The aim of this study is to present the possibility of using of co-processed dry binders for formulation of matrix tablets with drug controlled release. Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and different co-processed dry binders were prepared by direct compression method. Hypromelloses Methocel™ K4M Premium CR or Methocel™ K100M Premium CR were used as controlled release agents and Prosolv® SMCC 90 or Disintequik™ MCC 25 were used as co-processed dry binders. Homogeneity of the tablets was evaluated using scanning electron microscopy and energy dispersive X-ray microanalysis. The release of tramadol hydrochloride from prepared formulations was studied by dissolution test method. The dissolution profiles obtained were evaluated by non-linear regression analysis, release rate constants and other kinetic parameters were determined. It was found that matrix tablets based on Prosolv® SMCC 90 and Methocel™ Premium CR cannot control the tramadol release effectively for >12h and tablets containing Disintequik™ MCC 25 and Methocel™ Premium CR >8h.

• Keywords
• Co-processed dry binders, Dissolution kinetics, Hypromellose, Matrix tablets, Tramadol hydrochloride,
• MeSH
• Hypromellose Derivatives chemistry   pharmacokinetics   MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Hydrophobic and Hydrophilic Interactions * MeSH
• Solubility MeSH
• Tablets MeSH
• Tramadol chemistry   pharmacokinetics   MeSH
• Drug Liberation MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hypromellose Derivatives MeSH
• Tablets MeSH
• Tramadol MeSH

This paper evaluates and compares the properties of directly compressible tabletting materials and matrix tablets containing a combination of α-lactose monohydrate and microcrystalline cellulose in the 3:1 ratio in a physical mixture and in a coprocessed dry binder. Tested parameters include flow properties, compressibility, compactibility and the rate of drug release from tablets. Compressibility is evaluated by means of the energy profile of the compression process. Compactibility is evaluated by means of the tensile strength of the tablets. Dissolution testing is done using the rotating basket method. Dissolution profiles are evaluated by non-linear regression analysis. Total energy of compression and plasticity values were higher in tabletting materials with the coprocessed dry binder. Increasing additions of polyvinyl alcohol decreased the values of total energy of compression, plasticity, tensile strength of tablets and drug release rate. Dissolution behaviour of tablets, which contained the physical mixture or coprocessed dry binder and the same amount of polyvinyl alcohol, was comparable.

• Keywords
• coprocessed dry binder, dissolution testing, energy profile of compression, matrix tablets, polyvinyl alcohol, tensile strength of tablets,
• MeSH
• Cellulose chemistry   MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Technology, Pharmaceutical methods   MeSH
• Salicylic Acid administration & dosage   chemistry   MeSH
• Lactose chemistry   MeSH
• Nonlinear Dynamics MeSH
• Tensile Strength MeSH
• Polyvinyl Alcohol chemistry   MeSH
• Excipients chemistry   MeSH
• Solubility MeSH
• Tablets MeSH
• Drug Liberation MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Cellulose MeSH
• Salicylic Acid MeSH
• Lactose MeSH
• microcrystalline cellulose MeSH Browser
• Polyvinyl Alcohol MeSH
• Excipients MeSH
• Tablets MeSH

UNLABELLED: Eudragit® NM was investigated as a matrix former in combination with microcrystalline cellulose as an insoluble filler for preparing controlled-release tablets containing model drugs with different solubility. MATERIAL AND METHODS: Three sets of matrix tablets differing in the drug-to-filler ratio (1:1, 2:1, and 4:1) and polymer amount with diltiazem hydrochloride (freely soluble) or caffeine (sparingly soluble) were prepared. Samples were evaluated by the dissolution test at pH 6.8 corresponding to the upper part of the small intestine; the selected samples were tested at a changing pH level to better simulate in vivo conditions. RESULTS: The prepared matrix tablets fulfilled all the requirements of the European Pharmacopoeia. Tablets with Eudragit® NM showed excellent mechanical characteristics. In vitro studies showed that the set 1:1 was the most suitable for the sustained release of a freely soluble drug concerning the burst effect and the total drug amount released within 12 hours. The significant effect of the drug-to-filler ratio and polymer amount on the dissolution profile was confirmed by similarity factor analysis. A faster drug release was observed during the dissolution test within changing pH levels because of the pH-dependent solubility of diltiazem. A prolonged release of the sparingly soluble drug was not achieved, and a trend for fast disintegration was observed. CONCLUSIONS: The combination of Eudragit®NM with microcrystalline cellulose as an insoluble filler seems to be suitable only for freely soluble drugs, when the amount of the drug and the filler is similar.

• MeSH
• Cellulose chemistry   MeSH
• Polymethacrylic Acids chemistry   MeSH
• Delayed-Action Preparations chemistry   MeSH
• Drug Design * MeSH
• Solubility MeSH
• Tablets MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cellulose MeSH
• Polymethacrylic Acids MeSH
• Delayed-Action Preparations MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Browser
• Tablets MeSH

The purpose of this experimental work was the development of hydrophilic-lipophilic matrix tablets for controlled release of slightly soluble drug represented here by diclofenac sodium (DS). Drug dissolution profile optimization provided by soluble filler was studied. Matrix tablets were based on cetyl alcohol as the lipophilic carrier, povidone as the gel-forming agent, and common soluble filler, that is lactose or sucrose of different particle size. Physical properties of tablets prepared by melt granulation and drug release in a phosphate buffer of pH 6.8 were evaluated. In vitro studies showed that used filler type, filler to povidone ratio and sucrose particle size influenced the drug release rate. DS dissolution profile could be changed within a wide range from about 50% per 24 hours to almost 100% in 10 hours. The release constant values confirmed that DS was released from matrices by the diffusion and anomalous transport. The influence of sucrose particle size on the drug release rate was observed. As the particle size decreased, the drug release increased significantly and its dissolution profile became more uniform. Soluble fillers participated in the pore-forming process according to their solubility and particle size. Formulations containing 100 mg of the drug, 80 mg of cetyl alcohol, 40 mg of povidone, and 80 mg of either lactose or sucrose (particle size 250-125 microm) were considered optimal for 24-hour lasting dissolution of DS.

• MeSH
• Anti-Inflammatory Agents, Non-Steroidal administration & dosage   chemistry   MeSH
• Time Factors MeSH
• Diclofenac administration & dosage   chemistry   MeSH
• Lactose chemistry   MeSH
• Delayed-Action Preparations MeSH
• Fatty Alcohols chemistry   MeSH
• Drug Carriers chemistry   MeSH
• Excipients chemistry   MeSH
• Povidone chemistry   MeSH
• Solubility MeSH
• Sucrose chemistry   MeSH
• Tablets MeSH
• Particle Size MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• cetyl alcohol MeSH Browser
• Diclofenac MeSH
• Lactose MeSH
• Delayed-Action Preparations MeSH
• Fatty Alcohols MeSH
• Drug Carriers MeSH
• Excipients MeSH
• Povidone MeSH
• Sucrose MeSH
• Tablets MeSH

The objective of the present research is to evaluate directly compressible chitosan-based tableting materials for the formulation of mucoadhesive matrix tablets intended for targeted drug release to distal segments of the GIT. The influence of sodium alginate, hypromellose, and silicified microcrystalline cellulose (P90) on compressibility, compactability and lubricant sensitivity ratio was tested. Furthermore, the rheological properties of the hydrated surface layer of the matrix tablets and the mucoadhesion to a mucin substrate were analysed. Compressibility was evaluated using the energy profile of the compression process, compactability by means of the tensile strength of tablets, and lubricant sensitivity ratio was calculated to assess the sensitivity to lubricant. Addition of P90 to chitosan improved compressibility, which is demonstrated by the increase in the energy of plastic deformation and the higher tensile strength of tablets. P90 also significantly reduced the high lubricant sensitivity of chitosan. Presence of retarding components led to a decrease in Emax. All tested matrix tablets revealed a good mucoadhesion without a negative effect of P90 content. The viscosity of a gel layer on the surface of matrix tablets containing hypromellose was higher compared to those with sodium alginate. This was not reflected in the adhesive strength of the tablets. The formulated tableting materials combining chitosan and P90 are a suitable matrix for incorporation of an active ingredient, whose delayed release in the intestine can be achieved by the functionality of the chitosan-sodium alginate complex.

• Keywords
• chitosan, compactability, compressibility, matrix tablets, mucoadhesion, silicified microcrystalline cellulose,
• Publication type
• Journal Article MeSH

Hypromellose matrices exhibit extended burst effect immediately after contact with aqueous medium, especially when a water-soluble drug is incorporated. The objective of this study was to reduce burst effect and maintain complete dissolution of a very soluble levetiracetam over 12 h period from hypromellose K4M matrices to obtain zero-order kinetics. Desired changes were achieved by applying water dispersions of insoluble Eudragits® (NE, NM, RL, RS) as a granulation liquid to the drug/microcrystalline cellulose mixture during high-shear granulation (non-thermal treated set) and consequently by thermally treating granules or final tablets (TT), respectively. Applying Eudragit® water dispersions to the drug/microcrystalline cellulose mixture was recognized as an effective method of significantly reducing the burst release (25.4-33.7%) of levetiracetam in comparison with a reference sample without Eudragit®. Multivariate data analysis showed that the addition of Eudragit® reduced burst effect, increased fitting with zero-order kinetics, and supported matrix erosion as the supplementary mechanism to predominant diffusion. Moreover, resulting PCA sub-model revealed the addition of Eudragit® RL and thermal treatment of tablets to be the most suitable method of all. For a 12 h dissolution profile, characterized by low burst effect and drug release close to 100% at the 12th hour, sample RL_TT was the most suitable.

• Keywords
• Eudragit® NE, HPMC, NM, Prolonged drug release, RL, RS, burst effect, levetiracetam, matrix tablets, multivariate data analysis, thermal treatment,
• MeSH
• Anticonvulsants administration & dosage   chemistry   MeSH
• Cellulose chemistry   MeSH
• Hypromellose Derivatives chemistry   MeSH
• Polymethacrylic Acids chemistry   MeSH
• Delayed-Action Preparations chemistry   MeSH
• Levetiracetam MeSH
• Multivariate Analysis MeSH
• Piracetam administration & dosage   analogs & derivatives   chemistry   MeSH
• Drug Compounding methods   MeSH
• Solubility MeSH
• Tablets MeSH
• Temperature MeSH
• Drug Liberation MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticonvulsants MeSH
• Cellulose MeSH
• Hypromellose Derivatives MeSH
• Polymethacrylic Acids MeSH
• Delayed-Action Preparations MeSH
• Levetiracetam MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Browser
• microcrystalline cellulose MeSH Browser
• Piracetam MeSH
• Tablets MeSH

The present study focused on the more detailed characterization of chitosan-carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views of the physico-chemical processes involved in these stages. The initial swelling of the tablets in the acidic medium based on the combined microscopy-calorimetry point of view, the pH-induced differences in the erosion and swelling of the tested tablets, and the morphological characterization of the tablets are discussed. The dissolution kinetics correlated with the rheological properties and mucoadhesive behavior of the tablets are also reported, and, correspondingly, the formulations with suitable properties were identified. It was confirmed that the formation of the chitosan-carrageenan polyelectrolyte complex may be an elegant and beneficial alternative solution for the drug targeting to the intestine by the matrix tablet.

• Keywords
• carrageenan, chitosan, drug targeting, polyelectrolyte complex,
• Publication type
• Journal Article MeSH

Matrix tablets with a dispersed active ingredient are the simplest concept in the design of dosage forms with modified drug release. If they contain a swelling polymer as an auxiliary substance, the release from these systems, after initial liberation of a portion of the active ingredient from the surface, takes place by diffusion, erosion, or a combination of both mechanisms in dependence on the solubility of the contained active ingredient. Although hydrophilic matrix tablets have become a well-tried and widely used dosage form with retarded effects, their research continues and new auxiliary substances and their combinations are being tested. The present paper reviews the knowledge published in this field in recent years.

• MeSH
• Chemistry, Pharmaceutical MeSH
• Pharmaceutic Aids * MeSH
• Gels MeSH
• Delayed-Action Preparations MeSH
• Polymers * MeSH
• Tablets * MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Pharmaceutic Aids * MeSH
• Gels MeSH
• Delayed-Action Preparations MeSH
• Polymers * MeSH
• Tablets * MeSH

The aim of this work was to investigate and quantitatively evaluate the effect of presence of alcohol on in vitro release of ionizing and non-ionizing drug from hydrophilic, lipophilic and hydrophilic-lipophilic matrix tablets. The Food and Drug Administration (FDA) recommends in vitro dissolution testing of extended release formulations in ethanolic media up to 40% because of possible alcohol-induced dose dumping effect. This study is focused on comparison of the dissolution behavior of matrix tablets (based on hypromellose and/or glyceryl behenate as retarding agent) of the same composition containing different type of drug - ionizing tramadol hydrochloride (TH) and non-ionizing pentoxifylline (PTX). The dissolution tests were performed in acidic medium (pH 1.2) and in alcoholic medim (20%, 40% of ethanol) and the changes of tablets were observed also photographically. It was found that the alcohol resistence of the hydrophilic-lipophilic formulations with TH and the hydrophilic-lipophilic formulations with PTX containing a higher amount of hypromellose does not reflect the alcohol resistence of the formulations with pure hypromellose or glyceryl behenate. Both hydrophilic-lipophilic formulation with TH and more lipophilic formulation with PTX show significant alcohol dose dumping effect.

• Keywords
• Alcohol, Dissolution, Glyceryl behenate, Hypromellose, Pentoxifylline, Tramadol hydrochloride,
• Publication type
• Journal Article MeSH

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.

• Keywords
• 3D printing and coating, Affinisol, alcohol-induced dose dumping effect, dissolution testing, hot melt extrusion (HME), polyvinyl alcohol,
• Publication type
• Journal Article MeSH