Paddle Method Research Articles

The Quality Evaluation of Magnesium Oxide Tablets Using Acid Neutralization Test and Dissolution Test

For the purpose of quality evaluation of commercially available magnesium oxide (MgO) tablets, we studied their acid neutralization and dissolution behaviors. The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2). The dissolution amount of MgO from tablets was determined by chelatometric titration. The medium pH was periodically measured. The neutralization reaction in 750 ml of 1st fluid was markedly different between two kinds of commercial tablets. The pH of medium including Magmit tablet reached 8.9 and the dissolution rate of MgO was 81.1% after 20 min. Contrariwise, the final pH of medium including Maglax tablet was 2.5 and the dissolution rate of MgO was 77.1% after 60 min. These results indicate that the dissolution rate of MgO from tablets should be >81.1% to obtain significant acid neutralization action.

Estimation of the percolation thresholds in lobenzarit disodium native dextran matrix tablets

The objective of the present work is to estimate for the first time the percolation threshold of a new series of dextran (native dextran of high molecular weight [B110-1-2, Mw = 2 x 10(6)]), in matrices of lobenzarit disodium (LBD) and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The formulations studied were prepared with different amounts of excipient in the range of 20% to 70% wt/wt. Dissolution studies were performed using the paddle method (100 rpm) and one face water uptake measurements were performed using a modified Enslin apparatus. The Higuchi, zero-order, and Hixson-Crowell models as well as the nonlinear regression model were employed as empiric methods to study the release data. Values of diffusion exponent 0.563 < n < 0.786 (Korsmeyer equation) for dissolution profile and water uptake mechanism 0.715 < n < 1 (Davidson and Peppas equation) suggested anomalous or complex mechanisms. On the other hand, the contribution of the relaxation or erosion and of the diffusive mechanism in Peppas-Sahlin equation indicated that the main mechanism for drug delivery from tablets is swelling controlled delivery (K(r)/K(d) < 1). The critical points observed in kinetic parameters above 58.63% vol/vol of native dextran B110-1-2 plus initial porosity in the LBD-dextran matrices with a relative polymer/drug particle size of 4.17 were attributed to the existence of an excipient percolation threshold.

Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10 mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50 rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244 nm, with automatic sampling over a 24 h period using a marketed product as a reference to calculate the “ f 2” factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with “ f 2” of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.

펠로디핀 방출연장형 펠렛의 용출 특성 평가

This study aimed to evaluate and develop -coated pellets based on the dissolution using the paddle method. As coating materials, two types of were applied to obtain either sustained release form or fast released form. The dissolution test was carried out in phosphate buffer solution (pH 6.5) at , 100 rpm. In order to develop a sustained release preparation containing felodipine, a comparative dissolution study was done using commercial product as a control. The dissolution at 30 min of felodipine from RS or RL-coated pellets were 0.96% and 99.65, respectively. The weight ratio of RL pellets to RS pellets altered the dissolution rate, but did not optimize the dissolution rate. However, the sustained dissolution of felodipine from pellets was optimized by varying the coating ratios of RS. It is suggested that the coating ratio of pellets is the main factor which controls dissolution rate. Taken together, RS 30D-coated pellets showed the most comparable dissolution rate pattern to commercial product, . This sustained release pellets for oral delivery system of felodipine was simply manufactured, and drug release behavior was highly reproducible.

Enhancement of the dissolution of indomethacin in interactive mixtures using added fine lactose

The objective of the study was to investigate the effect of fine lactose on the in vitro dissolution of indomethacin in interactive mixtures containing spray-dried lactose and lactose monohydrate (106–250 μm). Dissolution of the indomethacin was measured using an automated dissolution apparatus following the USP paddle method at 100 rpm. The particle size distributions of indomethacin mixtures were measured using a Mastersizer S under non-sink conditions. Data fitted bi-exponential or tri-exponential dissolution models, representing dissolution from dispersed and agglomerated particle distributions. The addition of fine lactose (VMD 3.8 ± 0.4 μm) to 20% indomethacin-coarse lactose mixtures resulted in significantly increased rates of dissolution caused by increases in the estimated dissolution rate constants for dispersed particles ( K d) and by de-agglomeration. Agglomerates in the mixture showed little tendency to comminute under shear pressure. De-agglomeration in the dissolution medium was attributed to increased porosity of agglomerates, caused by dissolution of water soluble fine lactose in the agglomerate structure. The median particle size ( D 50) of the dispersed particle distribution decreased with increasing concentrations of added fine lactose, indicating increasing extents of de-agglomeration, and a good correlation between K d and ( D 50) 2 resulted for the coarse lactose-based mixtures ( R 2 > 0.984).

Tablet of captopril with a cross-linked system of alginate

Captopril has a short biological half life (1-3h) and has been used for long-term treatment of hypertension. The properties of captopril such as freely water-soluble and instability in intestinal environment lead to the difficulty of developing captopril as a sustained-release preparation. . In this study, sustained-release of captopril was prepared with a matrix system using sodium alginat as a polymeric forming-matrix. The ratio of sodium alginat and captopril was 1:2. Matrix system was obtained by forming alginate cross-linked with a various concentration of calcium acetate. Xanthan gum was used to help cross-linked reaction. Tablet was prepared by wet granulation and the dissolution test was performed in HCl 0.01 N, paddle method, 100 rpm, for 12 h. Although release profile of captopril from all formula developed were different, the release of captopril sustained up 12 h. Formula containing 30 % of xanthan gum and 40 % of sodium alginate showed the best release profile of captopril and the hardness of tablets do not influence to the release of captopril. Tablet of captopril with a crosslinked system of alginate sustained the release of captopril until 12 h . Key words : captopril, sustained-release, sodium alginat, calcium acetat.

Simultaneous RP-HPLC estimation of gatifloxacin and ornidazole in tablet dosage forms

The proposed method is a simple, accurate, precise, specific and rapid method for the simultaneous estimation of gatifloxacin and ornidazole in bulk and tablet formulations. A column in isocratic mode, with a mobile phase consisting of acetonitrile: 0.025 M potassium dihydrogen phosphate buffer (50:50 v/v) with 0.5% v/v of triethylamine and its pH adjusted to 3.0 with glacial acetic acid were used. The flow rate was set at 1.0 ml/min and UV detection was carried out at 300 nm. The retention time of gatifloxacin and ornidazole were 2.89±0.017 min and 4.21±0.022 min, respectively. Linearity of gatifloxacin and ornidazole were found in the range of 2-24 µg/ml and 5-60 µg/ml, respectively. The developed HPLC method was extended for dissolution studies. The dissolution testing was performed at 50 rpm and 100 rpm in 0.1 N hcL0 as dissolution medium by paddle method.

Modulation of a Pulsatile Release Drug Delivery System Using Different Swellable/Rupturable Materials

Diclofenac sodium tablets consisting of core coated with two layers of swelling and rupturable coatings were prepared and evaluated as a pulsatile drug delivery system. Cores containing the drug were prepared by direct compression using microcrystalline cellulose and Ludipress as hydrophilic excipients with the ratio of 1:1. Cores were then coated sequentially with an inner swelling layer of different swellable materials; either Explotab, Croscarmellose sodium, or Starch RX 1500, and an outer rupturable layer of different levels of ethylcellulose. The effect of the nature of the swelling layer and the level of the rupturable coating on the lag time and the water uptake were investigated. Drug release rate studies were performed using USP paddle method. Results showed the dependence of the lag time and water uptake prior to tablet rupture on the nature of the swelling layer and the coating levels. Explotab showed a significant decrease in the lag time, followed by Croscarmellose sodium and finally by Starch RX 1500. Increasing the level of ethylcellulose coating retarded the diffusion of the release medium to the swelling layer and the rupture of the coat, thus prolonging the lag time.

Preparation and characterization of etoricoxib-β-cyclodextrin complexes prepared by the kneading method

The binary system of etoricoxib with beta-cyklodextrin (beta-CD) was prepared by the kneading method. Drug-cyclodextrin interactions in solution were investigated by the phase solubility analysis. Differential scanning calorimetry, infrared spectroscopy, powder X-ray diffractometry and microscopic study were used to characterize the solid state of all binary systems, whereas their dissolution properties were evaluated according to the USP XXIII paddle method. The results indicate partial interaction of the drug with beta-CD in the physical mixture and complete interaction in the kneaded complex. The dissolution of etoricoxib was notably increased as compared to pure drug as well as its physical mixture. The complex showed more than 75% drug released in 30 min.

Dissolution profiles of nonprescription extended-release niacin and inositol niacinate products

The dissolution profiles of nonprescription extended-release niacin and inositol niacinate products were studied using the prescription extended-release niacin, Niaspan, as a reference. Seven nonprescription extended-release and 12 nonprescription inositol niacinate products were collected from community and online pharmacies in the United States. Extended-release Niaspan was used as a reference. Dissolution profiles were examined by the United States Pharmacopoeia dissolution test, using a paddle method. Release samples were removed every 30 minutes for up to 240 minutes. Niacin was quantified by high-performance liquid chromatography. Ten out of the 12 inositol niacinate products were capsules and 6 of the 7 extended-release formulations were tablets. During the initial 30-minute dissolution study of inositol niacinate products, free niacin was released to various degrees. One product achieved fast dissolution, with >30% cumulative release of niacin. The cumulative percentage of niacin released at 240 minutes of all inositol niacinate products was statistically different (p < 0.0001). The majority of these products reached a plateau of releasing niacin in one to two hours, which was maintained until the end of the study. Six out of the seven extended-release niacin products had extended-release profiles. Five products showed a statistically higher dissolution rate (p < 0.05) than that of Niaspan. Significant variations in dissolution profiles were noted among the 7 nonprescription extended-release and 12 nonprescription inositol niacinate products in vitro, and their dissolution rates were not comparable to that of the prescription extended-release niacin. Further studies are warranted to correlate such dissolution data with their in vivo efficacy.

&lt;i&gt;In vitro&lt;/i&gt; comparative evaluation of co-trimoxazole tablet products obtained from drug retail outlets in Addis Ababa

Bacterial resistance to trimethoprim-sulphamethoxazole is a rapidly increasing problem and is exacerbated by use of substandard products. In this work, it is aimed to evaluate the physical properties and the dissolution profiles of trimethoprim-sulphamethoxazole tablets which were obtained from drug retail outlets in Addis Ababa and produced by ten different manufacturers. Accordingly, the different tablets were evaluated for physical properties (diameter, thickness, hardness, and friability and disintegration time) and their dissolution profiles were compared by the USP XXVI paddle method. The very long t90% values of Cotreich and Cotrimol (60 & 45 min, respectively) for trimethoprim, the very long t50% & t90% values of Cotreich (38 and >60 min, respectively) for trimethoprim and sulphamethoxazole, and the very long t90% values of Cotreich, Cotrimol and Kanprim (>60 min) for sulphamethoxazole indicate that these products could result in lower rate and extent of bioavailability in the body. Similar problems could be encountered with the relatively long t90% values of cotrimoxazole (45 min) and Oriprim (40 min) for sulphamethoxazole. The smaller amount of sulphamethoxazole and trimethoprim released from products with delayed release could compromise the in vivo efficacy of these tablets. Keywords: co-trimoxazole, tablet, dissolution, formulation parameters, process parameters Ethiopian Pharmaceutical Journal Vol. 24, 2006: 31-40

Enhancement of dissolution profile by solid dispersion (kneading) technique

This article investigates enhancement of the dissolution profile of valdecoxib using solid dispersion with PVP. The article also describes the preparation of fast-dissolving tablets of valdecoxib by using a high amount of superdisintegrants. A phase solubility method was used to evaluate the effect of various water-soluble polymers on aqueous solubility of valdecoxib. Polyvinyl pyrrolidone (PVP K-30) was selected and solid dispersions were prepared by the method of kneading. Dissolution studies using the USP paddle method were performed for solid dispersions of valdecoxib. Infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffractometry (XRD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Tablets were formulated containing solid dispersion products and compared with commercial products. IR spectroscopy, XRD, and DSC showed no change in the crystal structure of valdecoxib. Dissolution of valdecoxib improved significantly in solid dispersion products (< 85% in 5 minutes). Tablets containing solid dispersion exhibited better dissolution profile than commercial tablets. Thus, the solid dispersion technique can be successfully used for improvement of dissolution of valdecoxib.

Estimation of the percolation thresholds in acyclovir hydrophilic matrix tablets

The principles of percolation theory were applied to design controlled release matrix tablets containing acyclovir. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice. The application of this theory to study the release and hydration rate of hydrophilic matrices allows to explain the changes in release and hydration kinetics of swellable matrix type controlled delivery systems. The objective of the present paper is to estimate the percolation threshold of HPMC K4M in matrices of acyclovir and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. Matrix tablets have been prepared using acyclovir as drug and HPMC K4M as matrix forming material, employing five different excipient/drug percentages. Dissolution studies were carried out using the paddle method. Water uptake measurements were performed using a modified Enslin apparatus. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the excipient volumetric fraction at time zero plus initial porosity was studied. According to percolation theory, the critical points observed in dissolution and water uptake studies can be attributed to the excipient percolation threshold. This threshold was situated between between 20.76% and 26.41% v/v of excipient plus initial porosity. The knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, reducing the time to market and second, increasing their robustness when they are prepared at Industrial scale, avoiding the formulation in the nearby of the percolation threshold.

Development and &lt;i&gt;In vitro&lt;/i&gt; Evaluation of Oral Controlled Release Formulations of Celecoxib Using Optimization Techniques

The objective of this study was to develop controlled release matrix embedded formulations of celecoxib (CCX) as candidate drug using hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC), either alone or in combination, using optimization techniques like polynomial method and composite design. This would enable development of controlled release formulations with predictable and better release characteristics in lesser number of trials. Controlled release matrix tablets of CCX were prepared by wet granulation method. The in vitro release rate studies were carried out in USP dissolution apparatus (paddle method) in 900 ml of sodium phosphate buffer (pH 7.4) with 1% v/v tween-80. The in vitro drug release data was suitably transformed and used to develop mathematical models using first order polynomial equation and composite design techniques of optimization. In the formulations prepared using HPMC alone, the release rate decreased as the polymer proportion in the matrix base was increased. Whereas in case of formulations prepared using EC alone, only marginal difference was observed in the release rate upon increasing the polymer proportion. In case of formulations containing combination of HPMC and EC, the release of the drug was found to be dependent on the relative proportions of HPMC and EC used in the tablet matrix. The release of the drug from these formulations was extended up to 21 h indicating they can serve as once daily controlled release formulations for CCX. Mathematical analysis of the release kinetics indicates a near approximate Fickian release character for most of the designed formulations. Mathematical equation developed by transforming the in vitro release data using composite design model showed better correlation between observed and predicted t(50%) (time required for 50% of the drug release) when compared to first order polynomial equation model. The equation thus developed can be used to predict the release characteristics of the drug from matrix embedded formulations depending upon the proportion of HPMC and EC used in the formulation.

Influence of PEG 4000 concentration dissolution rate of ketoprofen in solid dispersion system of ketoprofen-PEG 4000

Influence of PEG 4000 concentration dissolution rate of ketoprofen was studied in solid dispersion system of ketoprofen-PEG 4000. Solid dispersion system was prepared by melting method with various weight ratio of ketoprofen-PEG 4000, i.e. 2:1, 1:1, 1:3, and 1:4. The dissolution test was carried out using the paddle method at temperature of 37±0,5°C and 50 rotations per minute (rpm) in 900 mL of hydrochloric acid buffer solution at pH 1.2. The dissolution rate of ketoprofen improved by increasing PEG 4000 concentration. Incorporation of sodium lauryl sulfate into solid dispersion system of ketoprofen-PEG 4000 enhanced the dissolution rate of ketoprofen. Key words : solid dispersion, ketoprofen, PEG 4000, sodium lauryl sulfate

Catanionic mixtures involving a drug: A rather general concept that can be utilized for prolonged drug release from gels

The aim of this work was to study at what extent mixtures of drug substances and oppositely charged surfactants form catanionic aggregates and to apply these as a means of obtaining prolonged drug release from a gel. The properties of traditional catanionic mixtures are relatively well known, but only recently we found that not only traditional surfactants form these mixtures, but also structurally more complex surface active drug compounds. In this study, several different compositions of catanionic mixtures were studied visually, by cryogenic transmission electron microscopy (cryo-TEM) and rheologically using a Bohlin VOR Rheometer. Some of the catanionic vesicle and micelle phases were incorporated in and released from gels using the USP paddle method. The drug compounds investigated were lidocaine, ibuprofen, naproxen, alprenolol, propranolol, and orphenadrine. Of the six drug molecules used in this study, five, both positively and negatively charged, were capable of forming catanionic vesicles and/or micelles with oppositely charged surfactants. The drug release studies show that catanionic drug surfactant mixtures are beneficial for obtaining prolonged release from gels, as the drug release using catanionic vesicles and micelles was prolonged between 10 and 100 times compared to the release of pure drug substance from the gel.

Study of the critical points of HPMC hydrophilic matrices for controlled drug delivery

The knowledge of the percolation thresholds of a system results in a clear improvement of the design of controlled release dosage forms such as inert matrices. Despite hydrophilic matrices are one of the most used controlled delivery systems in the world, but actuality, the mechanisms of drug release from these systems continue to be a matter of debate nowadays. The objective of the present paper is to apply the percolation theory to study the release and hydration rate of hydrophilic matrices. Matrix tablets have been prepared using KCl as a drug model and HPMC K4M as matrix-forming material, employing five different excipient/drug particle size ratios (ranging from 0.42 to 2.33). The formulations studied containing a drug loading in the range of 20–90% (w/w). Dissolution studies were carried out using the paddle method and the water uptake measurements were performed using a modified Enslin apparatus. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. The percolation theory has been applied for the first time to the study of matrix type controlled delivery systems. The application of this theory allowed to explain changes in the release and hydration kinetics of these matrices. The critical points observed in dissolution and water uptake studies can be attributed to the excipient percolation threshold, being this threshold one of the main factors governing the gel layer formation and consequently, the drug release control from hydrophilic matrices.

Evaluation of Disintegrating Time of Rapidly Disintegrating Tablets by a Paddle Method

A paddle method for measurement of the disintegrating time of orally disintegrating tablets with rizatriptan benzoate as a model drug was evaluated. The paddle method employed a dissolution test assembly with tablets immersed in disintegrating medium through a fastened sinker. Paddle stirring rate, opening of the sinker sieve, and tablet crushing strength influenced disintegrating time greatly. A logarithmic relationship was observed between disintegrating time and paddle revolution speed, while disintegrating time values and tablet crushing strength were fitted to a linear equation. The paddle method values with limited deviation were in good correlation with in vivo results. The paddle method was employed to optimize the disintegrating time of rizatriptan benzoate orally disintegrating tablets using a factorial design. The best-fit quadratic equation with a regression coefficient of 0.996 was highly predictive, which was indicative that the paddle method was precise and applicable in formulation optimization.

Study of the Critical Points in Lobenzarit Disodium Hydrophilic Matrices for Controlled Drug Delivery

Percolation theory is a multidisciplinary theory that studies chaotic systems. It has been applied in the pharmaceutical field since 1987. The application of this theory to study the release and hydration rate of hydrophilic matrices allowed for first time to explain the changes in release and hydration kinetic of swellable matrices type controlled delivery systems. The objective of the present paper is to estimate the percolation threshold of HPMC K4M in matrices of lobenzarit disodium and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The materials used to prepare the tablets were Lobenzarit disodium (LBD) and HPMC of viscosity grade K4M. The drug mean particle size was 42+/-0.61 mum and the polymer was sieved and 150-200 microm granulometric fraction was selected. The formulations studied were prepared with different excipient contents in the range of 10-80% w/w. Dissolution studies were carried out using the paddle method and the water uptake measurements were performed using a modified Enslin apparatus. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. According to percolation theory, the critical points observed in dissolution and water uptake studies are attributed to the existence of an excipient percolation threshold. This threshold was situated between (18.58 to 24.33% v/v of HPMC). Therefore, the LBD-HPMC K4M matrices with a relative HPMC particle size of should be formulated with an excipient content above 24.33% v/v of HPMC, to obtain a control of the drug release from these systems.

Etodolac-Liquid-Filled Dispersion into Hard Gelatin Capsules: An Approach to Improve Dissolution and Stability of Etodolac Formulation

ABSTRACTThe formation of melt dispersion is an effective method of increasing the dissolution rate of poorly soluble drugs, and hence, of improving the bioavailability. The carrier fusion method was used to prepare different dispersion of etodolac using Gelucire 44/14 and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The physical characteristics of the binary systems were determined by differential scanning calorimetry (DSC), infrared spectroscopy (IR). The release rate from the resulting dispersion was determined from dissolution studies by use of USP dissolution apparatus II (paddle method). The dissolution rate of etodolac is increased in all the dispersion systems compared to that of pure drug. A liquid dispersion system of etodolac (20%) and Gelucire 44/14: TPGS blend (80%), in different ratios, was also prepared. The capsule formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. Physical and chemical properties of the dispersion didn't change during a period of storage at room temperature and at 4°C, 0% RH. It was found that etodolac was chemically stable against the effects of temperature and humidity. However, the relative humidity and storage time exerted an effect on the dissolution behavior of etodolac. The changes in dissolution behavior after storage under conditions of high humidity and temperature might be related to the formation of etodolac microcrystal and to water absorption by the carrier during storage. It is predicted that acceptable shelf-lives should result when moisture-resistant packaging is used for pharmaceutical formulations of this type.