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

Alginate/hydrophobic HPMC (60L) particulate systems: new matrix for controlled release of diclofenac potassium

This work is focused on the development of a new particulate drug delivery system using sodium alginate (SA) and modified hydrophobic hydroxyl propyl methyl cellulose (HPMC, 60L grade) containing diclofenac as a model drug molecule for intestinal drug prolonged release. Diclofenac loaded HPMC-SA beads have been developed by ion exchange methods and were characterized by encapsulation efficiency, drug release profile, swelling and matrix erosion rate. Matrix swelling of calcium alginate beads induced by phosphate buffer ends up in erosion and destruction. However, for HPMC-SA beads do not lead to complete erosion, which may be the main cause of diclofenac retention within the matrix. The release of diclofenac potassium is negligible at acidic pH, while is complete in 5-6 h when pH is raised up to 7.4. The alginate/HPMC ratio controls the release rate of the drug. The drug release is decreased as the polymer concentration is increased from 2.5 to 3.5 %. Release kinetic study was done to understand the correlation between the formulations. The results show that drug release is diffusion controlled and it is Anomalous type which means combined process of both swelling and erosion of polymer.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Alginate/hydrophobic HPMC (60L) particulate systems: new matrix for controlled release of diclofenac potassium

This work is focused on the development of a new particulate drug delivery system using sodium alginate (SA) and modified hydrophobic hydroxyl propyl methyl cellulose (HPMC, 60L grade) containing diclofenac as a model drug molecule for intestinal drug prolonged release. Diclofenac loaded HPMC-SA beads have been developed by ion exchange methods and were characterized by encapsulation efficiency, drug release profile, swelling and matrix erosion rate. Matrix swelling of calcium alginate beads induced by phosphate buffer ends up in erosion and destruction. However, for HPMC-SA beads do not lead to complete erosion, which may be the main cause of diclofenac retention within the matrix. The release of diclofenac potassium is negligible at acidic pH, while is complete in 5-6 h when pH is raised up to 7.4. The alginate/HPMC ratio controls the release rate of the drug. The drug release is decreased as the polymer concentration is increased from 2.5 to 3.5 %. Release kinetic study was done to understand the correlation between the formulations. The results show that drug release is diffusion controlled and it is Anomalous type which means combined process of both swelling and erosion of polymer.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of physicochemical properties and in-vitro release profile of glipizide-matrix patch

OBJECTIVES: The aim of the present investigation was to form matrix patches with ethyl cellulose (EC) as the base polymer, polyvinyl pyrrolidone (PVP) as the copolymer, plasticizer with dibutyl phthalate (DBP) or acetyl tributyl citrate (ATBC) and the drug glipizide (gz) by the solvent casting method. Physicochemical properties of the patches and in vitro drug release were determined in a modified Keshary-chien diffusion cell to optimize the patch formulations with the help of experimental data and figures for further studies. TECHNIQUES: EC and PVP of different proportions with different weight percentages of either DBP or ATBC and a fixed amount of glipizide were taken for matrix patch formations. The dried patches were used for measuring their drug contents as well as their thicknesses, tensile strengths, moisture contents and water absorption amounts in percentage. In vitro release amounts at different intervals were measured by UV-spectrophotometer. RESULTS: Drug contents varied from 96 - 99%. Thickness and tensile strength varied due to weight variation of the ingredients in the matrix patches. Moisture content and water absorption in wt % were greater for the patches containing higher amount of PVP due to its hydrophilic nature. Variations in drug release were observed among various formulations. It was found that all of the releases followed diffusion controlled zero order kinetics. Two DBP patches yielded better and more adequate release. CONCLUSIONS: The two formulations with DBP were the preferred choice for making matrix patches for further studies.O objetivo da presente pesquisa foi formar matrizes para bandagens de liberação transdérmica com etilcelulose (EC) como polímero base, polivinilpirrolidona (PVP), como copolímero, plastificante com ftalato de dibutila (DBP) ou citrato de tributilacetila (ATBC) e o fármaco glipizida (gz) pelo método de evaporação do solvente (moldagem com solvente). As propriedades físico-químicas das bandagens e a liberação do fármaco in vitro na célula de difusão de Keshary-chien modificada foram determinadas para aperfeiçoar as formulações das bandagens com o auxílio de dados experimentais e figuras para estudos posteriores. EC e PVP em diferentes proporções com porcentagens diferentes de massa tanto de DBP quanto de ATBC e quantidade fixa de glipizida foram utilizadas como matrizes para a formação de bandagens de liberação transdérmica. As bandagens secas foram empregadas para medir seus conteúdos em fármaco e, também, a sua espessura, resistência à tensão, conteúdos de umidade e porcentagem de absorção de água. As quantidades liberadas in vitro em diferentes intervalos de tempo foram medidas por espectrofotômetro de UV. Os conteúdos de fármaco variaram de 96 a 99%. A espessura e a resistência à ruptura variaram devido à variação de massa dos componentes da matriz das bandagens. O conteúdo de umidade e a água absorvida, em porcentagem de massa, foram maiores para as bandagens que continham grandes quantidades de PVP devido à sua natureza hidrofílica. As variações na liberação de fármaco foram observadas entre as várias formulações. Todas as liberações seguiram a cinética de difusão controlada de ordem zero. Duas bandagens DBP resultaram em melhor e mais adequada liberação. As duas formulações com DBP foram escolhidas para a preparação de matriz de bandagens para estudos posteriores

Formulation and characterization of both hydrophilic and hydrophobic HPMC based hydrogels containing diclofenac potassium

The aim of this study was to develop topical hydrogels containing diclofenac potassium (DP) at 1 % w/v concentration using conventional hydrophilic hydroxypropyl methyl cellulose (HPMC, 50cPs) and modified hydrophobic hydroxypropyl methyl cellulose (HPMC, 90L grade). The differences between in vitro release profiles of both types of polymer based hydrogels were studied using model dependent equations. Three formulations were prepared from hydrophobic HPMC at 1 %, 1.5 % and 2 % (w/v) concentration. Other two formulations were prepared from hydrophilic HPMC at 12 % and 15 % (w/v) concentration. Hydrophobic formulations of higher viscosity with small quantity of polymer show higher release compared to hydrophilic formulations of lower viscosity with higher polymer concentration. Combined effect of swelling and erosion leads to anomalous diffusion in case of hydrophobic HPMC based hydrogels whereas only swelling leads to Fickian diffusion in case of hydrophilic HPMC based hydrogels. The formulations follow Higuchi release pattern as well as Weibull model.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of GlimepirideCaptisol Inclusion Complexes

This present study investigated the effect of Captisol, a chemically modified cyclodextrin, on the in vitro dissolution of glimepiride. We prepared glimepirideCaptisol complexes of different mass ratios (1:1, 1:2, and 1:3 w/w) by a physical mixing or freeze-drying technique, and found that complexation with Captisol enhanced the water solubility of glimepiride. Molecular docking and dynamic simulation predicted complex formation; at the same time, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscope indicated molecular interactions that support complexation. We also found that an inclusion complex was better than a physical mixture in enhancing the complexation of glimepiride with Captisol and enhancing water solubility. Phase solubility study of the glimepirideCaptisol complex showed an AL-type profile, implying the formation of a 1:1 inclusion complex. The study also revealed that pH influenced the stability of the complex because the stability constant of the glimepirideCaptisol complex was higher in distilled water of pH 6.0 than in phosphate buffer of pH 7.2

Electrospinning over Solvent Casting: Tuning of Mechanical Properties of Membranes

We put forth our opinion regarding the enhanced plasticity and modulation of mechanical properties of polymeric films obtained through electrospinning process in this article. In majority of the pharmaceutical, biomedical, and packaging applications, it is desirable that polymer based matrices should be soft, flexible, and have a moderate toughness. In order to convert inflexible and brittle polymers, adjuvants in the form of plasticizers are added to improve the flexibility and smoothness of solvent casted polymer films. However, many of these plasticizers are under scrutiny for their toxic effects and environmental hazards. In addition, plasticizers also increase the cost of end products. This has motivated the scientific community to investigate alternate approaches. The changes imparted in membrane casted by electrospinning were tried to be proved by SEM, Mechanical property study, DSC and XRD studies. We have showed dramatic improvement in flexibility of poly(ε-caprolactone) based nanofiber matrix prepared by electrospinning method whereas solvent casting method without any plasticizer produced very brittle, inflexible film of PCL. Modulation capacity of mechanical properties is also recorded. We tried to support our opinion by citing several similar findings available in the open literature. The electrospinning method helps in plasticization and in tuning mechanical properties

Electrospinning tissue engineering and wound dressing scaffolds from polymer-titanium dioxide nanocomposites

Electrospinning is widely used to fabricate nanoscale fibers from natural and synthetic polymers. Electrospun fibers have potential application in tissue engineering as well as in the design of catalysts, batteries, electronic sensors, packages, filtration membranes, medical implants, wound dressings, and medical fabrics, and drug delivery systems. Fibers offer a porous structure with a high surface area to volume ratio, which is a highly desired property in various applications. Integrating other materials such as metals nanoparticles or ceramics in electrospun fibers is emerging as a route to new nanoscale composites materials with enhanced functional properties. Incorporating nanoparticles on or within the nanofibrous scaffold impart functional properties with implication for catalysis, optoelectronics, and biomedicine. Indeed, these electrospun polymer-nanoparticles composites are a new frontier in biomedicine, where their relevance to tissue engineering, wound dressing, drug delivery is emerging. Here, we summarise advances in electrospun tissue engineering and wound dressing platforms developed from polymer-titanium dioxide nanocomposites