Paddle Method Research Articles

Design and evaluation of Xanthan gum-based sustained release Matrix tablets of Diclofenac sodium

In the present investigation, an attempt has been made to increase therapeutic efficacy, reduce frequency of administration, and improve patient compliance, by developing sustained release matrix tablets of diclofenac sodium. Sustained release matrix tablets of diclofenac sodium, were developed by using different drug: polymer ratios, such as F1 (1:0.12), F2 (1:0.16), F3 (1:0.20), F4 (1:0.24) and F5 (1:0.28). Xanthan gum was used as matrix former, and microcrystalline cellulose as diluent. All the lubricated formulations were compressed using 8 mm flat faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution using basket method, and swelling index. All the formulations showed compliance with pharmacopoeial standards. Among different formulations, F1 showed sustained release of drug for 12 hours with 89.67% release. The effect of other parameters like addition of release modifier (PEG 6000), gum concentration, pH of dissolution medium, rotation speed and dissolution by paddle method, were also studied. Selected formulation (F1) was subjected to stability studies for three months at 0-4°, room temperature (28°), and 45° with RH 75±5%, and showed stability with respect to release pattern. The kinetic treatment showed that the release of drug follows zero order kinetic (R 2 = 0.9758). Korsmeyer and Peppas equation gave value of n = 0.9409 which was close to one, indicating that the drug was released by zero order kinetic. Thus, Xanthan gum can be used as an effective matrix former, to extend the release of diclofenac sodium.

Evaluation of Bitterness Suppression of Macrolide Dry Syrups by Jellies

The purpose of this study was to evaluate the bitterness-suppressing effect of three jellies, all commercially available on the Japanese market as swallowing aids, on two dry syrups containing the macrolides clarithromycin (CAM) or azithromycin (AZM). The bitterness intensities of mixtures of the dry syrups and acidic jellies were significantly greater than those of water suspensions of the dry syrups in human gustatory sensation tests. On the other hand, the mixture with a chocolate jelly, which has a neutral pH, was less bitter than water suspensions of the dry syrups. The bitterness intensities predicted by the taste sensor output values correlated well with the observed bitterness intensities in human gustatory sensation tests. When the concentrations of CAM and AZM in solutions extracted from physical mixtures of dry syrup and jelly were determined by HPLC, concentrations in the solutions extracted from mixtures with acidic jellies were higher than those from mixtures with a neutral jelly (almost 90 times higher for CAM, and almost 7-10 times higher for AZM). Thus, bitterness suppression is correlated with the pH of the jelly. Finally, a drug dissolution test for dry syrup with and without jelly was performed using the paddle method. There was no significance difference in dissolution profile. It was concluded the appropriate choice of jelly with the right pH is essential for taste masking. Suitable jellies might be used to improve patient compliance, especially in children. The taste sensor may be used to predict the bitterness-suppressing effect of the jelly.

In Vitro Dissolution Studies of Sodium Diclofenac Granules Coated with Eudragit L-30D-55® by Fluidized-Bed System

The objective of this work was to study the dissolution process of sodium diclofenac granules coated with a polymeric suspension of Eudragit L-30D-55® by fluidized bed. Methacrylic acid-methylmetacrylate copolymer, also known as Eudragit, has been used as a pH sensitive coating material to protect drug substances prior to delivery to the human intestines. The sodium diclofenac granules were prepared by wet granulation technology using microcrystalline cellulose (MICROCEL), sodium diclofenac, and polivinilpirrolidone K-30. The granules coating operation was carried out in a fluidized bed with top spraying by a double-fluid nozzle. The dissolutions studies of the coated granules were performed in triplicate in a dissolution test station according to “in vitro testing requirements” Method A (paddle method, rotation of 100 RPM and temperature fixed at 37°C). The dissolution mediums were 0.1N HCl solution and a pH 6.8 phosphate buffer solution, following the pH change dissolution procedure specified in USP for enteric-coated articles: 2 h of exposure to 750 mL of 0.1N HCl followed by testing in 1000 mL of pH 6.8 phosphate buffer, the pH being adjusted with 250 mL of 0.2 M tribasic sodium phosphate solution. The released amount of sodium diclofenac was periodically determined by UV spectrophotometry at wavelength of 276 nm, using a spectrophotometer UV-VIS HP 8453. The coated product showed gastric resistance properties confirming the feasibility of the fluidized bed for applying enteric coating in granules and pharmaceutical powders.

Prediction of Dissolution Profiles of Acetaminophen Beads Using Artificial Neural Networks

Immediate release acetaminophen (APAP) beads with 40% drug loading were prepared using the extrusion-spheronization process. Eighteen batches of beads were prepared based on a full factorial design by varying process variables such as extruder type, extruder screw speed, spheronization speed, and spheronization time. An in vitro dissolution test was carried out using the USP 27 Apparatus II (paddle) method. Artificial Neural Network (ANN) models were developed based on the aforementioned process variables and dissolution data. The trained ANN models were used to predict the dissolution profiles of APAP from the beads, which were prepared with various processing conditions. For training the ANN models, process variables were used as inputs, and percent drug released from APAP beads was used as the output. The dissolution data from one out of 18 batches of APAP beads was selected as the validation data set. The dissolution data of other 17 batches were used to train the ANN models using the ANN software (AI Trilogy®) with two different training strategies, namely, neural and genetic. The validation results showed that the ANN model trained with the genetic strategy had better predictability than the one trained with the neural strategy. The ANN model trained with the genetic strategy was then used to predict the drug release profiles of two new batches of APAP beads, which were prepared with process variables that were not used during the ANN model training process. However, the process variables used to prepare the two new batches of APAP beads were within the confines of the process variables used to prepare the 18 batches. The actual drug release profile of these two batches of APAP beads was similar to the ones predicted by the trained and validated ANN model, as indicated by the high f2 values. Furthermore, the ANN model trained with genetic strategy was also used to optimize process variables to achieve the desired dissolution profiles. These batches of APAP beads were then actually prepared using the process variables predicted by the trained and validated ANN model. The dissolution results showed that the actual dissolution profiles of the APAP beads prepared from the predicted process variables were similar to the desired dissolution profiles.

Preparation and Characterization of Metoprolol Controlled-Release Solid Dispersions

In recent years, great attention has been paid to using solid dispersions to make sustained-release drugs. The objective of this study is to produce sustained-release systems of metoprolol tartrate using solid dispersion techniques and to evaluate their physicochemical characteristics. The solid dispersions were produced by melting and solvent methods, containing 7%, 15%, or 25% of the drug and different ratios of Eudragit RLPO and RSPO in ratios of 0:10, 3:7, 5:5, 7:3, and 10:0. Drug release profiles were determined by USP XXIII rotating paddle method in phosphate buffer solution (pH 6.8). XRD, DSC, IR, and microscopic observations were performed to evaluate the physical characteristics of solid dispersions. Results showed that the drug release from dispersions was at a slower rate than pure drug and physical mixtures. Moreover, the formulations containing greater ratios of Eudragit RSPO showed slower release rates and smaller DE8% but larger mean dissolution time than those containing greater ratios of Eudragit RLPO. Dispersions with particle size of less than 100 μm containing 7% of metoprolol and Eudragit RL:RS 5:5 (solvent method) and those with the ratio of 3:7 (melting method) had similar release pattern to Lopressor® sustained-release tablets by zero-order and Higuchi kinetics, respectively.

Physicochemical Characterization and Dissolution Properties of CS-891 with Different Crystallinity

Ground CS-891 (N-[1-(4-methoxyphenyl)-1-methylethyl]-3-oxo-4-aza-5a-androst-1-ene--carboxamide) of poorly water soluble drug was obtained using a Heiko Seisakusho model TI-100 vibration mill, and samples with different crystallinity were prepared at mixture ratios of 10:0, 7:3, 5:5, 3:7 and 0:10 (intact;ground CS-891). Physicochemical characterizations were obtained using qualitative and quantitative X-ray diffractometry, different scanning calorimetry (DSC), scanning electron microscopy (SEM), Quantasorb surface area analyzer, and controlled atmosphere microbalance. With increase of amorphous CS-891 in mixture ratios, the intensities of X-ray diffraction peaks of crystalline CS-891 were decreased, whereas surface area, water absorption, and exothermic peaks in DSC were increased. The apparent solubility of ground CS-891 was and the solubility of intact CS-891 was at . The apparent precipitation rates of CS-891 in a supersaturated solution during the solubility test were increased with an increase of amorphous CS-891, and a crystalline form of CS-891 transformed from amorphous CS-891 after the solubility test was found by X-ray diffraction analysis, DSC and SEM. The dissolution profiles of CS-891 with different crystallinity at by the USP paddle method were investigated, and the apparent dissolution rate constant of ground CS-891 was about 5.9-fold higher than that of intact CS-891. A linear relationships between the crystallinity of CS-891 and the apparent dissolution rate constant (r>0.96) were obtained.

Evaluation ofin-vitro dissolution andin-vivo absorption for two different film-coated pellets of clarithromycin

The aim of this study was to compare two formulations of film-coated pellets containing clarithromycin after single oral dose study in healthy male volunteers. Two formulations with different coating polymers were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules and formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film. Release profiles of film-coated pellets were evaluated using paddle method under different conditions. Pharmacokinetic profiles of these formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. The relative bioavailability based on the AUC0-24h was found to be 96.2% and 58.7% for F-1 and F-2 compared with IR, and the Tmax was delayed.

Development of transdermal system containing nicotine by using sustained release dosage design

This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD). TFs were prepared with polyethylene membrane as a rate-controlling barrier; a carbomer was used as the gel reservoir with or without propylene glycol (PG). The in vitro target flux (0.0535 mg cm –2 h –1) was calculated according to SRDD calculations. Nicotine permeation through the membrane with or without transfer adhesive was also studied using diffusion cells. Nicotine permeated through membrane (without adhesive) with a flux of 0.0555 mg cm –2 h –1 and this value was similar to that of the in vitro target flux. The release from the TFs and from a commercial product (Nicotinell, 52.5 mg 30 cm –2) was studied using the FDA paddle method. The nicotine amount was increased from 22.7 to 56.5 mg in gel reservoir, and a plateau was reached beyond 45.4 mg of drug; the system attained the maximum thermodynamic activity with 56.5 mg of nicotine. The release rate from TFs (without adhesive layer) containing PG in the reservoir was very similar to the target release rate (1.07 mg h –1). The fluxes of nicotine from Nicotinell and TF containing 45.4 mg of nicotine were close to the in vitro target release rate.

The use of thiolated polymers as carrier matrix in oral peptide delivery—Proof of concept

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan–TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50 ± 2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Real-time monitoring in managing the decontamination of flexible gastrointestinal endoscopes

To evaluate the efficacy of endoscope reprocessing using bacteriologic methods and adenosine triphosphate (ATP) bioluminescence and to evaluate the potential benefits of the latter in managing the process. An endoscopy unit in each of 2 acute district general hospitals in the United Kingdom. Following visual observation, 8 locations important in the decontamination of gastrointestinal (GI) endoscopes were monitored during reprocessing by bacteriologic sampling (paddle method) and ATP bioluminescence. Endoscope reprocessing was conducted in accordance with British Society of Gastroenterology guidelines. Bacteriologic tests required 24 hours for results to be obtained; ATP tests were completed within 2 minutes. Of the 504 sites tested throughout the decontamination process, bacterial growth was recorded on 32 occasions, 3 from the end product. Throughout the decontamination process, ATP tests obtained 95 results above benchmark values and 1 from the end product. The bacteriologic results after terminal disinfection indicated that the reprocessing was carried out effectively overall. ATP results prior to disinfection indicated that manual cleaning might not have always been performed adequately and that this could have impaired the disinfection process. ATP provided a rapid means of assessing the efficacy of cleaning steps prior to terminal disinfection.

PENGARUH POLIVINIL PIROLIDON TERHADAP LAJU DISOLUSI FUROSEMID DALAM SISTEM DISPERSI PADAT

The research to accelerate furosemide dissolution rate has been done through physical property modification by solid dispersion forming polyvinylpyrolidone (PVP) carrier with solvent method. Pure furosemide posses property of being practically insoluble in water and has low bioavailability. In current research, six weight ratio of furosemide to PVP being used are 1:1; 1:3; 1:5; 1:9 and 1:15. Physical mixtures are made in equivalent weight ratio. The dissolution rate was examined by paddle method in phosphat buffer pH 5,8. Solid dispersion caracterised with in vitro dissolution study, X-ray diffraction, infra red spectrophotometer and differential scanning calorimetric. The result shows that solid dispersion of furosemide with PVP carrier is higher compare to physical mixture dissolution rate and pure furosemide. The ratio furosemide to PVP who has the highest dissolution rate is 1:15. The analyzing shows the existing of altering crystalline to amorphous state. Key word : furosemide, polyvinylpyrolidone, solid dispersion, dissolution rate.

Understanding agglomeration of indomethacin during the dissolution of micronised indomethacin mixtures through dissolution and de-agglomeration modeling approaches

The purpose of this research was to correlate the state of agglomeration determined by the modeling of dissolution and de-agglomeration profiles, using mixtures of micronised indomethacin designed to have different dissolution rates and extents of particle agglomeration in dissolution media. Dissolution profiles were determined using the USP paddle method. De-agglomeration profiles were obtained from laser diffraction particle sizing of mixtures of indomethacin in dissolution media under non-sink conditions. Data were modeled and key parameters estimated using a non-linear least squares estimation algorithm. The key parameters of initial apparent volume concentrations as dispersed and agglomerated particles, and dissolution rate constants (for dissolution modeling), and the apparent volume concentrations of dispersible and non-dispersible agglomerates and the de-agglomeration rate constant (for de-agglomeration modeling) were related to indomethacin and sodium lauryl sulphate concentrations in the lactose–povidone mixtures. Micronised sodium lauryl sulphate added to the mixture was more effective in de-agglomeration than equivalent concentrations in the dissolution media. An excellent correlation existed between the total initial apparent volume concentration of agglomerates determined by dissolution and de-agglomeration ( P=0.98). The use of key parameters estimated from the modeling of dissolution and de-agglomeration profiles provides a useful tool in dosage form development of formulations of poorly water soluble drugs.

카르바마제핀 정제 용출패턴과 용출액 조성과의 상관성

The objective of this study was to evaluate the effects of surfactant type and concentration upon dissolution rates of carbamazepine from an immediate-release tablet. The dissolution media used in this study were aqueous solutions containing 0.1-2% sodium lauryl sulfate, cetyltrimethylammonium bromide, or polysorbate 80. The solubility of carbamazepine in the dissolution media was determined at first. A dissolution study was then conducted by using the USP dissolution apparatus II (paddle method) with an agitation rate of 75 rpm. Aliquots of the dissolution media were taken at predetermined time intervals, and the amount of carbamazepine dissolved was measured spectrophotometrically at 285 nm. The dissolution data obtained were fitted into a biphasic exponential equation with four parameters. Excellent correlations were observed between the experimental data and the theoretical ones predicted by the equation. This equation permitted the calculation of (the time required for dissolving 50% of carbamazepine) under various experimental conditions. Differentiation of the equation also led to the attainment of dissolution rates at dissolution time points. The addition of a surfactant to an aqueous solution led to increasing the solubility of carbamazepine by 3- to 12-folds, depending upon its type and concentration. This event also resulted in enhancing the magnitude of a sink condition during the dissolution study. As a result, the dissolution rate of carbamazepine was affected by the aqueous surfactant concentration in a proportional manner. Subsequently, values declined rapidly, as the surfactant concentration increased. Such effects were observed in decreasing order of sodium lauryl sulfate, cetyltirmethylammonium bromide, and polysorbate 80. These results clearly demonstrated that it was possible to tailor a dissolution rate and of carbamazepine by manipulating the type and concentration of a surfactant. Relevant information would be beneficial to setting up dissolution specifications for poorly water-soluble drug products.

Release behavior and photo-image of nifedipine tablet coated with high viscosity grade hydroxypropylmethylcellulose: effect of coating conditions

An orally applicable nifedipine-loaded core tablets was coated using high viscosity grade HPMC (100,000 cps) in ethanol/water cosolvent. The release of coated tablet was evaluated using USP paddle method in 900 ml of simulated gastric fluid (pH 1.2) for 2 h followed by intestinal fluid (pH 6.8) for 10 h. The surface morphologies using scanning electron microscope and photo-images using digital camera of coated tablet during the release test were also visualized, respectively. The viscosity of hydro-alcoholic HPMC solution largely decreased as the amount of ethanol increased. There was no significant difference in viscosity among plasticizers used. The distinct and continuous coated layer was observed using scanning electron microscope. However, the surface morphologies were highly dependent on HPMC concentration and ratio of coating solvents. The higher ratio of ethanol/water gave a longer lag time prior to drug release. Lag time also increased as a function of the coating levels based on weight gains due to increased thickness of coated layer. Lag time is inversely correlated with HPMC concentration in ethanol/water (5:1) cosolvent. As the HPMC concentration slightly decreased from 3.8 to 3.2% in hydroalcoholic coating solution, a large increase of lag time was observed. As the swelling (mixing) time of high viscosity grade HPMC in ethanol/water cosolvent increased from 1 to 5 h, the release rate was decreased due to enough plasticization of polymer. Based on photo-imaging analysis, the coated tablet was initially swelled and gelled without erosion and disintegration over 5 h. The disintegration of the coated tablet was occurred approximately 7 h after dissolution, resulting in pulsed release of drug. The high viscosity grade HPMC can be applicable for polymeric coating after careful selection of solvent systems. The release behavior and lag time could be controlled by coating conditions such as HPMC concentration, ethanol/water ratio as a coating solvent, coating level and swelling (mixing) time of coating solution. The current time-controlled release tablet coated with high viscosity grade HPMC with a designated lag time followed by a rapid release may provide an alternative to site specific or colonic delivery of drugs. In addition, the release behavior can be matched with body’s circadian rhythm pattern in chronotherapy.

Development of pulsatile release tablets with swelling and rupturable layers

A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as pulsatile drug delivery system. Cores containing buflomedil HCl as model drug were prepared by direct compression of different ratios of spray-dried lactose and microcrystalline cellulose and were then coated sequentially with an inner swelling layer containing a superdisintegrant (croscarmellose sodium) and an outer rupturable layer of ethylcellulose. The effect of core composition, level of swelling layer and rupturable coating, and magnesium stearate in rupturable layer was investigated. Mechanical properties of ethylcellulose films in the dry and wet state were characterized with a puncture test. Rupture and dissolution tests were performed using the USP XXIV paddle method at 50 rpm in 0.1 N HCl. The lag time of the pulsatile release tablets decreased with increasing amount of microcrystalline cellulose in the cores and increased with increasing levels of both swelling layer and rupturable ethylcellulose coating. Increasing levels of the ethylcellulose coating retarded the water uptake and thus prolonged the lag time. Addition of magnesium stearate to the ethylcellulose coating lowered the mechanical strength of the film and improved the robustness of the system.

Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage

As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were produced with these three excipients (60% w/w) and theophylline as drug model (40%). On the one hand, in vitro dissolution studies were performed with the rotating paddle method displaying the different release behaviour of these three matrices (immediate release for MCC, steady release for HPMC and sustained release for EC). On the other hand, the evolution of the T 2m spin–spin relaxation time in NMR experiments during granules hydration was recorded. NMR findings shore up dissolution data, both depending on interactions between the matrix and water. NMR spectroscopy appears to be a valuable tool for obtaining, at an earlier stage of drug development, more information about drug release mechanism.

Effect of Hydrodynamic Environment on Tablets Dissolution Rate

The main objective of this research was to develop an experimental method to apply well‐defined flow fields to solid dosage forms, to study the rate process underlying tablet dissolution, and to better understand the role of external hydrodynamic condition on mass transfer rate and film thickness during dissolution. Two drugs models, Theophylline (class 1) and Naproxen (class 2), were selected and formulated into conventional tablets containing 105 mg Theophylline or 300 mg Naproxen using the wet granulation method. Tablets were tested for dissolution using both the basket and paddle methods at different rotational speed of 25, 50, 75, and 100 rpm. In general, the paddle method gave higher dissolution rates than the basket method and as the velocity of rotation was increased, drug release was also increased. Six different paddles and a tablet holder were designed and used to test dissolution rate. The rate of dissolution was dependent on the tablet surface area exposed to the dissolution medium, and on the shape, diameter, and area of the paddles used. Theophylline tablets showed increased mass transfer rate and decreased film thickness as basket rotation speed was increased. At 25 rpm, the mass transfer coefficient was 0.684 × 10− 4 cm/sec and film thickness was 12.003 × 10− 2 cm; at 100 rpm, the mass transfer coefficient was 3.884 × 10− 4 cm/sec and film thickness was 2.114 × 10− 2 cm. Paddle values tested at the same speed showed higher mass transfer coefficient and lower film thickness for Theophylline and Naproxen tablets. P values obtained by modification of the Stokes‐Einstein equation showed that diffusion is the rate‐limiting step to drug release and not mass transfer. This study demonstrated that hydrodynamic condition, type of dissolution testing used, and design of the paddles have an effect on dissolution rate, mass transfer rate, and the film thickness underlying the dissolution process.

Application of a new mathematical method for the estimation of the mean surface area to calculate the percolation threshold of lobenzarit disodium [correction of dissodium] salt in controlled release matrices.

One of the practical handicaps for the application of the percolation theory to estimate the percolation threshold of drugs in controlled release systems is the fact that the dissolution studies must be carried out so that only one surface of the tablet is exposed to the dissolution medium. The aim of this work is to estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium (LBD) in inert matrices prepared with the excipients Ethocel((R)) 100 and Eudragit((R)) RS-PO (10-75% w/w). Release assays were performed using the paddle method. The whole surface of the tablets was exposed to the dissolution medium. For the first time, a new mathematical method is developed to transform the amount of drug released in amount released per surface area in order to calculate the percolation thershold of LBD. The mathematical method proposed allows to calculate, using a new equation, the evolution of the mean surface area (O((t))). The new method was validated and three novel results were achieved: A constant value of (O((t))) at critical time (theta) in the matrices (O((theta))=1.272 cm(2)); a linear relationship between initial surface area (O((0))) and critical time; and a linear relationship between O((t)) and time. Employing the values of O((t)), it was possible to calculate for the first time, the percolation threshold (p(c1)) for LBD in Ethocel((R)) 100 (p(c1)=0.280+/-0.102) and Eudragit((R)) RS-PO (p(c1)=0.344+/-0.07) matrices.

Effect of sodium lauryl sulfate in dissolution media on dissolution of hard gelatin capsule shells.

Sodium lauryl sulfate (SLS) is a commonly used surfactant in dissolution media for poorly water soluble drugs. However, it has occasionally been observed that SLS negatively impacts the dissolution of drug products formulated in gelatin capsules. This study investigated the effect of SLS on the dissolution of hard gelatin capsule shells. The USP paddle method was used with online UV monitoring at 214 nm (peptide bond). Empty size #0 capsule shells were held to the bottom of the dissolution vessel by magnetic three-prong sinkers. SLS significantly slowed down the dissolution of gelatin shells at pH < 5. Visually, the gelatin shells transformed into some less-soluble precipitate under these conditions. This precipitate was found to contain a higher sulfur content than the gelatin control sample by elemental analysis, indicating that SLS is part of the precipitate. Additionally, the slowdown of capsule shell dissolution was shown to be dependent on the SLS concentration and the ionic strength of the media. SLS interacts with gelatin to form a less-soluble precipitate at pH < 5. The use of SLS in dissolution media at acidic pH should be carefully evaluated for gelatin capsule products.

Novel Chewable Sustained‐Release Tablet Containing Verapamil Hydrochloride

The aim of this research is to produce a compactable self‐sealing chewable tablet of verapamil hydrochloride. Tablets were prepared by compressing beads coated with multiple layers including drug, hydroxypropyl methylcellulose, polyethylene oxide, ethylcellulose, lactose, and sodium starch glycolate. Dissolution studies were carried out according to the USP XXII paddle method for 14 h. A new tablet formulation was evaluated in three different forms: 1) whole tablet, 2) crushed tablet using a commercial tablet crusher, and 3) tablet chewed in the mouth and then expelled into dissolution fluid. Sustained release from the new formulation was maintained and was similar in all three different treatments, and similar to drug release from intact commercially available Isoptin SR®, but crushing or chewing destroyed the sustained release property of Isoptin SR® (as expected). This new formulation can be administered either by swallowing the whole tablet or by first crushing or chewing the tablet. Controlled release properties of this new formulation do not change by chewing or crushing the tablet first. Such a tablet could be valuable for all patients including those who have difficulty swallowing, such as pediatrics and geriatrics.