Dissolution Of Aspirin Research Articles

Dissolution of pain-relief drugs: Does beverage choice matter?

Oral administration continues to be the most common route for drug delivery with the majority of approved medicines being tablets and capsule dosage forms. Standardised pharmacopeial media are typically used to test tablet dissolution in vitro, however patients use non-standard beverages to take with their medicines. Information about the dissolution of drugs in beverages consumed by patients has not been reported in the literature. Our aim was to investigate if the choice of beverage influences the dissolution of common pain relief tablets. The prevalence and type of alternative beverages used by patients to take their tablets was investigated in an online survey. The rate of dissolution of the common pain relief tablets, aspirin and acetaminophen, was measured in 15 different dissolution media including pharmacopeial dissolution media, simulated gastrointestinal fluids, and the common alternative beverages used by patients to take their tablets (including water, tea, coffee, soft drink and beer). The concentration of drug dissolved in each beverage over time was determined using either UV–vis spectroscopy or HPLC. The rate of dissolution of aspirin and acetaminophen tablets was in some cases significantly affected by the composition of the dissolution media. Factors such as mineral content, carbonation, and pH contributed to differences in the rate of dissolution for both aspirin and acetaminophen. The rate of dissolution of aspirin was significantly lower in some beverages compared to pharmacopeial media. When translated to the in vivo setting, these differences have the potential to alter the pharmacokinetics and bioavailability of orally administered medicines and so their efficacy.

Preparation and preliminary quality evaluation of aspirin/L-glutamate compound pellets

L-glutamate is an important component of protein. It can prevent gastrointestinal damage caused by NSAIDs. We constructed two-phase enteric-coated granules of aspirin and L-glutamate compound by extrusion spheronization method and fluidized bed coating. The subliminal effective dose of L-glutamate is 100 mg/kg tested by model of gastric ulcer of rats induced by aspirin and drug administration. HPLC-UV and UV–Vis methods were adopted to determine content and cumulative release of aspirin and L-glutamate as quality analysis method indexes. The prescription and process optimization were carried out with yield, sphericity and dissolution. The two-phase compound granules have good sphericity of 0.93 ± 0.05 (aspirin pellets) and 0.94 ± 0.02 (L-glutamate pellets), content of salicylic acid (0.24 ± 0.03)%, dissolution of aspirin (2.36 ± 0.11)%. Quality evaluation and preliminary stability meet the commercial requirements. The stored environment of compound preparation should be sealed in a cool and dark place.

Molecular dynamics simulation of aspirin dissolution

Molecular dynamics simulations of the dissolution of aspirin in water are reported. Crystals initially cubic and cylindrical in shape are considered, and the influence of temperature is examined. All simulations are carried out in a manner designed to prevent the build up of any significant concentration of aspirin in solution, physically corresponding to sink conditions. It is found that aspirin dissolution follows a three stage mechanism similar in most respects to earlier observations for nanocrystals of NaCl and urea. In the initial stage, molecules are first lost from corners and edges of the crystal, the crystal is solution annealed into a particular limiting shape, that then persists throughout a large fraction of the dissolution process. For aspirin, initially cubic crystals anneal into a cylindrical shape, in contrast with the near spherical shapes attained by cubic NaCl and urea crystals. In an intermediate stage, during which most of the crystal dissolves, the dissolution rate is well described by a simple classical model which assumes that the rate is proportional to the active surface area of the crystal. For aspirin, the active surface area is identified as the curved surface of a cylinder for both crystal shapes. In the final stage, the small remaining crystal looses its structure and rapidly dissolves. Given that a similar three stage mechanism applies to crystals as varied as NaCl, urea, and aspirin, we conjecture that this mechanism is possibly quite general, and might apply to many ionic and molecular crystals. As for NaCl and urea, an analysis of the activation energy associated with aspirin dissolution strongly suggests that detachment of molecules from the crystal is the rate determining step, at least under the sink conditions.

Multiscale modeling of aspirin dissolution: from molecular resolution to experimental scales of time and size

Predicted absolute and face-specific rate constants of aspirin dissolution are incorporated in a simulation based on the equations of classical mass transfer to reproduce kinetic dissolution in experiment using a Jamin-type interferometer.

Preparation and Evaluation of Oral Dosage Form Using Acylglycerols. II. Effect of Food Ingestion on Dissolution and Absorption of Aspirin from the Granules Prepared by Acylglycerols in Human Subjects.

The dissolution behavior of the aspirin enteric granule prepared using acylglycerols, glyceryl monostearate (GMS) and glyceryl trilaurate (GTL), was investigated in vitro and in human subjects in a fasting or non-fasting state. Aspirin was slowly released from the granule in vitro at pH 1.2. No acceleration of the aspirin dissolution rate in the medium without lipase and cholic acid was observed when the pH level of the medium increased to a neutral region (pH 6.4). However, the dissolution of aspirin was significantly increased by increasing the concentrations of lipase and cholic acid in the medium. Lipase appears to play an essential role in the dissolution process of aspirin granules. In human subjects, the average levels of the cumulative amount of total salicylate excreted in a urine-time curve, and the mean residence time (MRT) obtained after oral administration of a granule in the fasting state were markedly delayed in comparison with the results observed using an aqueous solution and a crystalline form of aspirin. In comparing the fasting condition with the non-fasting condition (after food ingestion), no significant difference was recognized in the total amount of salicylate excreted in urine to an infinite time (Ae(infinity)), whether the MRT was obtained by granule, crystalline form or aqueous solution. It can be concluded that aspirin granule prepared by GMS and GTL has a property of pancreatic lipase-sensitive dissolution, and its bioavailability is unaffected by food intake.

Enhanced dissolution rate of aspirin from aspirin-methacrylic acid, methyl methacrylate coacervates in a simulated intestinal fluid

Granular coacervates containing aspirin and methacrylic acid-methyl methacrylate (3:2) have been prepared by an evaporation technique and evaluated for dissolution rates in simulated gastric (pH 1.2) and intestinal juice (pH 7.5). In the acid medium (A), the amount of aspirin dissolved from the coacervate was 1% w/w of the initial amount of aspirin (300 mg) after 1 h and from the control (aspirin without polymer) 4.2% w/w after 1 h; a time lag of 45 min preceded the dissolution from the coacervate. In the alkaline medium (B), the amounts of aspirin dissolved were 54% w/w (coacervate) and 38% w/w (control) after 1 h. The polymer therefore reduced the aspirin dissolution rate in A but increased the rate in B. Dissolution ratios, B/A were 9.5 (control) and 54 (coacervate). The results relate to the insolubility of the polymer in A and its high solubility in B.

Complexation of aspirin with potato starch and improvement of dissolution rate by dry mixing.

Dry mixing of aspirin with potato starch in a centrifugal rotating mixer produced a novel powder, composed of potato starch particles with an aspirin layer adhering on their surfaces. Friction and collision which occurred in the dry mixing process micronized and spread aspirin over the potato starch surfaces, forming a thin aspirin layer. The powder gave a higher rate of aspirin dissolution than a physical mixture. It was suggested from powder X-ray diffractometry, differential scanning calorimetry, and contact angle measurements that the improvement of dissolution rate was caused by an increase in wettability and an increase in the available surface area aspirin.

Effect of antacids on aspirin dissolution and bioavailability.

The in vitrodissolution profile, in vitroand in vivobuffering characteristics, and single-dose bioavailability of various buffered aspirin tablet formulations were studied. Buffering agents,such as magnesium and aluminum hydroxides (formulations B and C) or magnesium carbonate and aluminum glycinate (formulation D), significantly increased the rate of aspirin dissolution from solid dosage forms as compared to an unbuffered tablet (formulation A). The extent of aspirin absorption was equivalent with all formulations;however, the faster rate of dissolution (t50and t90)with buffered formulations resulted in earlier and higher peak concentration of salicylate compared to that with unbuffered formulation, following a two-tablet dose in the fasting state. A comparison of the in vivobuffer capacity of a four-tablet dose of formulations B and D was performed in the postcibal state at the time of maximal meal-induced acid secretion, using a radiotelemetry procedure for determination of pH. Formulation B prolonged the interval of elevation of intragastric pH > 3 for 32 min as compared to 12 min for D.

高分子量マクロゴール中におけるアスピリン結晶の成長と分解

The state of aspirin mixed in the solid Macrogol was examined. Macrogol-6000 and 30% (w/w) aspirin were mixed at 70°, 90°, and 110°, and aged at the same temperature. After the mixture cooled, various tests were carried. As the aging time became longer and the temperature higher, the sample became more transparent and had less consistency by both transparency test and thermal analysis. When a high temperature was used or long time spent for aging, X-ray diffraction patterns and infrared (IR) spectra indicated that aspirin in the mixture was in a liquid state at room temperature. The presence of acetylated Macrogol in the mixture was estimated from nuclear magnetic resonance (NMR) and IR spectra, and by a stoichiometric method, and the presence of salicylic acid was confirmed from ultraviolet ( UV) spectra. It is concluded that transesterification between aspirin and Macrogol 6000 decomposed part of aspirin to salicylic acid, and formation of acetylated Macrogol from Macrogol. Lowering of consistency and increased transparency of the mixture may be due to one of the following three reasons : (1) Dissolution of aspirin into Macrogol, of lower molecular weight formed by lowering of molecular weight of Macrogol 6000 due to heating in the presence of aspirin, (2) complicated lowering of the melting point by four ingredients (aspirin, Macrogol, salicylic acid, and acetylated Macrogol), and (3) delay of crystal growth of aspirin in the mixture.

Evaluation of Dimethylpolysiloxane Fluids as Vehicles for Various Pharmaceuticals I: Effect on Stability and Dissolution of Aspirin

The physicochemical effects of dimethylpolysiloxane fluids as vehicles for aspirin on its stability and release characteristics were evaluated. Aspirin was extraordinarily stable in the silicone fluids. No decomposition was noted during 8 weeks of storage at 4 and 26°, and less than 0.5% degradation was detected after 8 weeks of storage at 45°. Moreover, the dissolution patterns of aspirin suspensions in the silicone fluids appeared to be quite satisfactory as compared with that of plain aspirin powder.

Dissolution of Aspirin from Tablets Containing Various Buffering Agents

Eleven different compounds representing various classes of buffering agents were studied with respect to their effect on the dissolution of aspirin from tablet formulations. In general, carbon dioxide-producing buffering agents (sodium bicarbonate, magnesium carbonate, and calcium carbonate) gave more rapid dissolution than the readily water-soluble buffering agents (sodium ascorbate and sodium citrate), and both of the preceding classes of buffering agents gave much faster dissolution than water-insoluble buffering agents such as magnesium and aluminum compounds.

Aspirin dissolution: polymorphism, crystal habit or crystal defects.

Journal Article Aspirin dissolution: polymorphism, crystal habit or crystal defects Get access A G Mitchell, A G Mitchell Faculty of Pharmaceutical Sciences, University of British Columbia, B.C., Canada Search for other works by this author on: Oxford Academic Google Scholar Barbara L Milaire, Barbara L Milaire Faculty of Pharmaceutical Sciences, University of British Columbia, B.C., Canada Search for other works by this author on: Oxford Academic Google Scholar Dorothy J Saville, Dorothy J Saville Pharmacy Department, University of Sydney, N.S.W., Australia Search for other works by this author on: Oxford Academic Google Scholar R V Griffiths R V Griffiths I.C.I. Ltd. Pharmaceutical Division, Macclesfield, UK Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 23, Issue 7, July 1971, Pages 534–535, https://doi.org/10.1111/j.2042-7158.1971.tb08703.x Published: 12 April 2011

Surface Transformation During Dissolution of Aspirin

A dissolution pattern that indicates a solvent-mediated phase change is observed when aspirin crystals are dissolved in aqueous media. It is suggested that the phase change is caused by the crystallization of a less soluble form on the crystal surface during dissolution. The kinetic and thermodynamic parameters of the two forms were determined using a rotating disk method of dissolution. An isergonic relation was demonstrated for the phase transformations of aspirin and other pharmaceutical compounds reported in the literature.

The dissolution of aspirin and aspirin tablets.

Abstract An attempt has been made to standardize the “beaker” method of measuring in vitro dissolution rates of tablets against published data for aspirin. An unexpected problem arose when it was found that samples of commercial aspirin have different intrinsic dissolution rates. The form of aspirin used in tablet manufacture is likely therefore to be of significance from the viewpoint of in vivo dissolution and drug availability.

Gastrointestinal Factors in Aspirin Absorption: A Quantitative Study

Three gastrointestinal factors influencing aspirin absorption have been selectively adjusted for quantitative measurement of their effect on the rate of salicylate absorption in humans and dogs. These are (a) gastric emptying, (b) aspirin dissolution rate, and (c) intragastric pH. Other factors such as tablet disintegration time, aspirin particle size, and intersubject variability have been eliminated or reduced where possible. The major portion of the salicylate in the blood during the first 20 minutes comes from the stomach. Impedance of gastric emptying by the use of atropine and placing the subjects in a left lateral position did not eliminate the higher plasma salicylate levels produced by the inclusion of the buffer antacids in aspirin tablets. The major effect of these antacids appears to be an acceleration of aspirin dissolution. This has been confirmed in this study by an in vivo demonstration of more rapid absorption from solutions of aspirin than from tablets. Aspirin in solution has a lower pH alone than with the inclusion of buffering antacids. Selective adjustment of the degree of aspirin and sodium salicylate ionization through the use of various buffers provided a method of study of the influence of intragastric pH on the rate of aspirin absorption. Support was obtained from dog and human studies in favor of the pH partition hypothesis that salicylates are absorbed more rapidly at low pH values.

Physico-Chemical Studies of Aspirin with Glycine

Abstract The relative solubility and rate of dissolution of aspirin in water and glycine solution have been measured. A technique involving a mathematical examination of the front profile of chromatograms has been used to study the extent of the adsorption of glycine from aqueous solution on aspirin. Aspirin is more soluble and more rapidly dissolved in glycine solution than water, and glycine is found to adsorb, in significant amounts, on aspirin crystals. The findings are discussed in an attempt to explain, in physico-chemical terms, differences in taste and adhesion to the oral mucosa that are discernible when aspirin tablets compounded with or without glycine are savoured. Attention is drawn to certain aspects of the results which have a bearing on the transport of aspirin.