Salicylic Acid Tablets Research Articles

Application of Salicylic Acid Tablets in the Performance Verification Test for the Flow-Through Cell Apparatus

Application of Salicylic Acid Tablets in the Performance Verification Test for the Flow-Through Cell Apparatus

Altered Media Flow and Tablet Position as Factors of How Air Bubbles Affect Dissolution of Disintegrating and Non-disintegrating Tablets Using a USP 4 Flow-Through Cell Apparatus

This study investigated how air bubbles in media affect tablet dissolution in a flow-through cell system (USP 4) using disintegrating (USP prednisone) and non-disintegrating (USP salicylic acid) tablets. Cell hydrodynamics were studied using particle image velocimetry (PIV) and computational fluid dynamics (CFD). The PIV analysis showed periodic changes in the local flow corresponding to the discharge and suction of the pump cycles. The absence of prior deaeration induced small air bubbles in the media and lower maximum flow during the cycle, explaining the slower dissolution of the USP salicylic acid tablets. Bubbles, occurring during the USP prednisone tablets study, induced the transition of floating disintegrated particles towards the cell outlet, whereas the particles precipitated to form a white layer on the glass beads used in the study with prior deaeration. CFD analysis showed local flow variation in multiple positions of small (ID 12 mm) and large (ID 22.6 mm) cells, explaining the different rates of dissolution of prednisone tablet particles depending on their distribution. These results emphasize the importance of prior deaeration in dissolution studies using a flow-through system. Bubbles in the flow-through cell system affected tablet dissolution by reducing the area in contact with the media (wettability), lowering the maximum instantaneous flow (pressure buffering), and altering the position of disintegrated particles in the cell.

Quantification and spatial distribution of salicylic acid in film tablets using FT-Raman mapping with multivariate curve resolution

In this study, we proposed a rapid and sensitive method for quantification and spatial distribution of salicylic acid in film tablets using FT-Raman spectroscopy with multivariate curve resolution (MCR). For this purpose, the constituents of film tablets were identified by using FT-Raman spectroscopy, and then eight different concentrations of salicylic acid tablets were visualized by Raman mapping. MCR was applied to mapping data to expose the active pharmaceutical ingredients in the presence of other excipients by monitoring distribution maps and combination of FT-Raman mapping with MCR enabled the determination of lower salicylic acid concentrations. In addition, the distribution of major excipient, lactose, was examined in the tablet form. A calibration curve was obtained by plotting the intensity of the Raman signal at 1635 cm−1 versus the concentration of salicylic acid and the correlation was found to be linear within the range of 0.5%–3.9% with a correlation coefficient of 0.99. The limit of detection for the technique was determined 0.35%. The ability of the technique to quantify salicylic acid in tablet test samples was also investigated.

English

The aim of this study was to enhance the classical adjuvant functionality of maize starch (Mst) by co-processing with small quantities of carbopol 974P (CaPol). A pre-processed maize starch (MpS) was coated with different concentrations of CaPol corresponding to 0.25, 0.5, 0.75 and 1.0 %w/w and spray-dried at controlled conditions to produce the CaPol-coated motifs (MpS-CaPol). The relevant physicochemical and functional properties of the new CaPol-coated starch, as a direct compression and rapid disintegrating adjuvant were evaluated in the preparation of acetyl salicylic acid (ASA) tablets. The yield of MpS-CaPol produced with the various mix were between 87 to 95% of the weight of the start ingredients. There were no remarkable differences in the relevant physicochemical and functional properties determined for Mst and MpS thus, the results of MpS were not presented. There were no remarkable morphological differences between the particles of Mst and those of the coated motifs. The variants of the new starch motif showed properties that were sensitive to the concentrations of CaPol used in the coating. All the variants of MpS-CaPol generally showed comparative enhanced flow and moisture uptake. The swelling capacity of the new excipients containing different concentrations of CaPol can be ranked thus: 1 > 0.75 > 0.5 > 0.25 > 0% (Mst). The ASA tablets showed relative increased tensile strength and dissolution as the concentrations of CaPol increased (0 to 0.75%). The disintegration time were remarkably modified: The tablets prepared with new excipients containing CaPol of concentrations 0.25 to 0.75 %w/w all disintegrated rapidly within 1 min while that containing 1% w/w disintegrated at 45 ± 0.5 min; ASA tablets without disintegrant did not disintegrate even after 120 min. This study has shown that spray-dried Mst granules coated with small quantities of CaPol produced an excipient with new basic physicochemical properties that enhanced its adjuvant functionality when used for direct compression of rapid release ASA tablets. Key words: Maize starch, carbopol, film-coating, spray-drying, acetyl salicylic acid tablets.

Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4).

To clarify the effects of pump pulsation and flow-through cell (FTC) dissolution system settings on the hydrodynamic properties and dissolution profiles of model formulations. Two FTC systems with different cell temperature control mechanisms were used. Particle image velocimetry (PIV) was used to analyze the hydrodynamic properties of test solutions in the flow-through dissolution test cell. Two pulsation pumps (semi-sine, full-sine) and a non-pulsatile pump were used to study the effects of varied flows on the dissolution profiles of United States Pharmacopeia standard tablets. PIV analysis showed periodic changes in the aligned upward fluid flow throughout the dissolution cell that was designed to reduce the temperature gradient during pump pulsation (0.5s/pulse). The maximum instantaneous flow from the semi-sine pump was higher than that of the full-sine pump under all conditions. The flow from the semi-sine wave pump showed faster dissolution of salicylic acid and prednisone tablets than those from other pumps. The semi-sine wave pump flow showed similar dissolution profiles in the two FTC systems. Variations in instantaneous fluid flow caused by pump pulsation that meets the requirements of pharmacopoeias are a factor that affects the dissolution profiles of tablets in FTC systems.

Effect of a Fiber-Optic Probe on the Dissolution of Salicylic Acid Tablets in USP Apparatus 2

Fiber-optic probes permanently inserted in the dissolution medium in dissolution vessels can automate the sampling process but can also potentially affect the hydrodynamics in the vessel, possibly resulting in increased drug dissolution rates. In this work, dissolution experiments with non-disintegrating salicylic acid calibrator tablets were conducted in dissolution testing Apparatus 2 in both the presence and absence of a commercially available fiber-optic probe (Opt-Diss). Tests were conducted using tablets dropped in the medium according to USP guidelines, as well as with tablets fixed at nine positions on the vessel bottom (i.e., either centered in the vessel or placed at different off-center locations with respect to the vessel vertical centerline). The results were compared using statistical tools. In many cases, the presence of the probe resulted in slightly faster dissolution rates. The difference between the results obtained in experimental systems with the probe and those obtained with the control system without the probe depended on tablet position. Larger differences were observed when the tablets were on inner circle positions (10° off-center circle), especially when the tablets were located immediately downstream of the probe. A paired t-test as well as the difference factor (f1) and similarity factor (f2) were used to statistically analyze the results. In most cases, the results obtained with the inserted probe were statistically different, according to the paired t-test, from those obtained without it. It can be concluded that fiber-optic sampling probes can often result in small but measurable enhancements in the dissolution rates, which can produce appreciable variations in test results.

Development of a Performance Verification Test for USP Apparatus 4

To evaluate salicylic acid tablets as a candidate reference material in a Performance Verification Test (PVT) when a USP performance test for dissolution (General Chapter <711>) relies on USP Apparatus 4 (flow-through cell). We developed a dissolution procedure relying on Apparatus 4 and salicylic acid tablets. Thereafter, a designed experiment was conducted to identify operational variables that significantly affect salicylic acid dissolution in this apparatus. Four variables (size of glass beads, cell temperature, flow rate, level of deaeration) and one combination effect (deaeration/bead size) were significant for mean percent dissolved. Two variables (tablet orientation, level of deaeration) were significant for standard deviation results, but these effects were less pronounced than those for mean percent dissolved results. Three variables (analyst, tester manufacturer, amount of glass beads) had no statistically significant effects on either the mean or standard deviation of the responses. The proposed PVT is capable of probing effects of changes in several critical operational parameters of Apparatus 4. Salicylic acid tablets were shown to be a suitable reference material for the PVT. The PVT using salicylic acid tablets satisfies important aspects of a PVT.

Attenuated total reflection infrared spectroscopy (ATR-IR) as an in s itu technique for dissolution studies

Dissolution studies are critical tests for measuring the performance of a drug product. We have developed a novel technique using in situ ATR-IR spectroscopy to monitor dissolutions of pharmaceutical drug products. The accuracy of this technique is ±3% relative to HPLC using salicylic acid calibrator tablets and acetaminophen OTC tablets. This novel approach also gives the research laboratory the capability of analyzing individual ingredients in multiple tablets; for example, individual components of salicylic acid and acetaminophen tablets are easily distinguished. In addition, the individual ingredients of a multi-component tablet containing acetylsalicylic acid and acetaminophen are readily distinguished. The ATR-IR system was found to have good sensitivity and can analyze samples as low as 0.03 mg/ml. With improved sensitivity, this is a promising method for monitoring dissolution of pharmaceutical tablets with an excellent in situ capability for distinguishing individual components.

In Vitro Dissolution Testing with Flow-Through Method: A Technical Note

In vitro dissolution testing is important for providing process control and quality assurance, determination of stability release characteristics of the product over time, and facilitating certain regulatory determinations (e.g., absence of effect of minor formulation changes or of change in manufacturing site on performance). In the past two decades, the dissolution test has also been widely discussed to serve as an indicator of how the formulation will perform in vivo (1–3). Although basket and paddle methods are currently the most popular methods for many drug products, both methods are operated under closed finite sink condition and cannot mimic the conditions present in the digestive system. A flow-through method using the official USP 4 apparatus operated in open-loop mode is capable of maintaining a continuous flow of fresh dissolution medium, thus, maintaining infinite sink conditions (3–6). This operational mode provides an environment potentially closer to that of the digestive tract. Thus, this technique may offer advantages for establishing in vitro and in vivo correlations (IVIVCs). To compare dissolution testing under finite and infinite sink conditions, this study applied both paddle and flow-through methods for dissolution testing with disintegrating prednisone and nondisintegrating salicylic acid tablets. The closed- and open-loop configurations of the flow-through method were used to provide comparisons with the paddle method. In addition to studies based on the official USP dissolution apparatus, several authors have reported development of novel, multicompartment dissolution apparatus in their efforts to develop good IVIVCs (7–9; Hughes et al., private communication). The reported novel systems have potential to simulate in vivo condition such as gastric volume and pH, gastric emptying to the intestine, and intestinal volume and pH etc., which may give a good in vivo and in vitro correlation. However, these novel apparatus require special configurations or parts, which may be difficult to duplicate in other labs. This study applies the idea of a multicompartment dissolution apparatus but attempts to minimize modifications to the current official USP apparatus so as to facilitate adoption by other labs for application to their specific studies. In this study, the flow-through apparatus with open-loop configuration has been modified by adding a flow-through reservoir after the flow-through cell. This reservoir is maintained at intestinal pH. Disintegrating prednisone and nondisintegrating salicylic acid were used as test drugs.

IN–VITRO PHARMACEUTICAL EVALUATION OF TWO BRANDS OF DISPERSIBLE ACETYL SALICYLIC ACID TABLETS AVAILABLE IN OMAN

Acetyl salicylic acid (ASA), a non-steroidal anti-inflammatory drug (NSAID) is widely used for its analgesic, antipyretic, antiinflammatory and anti-thrombotic action. The aim of the present study was to investigate the pharmaceutical equivalence of two brands of dispersible ASA tablets marketed in Oman. Two different brands of dispersible ASA tablets (300mg) were purchased from the retail pharmacy outlets and their pharmaceutical quality were assessed by using in-vitro tests as per the British Pharmacopoeia (BP) and unofficial standards as recommended by the manufacturers. The assessment of tablets included the evaluation of uniformity of weight and diameter, friability, crushing strength, disintegration and chemical assay by volumetric titration and colorimetric methods to determine the content of active pharmaceutical ingredient (API). Both brands of the ASA tablets passed the BP standards for uniformity of weight and diameter, disintegration, friability and crushing strength. However one of the two brands did not comply with the standard assay of content of active ingredient. Thus based on these results it can be concluded that these two brands of ASA are not pharmaceutically equivalent. Key words: ASA tablets, pharmaceutical equivalence, disintegration, volumetric method.

Improved drug dissolution and product characterization using a crescent-shaped spindle.

Drug release characteristics of two amoxicillin capsule products, 250 and 500 mg strength each, have been described using USP Paddle and crescent-shaped spindles. Using the same spindles, dissolution experiments were conducted with USP disintegrating (prednisone) and non-disintegrating (salicylic acid) calibrator tablets. Dissolution tests were conducted at 50 and 25 rev min(-1) using USP Paddle and crescent-shaped spindles, respectively. In all cases, even with the higher 50 rev min(-1), lower percent drug release results were observed with the Paddle spindle than with the crescent-shaped spindle, which was operated at 25 rev min(-1). The observed lower dissolution for amoxicillin capsule products (< 36 vs > 87% at 30 min) and USP prednisone calibrator tablets (45.5 vs 99.8% at 30 min) with Paddle spindles appeared to occur because of the accumulation of the disintegrated material (cone formation) at the bottom, thus restricting product-medium interaction. Crescent-shaped spindles did not allow any accumulation of the product and provided improved interaction by mixing and stirring, and thus appeared to provide true drug dissolution characteristics of the products. On the other hand, in the case of non-disintegrating USP salicylic acid tablets (18.5 vs 24.4% at 30 min), lower results with Paddle spindles appeared to be because of stagnation of the tablets, which provided poor product-medium interaction for the surface touching the vessel surface. In this case, the crescent-shaped spindles moved the tablets at the base of the vessel, providing improved and efficient product-medium interaction, thus appearing to reflect truer dissolution characteristics of the tablets. The results highlight the possible artifacts of the USP Paddle spindle, which could lead to inaccurate characterization of drug release properties of test products. As reported previously, the artifacts of high variability in results and lack of relevance to product properties appeared to be related to poor mixing and variable hydrodynamics within a dissolution vessel. Results from this study provide further evidence that these artifacts might be addressed adequately using the crescent-shaped spindle, thus resulting in improved drug release as well as better product characterization.

Use of ferric chloride to identify salicylate-containing poisons.

Ferric chloride (FeCl3) is used to qualitatively test the urine of patients with presumed salicylate exposure. FeCl3 testing of an unidentified poison might provide evidence of salicylate exposure in situations where FeCl3 urine testing cannot be used. Such situations include the absence of a urine sample, immediately after ingestion before urine contains a detectable quantity of salicylate, or for patients chronically using salicylatesfor which FeCl3 testing is unhelpful. This study seeks to determine if FeCl3 can be used to identify salicylate-containing products. We assessed the reactivity of FeCl3 with commercially available salicylate-containing products. We applied 0.1 mL of 10% FeCl3 solution to each of 15 various salicylate-containing products including: regular and buffered acetylsalicylic acid, bismuth subsalicylate, methylsalicylate, physostigmine salicylate, salicylic acid, trolamine salicylate, and herbal tablets with salicin-containing white willow bark (Salix sp.). These products tested were: regular and enteric-coatedpills (n = 4), powder (n = 1), topical creams (n = 5), topical liquids (n = 4), and intravenous solution (n = 1). FeCl3 was applied to crushed tablets and added directly to liquids and creams. Fifteen salicylate-free controls including liquids, pills, and creams similar in appearance to experimental samples were also tested. Three blinded physiciansfamiliar with FeCl3 testing independently observed the addition of FeCl3 to each sample and rated a positive or negative result. All salicylate-containing products were interpreted to be clearly FeCl3 positive and all control samples were interpreted to be clearly FeCl3 negative. Salicylate-containing products may be identified using FeCl33. When using FeCl3

Performance of USP calibrator tablets in flow-through cell apparatus

USP dissolution calibrator tablets were analysed by the flow-through cell method with the intention of examining its applicability for the flow-through cell apparatus suitability test. Test was performed with Dissotest CE-6 apparatus, (Sotax, Switzerland) in flow-through cells for tablets and capsules: smaller cells of 12 mm diameter and larger ones of 22.6 mm diameter. Analyses were performed with laminar and turbulent flow of dissolution medium. The flow rates were 16 and 8 ml/min for laminar flow and only 16 ml/min for turbulent flow. From the results it can be concluded that both salicylic acid tablets and prednisone tablets could be used for apparatus suitability test also for the flow-through cell under the conditions of laminar flows of 16 and 8 ml/min in cells φ 12 and 22.6 mm. As regards the turbulent flow of 16 ml/min, without a holder, cells φ 12 mm could be used for salicylic acid tablets and both cells (φ 12 and 22.6 mm) for prednisone tablets.

Cause of high variability in drug dissolution testing and its impact on setting tolerances

Considering a variable mixing/stirring and flow pattern in a drug dissolution vessel as a likely source of high variability in results, experiments were conducted using USP paddle apparatus by placing (aligned to the walls) a metal strip (1.7 mm thick×6.4 mm wide) in a dissolution vessel. The metal strip forces the undisintegrated tablet to settle about 3 mm away from the centre, facilitates spread of disintegrated material and diminishes the cone formation at the bottom of the vessel. To assess the impact of this altered environment in the vessel, but still maintaining the vessel dimensions within required specifications, drug release characteristics were evaluated for products having different formulation/manufacturing attributes. Tests were conducted with calibrator tablets (USP prednisone and salicylic acid tablets and FDA proposed NCDA No. 2 prednisone tablets) and two commercially available products (250 mg amoxicillin capsules and 5 mg glibenclamide tablets). Except for the glibenclamide tablet product, all products gave significantly ( P<0.01) higher dissolution results with vessels containing metal strip than without. The extent of increased dissolution with the metal strip varied from product to product i.e. USP prednisone tablet was the smallest (14.4%) and NCDA No. 2 was the largest (88.4%). Based on the results obtained from this study, it is concluded that employing the current apparatuses, in many cases products will provide lower than anticipated results which may not be reflective of the product drug release characteristics. Test-to-test variability, within or between laboratories, can also be very high depending on the settling position of the product once dropped in the vessel and/or due to slight aberration in the walls of the vessel by altering the extent of spread of disintegrated material at the bottom of the vessel. Thus, dissolution testing will require wider tolerances to be useful for comparison of batch-to-batch or interlaboratory results.

Predicting dissolution via hydrodynamics: salicylic acid tablets in flow through cell dissolution

A model was established for the dissolution of non-disintegrating salicylic acid tablets as a function of hydrodynamic conditions in the Flow Through Cell system (USP Apparatus 4). The approach was to model the dissolution rate of the material as a function of the Reynold’s number, the dimensionless engineering term that describes the degree of turbulence. The dissolution rate of USP calibrator salicylic acid tablets was measured as a function of tablet size, orientation within the cell, dissolution media flow rate, and cell size. All of these variables were found to have an effect on dissolution rate, consistent with theory. An equation to predict this dissolution was established as: N SH=−21.1+12.6× N RE 0.5, R 2=0.99; 10< N re<292.

Calibration—The USP Dissolution Apparatus Suitability Test

This report summarizes some trends observed in drug dissolution testing, based upon the United States Phannacopeia (USP) dissolution Apparatus Suitability Test results and the preliminary data obtained from an international collaborative study to assess the pharmaceutical quality of furosemide products in different countries. Based on the USP calibrator data submitted by the participants, representing four lots each of nondisintegrating (Salicylic Acid) and disintegrating (Prednisone) tablets, overall variability can be high and failures to meet the specijication in a dissolution run can be frequent. This high level of Variability andfailure seems to be dependent on the combination of calibrator and apparatus type. Although deaeration of dissolution media tends to reduce the frequency of failure, its effect on reducing the variability appears to be minimal. It appears that calibrator-apparatus combinations of Prednisone tablets/Basket Method and Salicylic Acid tablets/Paddle Method show some sort of interaction, therefore, use of these combinations to test suitability of dissolution apparatus needs to be evaluated. Prednisone Tablets with the Paddle Method and Salicylic Acid Tablets with the Basket Method, however, appear to provide suficient information for dissolution apparatus calibration and their use should be continued.

Comparative pH-Gradient Dissolution of Several Oral Dosage Forms of Iron

AbstractA comparative pH - gradient dissolution study was conducted for several brands of oral iron dosage forms on the Canadian market. The commercially available dissolution apparatus employed in the study met the requirements of the variety of pH media conditions necessary for conducting dissolution of conventional, enteric coated and slow release iron preparations. The reproducibility of the dissolution system was evaluated using the USP's non-disintegrating salicylic acid tablets. Dissolution results are discussed in reference to a recent bioavailability report concerning oral iron preparations. The applicability of the procedure in studying the dissolution of solid dosage forms of iron is discussed.

Automated Dissolution Testing with Flow-Injection Analysis. Dissolution Profiles for the Antiviral Drugs, Dhpg and Acyclovir, in Capsule Formulations.

We have designed, assembled, and tested an automatic dissolution apparatus using flow-injection analysis (FIA) techniques with spectrophotometric detection. The components (pumps, switching valves, detector, and so forth) that comprise the system are all readily-available items used primarily for high-performance liquid chromatography. The system performs well as evidenced by the usual tests for precision, response linearity, and dissolution behavior of standard U.S.P. calibrator (salicylic acid and prednisone) tablets, and offers siqnificant advantages over conventional continuous-flow dissolution testing methods with respect to simplicity, cost, and versatility. Dissolution tests on capsules of the antiviral drugs, DHPG and acyclovir, showed very similar drug release profiles for both formulations.

Design and evaluation of a rotating filter-magnetic basket apparatus: tablet and basket position

The authors have designed a dissolution device which combines the properties of a rotating filter device developed by Shah and a magnetic basket designed by Shepard et al. The effects of stirring, tablet and basket placement were investigated. Visualization of flow and dissolution patterns was possible by testing non-disintegrating salicylic acid tablets containing 3% phenolphthalein in 0.1 N sodium hydroxide solution. Dissolution experiments were conducted on non-disintegrating salicylic acid in pH 7.4 U.S.P. phosphate buffer at 37°C. For the tablet placement experiments one tablet face and the tablet land was coated so that only a single tablet face was available for dissolution. The data for the same size tablets placed at the side of the bottom and at the center of the bottom of the dissolution fluid container indicated the importance of exact placement of a tablet in a dissolution fluid container. The differences in face position of the tablet either with or without a magnetic basket present indicates the importance of face position which must be accounted for especially in the testing of double-layer sustained release products. Through the dissolution data and the visualization studies the authors have characterized the hydrodynamics of this device.

Evaluation of a rotating filter apparatus: hydrodynamic characterization through modeling

In this study a rotating filter was evaluated using a two-dimensional convective diffusion model. Experimental model testing involved analysis of dissolution rates from non-disintegrating salicylic acid discs. For each dissolution run the disc was positioned at the bottom of the dissolution container. The tablets were coated so only a single salicyclic acid face on the side facing the stirrer was exposed for dissolution. Experimental variables included stirring speed, tablet radius and the distance of the tablet from the center of the container. From the data and visualization studies liquid flow inside the dissolution fluid container was described. The single-faced salicylic acid tablets proved to be an excellent system with which to test the convective diffusion model. The results seem to support the proposed convective diffusion theory which indicates the numerical exponents for stirring speed and tablet radius are 0.5 and 1.5, respectively.