Swelling and drug release in hydrogel matrices: polymer viscosity and matrix porosity effects (original) (raw)
Related papers
2013
Polymers are very popular and widely used in formulating sustained release tablets because they are excellent drug carriers. The current study examines the relationship between swelling and drug release from the hydrophilic matrices of diltiazem hydrochloride prepared using different grades of hydroxypropyl methylcellulose (HPMC), viz, HPMCK4M, HPMCK15M and HPMCK100M. The results indicate that swelling and release profiles were affected by concentration and viscosity grade of the polymer. When the amount of polymer in the matrix is high, wetting improves and water uptake into matrices is enhanced. The higher amount of polymer causes a greater degree of swelling this in turn reduces the drug release, as the diffusional path length of drug is now longer. Conversely, reduction in the amount of polymer reduces the degree of swelling and the thickness of gel layer, this enables faster drug release. Swelling studies reveals an inverse relationship between swelling and drug release in the ...
European Journal of Pharmaceutical Sciences, 1999
In the present work, the drug volume fraction profiles of a colored and very soluble drug, buflomedil pyridoxal phosphate, in the gel layer of initially glassy hydroxypropylmethyl cellulose matrices were studied, using image analysis of pictures of the matrices during swelling and release. The goal was to correlate the drug release kinetics with the dynamic behavior of the drug gradient in the gel layer. An inert (nonswellable) matrix, manufactured by substituting hydroxypropylmethyl cellulose with an inert polymer and containing the same amount of buflomedil pyridoxal phosphate, was prepared as well. The drug color gradient in the partially extracted region and the flux of this matrix were compared to the swellable matrix. The drug gradient in the dissolved drug gel layer of swellable matrices was observed. It was demonstrated that drug release kinetics does not only depend on drug diffusion and matrix erosion, but also on drug dissolution in the gel and on polymer relaxation.
International Journal of Pharmaceutics, 2011
Design and realization of drug delivery systems based on polymer matrices could be greatly improved by modeling the phenomena which take place after the systems administration. Availability of a reliable mathematical model, able to predict the release kinetic from drug delivery systems, could actually replace the resource-consuming trial-and-error procedures usually followed in the manufacture of these latter.
Controlled drug release from hydrogel-based matrices: experiments and modeling
International journal of pharmaceutics, 2015
Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.
Modeling the Drug Release from Hydrogel-Based Matrices
Molecular Pharmaceutics, 2014
In this work the behavior of hydrogel-based matrices, the most widespread systems for oral controlled release of pharmaceuticals, has been mathematically described. In addition, the calculations of the model have been validated against a rich set of experimental data obtained working with tablets made of hydroxypropyl methylcellulose (a hydrogel) and theophylline (a model drug). The model takes into account water uptake, hydrogel swelling, drug release, and polymer erosion. The model was obtained as an improvement of a previous code, describing the diffusion in concentrated systems, and obtaining the erosion front (which is a moving boundary) from the polymer mass balance (in this way, the number of fitting parameters was also reduced by one). The proposed model was found able to describe all the observed phenomena, and then it can be considered a tool with predictive capabilities, useful in design and testing of new dosage systems based on hydrogels.
To Evaluate and Study the Swelling and Drug Release Behavior of Poly (N-Vinyl-2-Pyrrolidone) Gel
The drug loading and drug release efficiency of the P (N-vinyl-2-pyrrolidone) hydrogel was evaluated using the ketotifen as model drugs. The hydrogel was cut into small discs (3 mm thickness and diameter) and immersed in the solutions of the ketotifen for three days to achieve the maximum (equilibrium) swelling. The hydrogel immersed in 0.1 N HCl and phosphate buffers (pH 6.8) showed the 31.828 % and 29.783 % loading of the ketotifen by weight of the dried hydrogel, respectively that was not significantly difference (p was greater than 0.05). However, the slow swelling behavior of the hydrogel in the acidic medium was observed in the absence of the drug. The method of analysis of ketotifen using U.V-visible spectrophotometer and HPLC was developed for the analysis of these components in the dissolution medium. The methods were linear (r = 0.9967) over the range of 0.1 to 10 µg.ml for ketotifen using U.V Visible spectrophotometer and 2 1 HPLC respectively. The precision, accuracy and reproducibility of the methods were in an agreeable range to analyze the samples obtained from the dissolution medium. The various parameters for the methods of analysis of the ketotifen using spectrophotometer and HPLC methods were validated. The linearity of the method using UV Visible spectrophotometer and HPLC were (r = 0.9967). The release of ketotifen from the P (N-vinyl-2-2 pyrrolidone) hydrogel under acidic condition was only 10 % of the drug released in about 72 hours and followed Higuchi model and drugs were released through Fickian diffusion. The data was best fitted in the Higuchi model (R = 0.9566) indicating the drug release followed Fickian diffusion. The application of the 2 Korsmeyer's equation showed that the release of ketotifen release from the hydrogel disc followed the Fickian diffusion. Under basic conditions (pH 6.8), it was observed that the in-vitro release of ketotifen from hydrogel disc GS2 best fitted to the Hixon-Crowell (0.9917) indicating the erosion and dissolution of hydrogel. As the value of (n) for the GS2 was 1.2634, it indicating that the release of ketotifen from hydrogel disc followed non-Fickian super case II release. Under mixed conditions (for the first two hours in acidic condition (pH 0.1N HCl) and then for the rest of time at (pH 6.8), it was found that the in-vitro release of ketotifen from hydrogel loaded disc GS3 best fitted to the Higuchi model (0.9821) indicating the drug release followed Fickian diffusion. The value (0.9216) of release exponent "n" obtained with Korsmeyer's-Pappas equation suggested that drug release from GS3 formulation followed anomalous transport.
Characterisation and controlled drug release from novel drug-loaded hydrogels
European Journal of Pharmaceutics and Biopharmaceutics, 2008
Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly(N-isopropylacrylamide)-poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for 'smart' drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.
International Journal of Pharmaceutics, 2007
The objective of this investigation was to explore the effects of drug solubility on the evolution of matrix dimensions and gel layer's during drug release and investigate the relationship between these effects and the mechanism and the rate of drug release. Two hydrophilic swellable polymers Polyox (POL) and cross-linked Carbopol (CARB) were employed as carriers. Caffeine (CAF) and theophylline (THE), two drugs having similar chemical structure but different aqueous solubility, were used as model drugs. Both drug and polymer characteristics were found to influence the dimensional changes of matrices and the development of the gel layer formed around the glassy core. The dimensional expansion in CAF matrices was always more pronounced than the THE matrices. Also the CARB matrices demonstrated greater maximum expansion and lower drug release than the POL matrices, due to a smaller degree of erosion of CARB. The dimensions of CARB/CAF matrices, unlike all the other matrices studied, exhibited a biphasic increase at early times, which was attributed to the cross-linked structure of CARB and the high solubility of CAF. With both polymers, a thinner gel layer was developed in the matrices containing the less soluble THE compared to the CAF matrices. The thickness of the gel layer increased continuously with time in the CAF matrices whereas it increased initially and after reaching a maximum started to decrease in THE matrices. All formulations except those of CARB/THE exhibited burst release, which depended on drug and polymer characteristics. The gel layer thickness and erosion rate appeared to determine the rate of drug release from the CARB and POL formulations. The results clearly indicate that for these matrices gel thickness and fluctuation of gel thickness affect the release rate/h of drug proportionally. Analysis of the release kinetics indicated that CAF was released mainly through diffusion whereas, THE was released mainly through matrix erosion.
Swellable Hydrogel-based Systems for Controlled Drug Delivery
Smart Drug Delivery System, 2016
The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles. When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass-rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, "eroding" the matrix. This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.
Controlled Release of Drugs FromHydrogel Based Matrices Systems: Experiments and Modeling
2012
Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of experimental data, obtained working with matrices systems based on HPMC (Hydroxy Propyl Methyl Cellulose). The proposed model was found able to reproduce main features of the observed phenomena, it can thus be adopted for prediction of the performances of drug release systems from hydrogel matrices.