Polymer Matrix Tablets Research Articles

The Effect of Polymer-Solvent Interaction on the Swelling of Polymer Matrix Tablets: A Magnetic Resonance Microscopy Study Complemented by Bond Fluctuation Model Simulations.

Polymer matrix tablets are an important drug-delivery system widely used for oral drug administration. Understanding the tablet hydration process, both experimentally and theoretically, is, thus, very important for the development of drug delivery systems that exhibit high drug loading capacity and controlled release potential. In this study, we used magnetic resonance microscopy (MRM) to nondestructively and dynamically analyze the water hydration process of xanthan-based tablets. The swelling process was characterized by well-resolved fronts of erosion, swelling, and penetration. The experimental results were complemented by numerical simulations of the polymer matrix hydration process. In the simulations, the polymer tablet matrix was modeled as an assembly of interacting chains with embedded drug particles, while its hydration process was mediated by interaction with solvent particles. The swelling dynamics were modeled within a Monte Carlo-based bond fluctuation model (BFM) that elegantly accounted for steric and nearest-neighbor interactions. This study provides an efficient experimental-theoretical approach for the study of polymer matrix swelling processes.

Polymer Tablet Matrix Systems for the Controlled Release of Dry Betula pendula Leaf Extract.

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 33 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Development composite polymer matrix tablets with a preset time of isosorbide dinitrate release by the method of mathematical modeling

The kinetics of release of isosorbide dinitrate from coated and uncoated granules with a diameter of 0.5–0.8 mm and 0.8–1.25 mm used for the preparation of matrix tablets was studied. A statistical analysis of the results is made. For the same time value and different pH values, the mean values of release and empirical values of the Shapiro – Wilk criterion were calculated. For a series of series at the same time and different pH, the empirical values of the Cochren test and the non-parametric Cruskell – Wallis test are calculated considering the repeating groups and the Iman – Davenport correction for the number of elements in the sample. A low pH effect on release kinetics has been established. When modeling the release of pellet-based tablets, the characteristics of the normal distribution for each of the granule types and each time value are used. The amount of each type of granules that make up the tablet core is calculated to achieve the desired release profile in Excel using the Search Solver add-in. For the mean values of release for the granules of three types by the least square’s method, we obtained the mass values of the total content of isosorbide dinitrate. For experimental verification of the model, a batch of matrix tablets was prepared using coated and uncoated granules with a diameter of 0.5–0.8 mm. A study of the kinetics of release of isosorbide dinitrate from tablets at pH 1.2; 4.5; 6.8. A statistical analysis of the obtained data and a comparison of the results with calculations by the model were carried out. It has been established that the approach used makes it possible to describe the release of isosorbide dinitrate from tablets with an acceptable accuracy. The accuracy criterion is established - the experimental profile of release of the developed composition falls within the boundaries between the maximum and minimum desired profile. As a result of the research, a composite drug of prolonged action Dikor Long based on isosorbide dinitrate has been developed. The drug has passed state tests, its industrial production has been adjusted in Research and Production Company "Microkhim".

Evaluation of swelling processes of various natural polymer matrix tablets by X-ray computed tomography and controlled drug release.

The swelling properties and the drug-release sustainability of pre-gelatinized starches (𝛼-starch) tablets depend on the polymer characteristics. In order to clarify the drug release form, the natural polymers (NPs) were investigated. The relationship between drug release and swelling of natural polymers (NPs), the swelling processes of various starch polymers, were investigated using a drug-release test (DRT) and X-ray computed tomography (XCT). NPs consisting of various starches such as glutinous rice starch (GRS), corn starch (CS), and tapioca starch (TS) were used as additives for sustained drug-release tablets. Tablets consisted of 5% theophylline, 94% 𝛼-starch, and 1% magnesium stearate and were compressed at 6 kN. DRTs were measured in distilled water at 37 °C, and the drug concentrations were measured using UV (271 nm). Swelling ratio (R) profiles of the tablets during DRTs were evaluated based on XCT images. The order of the drug-release rate constant of the tablets was TS < GRS < CS. XCT images of the tablets were measured during the DRTs, and CS, GRS, and TS tablets swelled and showed increased gel-layers, and then finally disintegrated at 6, 9, and 11 h, respectively. The relationship between R profile and the % drug release of the tablets differed depending on the kind of NP used.

Mechanochemical effect on swelling and drug release of natural polymer matrix tablets by X-ray computed tomography

The relationships between the physicochemical properties of milled starch and drug release from tablets were investigated quantitatively using a drug release kinetic method and X-ray computed tomography (XCT). The samples were prepared from raw β-starch by milling in a planetary ball mill. The tablets, containing 5% theophylline (TH), 94% milled starch, and 1% magnesium stearate, were compressed at 6 kN. The drug-release and gel-forming processes were measured simultaneously using an original dissolution tester with an XCT instrument. Drug release from the tablet was delayed with increasing milling time, because the TH tablet formed a typical gel-layer on the outside of the tablet. The relationship between the crystallinity of milled starch and mean drug release time (MDT) for the TH tablets showed almost a straight inverse proportional relationship. The plots of MDT against area under the curve of the swelling ratio profiles of the TH tablets had a good straight line.

Control of the Dissolution Profile of Paracetamol from Carbomer Matrix Tablets

Results of experiments on prolonged release of paracetamol from polymer matrix tablets with cross-linked poly(acrylic acid) Carbopol® Ultrez 21 as the prolonging polymer were reported. The effects of factors such as tableting technology, type of alkaline agent, and ratio of Carbopol® to alkaline agent on paracetamol release kinetics were studied. It was established that matrices prepared by wet granulation had the best potential for prolonging the release. The ratio of Carbopol® to alkaline agent and their relative amounts also enabled the drug release rate to be prolonged.

Swelling, erosion and drug release characteristics of Sodium Diclofenac from heterogeneous matrix tablets

The aim of this study was to investigate the effect of combination lipophilic (Acryl-EZE®) and hydrophilic (HPMC) polymers on the release of Sodium Diclofenac (DS) from a tablet. The microgranules were prepared using a fluidized bed followed by direct compression. Swelling and erosion studies of polymer matrix tablets were carried out in various media. The matrix tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. The swelling action of matrices was controlled by the rate of its hydration in the medium. The in vitro release was examined with and without rat caecal contents. Release studies showed that the swelling and erosion influenced the drug release. The good fit to Higuchi equation, the n values from Korsmeyer equation and the prevalence of kd over kr in Peppas-Sahlin equation revealed a drug release mechanism controlled mainly by diffusion.

Quantifying the release of lactose from polymer matrix tablets with an amperometric biosensor utilizing cellobiose dehydrogenase.

The release of lactose (hydrophilic) from polymer tablets made with hydrophobically modified poly(acrylic acid) (HMPAA) have been studied and compared to the release of ibuprofen, a hydrophobic active substance. Lactose is one of the most used excipients for tablets, but lactose release has not been widely studied. One reason could be a lack of good analytical tools. A novel biosensor with cellobiose dehydrogenase (CDH) was used to detect the lactose release, which has a polydiallyldimethylammonium chloride (PDADMAC) layer that increases the response. A sample treatment using polyethylenimine (PEI) was developed to eliminate possible denaturants. The developed methodology provided a good approach to detect and quantify the released lactose. The release was studied with or without the presence of a model amphiphilic substance, sodium dodecyl sulphate (SDS), in the release medium. Ibuprofen showed very different release rates in the different media, which was attributed to hydrophobic interactions between the drug, the HMPAA and the SDS in the release medium. The release of hydrophilic lactose, which did not associate to any of the other components, was rapid and showed only minor differences. The new methodology provides a useful tool to further evaluate tablet formulations by a relatively simple set of experiments.

Microwave assisted synthesis and optimization of Aegle marmelos-g-poly(acrylamide): Release kinetics studies

Microwave assisted grafting of poly(acrylamide) on to Aegle marmelos gum was carried out employing 3-factor 3-level full factorial design. Microwave power, microwave exposure time and concentration of gum were selected as independent variable and grafting efficiency was taken as dependent variable. A. marmelos-g-poly(acrylamide) was characterized by FTIR, DSC, X-ray diffraction and scanning electron microscopy.Microwave power, microwave exposure time had synergistic effect on grafting efficiency where as concentration of the gum did not contributed much to grafting efficiency. Batch having microwave power – 80%, microwave exposure time −120s and concentration of A. marmelos gum – 2% was selected as the optimized formulation. Comparative release behaviour of diclofenac sodium from the matrix tablets of A. marmelos gum and A. marmelos-g-polyacrylamide was evaluated. The results of kinetic studies revealed that the graft copolymer matrix, marketed tablets and polymer matrix tablets of A. marmelos gum released the drug by zero order kinetics and with n value greater than 1, indicating that the mechanism for release as super case II transport i.e. dominated by the erosion and swelling of the polymer.

Quantification of the types of water in Eudragit RLPO polymer and the kinetics of water loss using FTIR

Coalescence of polymer particles in polymer matrix tablets influences drug release. The literature has emphasized that coalescence occurs above the glass transition temperature (Tg) of the polymer and that water may plasticize (lower Tg) the polymer. However, we have shown previously that nonplasticizing water also influences coalescence of Eudragit RLPO; so there is a need to quantify the different types of water in Eudragit RLPO. The purpose of this study was to distinguish the types of water present in Eudragit RLPO polymer and to investigate the water loss kinetics for these different types of water. Eudragit RLPO was stored in tightly closed chambers at various relative humidities (0, 33, 56, 75, and 94%) until equilibrium was reached. Fourier transform infrared spectroscopy (FTIR)-DRIFTS was used to investigate molecular interactions between water and polymer, and water loss over time. Using a curve fitting procedure, the water region (3100-3,700 cm(-1)) of the spectra was analyzed, and used to identify water present in differing environments in the polymer and to determine the water loss kinetics upon purging the sample with dry compressed air. It was found that four environments can be differentiated (dipole interaction of water with quaternary ammonium groups, water cluster, and water indirectly and directly binding to the carbonyl groups of the polymer) but it was not possible to distinguish whether the different types of water were lost at different rates. It is suggested that water is trapped in the polymer in different forms and this should be considered when investigating coalescence of polymer matrices.

Addressing potent single molecule AFM study in prediction of swelling and dissolution rate in polymer matrix tablets

Our goal was to understand and thus be able to predict the swelling behavior of xanthan matrix tablets in media of various pH and ionic strengths using data obtained from single xanthan molecules and films with atomic force microscopy. Imaging was performed in 1-butanol using contact mode AFM in order to characterize single xanthan chains prepared from various solutions. Image analysis was used to calculate the molecular contour, persistence length, and radius of gyration. Nanoindentation measurements of xanthan films were carried out to evaluate their mechanical properties. Increasing the ionic strength of solutions induced reductions in chain parameters such as molecular contour, persistence length, and radius of gyration. Nanomechanical measurements demonstrated that Young’s moduli of xanthan films prepared from solutions with higher ionic strengths are twice as large as those prepared at lower ionic strengths. This may help explain xanthan matrix tablets’ reduced degree of swelling and faster dissolution rate in the presence of salts or ions. We successfully come to conclusion that microscopic polymer properties such as radius of gyration and persistence length are responsible for the macroscopic polymer behavior. For instance, longer persistence lengths and radius of gyration of xanthan’s chains result in a higher degree of swelling, corresponding to softer polymer films, increased gel layers in matrix, and a slower release rate of the incorporated drug from the tablets.

Using quantitative magnetic resonance methods to understand better the gel-layer formation on polymer-matrix tablets

Introduction: Magnetic resonance imaging is a powerful, non-invasive technique that can help improve our understanding of the hydrogel layer formed on swellable, polymer-matrix tablets, as well as the layer's properties and its influence on drug release.Areas covered: In this paper, the authors review the NMR and MRI investigations of hydrophilic, swellable polymers published since 1994. The review covers NMR studies on the properties of water and drugs within hydrated polymers. In addition, MRI studies using techniques for determining the different moving-front positions within the swollen tablets, the polymer concentration profiles across them, the influence of the incorporated drug, and so on, are presented. Some complementary methods are also briefly presented and discussed.Expert opinion: Using MRI, the formation of a hydrogel along with simultaneous determination of the drug's position within it can be observed non-invasively. However, the MRI parameters can influence the signal's intensity and therefore they need to be considered carefully in order to prevent any misinterpretation of the results. MRI makes possible an in situ investigation of swollen-matrix tablets and provides valuable information that can lead, when combined with other techniques, to a better understanding of polymeric systems and a more effective development of optimal dosage forms.

Monitoring of swelling of hydrophilic polymer matrix tablets by ultrasound techniques

The aim of this study was to investigate the ability of ultrasound (US) techniques to monitor the swelling behaviour of hydrophilic polymer matrix tablets. Tablets were prepared from hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) polymers. The movement of the eroding front was investigated with ultrasound scanning techniques on each tablet's outer interface during tablet immersion in phosphate buffer (PB). In addition, a US window technique was utilized to simultaneously evaluate eroding and swelling front movements during the tablet dissolution process. An optical monitoring was used as the reference method. The focused pulsed echo ultrasound method was found to be applicable for evaluating the swelling process of hydrophilic polymer matrix tablets. Furthermore, it was noted that the sensitivity to follow hydrogel formation and thickening by US monitoring varied depending on the polymer under study. Thus, multifront detection is challenging since the hydrogels formed by different polymers may have totally different acoustic properties. It was found that the microbubbles formed inside the hydrogel were acting as a “contrast agent”, characteristic of some polymers during immersion. In spite of these challenges, the US window technique introduced in this study was proven to be a promising method for simultaneous multifront detection.

Mechanical properties of excipients do not affect polymer matrix formation

Coalescence of polymer particles has been identified as a crucial step in film formation on tablets, pellets and granules. Though the significance of thermal treatment on matrix dosage forms is well established the process of coalescence in matrix formation and the forces driving it remain unexplored. The aim of this study was to investigate whether stresses in tablets, caused by deformation of excipient during compression, provide a driving force for polymer matrix formation. Polymer matrix tablets containing Eudragit-RLPO, a pH independent and permeable polymer at two levels 10 and 40% (w/w) were prepared by direct compression. Either lactose monohydrate (brittle) or mannitol (plastic) was used as a diluent at 80 or 50% (w/w) and indomethacin, a model drug was present at 10% (w/w). Tablets from each formulation type were prepared at two compression pressures either 221 MPa (above the yield pressure of both excipients) or 74 MPa (below the yield pressure of both excipients). Tablets from each formulation type compressed at the two compression pressures were thermally treated at 40 °C (below T g) or 70 °C (above T g) for 24 h. The rotating basket (100 rpm) method was used for the release studies conducted at 37 °C in 900 ml phosphate buffer (0.2 M) pH 7.2 as the dissolution medium. Morphological characteristics of the tablets were observed by scanning electron microscopy. Differences in tablet structure due to the formulation and processing variables were further evaluated by disintegration and tensile strength testing. Data from this factorial study were analysed by analysis of variance. Excipient mechanical properties determine matrix properties only at low polymer level independent of curing temperature and at high polymer level cured at 40 °C only. Though lactose and mannitol have different mechanical properties and therefore different deformation behaviors, this did not influence the properties of tablets containing 40% (w/w) polymer cured at 70 °C, suggesting stresses in these tablets are not a significant driving force for matrix formation.

Evaluation of the bioadhesive property of Grewia gum in indomethacin tablet formulation in pig gastric mucus

The bioadhesive property of grewia gum for sustained release of Indomethacin from tablets was evaluated using pig gastric mucus as substrate. The tablets formulated by wet granulation contained 75 mg of the drug and 15 or 20 %w/w of the gum. Similar tablets made differently with carbopol 934, tragacanth and sodium carboxymethylcellulose (SCMC) were used as basis for comparison. Hydration of tablets and substrate surfaces was done using 0.1N hydrochloric acid and phosphate buffer providing pH values of 1.2 and 7.4 respectively. The force required to detach the tablets from substrate surface was determined in a testometric material testing machine. Drug release from polymer matrix tablets was fastest for tragacanth and slowest for carbopol 934. The detachment force of tablets from substrate was found to increase in the order: carbopol 934 > SCMC > grewia gum > tragacanth. The detachment force was affected by the pH of the hydration medium. On the basis of these grewia gum may find application as bioadhesive polymer for sustained release tablet formulation. Keywords: Indomethacin; Pig gastric mucus, Grewia gum, Bioadhesive performance Journal of Pharmacy and Bioresources Vol. 3 (2) 2006: pp. 62-69

Factors Influencing Drug Dissolution Characteristic from Hydrophilic Polymer Matrix Tablet

The aim of this work was to investigate the factors influencing the dissolution characteristics of drug substances from hydrophilic polymer matrix tablets. Various kinds of cellulose derivative polymers were used in for matrix formation. Their swelling propertiesy waswere measured. The effects on drug release was firstly carried were studiedout in comparison with lactose. Results showedindicate that drug release characteristics from polymer matrix tablets followed a Higuchi square root time kinetics. It was found that the polymers could retard the release of drugs in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), but at different levels. The dissolution constants of drugs exhibitedwere higher when the pH of the dissolution medium was increased. Results also demonstratedindicate a the linear correlation between the proportions of matrix-forming structures in the tablets and the extent of dissolution retardation. It was found that not only the swelling property of the polymer but also its hydrophobicity and the hardness of the tablet played an important role onin the retardation of drug release. Results also revealedindicate that PVP K30 could supports cellulose polymers so as to improve the release behavior in order keep a better control to maintain a constant drug release in each time interval.in order to better keep drug release constant in each time interval.

Acrylamide‐grafted‐acacia gum polymer matrix tablets as erosion‐controlled drug delivery systems

AbstractAcrylamide was grafted onto acacia gum in different ratios (1 : 1, 1 : 3, and 1 : 5). The graft copolymers formed were characterized by FTIR, rheological measurements, and differential thermal analysis. Tablets were prepared from these polymers loaded with two antihypertensive drugs, viz., diltiazem hydrochloride and nifedipine. The in vitro release experiments were carried out in simulated gastric and intestinal conditions. The graft copolymer prepared in the ratio 1 : 5 of acacia gum : acrylamide matrix was found to be a suitable matrix to investigate the controlled release of diltiazem hydrochloride and nifedipine. The drug release continued up to 6 and 14 h, respectively, for diltiazem hydrochloride and nifedipine. The release mechanism was investigated by using the mathematical equations proposed by Higuchi, Hixson‐Crowell, and Kopcha. Based on the release kinetics data, a correlation was attempted between the erosion‐controlled release and the dissolution‐controlled release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2245–2253, 2004

Sustained-release hydrophilic matrix tablets of zileuton: formulation and in vitro/in vivo studies

Zileuton is a new active 5-lipoxygenase inhibitor which has been shown to be clinically effective in the treatment of asthma. It is a racemic mixture of S- and R-enantiomers. In the present study, hydrophilic polymer matrix tablets were used for oral controlled delivery of zileuton. The prototype formulations with drug loading of 50–60% were prepared and tested in vitro using USP apparatus I, II and III. In vivo absorption of three formulations with differing release rates was evaluated using crossover designs in beagle dogs. Plasma concentrations of the two enantiomers of zileuton were analyzed by a chiral HPLC method. The results indicated that the release of zileuton from the matrix tablets followed apparent zero-order kinetics when tested using USP apparatus I and II. Prolonged absorption of zileuton was achieved using the hydrophilic matrix system. In vivo drug release estimated by deconvolution based on the data of both S- and R-enantiomers was correlated with in vitro release. Linear relationships between in vitro and in vivo release were obtained with more rapid in vivo release than in vitro.

&lt;i&gt;In vitro&lt;/i&gt; Release Kinetic Study of Theophylline from Eudragit RS PO and Eudragit RL PO Matrix Tablets

The aim of the present study was to investigate the release kinetics of theophylline from permeableacrylic polymer matrix tablets. Matrix tablets were prepared by direct compression method using Eudragit RS PO andEudragit RL PO. Two batches of matrix tablets were prepared. Only Eudragit RS PO was used in the first batch, andin the second batch both Eudragit RS PO and Eudragit RL PO were used as the rate retarding polymers in differentproportions. The variation of hardness was insignificant in batches. Drug release was investigated by using USPbasket method and the results of release rates were analyzed by using correlation coefficient value of Zero orderrelease plot &amp; Higuchi plot and exponent value of Bi-exponential release profile. Theophylline tablets having onlyEudragit RS PO showed comparatively slow release but release rate improved significantly as seen in formulationscontaining Eudragit RL PO and Eudragit RS PO. It was also revealed that, in all cases the release of theophyllinefollowed mixed release kinetics where Zero order release kinetics was predominant.Key words: Sustained release; matrix tablet; theophylline; acrylic polymers; eudragit; release rate; dissolution;hardness.DOI: 10.3329/dujps.v8i1.5328Dhaka Univ. J. Pharm. Sci. 8(1): 1-6, 2009 (June)