Background: Inflammatory bowel diseases (IBD) require effective colon-targeted drug delivery for improved therapeutic efficacy and minimized systemic side effects. Objectives: The objective of this ...research was to develop and evaluate novel colon-targeted matrix tablet formulations of mesalamine (5-aminosalicylic acid) for the treatment of IBD. Materials and Methods: Mesalamine matrix tablets were prepared by wet granulation technique using pH-sensitive polymers (HPMC K4M) and biodegradable natural polysaccharides (pectin, chitosan, and guar gum). Tablets were characterized for physicochemical properties, drug content, and in vitro drug release. Compatibility studies using FTIR and DSC confirmed no interaction between mesalamine and polymers. The optimized formulations were enteric-coated with Eudragit S100 and ethyl cellulose. Drug release kinetics and stability studies were conducted. Results and Discussion: The uncoated formulations (M3, M6, M7) showed adequate protection against drug release in simulated gastric (0-2 h) and intestinal (2-5 h) fluids. The enteric-coated formulations (ME3, ME6, ME7) exhibited a lag time of around 2 hours and restricted drug release (<5%) in simulated gastric and intestinal fluids up to 5 hours. However, in simulated colonic fluid (pH 6.8) containing 4% rat cecal contents, these formulations showed enhanced drug release (71-83% in 12 h) due to biodegradation of polymeric matrices by colonic enzymes. Drug release kinetics indicated anomalous transport or super case-II transport mechanisms. Stability studies at 40°C/75% RH for 3 months revealed no significant changes. Conclusion: The developed colon-targeted mesalamine matrix tablets demonstrated the potential to protect the drug from release in the upper GIT while facilitating targeted drug delivery to the colon, which could improve therapeutic efficacy and minimize systemic side effects in the treatment of IBD.
In this paper we review the mathematical models used to determine the kinetics of drug release from drug delivery systems. The quantitative analysis of the values obtained in dissolution/release ...rates is easier when mathematical formulae are used to describe the process. The mathematical modeling can ultimately help to optimize the design of a therapeutic device to yield information on the efficacy of various release models.
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.
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 the solubility and dissolution rate of the drug in these formulations were increased. The used hydrophilic carriers showed a 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, whereas 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 the absence of well-defined drug polymer interactions, though the shift in peaks was observed due to the 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.
Objective: To evaluate the anti-inflammatory effect of Nardostachys jatamansi (N. jatamansi) rhizome against acute, subacute and chronic models of inflammation in experimental animals. Methods: N. ...jatamansi rhizome extract (150 and 300 mg/kg, p.o.) and the reference drugs phenylbutazone (100 mg/kg, p.o.) and acetylsalicylic acid (300 mg/kg, p.o.) were evaluated using models for inflammation (autacoids induced hind paw oedema, formaldehyde induced hind paw oedema, carrageenin-induced paw oedema, cotton pellet granuloma and subcutaneous air pouch model). Results: In acute inflammation as produced by carrageenin 29.06% and 55.81%, by histamine 25.0% and 39.28%, by 5-hydroxytryptamine 21.37% and 36.95% and by prostaglandin E2-induced hind paw oedema 31.03% and 44.82% protection was observed. While in subacute anti-inflammatory models using formaldehyde-induced hind paw oedema (after 1.5 h) 13.88% and 33.33% and in chronic anti-inflammatory model using cotton pellet granuloma 7.4% and 17.58% protection from inflammation was observed. N. jatamansi rhizome extract also inhibited the inflammatory mediators (nitric oxide by 12.81% and 38.41%, by prostaglandin E2 12.58% and 47.82% while by TNF- alpha 13.51% and 41.89%) produced in the pouch. Conclusions: The results of this study strongly indicate the protective effect of N. jatamansi rhizome extract against acute, subacute and chronic models of inflammation, which may be attributed to its anti-inflammatory potential.
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