Zein and hydroxypropyl methylcellulose acetate succinate microfibers combined with metronidazole benzoate and/or metronidazole-incorporated cellulose nanofibrils for potential periodontal treatment.

The development of flexible and porous materials to control antibacterial delivery is a pivotal endeavor in medical science. In this study, we aimed to produce long and defect-free fibers made of zein and hydroxypropyl methylcellulose acetate succinate (HPMCAS) to be used as a platform for the release of metronidazole (MDZ) and metronidazole benzoate (BMDZ) to be potentially used in periodontal treatment. Microfibers prepared via electrospinning under a 2:3 (w/w) zein to HPMCAS ratio, containing 0.5 % (w/w) poly(ethylene oxide) (PEO) and 1 % (w/w) cellulose nanofibril (CNF) were loaded with 40 % (w/w) MDZ, 40 % (w/w) BMDZ, or a combination of 20 % (w/w) of each drug. The addition of CNF improved the electrospinning process, resulting in long fibers with reduced MDZ and BMDZ surface crystallization. MDZ- and BMDZ-incorporated fibers were semicrystalline and displayed commendable compatibility among drugs, nanocellulose and polymeric chains. Release tests showed that zein/HPMCAS/PEO fibers without CNF and with 20 % (w/w) MDZ/ 20 % (w/w) BMDZ released the drug at a slower and more sustained rate compared to other samples over extended periods (up to 5 days), which is a favorable aspect concerning periodontitis treatment.

Boosting the photodynamic activity of erythrosine B by using thermoresponsive and adhesive systems containing cellulose derivatives for topical delivery.

Erythrosine displays potential photodynamic activity against microorganisms and unhealthy cells. However, erythrosine has high hydrophilicity, negatively impacting on permeation through biological membranes. Combining biological macromolecules and thermoresponsive polymers may overcome these erythrosine-related issues, enhancing retention of topically applied drugs. The aim of this work was to investigate the performance of adhesive and thermoresponsive micellar polymeric systems, containing erythrosine in neutral (ERI) or disodium salt (ERIs) states. Optimized combinations of poloxamer 407 (polox407) and sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as platforms for ERI/ERIs delivery. The rheological and mechanical properties of the systems was explored. Most of the formulations were plastic, thixotropic and viscoelastic at 37 °C, with suitable gelation temperature for in situ gelation. Mechanical parameters were reduced in the presence of the photosensitizer, improving the softness index. Bioadhesion was efficient for all hydrogels, with improved parameters for mucosa in contrast to skin. Formulations composed of 17.5 % polox407 and 3 % HPMC or 1 % NaCMC with 1 % (w/w) ERI/ERIs could release the photosensitizer, reaching different layers of the skin/mucosa, ensuring enough production of cytotoxic species for photodynamic therapy. Functional micelles could boost the photodynamic activity of ERI and ERIs, improving their delivery and contact time with the cells.

The effect of the molecular structure of hydroxypropyl methylcellulose on the states of water, wettability, and swelling properties of cryogels prepared with and without CaO2.

Hydroxypropyl methylcellulose (HPMC) belongs to the cellulose ether family that has hydroxyl groups substituted by hydrophobic methyl groups (DS) and hydrophilic hydroxypropyl groups (MS). Herein, the interactions between water molecules and cryogels prepared with HPMC in the presence and absence of a linear nonionic surfactant, as well as CaO2 microparticles, which react with water producing O2, were systematically investigated by sorption experiments and Time-Domain Nuclear Magnetic Resonance. Regardless of the DS and MS, most water molecules presented transverse relaxation time t2 typical of intermediate water and a small population of more tightly bound water. HPMC cryogels with the highest DS of 1.9 presented the slowest swelling rate of 0.519 ± 0.053 gwater/(g.s) and the highest contact angle values 85.250o ± 0.004o, providing the best conditions for a slow reaction between CaO2 and water. The presence of surfactant favored hydrophobic interactions that allowed the polar head of the surfactant to be exposed to the medium, resulting in a higher swelling rate and lower contact angle values. The HPMC with the highest MS presented the fastest swelling rate and the lowest contact angle. These findings are relevant for the formulations and reactions, where tuning the swelling kinetics is crucial for the final application.

Hydroxypropyl methylcellulose-sugarcane bagasse adsorbents for removal of 17α-ethinylestradiol from aqueous solution and freshwater.

Adsorbents made of hydroxypropyl methylcellulose (HPMC) and sugarcane bagasse (BG) microparticles were applied for the separation of 17α-ethinylestradiol (EE2) from aqueous solution in batch, and from aqueous solution and freshwater in fixed-bed columns. HPMC chains and BG microparticles were crosslinked by the esterification with citric acid. The adsorbents presented compression modulus values that increased from 208 ± 20 kPa (pure HPMC) to 917 ± 90 kPa, when the content of BG particles added to HPMC was 50 wt% (HPMC50BG). The porosity (~ 97%), specific surface area (1.16 ± 0.10 m2/g) and swelling degree (20 ± 1 g water/g) values were not affected by the addition of BG particles. The adsorption isotherms determined for EE2 on HPMC and on HPMC50BG fitted to the Langmuir and Freundlich models; the adsorption capacity of HPMC was slightly higher than that of composite HPMC50BG. Nevertheless, the addition of BG particles rendered outstanding mechanical reinforcement and dimensional stability to the adsorbents. The adsorption was driven by (i) hydrophobic interactions between EE2 methylene and aromatic groups and HPMC methyl groups, as evidenced by FTIR spectroscopy, and (ii) H bonds between HPMC and EE2 hydroxyl groups, as revealed by the adsorption enthalpy change (ΔHads) of - 45 kJ/mol. Column adsorption experiments of EE2 from aqueous solution on HPMC and HPMC50BG indicated adsorptive capacity (q0) values of 8.06 mg/g and 4.07 mg/g, respectively. These values decreased considerably for the adsorption of EE2 from river water, probably due to the competition of EE2 with humic substances dissolved in natural water. The HPMC adsorbents could be recycled retaining up to 83% of the original efficiency.

The effect of erythrosine-B on the structuration of poloxamer 407 and cellulose derivative blends: In silico modelling supporting experimental studies.

Erythrosine is a dye approved for medical use that has shown promising photodynamic activity, allowing for the inactivation of microorganisms and activity against malignant cells. Despite the great photodynamic potential, erythrosine exhibits hydrophilicity, negatively impacting its action in biological membranes. Therefore, the incorporation of erythrosine in micellar polymeric systems, such as poloxamers, may overcome this limitation. Moreover, using bioadhesive and thermoresponsive polymers to combine in situ gelation and bioadhesion may enhance retention of this topically applied drug. In this work, mucoadhesive and thermoresponsive micellar systems were prepared containing erythrosine in two states: the native form (ERI) and the disodium salt (ERIs). The systems were evaluated based on the effect of ERI/ERIs on the micellar structure of the binary polymer mixtures. Optimised combinations of poloxamer 407 (polox407) and mucoadhesive sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as micellar systems for ERI or ERIs delivery. The systems were studied with respect to theoretical interactions, qualitative composition, morphology, and micellar properties. In silico modelling indicated a higher interaction of the drug with poly(ethylene oxide) (PEO) than poly(propylene oxide) (PPO) fragments of polox407. Systems containing NaCMC displayed a repulsive effect in the presence of erythrosine, due to the polymer's charge density. Both systems could convert the photosensitizer in its monomeric form, ensuring photodynamic activity. In these mixtures, crystallinity, critical micellar temperature and enthalpy of polox407 micellisation were reduced, and micellar size, evaluated by transmission electron microscopy (TEM), showed low impact of ERI/ERIs in HPMC preparations. Aiming toward photodynamic applications, the findings showed how ERI or ERIs can affect the micellar formation of gels composed of 17.5% (w/w) polox407 and 3% (w/w) HPMC or 1% (w/w) NaCMC, important for understating their behaviour and future utilisation as erythrosine delivery systems.

Tuning the Mechanical and Thermal Properties of Hydroxypropyl Methylcellulose Cryogels with the Aid of Surfactants.

The mechanical and thermal properties of cryogels depend on their microstructure. In this study, the microstructure of hydroxypropyl methylcellulose (HPMC) cryogels was modified by the addition of ionic (bis (2-ethylhexyl) sodium sulfosuccinate, AOT) and non-ionic (Kolliphor® EL) surfactants to the precursor hydrogels (30 g/L). The surfactant concentrations varied from 0.2 mmol/L to 3.0 mmol/L. All of the hydrogels presented viscous behavior (G″ > G'). Hydrogels containing AOT (c > 2.0 mmol/L) led to cryogels with the lowest compressive modulus (13 ± 1 kPa), the highest specific surface area (2.31 m2/g), the lowest thermal conductivity (0.030 W/(m·°C)), and less hygroscopic walls. The addition of Kolliphor® EL to the hydrogels yielded the stiffest cryogels (320 ± 32 kPa) with the lowest specific surface area (1.11 m2/g) and the highest thermal conductivity (0.055 W/(m·°C)). Density functional theory (DFT) calculations indicated an interaction energy of -31.8 kcal/mol due to the interaction between the AOT sulfonate group and the HPMC hydroxyl group and the hydrogen bond between the AOT carbonyl group and the HPMC hydroxyl group. The interaction energy between the HPMC hydroxyl group and the Kolliphor® EL hydroxyl group was calculated as -7.91 kcal/mol. A model was proposed to describe the effects of AOT or Kolliphor® EL on the microstructures and the mechanical/thermal properties of HPMC cryogels.

Hydroxypropyl methylcellulose: Physicochemical properties and ocular drug delivery formulations.

Hydroxypropyl methylcellulose (HPMC) is a cellulose ether widely used in drug formulations due to its biocompatibility, uncharged nature, solubility in water and thermoplastic behavior. Particularly for ocular and ophthalmic formulations, HPMC is applied as viscosity enhancer agent in eye drops, gelling agent in injections, and polymeric matrix in films, filaments and inserts. The different therapeutic approaches are necessary due to the complex anatomic structure of the eye. The natural ocular barriers and the low drug permeation into the circulatory system make the drug administration challenging. This review presents the eye anatomy and the usual local routes of drugs administration, which are facilitated by the physicochemical properties of HPMC. The relationship between chemical structure and physicochemical properties of HPMC is displayed. The different types of formulations (local application) including HPMC for ocular drug delivery are discussed with basis on recent literature reports and patents.

Interaction between mucoadhesive cellulose derivatives and Pluronic F127: Investigation on the micelle structure and mucoadhesive performance.

Systems composed of bioadhesive and thermoresponsive polymers can combine in situ gelation with bio/mucoadhesion, enhancing retention of topically applied drugs. The effect of bioadhesive sodium carboxymethylcellulose (NaCMC) and hydroxypropyl methylcellulose cellulose (HPMC) on the properties of thermoresponsive Pluronic® F127 (F127) was explored, including micellization and the mucoadhesion. A computational analysis between these polymers and their molecular interactions were also studied, rationalising the design of improved binary polymeric systems for pharmaceutical and biomedical applications. The morphological characterization of polymeric systems was conducted by SEM. DSC analysis was used to investigate the crystallization and micellization enthalpy of F127 and the mixed systems. Micelle size measurements and TEM micrographs allowed for investigation into the interference of cellulose derivatives on F127 micellization. Both cellulose derivatives reduced the critical micellar concentration and enthalpy of micellization of F127, altering hydrodynamic diameters of the aggregates. Mucoadhesion performance was useful to select the best systems for mucosal application. The systems composed of 17.5% (w/w) F127 and 3% (w/w) HPMC or 1% (w/w) NaCMC are promising as topical drug delivery systems, mainly on mucosal surfaces. They were biocompatible when tested against Artemia salina, and also able to release a model of hydrophilic drug in a controlled manner.

Synergy between surfactants and mucoadhesive polymers enhances the transbuccal permeation of local anesthetics from freeze-dried tablets.

We report on the advance of freeze-dried mucoadhesive orodispersible tablets (ODTs) loaded with prilocaine (PRC) and lidocaine (LDC) hydrochlorides, aiming to promote noninvasive buccal anesthesia. The influences of combining biocompatible polymers (pullulan and HPMC K100 LV) and a blend of surfactants (oleic acid, polysorbate 80 and propylene glycol) acting as chemical enhancers on the permeation of such drugs through the esophageal porcine epithelium and in vitro mucoadhesion were investigated. The ODTs were also characterized in terms of average weight, thickness, pH, drug content, in vitro release, thermal behavior and scanning electronic microscopy. A dissolution test showed fast drug release within one hour. The drug release data for all ODTs fitted first order. No significant influence of the type of mucoadhesive polymer on release was observed, while the drug release from ODTs decreased in the presence of chemical enhancers. For the ODT containing pullulan the drug release mechanism was anomalous transport, whist for all others it was case-II transport. A remarkable synergic effect between pullulan and chemical enhancers on the permeation flux, lag time, and permeability coefficient of both drugs, but mainly for PRC was observed. Pullulan together with permeation enhancers also substantially improved the work of mucoadhesion as compared to HPMC. In contrast, HPMC improved drug retention in the epithelium. The novel drug delivery platform achieved by combining a freeze-drying technique, mucoadhesive biocompatible polymers, and chemical permeation enhancers displayed an effective strategy for the transbuccal delivery of PRC and LDC that can be used to improve needle-free buccal anesthesia.

Composite Microparticles Based on Natural Mucoadhesive Polymers with Promising Structural Properties to Protect and Improve the Antifungal Activity of Miconazole Nitrate.

Oropharyngeal candidiasis is a recurrent oral infection caused by Candida species. Gel formulation containing miconazole nitrate is the most common approach for treating oral candidiasis. However, traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the necessity to administrate various doses per day. Thus, the aim of this work was to formulate composited microparticulated systems based on combinations of mucoadhesive cationic, anionic, and nonionic polymers that could protect and modify the drug release rate and therefore avoid a fast dilution of the drug by saliva. Microparticulated systems were prepared by the spray drying method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The morphology of the systems was investigated by scanning electron microscopy; drug crystallinity was studied by X-ray, while interactions between polymers were analyzed by infrared spectroscopy. Drug release and halo zone test were employed to analyze the release and activity of the systems loaded with miconazole against Candida albicans cultures. The most appropriate microparticulated system was the one based on chitosan and gelatin which showed homogeneous morphology (mean size of 1.7 ± 0.5 µm), a protective effect of the drug, and better antifungal effect against Candida culture than miconazole nitrate and the other assayed systems. Taking into account these results, this approach should be seriously considered for further evaluation of its safety and in vivo efficacy to be considered as an alternative therapeutic system for the treatment of oral candidiasis.

Sustainable hydroxypropyl methylcellulose/xyloglucan/gentamicin films with antimicrobial properties.

Hydroxypropyl methylcellulose (HPMC) and xyloglucan (XG) crosslinked with citric acid over a range of HPMC/XG weight ratios formed sustainable blend films characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, tensile tests, circular dichroism and determination of inhibitory activity against Staphylococcus aureus and Escherichia coli. Both in solution and in the crosslinked films, HPMC chains lost the original ordered conformation upon interacting with XG, giving rise to an entropic gain. The highest values of tensile strength (25MPa) and Young's modulus (689MPa) occurred for the 50:50 HPMC/XG blend films. In vitro loading of gentamicin sulfate (GS) in the films amounted to 0.18±0.05 -0.37±0.05g of GS per g polymer. At pH 7.4 and 37°C, the GS release kinetics from the films fitted with the Korsmeyer-Peppas model revealed a non-Fickian release mechanism with diffusional coefficient n∼0.7. The cross-linked films of HPMC, XG and their blends loaded with GS showed outstanding antibacterial activity against Staphylococcus aureus and Escherichia coli, disclosing their potential for novel biomedical applications.

Hydroxypropyl Methylcellulose Sponges for the Adsorption of Estrogenic Pollutant.

Hydroxypropyl methylcellulose (HPMC) E4M chains are crosslinked with citric acid and ethylenediaminetetraacetic acid (EDTA), resulting in adsorbent sponges (SpE4M), which are impregnated with magnetic nanoparticles (SpE4M-mag) for the adsorption of 17 α-ethinyl estradiol (EE). The characterization of SpE4M and SpE4M-mag characterization includes X-ray microcomputer tomography (Micro-CT), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) vibrational spectroscopy, elemental analysis, inductively coupled plasma optical emission spectrometry (ICP-OES), and X-ray diffraction (XRD). SpE4M and SpE4M-mag present porosities of 72±6 % and 80±7 %, respectively, and outstanding stability in water, in the pH range 4 to 8, and in alcohols, alkanes, and acetone. The compressive moduli of SpE4M and SpE4M-mag amount to 2.75 and 4.37 MPa, respectively. The adsorption of 17 α-ethinyl estradiol (EE), an estrogenic pollutant, on SpE4M and SpE4M-mag follows the pseudo-first-order kinetic model. The EE removal capacity by SpE4M is 78±5 %, which is twice that presented by SpE4M-mag. The new sponges are recovered successfully either by flotation or by an external magnet, and can be recycled five times keeping 80 % of their initial removal capacity after the fifth cycle, disclosing their potential for environmental remediation.

Floating ability and drug release evaluation of gastroretentive microparticles system containing metronidazole obtained by spray drying

Abstract Gastroretentive floating microparticles were developed and evaluated for the controlled metronidazole delivery for treatment of gastric disease. Floating microparticles, varying in proportions of chitosan and hydroxypropyl methylcellulose or ethylcellulose, were obtained by spray drying. Floating microparticles were characterized by physicochemical and in vitro studies, according to their floating ability and drug delivery. Microparticles presented mean diameter from 1.05 to 2.20 µm. The infrared spectroscopy confirmed the drug encapsulation and showed no chemical linkage between microparticles components. X-ray diffraction showed changes in the drug`s solid state, from crystalline to amorphous, indicating partial drug encapsulation, due to the presence of some crystalline peaks of metronidazole in microparticles. All microparticles floated immediately in contact of simulated gastric fluid and both floating and drug release profiles were dependent of microparticles composition. Microparticles samples constituted by chitosan and hydroxypropyl methylcellulose revealed the best relationship between floating duration and drug release, remaining floating during the occurrence of the drug release, ideal condition for the floating gastroretentive systems.

In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

ABSTRACT A matrix system was developed that releases ibuprofen (IB) over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP), hydroxypropyl methylcellulose (HPMC), or ethyl cellulose (EC) were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r)971P 8% formulation showed the best linearity (r 2 =0.977) in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

Aplicación y efecto de un recubrimiento comestible sobre la vida útil de la mora de castilla (Rubus glaucus Benth) / Edible coating application and effect on blackberry (Rubus glaucus Benth) shelf life

Antecedentes: En los últimos años ha incrementado el interés por el consumo de frutas en estado fresco debido al potencial nutricional que estas contienen. Además, por el alto consumo energético que se generan en la aplicación de una cadena en frío, se ha incursionado en la aplicación de recubrimientos comestibles como una técnica alternativa para la conservación de frutas. Objetivos: Por tal razón, este trabajo tuvo como objetivo aplicar un recubrimiento a base de hidroxipropil metilcelulosa con la inclusión de cera de abejas en mora de castilla y evaluar su efecto en la conservación de esta fruta. Métodos: Se trabajó con un diseño multifactorial categórico y el análisis estadístico utilizado fue el LSD de Fisher con un nivel de confianza del 95%; determinándose propiedades fisiológicas tales como respiración y pérdida de peso, propiedades fisicoquímicas como pH, acidez titulable, sólidos solubles totales e índice de maduración durante un periodo de 15 días a una temperatura de 4°C. Resultados: Se obtuvo diferencias significativas (p < 0,05) entre los tratamientos evaluados a partir del tercer día de almacenamiento tanto para los parámetros fisicoquímicos como fisiológicos. La acidez titulable tuvo un decrecimiento marcado en el tratamiento control (T5) con respecto a los tratamientos donde se aplicó los recubrimientos (T1, T2, T3, T4) donde el descenso de la acidez fue menor. Por otro lado, la pérdida de peso, los sólidos solubles totales, el pH, el índice de maduración y el índice de respiración incrementaron a medida que el tiempo de almacenamiento transcurrió, indicando que las moras tratadas con los recubrimientos tuvieron un incremento menor con respecto a las moras sin recubrimiento. Conclusiones: Los recubrimientos comestibles aplicados a la mora de castilla tuvieron un efecto positivo sobre las propiedades evaluadas, siendo los mejores tratamientos el T3 y T4. En general, la aplicación de un recubrimiento comestible a base de hidroxipropil metilcelulosa y cera de abejas logró aumentar la vida útil de la mora de castilla.

Background: On the last years the interest on fresh fruits consumption has been increased due to its nutritional potential as well as high energetic demand generated by the cold-chains storage. It is the reason why it has been dabbled on edible coating as an alternative method on fruits preservation. Objectives: This investigation focused on the coating application using a hydroxypropyl methylcellulose based with bees wax applied all over blackberry fruits in order to evaluate the effects on its preservation. Methods: A multifactorial categorical design was used through the Fisher LSD method as an statistical analysis with a confidence level of 95%; it were determined physiological properties such respiration and weight loss, and physicochemical properties like pH, titratable acidity, soluble solids, and ripeness index within a period of 15 days at 4°C. Results: It were obtained significant differences (p<0.05) between the evaluated treatments from the third storage day for physicochemical and physiological parameters. The titratable acidity has a marked decrease on the control treatment (T5) regarding treatments where coatings were applied (T1, T2, T3, T4) where a smaller decrease on acidity was obtained. In other hand, the weight loss, total soluble solids, pH, ripening and respiration index showed an increase over storage time. The blackberry fruits processed with edible coating presented a slight increase compared to control samples. Conclusions: Edible coatings applied on blackberry fruits had a positive effect in the evaluated properties, treatments T3 and T4. Generally, edible coatings with hydroxypropyl methylcellulose base and beeswax increase the shelf life of blackberry.

Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f 2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

O objetivo do presente estudo foi desenvolver matriz de de tizanidina de liberação controlada. As formulações foram projetadas usando o método do componente, central com a ajuda de software Design expert(r), versão 7.0. Utilizou-se Avicel pH 101, no intervalo de 14-50%, como material de preenchimento, enquanto HPMC K4M e K100M, no intervalo de 25-55%, Etilcelulose 10 ST e 10FP, no intervalo de 15-45% e Kollidon SR, na faixa de 25-60% foram utilizados como agentes de liberação controlada, no planejamento de formulações diferentes. Vários parâmetros físicos, incluindo o fluxo de pó para as misturas e variação de peso, espessura, dureza, friabilidade, tempo de desintegração e liberação in vitro, foram testados para comprimidos. Ensaios dos comprimidos foram, também, realizados, tal como especificado em USP 35 NF 32. Avaliaram-se os parâmetros físicos de ambos, mistura em pó e comprimidos, como índice de compressibilidade, ângulo de repouso, variação de peso, espessura, dureza, friabilidade, tempo de desintegração e de ensaio, considerando-os satisfatórios para as formulações K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 e KSR9. O estudo de dissolução in vitro foi realizado em 900 mL de HCl 0,1 N, tampão de fosfato pH 4,5 e meio 6,8, usando aparelho USP II. Os perfis de liberação in vitro indicaram que as formulações preparadas com Ethocel 10 padrão não foram capazes de controlar a liberação do fármaco, enquanto as formulações K4M2, K100M9, E10FP2e KSR2, com teor de polímero variando entre 40 e 55% apresentaram padrão de liberação controlada de fármaco no meio anteriormente mencionado. Observou-se cinética de liberação de fármaco de ordem zero para as formulações K4M2 , K100M9, E10FP2 e KSR2. Resultados do teste de similaridade (f 2) para K4M2, E10FP2 e KSR2 foram comparáveis com a formulação de referência K100M9. Gráficos de superfície de resposta também avaliaram o efeito da variável independente sobre as respostas. Estudo de estabilidade foi realizado conforme as diretrizes do ICH e a vida de prateleira calculada foi de 24-30 meses para as formulações K4M2, K100M9 e E10FP2.

Alginate/hydrophobic HPMC (60M) particulate systems: new matrix for site-specific and controlled drug delivery

This study aimed to obtain site-specific and controlled drug release particulate systems. Some particulates were prepared using different concentrations of sodium alginate (Na-Alg) alone and others were formulated using different proportions of Na-Alg with hydroxypropyl methylcellulose (HPMC) stearoxy ether (60M viscosity grade), a hydrophobic form of conventional HPMC, using diclofenac potassium (DP) by ion-exchange methods. Beads were characterized by encapsulation efficiency, release profile, swelling, and erosion rate. The suitability of common empirical (zero-order, first-order and Higuchi) and semi-empirical (Ritger-Peppas and Peppas-Sahlin) models was studied to describe the drug release profile. The Weibull model was also studied. Models were tested by non-linear least-square curve fitting. A general purpose mathematical software (MATLAB) was used as an analysis tool. In addition, instead of the widely used linear fitting of log-transformed data, direct fitting was used to avoid any sort of truncation or transformation errors. The release kinetics of the beads indicated a purely relaxation-controlled delivery, referred to as case II transport. Weibull distribution showed a close fit. The release of DP from Na-Alg particulates was complete in 5-6 hours, whereas from Na-Alg hydrophobic HPMC particulate systems, release was sustained up to 10 hours. Hydrophobic HPMC with Na-Alg is an excellent matrix to formulate site-specific and controlled drug release particulate systems.

Este estudo teve como objetivo a obtenção de sistemas particulados para a liberação controlada de fármacos em sítios de ação específicos. Algumas partículas foram preparadas utilizando-se diferentes concentrações de alginato de sódio (Na-Alg) e outras foram formuladas por diferentes proporções de Na-Alg com estearoxílico éter de hidroxipropilmetilcelulose (HPMC) (grau de viscosidade 60M), uma forma hidrofóbica do convencional HPMC, utilizando o diclofenaco de potássio (DP) por métodos de troca iônica. Os grânulos foram caracterizados pela eficiência de encapsulação, perfil de liberação, inchaço e taxa de erosão. A adequação de diferentes modelos empíricos (de ordem zero, primeira ordem e Higuchi) e semi-empíricos (Ritger-Peppas e Peppas-Sahlin) foi estudada para descrever o perfil de liberação do fármaco. O modelo de Weibull também foi estudado. Os modelos foram testados através de ajuste não linear de curva pelo método dos mínimos quadrados. O software matemático MATLAB foi utilizado como ferramenta de análise matemática. Além disso, em vez do método de ajuste linear de dados transformados, foi utilizado o ajuste direto para evitar qualquer tipo de erro de truncamento ou de transformação. A cinética de liberação dos grânulos indicou liberação controlada puramente pelo processo de relaxamento, referida como transporte caso II. A distribuição de Weibull apresentou bom ajuste. A liberação do DP a partir de partículas de Na-Alg foi concluída em 5-6 horas, enquanto que a partir de sistemas particulados de Na-Alg HPMC hidrofóbico, a liberação foi mantida por até 10 horas. O HPMC hidrofóbico com Na-Alg é uma excelente matriz para a formulação de sistemas particulados para a liberação controlada de fármacos em sítios de ação específicos.