Dissolution Kinetics Evaluation of Controlled-Release Tablets Containing Propranolol Hydrochloride

In the present research, controlled-release propranolol hydrochloride tablets were prepared for twice-daily administration, allowing more uniform plasmatic levels of the drug. Pharmaceutical formulations were prepared with hydrophobic Eudragit® RSPO. The physical properties of the tablets were determined. Dissolution tests were performed in capsules containing the raw material using the following dissolution media: (A) distilled water, (B) simulated gastric juice without enzymes, and (C) simulated enteric juice without enzymes. A dissolution test was also performed for simulated samples (tablets) using distilled water as the dissolution medium.     

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation

This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 3² full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f₂) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).     

Kinetics and Mechanism of Drug Release From Calcium Alginate Membrane Coated Tablets

Compressed tablets containing guaifenesin (model drug), calcium acetate (reactant) and pharmaceutical excipients were prepared. The tablets were coated with calcium alginate hydrogel using a novel, self-correcting membrane coating technique. Effects of coating time, the type of alginate polymer and pH of the dissolution medium on the rate of drug release were evaluated. In distilled water, zero order drug release profiles were obtained from the coated tablets. The release rate decreased with an increase in the coating time (increased coat thickness) and molecular weight of alginate polymer. The release rate constants correlated with model for spherical reservoir system and, were used to calculate permeability of guaifenesin in the calcium alginate coatings. Alginate polymer with higher guluronic acid content provided acid stable coating and higher molecular weight polymer produced membrane with lower permeability for guaifenesin.     

Influence of admixed citric acid and physiological variables on the vinpocetine release from sodium alginate compressed matrix tablets

In this study, the controlled release matrix tablets of vinpocetine were prepared by direct compression using sodium alginate (SAL) as hydrophilic polymer and different amounts of citric acid as hydrosoluble acidic excipient to set up a system bringing about zero-order release of this drug in distilled water containing 0.5% sodium dodecyl sulfate. At the critical content of admixed citric acid (60 mg/tab.), the lowest drug-release rate was observed. In order to explain the effect of this critical content on drug-release rate from SAL matrices, investigation of the possibility of interaction of citric acid with SAL was performed using differential scanning calorimetric analysis and infrared analysis, which confirmed the existence of direct citric acid-SAL interaction when these two excipients came in contact with water. A zero-order drug-release system could be obtained by regulating the ratio of citric acid-to-SAL and the capacity of this system in controlling drug-release rate depended on the extent of interaction between citric acid and SAL. It is worth noticing that pH and the ionic strength of the dissolution medium were found to exert an influence on the drug-release performance of SAL tablets.     

In vitro conditions for the study of the in vivo performance of sustained-release theophylline matrix tablets administered in fasted conditions and with a high-fat diet

Dissolution profiles of theophylline (TP) from three types of sustained-release (SR) matrix tablets (plastic [PL], lipid [LP], and hydrophilic [HP]) in different dissolution media, with and without enzymes, were established. Also investigated was the influence of a treatment of the tablets with peanut oil prior to the dissolution test. The in vivo behavior of the tablets under the fasted state and with the concomitant administration with a high-fat diet was previously evaluated; the diet produced changes in the absorption profiles for the three matrix tablets in comparison with fasted administration. Level A correlations were obtained between cumulative percentage dissolved (CPD) and cumulative percentage absorbed (CPA). For the fasted condition, better correlations were obtained with water as the dissolution medium for the HP and LP matrix; for PL matrix, the best correlation was obtained with a medium with gradual change of pH. The pretreatment with peanut oil showed better correlations for the fed state.     

The Effects of Formulation Factors on the Moist Granulation Technique for Controlled-Release Tablets

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release.     

The Effects of Formulation Factors on the Moist Granulation Technique for Controlled-Release Tablets

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release.     

The Effect of Four Tablet Binders on the Bioavailability of Frusemide from 40MG Tablets

Tablets containing frusemide 40mg have been prepared using four different binders; polyvinylpyrrolidone, starch mucilage, stearic acid and methylhydroxyethyl cellulose. With the exception of the tablets prepared using stearic acid, all the tablets disintegrated in under 2 minutes and exhibited hardnesses ranging from 12 to 17 s.c.u. The dissolution rate, measured in the B.P. apparatus as the time to achieve 50% solution in distilled water, discriminated more effectively between the tablet batches. Tablets made using polyvinylpyrrolidone and methylhydroxyethyl cellulose had dissolution half lives of 3.65 and 3.30 minutes respectively, whilst tablets incorporating stearic acid and starch mucilage exhibited respective values of greater than 200 minutes and 117 minutes. The bioavailabilities of the four tablet formulations were assessed on a double blind basis in four healthy males aged 18-30 with reference to an oral frusemide solution. The bioavailability of each formulation was determined by two different methods and it was found that polyvinylpyrrolidone and methylhydroxyethyl cellulose rendered frusemide equally bioavailable (71.7% and 71.6% respectively) whilst the starch mucilage formulation rendered frusemide 25% less bioavailable (54.10%). The poorest binding agent was stearic acid which decreased the bioavailability of frusemide by 50% (35.04%). The results indicate that the choice of binding agent can significantly affect the bioavailability of frusemide from tablets and that these bioavailability differences can best be detected in vitro by dissolution rate measurements.     

Fabrication of Multiunit Controlled-Release Phenylpropanolamine Hydrochloride Tablets

Abstract

Phenylpropanolamine hydrochloride (PPA) pellets were prepared in a fluidized-bed rotary granulator. Microcrystalline cellulose and distilled water were used as pelletization enhancer and binder, respectively. The pellets were coated with methacry-late ester copolymer (Eudragit® RS 100) solution containing a 1:1 ratio mixture of triethyl citrate and castor oil as plasticizers. The addition of approximately 30% microcrystalline cellulose and 2% croscarmellose sodium to the 50% coated pellets produced fast disintegrating tablets. Dissolution profiles of both pellets and their respective matrix tablets were comparable and conformed to the USP dissolution requirement for PPA extended-release capsules.     

The effect of carboxymethyl chitin on sustained drug release of aspirin tablet

Carboxymethyl chitin (CM-chitin) was prepared at room temperature and characterized using ¹H NMR, FTIR and elemental analysis methods. The prepared CM-chitin was then used as a hydrophilic matrix for the preparation of the aspirin sustained release tablets via the wet granulation technique. The aspirin release profiles of the prepared tablets in a simulated gastric fluid and simulated intestinal fluid, respectively, were studied with the rotating-basket dissolution method. The results showed that the aspirin release rate in simulated gastric fluid was lower than that in simulated intestinal fluid. Thus, CM-chitin proved to be a pH-sensitive hydrophilic matrix.     

Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

High-throughput evaluation of non-swellable controlled release matrix tablets

Drug release from controlled-release (CR) matrix tablets involves the permeation and diffusion of water through the system. In this study, a new methodology is proposed for the measurement of water permeation and simultaneous drug release from the inert, non-swellable CR matrix tablet of diltiazem (DLT) and a correlation is made between these two processes. Cylindrical matrices were readily prepared by direct compression of pellets obtained by extrusion-spheronization. Water transport was studied using tritiated water (HTO) as a permeant in a Franz-diffusion cell and simultaneously drug release was measured. Further, dissolution was performed on USP XXI/XXII dissolution apparatus I using demineralized water. Matrices showed a steady water-uptake up to 6 h and the steady state for HTO permeation lasting from 6-h to 24-h Flux of water permeated and flux of drug released correlated well. Thus, HTO permeation through the matrix tablet and the proposed methodology can be used as a tool and/or surrogate marker for evaluation of controlled release matrix tablets. This methodology can be coined as “high-throughput” in terms of amount of labor and resources required in comparison to that of dissolution.     

Development of Polysaccharide-Based Colon Targeted Drug Delivery Systems for the Treatment of Amoebiasis

ABSTRACT

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30–40% drug release during the initial 4–5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18–24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

High-Throughput Evaluation of Non-Swellable Controlled Release Matrix Tablets

Abstract

Drug release from controlled-release (CR) matrix tablets involves the permeation and diffusion of water through the system. In this study, a new methodology is proposed for the measurement of water permeation and simultaneous drug release from the inert, non-swellable CR matrix tablet of diltiazem (DLT) and a correlation is made between these two processes. Cylindrical matrices were readily prepared by direct compression of pellets obtained by extrusion-spheronization. Water transport was studied using tritiated water (HTO) as a permeant in a Franz-diffusion cell and simultaneously drug release was measured. Further, dissolution was performed on USP XXI/XXII dissolution apparatus I using demineralized water. Matrices showed a steady water-uptake up to 6 h and the steady state for HTO permeation lasting from 6-h to 24-h Flux of water permeated and flux of drug released correlated well. Thus, HTO permeation through the matrix tablet and the proposed methodology can be used as a tool and/or surrogate marker for evaluation of controlled release matrix tablets. This methodology can be coined as “high-throughput” in terms of amount of labor and resources required in comparison to that of dissolution.     

Optimization of Digoxin Tablets

Abstract

Four digoxin tablets have been formulated using potassium chloride and urea as water soluble directly compressible fillers. Simple blending and solvent deposition techniques were used for drug incorporation. The physical characteristics and content uniformity of the formulated tablets were comparable to those of two commercial brands of digoxin tablets. However, the dissolution rate of digoxin from tablets prepared by solvent deposition either on potassium chloride or urea (% dissolution after 1 h was 94 and 83 respectively) was higher than that from tablets made by simple blending (39 and 45% respectively)and superior to that of the two commercial brands (75.5% for both).     

Effect of glass phase on the dissolution of hydroxyapatite

Nano size defect formation at grain boundary during the dissolution of hydroxyapatite in water was evaluated by adding several sintering additives for sinterability enhancement. In the case of sintered pure hydroxyapatite, significant dissolution occurred after immersion in distilled water or in simulated body fluid. The dissolution initiated at the grain boundaries creating nano-size defects like small pores that afterwards grew up to micro scale by increasing immersion time. This dissolution resulted in grain separation at the surfaces and finally in fracture. The dissolution concentrated on the grains adjacent to pores rather than those in the dense region. So hydroxyapatite ceramics containing glass powders were prepared to prevent the dissolution by strengthening grain boundary. Calcium silicate and phosphate glasses were added at 0 to 10 mass% and sintered at 1200 degrees C for 2 h in air with moisture protection. Glass phase was incorporated into hydroxyapatite to act as the sintering aid followed by crystallization in order to improve the mechanical properties without reducing biocompatibility. Dissolution tests, as well as X-ray diffraction and SEM showed little decomposition of hydroxyapatite to secondary phases and the fracture toughness increased compared to pure hydroxyapatite.     

Ontrolled-Release Theophylline Tablet Formulations Containing Acrylic Resins. I. Dissolution Properties of Tablets

The dissolution properties of controlled-release theophylline tablets containing acrylic resins are presented. Four different resins (Eudragit RSPM, RLPM, Sl00 and Ll00) were incorporated into theophylline tablets by direct compression techniques and the properties of the resulting dosage form were evaluated in dilute acid, buffer media pH 4.0 and simulated intestinal media pH 7.5. Tablets (500 mg) containing 300 mg of theophylline were prepared with each of the four resins and compressed to a hardness level of 6.5 to 7.5 kg. Excellent flow properties, weight uniformity and drug content uniformity were observed with all tablet formulations. Preliminary data suggest that three of the four resins tested showed great promise as a retardant in a matrix controlled drug delivery system. The dissolution properties of three commercially available sustained-release theophylline tablets were also determined. A comparison of profiles from Theodur^R (300 mg) in acid and simulated intestinal media showed a similarity in release properties to those of theophylline in tablets containing the RLPM resin.     

Application of near-infrared spectroscopy to optimize dissolution profiles of tablets according to the granulation mechanism

We developed a method for the optimization of dissolution properties of solid oral dosage forms manufacturing using high shear wet granulation (HSWG) by using near-infrared spectroscopy (NIRS) with chemometrics in small-scale experiments. The changes in rheology and NIR spectra of the granules were monitored to verify the granulation mechanism and determine the suitable water amount for model formulation during the HSWG. Tablets were manufactured by altering the added water amount to investigate the impact of the granulation mechanism on drug product qualities. Model formulation granules were prepared with 10–20% w/w water in a funicular state, corresponding to the plateau region in score plots obtained by principal component analysis (PCA). The dissolution rate of model formulation tablets manufactured with more than 20% w/w of water was significantly delayed while tablets manufactured with 15% w/w water showed 100% dissolution at 15?min. NIRS and PCA are applicable to the optimization of dissolution properties via the process understanding of HSWG at the early formulation development stage and could facilitate drug development.     

Michoencapsulation and in Vitro Dissolution of Oxazepam from Ethyl Cellulose Microcapsules

Microcapsules of oxazepam with core:wall ratios 1:1 and 1:2 have been prepared by coacervation-phase separation method, using ethyl cellulose as a coating material. Phase separation was obtained by adding a salt solution to the dispersion of a water insoluble material in organic solution. Mioroencapsulation process protected oxazepam from photochemical decomposition and retarded its release. Release of the drug into simulated gastric and intestinal juice was studied. In vitro dissolution studies showed that first order release characteristics were exhibited.     

Ontrolled-Release Theophylline Tablet Formulations Containing Acrylic Resins. I. Dissolution Properties of Tablets

Abstract

The dissolution properties of controlled-release theophylline tablets containing acrylic resins are presented. Four different resins (Eudragit RSPM, RLPM, Sl00 and Ll00) were incorporated into theophylline tablets by direct compression techniques and the properties of the resulting dosage form were evaluated in dilute acid, buffer media pH 4.0 and simulated intestinal media pH 7.5. Tablets (500 mg) containing 300 mg of theophylline were prepared with each of the four resins and compressed to a hardness level of 6.5 to 7.5 kg. Excellent flow properties, weight uniformity and drug content uniformity were observed with all tablet formulations. Preliminary data suggest that three of the four resins tested showed great promise as a retardant in a matrix controlled drug delivery system. The dissolution properties of three commercially available sustained-release theophylline tablets were also determined. A comparison of profiles from Theodur^R (300 mg) in acid and simulated intestinal media showed a similarity in release properties to those of theophylline in tablets containing the RLPM resin.