Hydrophilic Matrix Systems Research Articles

HYDROPHILIC MATRIX TABLETS AS ORAL CONTROLLED DRUG DELIVERY SYSTEMS IN 20TH CENTURY: A REVIEW

Matrix systems are easy to formulate compared to other controlled release dosage forms. The manufacture of matrix tablets involves the direct compression of blend of drug, retardant material and additives to form a tablet in which drug is embedded in a matrix core of the retardant. Alternatively, retardant-drug blends may be granulated prior to compression. Of the three classes of retardant material used to formulate matrix tablets, polymers that form hydrophilic matrices are attracting the attention of pharmaceutical technologists. These polymers include Methyl cellulose (MC), Hydroxy ethyl cellulose (HEC), Hydroxy popyl methyl cellulose (HPMC), Sodium carboxy methyl cellulose (NaCMC), carbomers, chitosan, plant gums etc. The hydrophilic matrix-formers alone or in combination with other excipients form gels in situ on coming in contact with biological fluids which control the drug release. The present review gives a detailed account on the factors to be considered in the design of hydrophilic matrix systems, formulation of hydrophilic matrix tablets, in vitro and in vivo evaluation methods and advances in the design of hydrophilic matrix tablets. This review further focuses on the development of oral controlled drug delivery systems using hydrophilic matrix carriers in 20th century.

Recent Approaches of Matrix Release Tablet in NDDS System

The purpose of this analysis is to categorize matrix tablets according to the kind of polymer they are made of as well as the rate at which they release their contents. When it came to medicinal applications, the matrix system was the very first oral extended release platform ever developed. The utilization of matrix tablets enables the modification of drug release characteristics. They are highly favored for this kind of treatment because of the benefits they give for the patient in terms of better adherence to the treatment, more stable medication levels, decreased dose and bad effects, and a bigger safety margin for highly potent medications. Because of their versatility in delivering a desired drug release profile, cheap cost, and general regulatory acceptability, hydrophilic polymer matrix systems are frequently used in oral controlled drug delivery dosage forms. Because of the rapid diffusion of the dissolved medication via the hydrophilic gel network, the use of hydrophilic matrix alone for delayed drug release is not possible for medicines that are very water soluble. It is now generally accepted that the formulation of such drugs requires the use of matrix systems that incorporate hydrophobic polymers. It would appear that the most successful strategy would be to create a formulation for oral controlled release by employing matrix tablets.

Preparation, Characterization and Optimization of Sustained Release Matrix Tablets of Repaglinide using Box–Behnken Design

The aim of this investigation was to develop and optimize the Sustained release Matrix formulations of Repaglinide (RLD) using response surface methodology by employing a 3-factor, 3-level Box–Behnken statistical design. The independent variables studied were the amount of hydroxypropyl methylcellulose (HPMC K4M), Ethyl cellulose (EC) and PVP K30. The Swelling index (Y1), drug release at 8 hr and 12hr were the target responses. The response surface methodology and multiple response optimizations utilizing a polynomial equation were used to search for the optimal formulation with a specific release rate at different time intervals. The results showed that the effect of combination of HPMC K4M and EC was the most influencing factor on the drug release from ER matrix tablets. The mechanism of drug release from RLD Matrix tablets was dependent on the added amount of EC. Validation of the optimization technique demonstrated the reliability of the model. The optimized formulation containing 50mg of HPMC K4, 35mg of EC, and 30mg of PVP K30 was prepared according to the software determined levels. DSC and FTIR studies combined with the stability study of the optimized formulation proved the integrity of the developed formulation. The Box–Behnken experimental design facilitated the formulation and optimization of extended release hydrophilic matrix systems of RLD in a short period of time and with the fewest number of experiments. The optimized Matrix tablet of Repaglinide showed good pharmacokinetic result over conventional formulation.

Hydrophilic matrix system coated by polyvinyl acetate emulsion versus calcium alginate for sustained acetylsalicylic acid release

Hydrophilic matrix system coated by polyvinyl acetate emulsion versus calcium alginate for sustained acetylsalicylic acid release

The role of matrix tablet in controlled release drug delivery system

The purpose of this review article is to characterize all of the parameters regarding the types, polymers used, and release kinetics of matrix tablets. Matrix system was the earliest oral extended-release platform for medicinal use. Matrix tablets are most commonly used methods to modulate the release profile of drugs. They are much desirable and preferred for such therapy because they offer better patient compliance, maintain uniform drug levels, reduce dose and side effects, and increase safety margin for high potency drugs. Hydrophilic polymer matrix systems are widely used for designing oral controlled drug delivery dosage forms because of their flexibility to provide a desirable drug release profile, cost effectiveness, and broad regulatory acceptance. However, the use of hydrophilic matrix alone for extending drug release for highly water-soluble drugs is restricted due to rapid diffusion of the dissolved drug through the hydrophilic gel network. For such drugs it becomes essential to include hydrophobic polymers in the matrix system. This leads to the conclusion that matrix tablets seem to be most promising when developing an oral controlled release formulation.

Role of Aminated Derivatives of Natural Gum in Release Modulating Matrix System of Losartan Potassium

Objective: The investigation aimed to synthesize amino derivatives of various natural gums like Xanthan gum and Tamarind gum for using them as a release modulating polymer in the formulation of the hydrophilic matrix system of losartan potassium and to find the best amongst them. Developing oral sustained release matrix tablets for a drug with a constant release rate has always been a challenge to the pharmaceutical technologist. 
 Materials and Methods: Release modulating hydrophilic matrix tablets of losartan potassium were prepared by wet granulation method. A total number of 6 formulations of release modulating hydrophilic matrix tablets of losartan potassium were prepared using different polymeric ratios of Carbopol 934, aminated Tamarind gum and aminated Xanthan gum based on preliminary trial bathes. The formulated tablets were evaluated for both pre-compression and post-compression evaluation studies. 
 Results: Based on in vitro drug release study the effective formulations AXG 3 are shows a maximum similar release profile to other remains formulations with a theoretical drug release profile of losartan potassium for sustained release. Finally optimized formulation AXG 3 containing carbopol 934 (60 mg), aminated xanthan gum (40 mg), MCC (190 mg) and magnesium stearate (10 mg) showed 100±0.024 % drug release in 12 hr which is acceptable with theoretical drug release of losartan potassium for sustain release dose. Conclusion: Aminated derivatives of xanthan gum and Tamarind gum extend the drug release for 12 hr. Based on in vitro drug release studies of formulations, we concluded that the alteration in the concentration of carbopol 934 with an aminated derivative of xanthan gum in sustain release formulation development was more effective and economical.

Formulation, evaluation and optimization of orally disintegrating films of Azithromycin using DOE approach for the pediatrics with acute otitis media

Acute otitis media (AOM) is a common infection of early childhood with an inflammation of the middle ear and tympanic membrane. Azithromycin is a macrolide antibiotic which is proficient to provide effective treatment for pediatric AOM due to its in-vitro activity against the most common upper respiratory tract pathogens. The objective of this study was to develop and optimize orally disintegrating films (ODF) of azithromycin as an alternative patient compliant dosage form. Using casting method of films, five formulations (F1-F5) were fabricated and evaluated for different physico-chemical and mechanical parameters along with drug release kinetics. Design of Experiment approach was applied to discover the optimized ratio of the two disintegrants used in the formulations. FT-IR spectra confirmed the identity of azithromycin and absence of any chemical interaction between the drug and excipients. Optimized formulation was selected as F2 which comprised of two disintegrants i.e. crospovidone and croscarmellose sodium in 1:1 ratio. F2 possessed excellent physico-chemical, mechanical properties along with rapid dissolution. F2 demonstrated concentration dependent erosional type release pattern from a planer surface of hydrophilic matrix system. Addition of the disintegrating agents resulted in rapid fragmentation of the films following the above process. Accelerated stability study assured the longer shelf life of optimized ODFs. Rapid disintegration and dissolution may accelerate the onset of action bypassing hepatic first-pass metabolism which confirmed the utility of azithromycin loaded ODFs as alternative dosage form in management of pediatric AOM.

Release Kinetics of Hydroxypropyl Methylcellulose Governing Drug Release and Hydrodynamic Changes of Matrix Tablet.

Hydrophilic Hydroxypropyl Methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet. Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-Nuclear Magnetic Resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive Near-Infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process. High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC. The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release- modulating mechanism in the hydrophilic matrix system.

Application of Focus Variation Microscopy and Dissolution Imaging in Understanding the Behaviour of Hydrophilic Matrices.

Hydrophilic matrix systems can be found in a wide range of extended release pharmaceutical formulations. The main principle of these systems is that upon contact with water, the hydrophilic component swells to form a hydrated gel layer which controls drug release. The following work demonstrates an explorative study into the use of dissolution imaging and focus variation microscopy with hydrophilic polymers. This study investigated the surface properties of xanthan gum (XG), polyethylene oxide (PEO), and hypromellose (hydroxypropyl methylcellulose, HPMC) compacts with each of these three hydrophilic polymers from one of each classification of natural, semi-synthetic, or synthetic polymer using a focus variation instrument. The auto correlation length (Sal) showed all surface profiles from the compacts displayed a value below 0.1 mm, indicating that only high frequency components (i.e., roughness) were considered and that the analysis had been successful. The developed interfacial area ratio (Sdr) displayed values below 5% in line with ISO guidelines for all the polymers studied with their texture aspect ratio values (Str) > 0.5, indicating uniformity of the surfaces of the produced compacts. Of the various parameters studied, areal material ratio (Smr2) predicted XG to wet and hydrate quicker than PEO, with PEO also wetting and hydrating quicker than the HPMC. The dissolution imaging and initial swelling studies proved to concur with the findings from the areal material ratio (Smr2) parameter, suggesting porosity was not an indicator for the ease with which water ingress occurs. This study suggests the Smr2 surface parameter to potentially predict wetting and initial hydration of hydrophilic polymers, however care should be taken as this study consists of a selected number of hydrophilic polymers.

Simulated migrating motor complex and its impact on the release properties of hydrophilic matrix systems

Following ingestion, the dosage forms are exposed to high mechanical stresses, mainly due to the movement of gastric musculature and passage through the sphincters. The generated mechanical forces can have a profound impact on the release properties of the mechanically sensitive formulations, which may result in greater in vivo variability. The aim of the study was to prepare a new programme sequence for our bio-relevant in vitro dissolution model, the advanced gastric simulator (AGS), which would closely resemble the four phases of the migrating motor complex (MMC) and to evaluate the influence of the simulated mechanical stress on the drug release rate and the gel layer properties of the model hydrophilic matrix system. For this purpose, two kinds of HPMC matrix tablets were used, which have previously been tested in vivo. In vivo pressure measurements in human fasted stomach were gathered from literature and compared to the measurements obtained with the wireless motility capsule (WMC) in AGS. Dissolution studies conducted in AGS were compared to the experiments performed in USP2. Properties of the gel layer were evaluated with texture analysis and matrix erosion determination. Our in vitro measured pressure profiles of simulated MMC were found to be within the same range as those observed in vivo. The simulated MMC was shown to significantly affect the drug release kinetics from tested hydrophilic matrices. Compared to USP2, the AGS was shown to have a higher discriminatory power in distinguishing the differences in behaviour of the tested formulations, in accordance with in vivo data.

Formulation development and Stability Studies of Meropenem Extended-Release matrix Tablets

The aim of this research was to develop a new hydrophilic matrix system containing meropenem (MEX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxyl propyl methyl cellulose or poly (ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75± 5% relative humidity), and the film-coating process is recommended to avoid MEX photo-degradation. The dissolution profiles demonstrated an extended-release of MEX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

Matéria Evaluation of zinc oxide nanoparticles influence on hydrophilic polymer matrix systems

Hydrophilic polymer matrix systems (HPMSs) are a highly relevant tool for drugs delivery whose bioavailability is impaired by low hydrosolubility. Besides this, when associated with nanoparticles these systems can provide better control over release profile of the active drug, maintaining the posology. Since polyvinylpyrrolidone (PVP) and zinc oxide (ZnO) are safe materials for use in the human body, we studied the effects of ZnO nanoparticle ratios on the characteristics of PVP matrix. For that purpose, nanocomposites were prepared by solution casting method and characterized by X-ray Fluorescence (XRF), Fourier Transform Infrared (FTIR), Thermal Gravimetric Analyses (TGA), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XDR) and Low-field Nuclear Magnetic Resonance (LF-NMR) technique, using relaxometry. We also analyzed the effects of the system on two broad-spectrum antimicrobial drugs. The characterization results of the new materials indicate good interaction of the nanoparticles with the polymer, and this fact suggests that these new materials may have a retarding effect on drug release. The results also showed no disruptive interaction of the matrix system important to the action of the antimicrobials. Keywords: Polymer, Nanotechnology, Drug delivery, ZnO.

Novel hydrophilic matrix system with non-uniform drug distribution for zero-order release kinetics

A decrease in the release rate over time is typically encountered when dealing with hydrophilic matrix systems for oral prolonged release due to progressive increase of the distance the drug molecules have to cover to diffuse outwards and reduction of the area of the glassy matrix at the swelling front. In order to solve this issue, a novel formulation approach based on non-uniform distribution of the active ingredient throughout the swellable polymer matrix was proposed and evaluated. Various physical mixtures of polymer (high-viscosity hypromellose) and drug tracer (acetaminophen), having decreasing concentrations of the latter, were applied by powder-layering onto inert core seeds. The resulting gradient matrices showed to possess satisfactory physico-technological characteristics, with spherical shape and consistent thickness of the layers sequentially applied. The non-uniform matrix composition pursued was confirmed by Raman mapping analysis. As compared with a system having uniform distribution of the drug tracer, the multi-layer formulations were proved to enhance linearity of release. The simple design concept, advantageous technique, which involves no solvents nor high-impact drying operations, and the polymeric material of established use make the delivery platform hereby proposed a valuable strategy to improve the performance of hydrophilic matrix systems.

A Clinician's Guide to Oral Extended-Release Drug Delivery Systems in Epilepsy.

Epilepsy is one of the most common chronic neurologic disorders that affects individuals of all ages. It is primarily managed with antiepileptic drugs (AEDs), with the goal of maintaining complete seizure control combined with minimal or no adverse effects. Oral administration is the mainstay of AED delivery for patients with chronic epilepsy and consists essentially of immediate-release (IR) and modified-release (delayed-release and extended-release [ER]) dosage formulations. Extended-release formulations (hydrophilic or hydrophobic matrix systems, reservoir systems, and osmotic-release systems) release a drug in a controlled manner during an extended period of time following administration. Extended-release formulations have many advantages compared with IR formulations, including simplification of dosing regimens, reduction in pill burden, and reduction in the peak-to-trough fluctuations in serum drug concentration that may be associated with a decreased risk of adverse effects and of seizures. These advantages have the potential to increase adherence to antiepileptic therapy, improve the quality of life of patients, and reduce health care costs. This article, which is intended as a practical guide for clinicians, reviews the properties of the different ER AED formulations currently available and discusses the advantages of ER over IR formulations. Subsequently, an explanation of the technologic basis of the different oral ER formulations, the critical attributes that differentiate ER products, and their individual strengths and weaknesses is provided. Specific recommendations to practitioners on treating patients with ER formulations are included.

Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug

The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH6.8 and pH1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24h in acidic media (pH1.2). The release profile in acidic media was similar to the alkaline media (pH6.8) with a similarity factor (f2) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile.

Modified in vitro release of the chronobiotic hormone melatonin from matrix tablets based on the marine sulfated polysaccharide ulvan

In the last decades the paradigm of including excipients in the formulations as inert substances, aiding production processes, has changed and they are now approached as multifunctional compounds. This means that several functions apply, spreading from the stabilization and modified release, to providing biocompatible properties and targeting moieties. In the present work, the algal sulfated polysaccharide ulvan, which remains a rather unexploited biomaterial for applications in the design of drug delivery systems, was used as a formulant in hydrophilic matrix systems, containing the chronobiotic hormone melatonin (MLT). The MLT's in vitro modified release profile in gastrointestinal-like fluids was probed. In general, the % release profile of MLT from ulvan-based tablets, was found to be relatively higher than that of the market drug Circadin® at pH 1.2 (2 h), with the exception of the formulations containing HPMC K15M. The release of most of the ulvan-based formulations follow a sigmoidal pattern (Super Case II mechanism, n > 0.89), which denotes that the drug release is controlled by polymer relaxation and/or erosion.

Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets

Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected.Graphical abstractᅟ

Amorphous-based controlled-release gliclazide matrix system.

The aim of this study was to develop a hydrophilic oral controlled release system (CRS) using the amorphous form of gliclazide, a BCS class II compound, listed on the WHO list of essential medicines. For this purpose, spray-dried dispersions (SDDs) of gliclazide were produced using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) or copovidone as carrier under fully automated conditions. The solid-state properties of prepared SDDs were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), and Fourier transform infrared spectroscopy (FTIR). Supersaturated micro-dissolution testing of SDDs in fasted state-simulated intestinal fluid showed prolonged supersaturation state, with solubility increases of 1.5- to 4.0-fold. Solubility and stability characteristics of the most desirable SDDs in terms of relative dissolution area under the curves (AUCs) (AUC(SDD)/AUC(crystalline)) and stable supersaturated state concentration ratio up to 180min (C180/Cmax) were determined. The optimized gliclazide-SDD amorphous forms were included into matrix tablets with HPMC blends using compaction simulator. Developed matrix systems were subjected to standard USP dissolution testing. Dissolution profiles obtained were linear with different slopes indicating varying rates of dissolution. Six-month storage stability testing was performed, and dissolution profiles remained stable with "similarity factor" (f 2 = 85). Results show that the use of various HPMCAS as a drug carrier in the spray-drying process produces homogeneous single-phase SDDs which are stable and promising for inclusion into HPMC-based hydrophilic matrix systems.

Design and Evaluation of Hydrophilic Matrix System Containing Polyethylene Oxides for the Zero-Order Controlled Delivery of Water-Insoluble Drugs.

The aim of this study was to design a polyethylene oxide (PEO) binary hydrophilic matrix controlled system and investigate the most important influence(s) on the in vitro water-insoluble drug release behavior of this controlled system. Direct-compressed PEO binary matrix tablets were obtained from a variety of low viscosity hydrophilic materials as a sustained agent, using anhydrous drugs as a model drug. Water uptake rate, swelling rate, and erosion rate of matrices were investigated for the evaluation of the PEO hydrophilic matrix systems. The effect of the dose, the solubility of water-insoluble drug, and the rheology of polymers on in vitro release were also discussed. Based on the in vitro release kinetics study, three optimized PEO binary matrices were selected for further research. And, these PEO binary matrices had shown the similar release behavior that had been evaluated by the similarity factor f 2. Further study indicated that they had identical hydration, swelling, and erosion rate. Moreover, rheology study exhibited the similar rheological equation of Herschel-Bulkley and their viscosity was also within the same magnitude. Therefore, viscosity plays the most important role to control drug release compared to other factors in PEO binary matrix system. This research provides fundamental understanding of in vitro drug release of PEO binary hydrophilic matrix tablets and helps pharmaceutical workers to develop a hydrophilic controlled system, which will effectively shorten the process of formulation development by reducing trial-and-error.

Application of NMR Relaxometry to Study Nanostructured Poly(vinyl alcohol)/MMT/Cephalexin Materials for Use in Drug Delivery Systems

Polymers containing nanoparticles dispersed and distributed in the matrix can be used for control of drug release. In this work, hydrophilic matrix systems were prepared using poly(vinyl alcohol) and unmodified clay containing the same amount of cephalexin. The materials were obtained through in situ polymerization and were characterized by the conventional technique of FTIR and NMR relaxometry, through determination of proton spin-lattice relaxation time, in order to understand the molecular behavior of the new materials. The NMR relaxometry data showed that the new materials containing low quantities of clay (0.25% and 0.75%) and the same amount of cephalexin (0.5 g) had very good dispersion and distribution of the clay and drug in the polymer matrix. The combination of clay and cephalexin formed a more homogenous material with a narrow domain curve and low relaxation values. The material containing 0.25% clay presented a mixed morphology, with part exfoliated and part intercalated, as could be seen from the relaxation domain distribution, which was larger than that for material with 0.75% clay.