Formulation and evaluation of carvedilol microcapsules using Eudragit NE30D and sodium alginate

Inclusion complexes of carvedilol(CR) with hydroxyl propyl beta-cyclodextrin (HPBCD) was prepared using co-grinding technique. Then, the inclusion complex was microencapsulated using combinations of Eudragit NE30D (EU) and sodium alginate (SA) utilizing orifice gelation technique. The formulations were analysed by using Scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR), Differential scanning Calorimetry (DSC) and X-ray diffractometer (XRD) and also evaluated for particle size, encapsulation efficiency, production yield, swelling capacity, mucoadhesive properties, zeta potential and drug release. The microcapsules were smooth and showed no visible cracks and extended drug release of 55.2006% up to 12 hours in phosphate buffer of pH 6.8, showing particle size within the range of 264.5-358.5 µm, and encapsulation efficiency of 99.337±0.0100-66.2753±0.0014%.The in vitro release data of optimized batch of microcapsules were plotted in various kinetic equations to understand the mechanisms and kinetics of drug release, which followed first order kinetics, value of "n" is calculated to be 0.459 and drug release was diffusion controlled. The mice were fed with diet for inducing high blood pressure and the in vivo antihypertensive activity of formulations was carried out administering the optimized formulations and pure drug separately by oral feeding and measured by B.P Monwin IITC Life Science instrument and the results indicated that the bioavailability of carvedilol was increased both in vitro and in vivo with the mucoadhesive polymers showing primary role in retarding the drug release.Prepararam-se complexos de carvedilol (CR) com hidroxipropil beta-ciclodextrina (HPBCD), utilizando a técnica de co-moagem. O complexo de inclusão foi microencapsulado empregando-se associações de Eudragit NE30D (EU) e alginato de sódio (AS), utilizando a técnica de gelificação de orifício. As formulações foram analisadas utilizando-se microscopia eletrônica de varredura (SEM), espectroscopia no infravermelho com Transformada de Fourier, calorimetria diferencial de varredura (DSC) e difratometria de raios X (XDR) e, também, avaliadas por tamanho de partícula, eficiência de encapsulação, rendimento de produção, capacidade de inchamento, propriedades mucoadesivas, potencial zeta e liberação do fármaco. Obtiveram-se microcápsulas lisas e sem fendas visíveis, com liberação prolongada do fármaco de 55,2006% em 12 horas em tampão fosfato pH 6,8, com tamanho de partículas na faixa de 264,5-358,5 mm e eficiência de encapsulação de 99,3337±0,0100-66,2753±0,0014%. Os dados de liberação in vitro de lote otimizado de microcápsulas foram plotados em várias equações cinéticas para se entender os mecanismos e a cinética de liberação do fármaco, que é de primeira ordem, o valor de "n" foi de 0,459 e a liberação do fármaco foi por difusão controlada. Os camundongos foram alimentados com dieta para induzir pressão sanguínea alta e a atividade anti-hipertensiva in vivo das formulações foi obtida por administração de formulações otimizadas e fármaco puro, separadamente, por via oral e medida pelo equipamento BP Monwin IITC Life Science. Os resultados mostraram que a biodisponibilidade do carvedilol aumentou tanto in vitro quanto in vivo com os polímeros mucoadesivos, mostrando papel principal no retardamento da liberação do fármaco

Development and Statistical optimization of mucoadhesive drug delivery system of famotidine using Hibiscus esculentus polysaccharide

The presentstudy was aimed to formulate and evaluate oral mucoadhesive drug deliverysystem of purified Hibiscus esculentusL polysaccharide (HEP) using famotidine as model drug. A centralcomposite design for 2 factors at 3 levels each was employed to evaluate theeffect of critical variables i.e. concentration of HEP and PVP K30 on drugrelease and mucoadhesive properties of the formulated tablets. FT-IRspectroscopy and Differential Scanning Calorimetry was carried out to evaluatedrug polymer interaction. Formulated tablets were evaluated for physicalproperties, drug release characteristic and physical stability. Ex-vivo mucoadhesion study using goatgastric mucosa was carried out to ascertain the mucoadhesion potential offormulated tablets.The responsesurface analysis clearly indicated the dominating effect of HEP on mucoadhesivestrength, mucoadhesion time and dissolution half life, while PVP K30 has anadditive effect on all afore mentioned responses. The drug release from thematrix tablets was highly affected by the concentration of release retardantspolysaccharide. The kinetics of drug release was found to be first order in lowconcentration but with increase in polymer concentration the release patternshifted towards zero order and is governed by both Higuchi and Hixson-Crowelequation indicating a coupling effect of diffusion and erosion. The result ofthe study suggests that, HEP can be optimistically explored as excellentmucoadhesive agent with controlled release characteristics

Proizvodne varijable koje utječu na svojstva peleta u peletiranju taljenjem sa smjesom voskova u sferonizatoru za laboratorijsku proizvodnju

The purpose of the study was to evaluate the suitability of laboratory scale spheronizer for the production of spherical pellets loaded with diltiazem hydrochloride by wax combination. The 1:1 combination of cetyl alcohol and hydrogenated castor oil, as low and high melting point waxes, were used. The various production variables affecting the different characteristics of pellets and the process efficiency were evaluated. Drug loaded pellets were evaluated for drug release in distilled water. Bowl temperature primarily affects the sphericity and adhesion of pellets to the bowl. Mass temperature has a pronounced effect on size, size distribution and sphericity of pellets. Wax concentration affects all characteristics of pellets but adhesion was least affected. The effect of these three variables can be compensated by optimizing the friction plate speed. It has been found that the highest yield of pellets (8501400 m) with maximum sphericity can be produced by using 45 C bowl temperature, 52 C mass temperature and 1400 rpm friction plate speed.Cilj rada bio je pripraviti sferične pelete u laboratorijskom sferonizatoru koristeći smjesu voskova. Cetilni alkohol kao vosak niskog tališta i hidrogenirano ricinusovo ulje kao vosak visokog tališta, upotrebljeni su u omjeru 1:1. Proučavan je utjecaj proizvodnih varijabli na svojstva peleta i efikasnost proizvodnje te brzinu oslobađanja ljekovite tvari iz peleta u destiliranoj vodi. Na sferičnost i adhezivnost peleta najviše utječe temperatura peletiranja. Temperatura mase ima i značajan utjecaj na veličinu, raspodjelu veličine peleta i sferičnost. Koncentracija voska utječe na sva svojstva peleta, ali najmanje na adhezivnost. Učinak tih triju varijabli može se kompenzirati optimiziranjem brzine ploče za trenje. Pronađeno je da najveće iskorištenje peleta (8501400 microm) s najboljom sferičnošću ako je temperatura peletiranja 45 oC, temperatura mase 52 oC, a brzina ploče za trenje 1400 rpm

Formulation and evaluation of carvedilol microcapsules using Eudragit NE30D and sodium alginate

Inclusion complexes of carvedilol(CR) with hydroxyl propyl beta-cyclodextrin (HPBCD) was prepared using co-grinding technique. Then, the inclusion complex was microencapsulated using combinations of Eudragit NE30D (EU) and sodium alginate (SA) utilizing orifice gelation technique. The formulations were analysed by using Scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR), Differential scanning Calorimetry (DSC) and X-ray diffractometer (XRD) and also evaluated for particle size, encapsulation efficiency, production yield, swelling capacity, mucoadhesive properties, zeta potential and drug release. The microcapsules were smooth and showed no visible cracks and extended drug release of 55.2006% up to 12 hours in phosphate buffer of pH 6.8, showing particle size within the range of 264.5-358.5 µm, and encapsulation efficiency of 99.337±0.0100-66.2753±0.0014%.The in vitro release data of optimized batch of microcapsules were plotted in various kinetic equations to understand the mechanisms and kinetics of drug release, which followed first order kinetics, value of "n" is calculated to be 0.459 and drug release was diffusion controlled. The mice were fed with diet for inducing high blood pressure and the in vivo antihypertensive activity of formulations was carried out administering the optimized formulations and pure drug separately by oral feeding and measured by B.P Monwin IITC Life Science instrument and the results indicated that the bioavailability of carvedilol was increased both in vitro and in vivo with the mucoadhesive polymers showing primary role in retarding the drug release

SOLUBILITY ENHANCEMENT OF RIVAROXABAN BY SOLID DISPERSION WITH POLYETHYLENE GLYCOL 4000

Objective: The aim of the work was to enhance the dissolution rate of rivaroxaban by preparing its solid dispersions (SDs) using hydrophilic carrier PEG 4000. Methods: The SDs of rivaroxaban with PEG 4000 were prepared at 1:1, 1:2 and 1:3 w/w ratios by physical mixing, melting and solvent evaporation techniques. The prepared solid dispersions were characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Both solubility and dissolution rate of the drug in these formulations were increased. The used hydrophilic carriers showed more than two fold increase in dissolution rate in their prepared solid dispersions by melting or solvent evaporation techniques. The pure drug rivaroxaban as the pure drug shows a dissolution rate of nearly 39 % after 60 m, where as the solid dispersions by melting or solvent evaporation showed 90% of dissolution after 60 m. The FTIR spectroscopic and DCS thermal studies showed the compatibility of rivaroxaban and absence of well-defined drug polymer interactions, though shift in peaks observed due to formation of new bonds. Conclusion: Formulation of solid dispersions of drug with hydrophilic carriers is a successful approach for solubility or dissolution rate enhancement of low soluble drug(s). In this work for solubility enhancement of rivaroxaban the hydrophilic carrier PEG 4000 showed significant solubility enhancement