânicas dos filmes também foram avaliadas. Além disso, realizou-se os ensaios de mucoadesividade e de dissolução do fármaco. Os comprimidos foram preparados por com-pressão direta usando como base os polímeros naturais. Diferentes parâmetros em relação as misturas e as formulações foram avaliados tais como as propriedades de fluxo dos pós constituintes, peso médio, dureza, friabilidade e desintegração. Em relação aos filmes bucais, estes foram obtidos com sucesso através de um método simples, sem a utilização de agentes reticulantes, ácidos ou solventes orgânicos. Todos apresentaram bons resultados nas propriedades avaliadas, no entanto as formulações com quantidades intermediarias de polímeros foram as melhores. Dentre as formulações de comprimidos preparadas, apenas 4 apresentaram boas características, no entanto, os resultados dos ensaios de dissolução mostraram que estas formulações têm capacidade de agir como sistema de liberação controlada de fármacos

Pharmacological treatment of oral pathologies is usually conducted by local administration. However, due to the short time the drug stays in the site of action, this treatment can be quite compromised. Thus, the objective of this work was to develop pharmaceutical forms that pro-vide the local release of triamcinolone in the oral cavity. Mucoadhesive films and tablets were made from natural polymers such as gellan and pectin. The buccal films were prepared by sol-vent casting using different amounts of polymers. The raw materials and films were characte-rized physically chemically using vibrational spectroscopy (FTIR and Raman) and X-ray diffraction. The physical and mechanical properties of the films were also evaluated. In addi-tion, the mucoadhesive and drug dissolution tests were performed. The tablets were prepared by direct pressing with the natural polymers. Different parameters in relation to mixtures and formulations were evaluated such as the flow properties of the constituent powders, average weight, hardness, friability and disintegration. In relation to oral films, these were successfully obtained by a simple method, without the use of crosslinking agents, acids or organic solvents. All presented good results in the evaluated properties, however the formulations with interme-diate amounts of polymers were the best. Among the tablet formulations prepared, only 4 sho-wed good characteristics, however, the dissolution test results showed that these formulations have the ability to act as a controlled drug delivery system

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

ABSTRACT Zidovudine (AZT) mucoadhesive solid dispersions (SD) were prepared using a sodium starch glycolate (SSG) and hypromellose phthalate (HPMCP) mixtures as carrier to enhance the intestinal permeability and bioavailability of zidovudine. SDs were prepared using the co-precipitation method followed by solvent evaporation and characterized according to their physicochemical properties such as particle size, crystallinity, thermal behavior, and liquid uptake ability. In vitro drug dissolution, mucoadhesiveness and AZT intestinal permeability were also determined. Thermal behavior and X-ray diffraction patterns demonstrated the amorphous state of AZT in SD systems. The HPMCP polymer restricted the liquid uptake ability in the acid medium; however, this property significantly increased with higher pH values. SDs allowed drug dissolution to occur in a controlled manner. HPMCP decreased the dissolution rates in the acid medium. The mucoadhesiveness of SDs was demonstrated and the permeability of AZT carried in solid dispersions was significantly improved. The effect of the SD carrier polymers on blocking efflux pump can be an important approach to improve the bioavailability of AZT.

Diseño de un sistema bioadhesivo de clorhexidina empleando pullulan como matriz para uso en mucosa oral / Design of a bioadhesive system with chlorhexidine using pullulan as matrix for use in oral mucous

Se desarrollaron sistemas poliméricos bioadhesivos del tipo película polimérica y comprimido empleando el biopolímero pullulan, para el transporte de digluconato de clorhexidina, el cual es un principio activo utilizado como alternativa terapéutica en el tratamiento de la gingivitis y de la enfermedad periodontal. Inicialmente, se evaluó la capacidad del polímero para formar películas y tabletas, luego, fueron propuestas formulaciones de cada uno de los sistemas. A las películas y comprimidos obtenidos se les determinaron propiedades mecánicas y de transporte, actividad antiséptica, caracterización de las microestructuras obtenidas, además, se comprobó la liberación del fármaco desde los sistemas estudiados. Con las formulaciones seleccionadas se determinó su capacidad mucoadhesiva in vitro, empleando como sustrato mucosa oral porcina.

As a therapeutic alternative in the transport of active substances in treatment of gingivitis and periodontal disease, bioadhesive polymeric systems type polymeric film and tablet were developed using the biopolymer pullulan. First, the ability of pullulan polymer to form films and tablets was evaluated and formulations were proposed for each system. Mechanical and transport properties, as well as antiseptic activity and microstructures characteristics were determined for these polymeric systems. Drug release behavior in the studied systems was also verified. The in vitro mucoadhesive capacity was determined with the formulations selected, using porcine oral mucous membrane like substrate.

Preparation of gastrodin starch microsphere and its nasal mucoadhesion and in vitro release characteristics / 中草药

Objective: To determine the prescription technology of gastrodin starch microsphere and investigate its nasal mucoadhesion and in vitro release characteristics. Methods: Gastrodin starch microspheres were prepared by compound emulsion crosslinking method. According to the particle diameter, drug loading efficiency (DLE), and entrapment efficiency (EE), the best prescription technology was selected by using single-factor investigation and uniform design. Using toad palate mucosa as model and average residence time as indicator, mucoadhesion of gastrodin starch microsphere was evaluated. Using gastrodin API as a control, paddle method was applied to in vitro release test of gastrodin starch microspheres. The content of gastrodin was determined to calculate the cumulative release percentage. In addition, the curve of drug release in vitro was fitted with different release model to analyze the in vitro release characteristics of gastrodin starch microsphere in nasal cavity, synthetically. Results: The optimum prescription and preparation technology of gastrodin starch microsphere were as follows: gastrodin 2.0 g, starch 4.5 g, liquid paraffin 100.0 mL, Span80 3.5 g, ECH 5.1 mL, preparation temperature 40℃, and rotational speed 1000 r/min. The particle diameter of gastrodin starch microsphere was (47.69±1.92) μm, the DLE and EE of microsphere were (9.78±0.70)% and (35.72±3.28)%, respectively. It was about (176.92±23.25) s that in adhesive powder resided in nasal cavity, which translated into human nasal residence time was just 20-30 min, while the average residence time of gastrodin starch microspheres was extended to (944.33±68.29) s, translated into human nasal residence time was about 3 h. The cumulated release percent of gastrodin starch microspheres was more than 90% in 3 h. Compared with other in vitro release models, Weibull model was the fittest model to gastrodin starch microspheres, the t50 of gastrodin starch microspheres was 40.08 min, and t90 was 245.73 min. Conclusion: Gastrodin starch microspheres prepared with optimum prescription technology have uniform particle diameter, high DLE and EE. Microspheres have good mucoadhesion and sustained release, ensure that gastrodin release gently and completely during the nasal retention period.

Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI) was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI) and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM) study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS). The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

O objetivo deste trabalho foi planejar microemulsão/mucoaesiva em gel a fim de melhorar a captação cerebral de ibuprofeno por via intranasal. A microemulsão para mucoadesão com ibuprofeno (MMEI) foi desenvolvida pela incorporação de policarbofil como polímero mucoadesivo em microemulsão otimizada (MEI) com base em Capmul (MCM) e foi submetida à caracterização, estabilidade, mucoadesão e naso-ciliotoxicidade. A captação cerebral de ibuprofeno pela via nasal foi estudada por meio de estudo de biodistribuição em ratos albinos suíços. MEI se mostrou transparente, estável e não ciliotóxica, com 66,29 ± 4,15 nm, -20,9 ± 3,98 mV e 98,66 ± 1,01%, respectivamente, de tamanho médio dos glóbulos, potencial zeta e conteúdo do fármaco. O estudo revelou o estreita distribuição do tamanho dos glóbulos de MEI. Após administração intranasal única de MMEI e MEI, em dose de 2,86 mg/kg, a captação de ibuprofeno no bulbo olfativo foi em torno de 3,0 e 1,7 vezes maior, comparativamente, à injeção endovenosa de ibuprofeno (IDS). As taxas de ASC em tecido cerebral em relação ao plasma, obtidas após administração da MMEI nasal, foram, significativamente, mais elevadas do que aquelas observadas após a administração intravenosa de IDS. Os resultados do presente estudo mostraram que a microemulsão/mucoadesiva em gel poderia ser uma abordagem promissora para o direcionamento cerebral de ibuprofeno por via intranasal.

Effect of surface roughness on mucosal adhesion properties of oral film / 中国药学杂志

OBJECTIVE: To study the relationship between surface roughness and mucoadhesion properties of oral film. METHODS: Polydimethylsiloxane reverse templates were fabricated from sandpapers with different roughness, and were used as the mold to prepare films by solvent casting method. The obtained films were then evaluated for mucoadhesive force, shear force, mucoadhesion time, and their morphology was investigated by scanning electron microscopy (SEM). RESULTS: Films of c-hitosan showed more favorable mucoadhesive performance than those of Bletilla striata gum. Generally, the prepared films exhibited different mucoadhesion properties, among which #400 films showed the best performance. CONCLUSION: The mucoadhesion properties of films were significantly affected by their surface roughness, which are wo-rthy of further study.

Screening of mucoadhesive vaginal gel formulations

Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum). The gels were characterised using in vitro adhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests) and the effect of dilution with simulated vaginal fluid (SVF) on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

O planejamento racional de formulações para a liberação vaginal de fármacos requer atenção especial às propriedades do veículo, que otimizem o revestimento e a retenção vaginal. O objetivo do presente trabalho foi realizar uma triagem de géis vaginais mucoadesivos formulados com carbomero ou carragenina em combinação binária com um segundo polímero (carbomero, goma guár ou xantana). Os géis foram caracterizados usando estudos in vitro de aderência, espalhabilidade e potencial de vazamento, bem como medições reológicas (testes de varredura de tensão e frequência) e o efeito de diluição com fluido vaginal simulado (SVF) na espalhabilidade. Os resultados foram analisados utilizando a análise de variância e de fator múltiplo. A combinação de polímeros reforçou a adesão de ambos os agentes gelificantes primários, carbomero e carragenina. Do ponto de vista reológico todas as formulações apresentaram comportamento semelhante, predominantemente elástico e caracterizado por valores de tangente de perda bem abaixo de 1. Não se encontrou correlação entre as medições reológicas e o comportamento de adesão. Os géis de carbomero e carragenina contendo o maior porcentual de goma xantana apresentaram melhor mucoadesão e espalhabilidade, menor potencial de vazamento e maior resistência à diluição in vitro. Os resultados positivos obtidos com géis de carragenina-goma xantana podem incentivar o uso de adjuvantes biocompatíveis naturais na composição dos produtos vaginais, um campo de formulação atualmente sob o domínio de produtos sintéticos.

Preparation and Characterization of Mucoadhesive Buccal Film for Delivery of Meloxicam.

Aims: Preparation of mucoadhesive buccal films able to deliver the meloxicam drug to the site of application through oral mucosal tissues. This dosage form is advantageous due to absence the problems of the ordinary dosage forms. Study Design: In this research, it was prepared a lot of formulations from different polymers and plasticizers to select the best one which has the optimum and required characteristics. Place and Duration of Study: Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University and Misr International University, Egypt, between July 2009 and July 2012. Methodology: There are different polymers used in preparation of the films which are hydroxypropylmethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, pectin and polyvinyl alcohol. Also, the plasticizers used are glycerin, propylene glycol and polyethylene glycol. The film was prepared by solvent casting technique. Firstly, the calibration curve of meloxicam was carried out. Then, the properties of the formulations were examined through some experiments which are determination of drug content, study of efficacy of mucoadhesion, in-vitro drug release studies and differential scanning calorimetry. Results: It was found that the formula containing polyvinyl alcohol 2% (w/w) and propylene glycol 20% from the weight of the polymer has ideal characteristics. Results showed that this formula has optimum drug content, acceptable mucoadhesion and fast drug release with compatibility between drug and excipents.

Diltiazem-loaded buccoadhesive patches for oral mucosal delivery: Formulation and in vitro characterization.

The objective of the present study was to develop and evaluate bioadhesive buccal patches for mucosal delivery of diltiazem. The antihypertensive agent, diltiazem, undergoes first pass metabolism which compromises its bioavailability and the buccal route is a viable alternative to bypass this metabolism. In the present study, the buccal patches were fabricated with Eudragit L100 as the film forming polymer and hydroxypropyl methylcelluose, Carbopol 934 and sodium carboxymethylcellulose as the mucoadhesive polymer. The patches were characterized for various physicochemical attributes viz., weight uniformity, surface pH, folding endurance, swelling profile, content uniformity, permeability study, in vitro drug release profile and stability study in saliva. The results indicate that the Carbopol 934 is suitable for fabricating buccoadhesive patches with requisite release and stability profile.

Design and evaluation of famotidine mucoadhesive nanoparticles for aspirin induced ulcer treatment

The present study was performed to design and evaluate the famotidine loaded mucoadhesive nanosuspension for aspirin induced ulcer. A 3-factor, 3-level Box-Behnken design was applied to study the effects of amount of the beads (X1), PVPK-30(X2) and Tween-80 (X3) on the particle size (Y1), and cumulative percentage drug released after 1h (Y2). The optimization was performed using the desirability function and contour plots. The scanning electron microscopy (SEM) showed the nanoparticles as spherical in shape. The differential scanning calorimetry (DSC) analysis indicated that there was substantial crystallinity change in the nanoparticle compared with the pure drug. Ex-vivo mucoadhesion study showed that famotidine mucoadhesive nanoparticles possessed higher mucoadhesion than the famotidine nanoparticles. The in vivo studies on aspirin-induced rats indicated the lowering in ulcer index for famotidine mucoadhesive nanoparticles was 0.46+0.011, which was significantly better than the effect of traditional famotidine suspension (0.66+0.035). Famotidine mucoadhesive nanosuspension could be prepared using the media milling technique and allowing significant reduction in ulcer index compared to famotidine suspension.

Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

Objective:To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods:Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite? Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results: The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84%and FB16 released 99.01%of drug in 140 min. Conclusions: The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine.

Synthesis and characterization of a cysteine xyloglucan conjugate as mucoadhesive polymer

The aim of this study was to improve the mucoadhesive potential of xyloglucan polymer by the covalent attachment of cysteine as thiol moiety. The parent polymer xyloglucan was chemically modified by introducing sulphydryl bearing compound L-cysteine HCl. Different batches of xyloglucan-cysteine conjugates were prepared at varying reaction pH (2-6) and evaluated for optimum thiol incorporation, disulphide group content, swelling behavior, rheological properties and mucoadhesive properties. The obtained conjugates characterized in vitro by quantification of immobilized thiol groups; showed maximum thiol incorporation on xyloglucan (7.67 ± 0.14 %) at pH 5. The disulphide group content was found maximum (2.83 ± 0.12) at pH 6. The water uptake at end of 4 h was 5.0 for xyloglucan and was found to decrease in thiolated derivatives with increase in thiolation. Mucoadhesion studies revealed that mucoadhesion of xyloglucan-cysteine conjugate increased more than twice compared to the unmodified polymer. The viscosity of thiomer was more than that of xyloglucan because of formation of disulphide bonds.

O objetivo deste estudo foi melhorar o potencial mucoadesivo do polímero xiloglicano pela ligação covalente de cisteína como unidade de tiol. O polímero xiloglicano foi quimicamente modificado pela introdução de cloridrato de cisteína como grupo contendo sulfidrila. Prepararam-se diferentes lotes de conjugados cisteína-xiloglicano em pH variando de 2 a 6, avaliando-se a incorporação ótima de tiol, o conteúdo de dissulfeto, o comportamento de inchamento, as propriedades reológicas e mucoadesivas. Os conjugados obtidos foram caracterizados in vitro pela quantificação de grupos tiol, mostrando máxima incorporação na xiloglicana (7.67 ± 0.14 %) em pH 5. O conteúdo de grupos dissulfeto foi máximo (2.83 ± 0.12) em pH 6. O índice de inchamento em % no fim de 4 h foi 83.87 para o xiloglicano e diminuiu para os derivados tiolados. O conteúdo foi mínimo para TH2 (78.26), aumentou pouco até TH5 (83.33) e diminuiu, posteriormente, para TH6 (80.13). Os estudos de mucoadesão revelaram que o conjugado xiloglicano-cisteína aumentou mais que duas vezes comparativamente ao polímero não modificado. A viscosidade do tiômero foi maior do que a do xiloglicano devido à formação das ligações dissulfeto.

Mucoadhesive Polymeric Hydrogels for Nasal Delivery of Penciclovir.

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of penciclovir . Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.