pH Dissolution Research Articles

Predicting the Dissolution of Rock Phosphates in Flooded Acid Sulfate Soils

Seven hundred sixty thousand hectares of acid sulfate soils in Central Plain of Thailand are used for rice (Oryza sativa L.) cultivation. Insufficient nutrient P seriously limits rice growth and yield. A local rock phosphate (RP) Kanchanaburi RP (KRP), a reference RP (Gafsa from Tunisia), and a KRP containing soluble P (KRPS) were used to investigate the dissolution and availability in six acid sulfate soils under flooded conditions. The soil properties that have a major influence on RP dissolution and P sorption were investigated for developing a model and algorithms for estimating the RP requirement for rice. High KCl‐extractable aluminum (Al_KCl) and low soil pH enhanced the dissolution of KRP, Gafsa, and KRPS. The substantial calcium carbonate equivalent of the RP increased the pH of soils and limited RP dissolution. The P sorption of the soils was estimated using Bray 1 and 2 extractions. The P sorption was apparently greater than RP dissolution a few days after submergence in some acid sulfate soils, decreasing the Bray 1 level. Phosphorus extractable by Bray 2 increased with incubation time where KRP, Gafsa, and KRPS were applied. Amounts of RP predicted using an algorithm based on predicted dissolution and sorption in the various soils were similar to a local estimate of RP requirement.

Dissolution of whey protein concentrate gels in alkali

AbstractThe dissolution of whey protein concentrate (WPC) gels has been studied in detail, and the different mechanisms involved have been quantitatively analyzed. The NaOH diffusivity in gels has been determined at different pH at 22°C. Dissolution experiments of gels under several conditions have been performed and compared. Both heat‐induced gels (HIG) and caustic‐induced gels (CIG) have been studied as models to heat‐exchanger fouling deposits. It is proposed that the constant dissolution rate observed at low pH is controlled by the reactions that break down the gel structure, particularly the β‐elimination of intermolecular disulfide bonds. Alkali dissolution of CIG is reduced with increasing the gelation pH, as more crosslinks are present in the gel. It is proposed that a similar mechanism of crosslink formation may explain the low dissolution rates observed in HIG at dissolution pH above 13.1. NaOH diffusion is observed to limit the dissolution process at high temperatures and pH close to 13. © 2005 American Institute of Chemical Engineers AIChE J, 2006

Carbon-Bound Diazeniumdiolates from the Reaction of Nitric Oxide with Amidines

[reaction: see text] The enediamine tautomer of a variety of substituted amidine free bases reacts with nitric oxide (NO) to produce compounds containing a carbon-bound diazeniumdiolate [R1R2R3C-N(O)=NO-] functional group (previously called "nitrosohydroxylamines"). The new reaction has been shown to be quite general, although the nature of the products does vary. Amidines containing more than one replaceable hydrogen produce polydiazeniumdiolates as intermolecular salts, while those in which only one diazeniumdiolation can occur provide zwitterionic salts. These diazeniumdiolated amidines are shown to be useful NO donor compounds which undergo very slow spontaneous dissociation on dissolution in pH 7.4 phosphate buffer to produce mixtures of NO and nitrous oxide containing mostly NO. The most advantageous manifestation of the new discovery is the preparation of the monodiazeniumdiolated amidine zwitterions. Reaction of the medically relevant alpha-adrenergic agonists tetrahydrozoline and idazoxan produced monodiazeniumdiolated amidine zwitterions from which NO release was observed for up to 28 days and showed little sign of ending. The reaction should be applicable to a variety of pharmaceutical agents, including NO synthase inhibitors, antitumor agents, and antibacterials.

Effects of dissolution medium, pH and temperature on the <i>in vitro</i> release properties of metronidazole tablets

The effects of dissolution medium, pH and temperature on the in vitro release properties of metronidazole, a commonly used antiprotozoal, from its tablet dosage forms have been studied. Metronidazole tablets were formulated using the conventional wet granulation technique. The standard tablet characteristics such as uniformity of weight, hardness and friabliity wer determined. Different dissolution media namely – simulated intestinal fluid (S. I. F.), simulated gastric fluid (S. G. F.) and buffer solutions (pH 2 to 11) were employed for disolution and disntegration studies. Similarly, disssolution studies were carrtied out at varying temperatures to determine the effect of temperature onn release and disintegration. Results obtained showed that the tablets possessed officailly acceptable hardness, uniformity of weight, and absolute drug content, but a high friablity. The drugs were released faster in the less acidic S. I. F. than in th S. G. F. while the dissolution and disintegration rates increased as the pH increased.. Temperature also increased the dissolution and disintegration rates. Key words: dissolution medium, pH, temperature, release, metronidazole Journal of Pharmaceutical and Allied Sciences Vol.2(2) 2005: 209-213

Exploiting gastrointestinal bacteria to target drugs to the colon: An in vitro study using amylose coated tablets

The bacterial substrate amorphous amylose, in the form of a film coating, provides a means of delivering drugs to the colon. This coating has traditionally been applied to multi-unit systems, in part because of the small size and divided nature of this type of dosage form, which provides a large surface area for enzymatic attack and drug release. The present study was conducted to explore the utility of the coating for colonic targeting of single unit tablet systems. Amylose was combined with the water-insoluble polymer ethylcellulose, which acts as a structuring agent, in different proportions to produce film coatings of various thicknesses for application to mesalazine (mesalamine or 5-aminosalicylic acid)-containing tablets. Drug release from the coated products was assessed under pH dissolution conditions resembling the stomach and small intestine, and also in conditions simulating the colon using a batch culture fermenter inoculated with human faecal bacteria. The rate and extent of drug release was related to the ratio of amylose to ethylcellulose in the film and the thickness of the coating. Increasing the proportion of ethylcellulose in the film and/or the thickness of the coating depressed the rate of drug release in the conditions of the upper gastrointestinal tract. Drug release from the coated products was accelerated in the fermentation environment of the colon. This is attributed to bacterial digestion of the amylose component of the film coat producing pores for drug diffusion. This work indicates that amylose coated tablet formulations are promising vehicles for drug delivery to the colon.

Enzyme Content and Acid Stability of Enteric-Coated Pancreatic Enzyme Products In Vitro

Pancreatic enzymes are prescribed routinely for pancreatic insufficiency. In the current health care environment, drug substitution is commonly performed although there is no proof of therapeutic or bioequivalence for these products. The purpose of this in vitro, prospective study was to evaluate the enzyme contents and dissolution of various capsules of pancreatic enzyme using current United States Pharmacopoeia (USP) methodology. Nine different pancreatic enzyme products were purchased on the market and supplied to Irvine Analytical Laboratories (IAL) (Irvine, CA). All test products were maintained in the laboratory environment, at room temperature, throughout the testing period by IAL. USP procedures for assay and dissolution testing of pancrelipase delayed-release capsules, as described in the latest USP supplement were observed during product testing, including determination of amylase, lipase, and protease activity. In addition, a point assay with measurement of lipase after dissolution in simulated gastric fluid pH of 1.0 for 1 hour and then dissolution in pH 6 phosphate buffer for 30 minutes performed in accordance with USP guidelines. Assay results of amylase, protease, and lipase from the 9 tested products are within USP specified limits. The percentage of label claim for these enzymes was higher than depicted in their label except for one drug batch. However, the percentage of lipase activity after dissolution varied with 2 of 3 batches of 1 drug not dissolving, and 1 batch of another drug, revealing only 8% lipase activity in the USP dissolution test. While assay of pancreatic enzymes reveal they were equal to their USP claims regarding their enzyme content, not all pancreatic enzyme replacements are equal in their release of lipase activity according to USP requirements. The findings maybe clinically seen with therapeutic failures of enzyme products. The FDA has recently decreed that all pancreatic enzyme products will require an approved NDA as differences in pharmaceutical quality have been identified in this product. Thus, it is considered that substitution of these products maybe questionable. Things are seldom what they seem- not all pancreatic enzyme replacements are equal. Further studies are warranted to investigate dissolution characteristics.

In vitro controlled release of vinpocetine–cyclodextrin–tartaric acid multicomponent complexes from HPMC swellable tablets

The objective of this study was to investigate the effect of multicomponent complexation (MCC) of vinpocetine (VP), a poorly soluble base-type drug, with β-cyclodextrin (βCD), sulfobutylether β-cyclodextrin (SBEβCD), tartaric acid (TA), polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC), on the design of controlled release hydrophilic HPMC tablets and to evaluate their in vitro release profiles by a pH gradient method. Multicomponent complexation led to enhanced dissolution properties of VP both in simulated gastric and intestinal fluids, and became possible the development of HPMC tablet formulations with more independent pH dissolution profiles. Drug release process was investigated experimentally using USP apparatus 3 and by means of model-independent parameters. Responses studied included similarity of dissolution profiles, time for 60% of the drug to dissolve ( T 60%), percent of VP released after 7h (PD 7 h) and the dissolution efficiency parameter at 12 h (DE 12 h). Influence of multicomponent complexation was proved to increase the release of VP from HPMC tablets and superior PD 7 h and DE 12 h values were obtained in formulations containing VP–CD–TA complexes. Results supported the use of HPMC matrices to provide a useful tool in retarding the release of VP and that dissolution characteristics of the drug may be modulated by multicomponent complexation in these delivery systems, suggesting an improvement on VP bioavailability.

Microscopic observations of reductive manganite dissolution under oxic conditions.

At oxic/anoxic transition zones, manganese release from (hydr)oxide minerals into aqueous solution is a dynamic balance between mineral dissolution and Mn2+(aq) oxidation and precipitation, which are processes respectively promoted by organic reductants and molecular oxygen. We employ a flow-through atomic force microscope reactor (AFM-R) to investigate the reductive dissolution of the [010] surface of manganite (gamma-MnOOH) across a range of pH values and ascorbic acid concentrations in aqueous solutions equilibrated with atmospheric CO2 and O2. The apparent dissolution rate increases with higher ascorbic acid concentrations and lower pH values. Concurrent changes in surface morphology show that dissolution proceeds at low pH via etching and step retreat, while at high pH dissolution is concurrent with precipitation. The precipitates are characterized ex situ by X-ray photoelectron spectroscopy (XPS) and found to be Mn(III)-oxide. The onset of precipitation is consistent with an analysis of the thermodynamic driving forces for the reactions of a two-step mechanism. In the first step, Mn2+ is released to aqueous solution by reduction of gamma-MnOOH in reaction with ascorbic acid. This step is thermodynamically favorable under all conditions employed. In the second step, which leads to precipitation, surface adsorbed Mn2+ is oxidized by O2 to yield a Mn(III)-oxide precipitate. This step is thermodynamically possible only at pH > 5 for our experimental conditions. When the second step is active, the apparent dissolution rate equals the intrinsic dissolution rate minus the precipitation rate. Analysis of the growth rates observed in AFM indicates the precipitation rate reaches 71% of the intrinsic dissolution rate under some reactor conditions. Comparison of our gamma-MnOOH results to literature reports for Mn2+ oxidation on gamma-FeOOH indicates gamma-MnOOH is a more effective surface catalyst by a factor of 10(8).

Effect of Fill Weight, Capsule Shell, and Sinker Design on the Dissolution Behavior of Capsule Formulations of a Weak Acid Drug Candidate BMS‐309403

Two strengths of BMS‐309403 capsules were developed from a common stock granulation. Dissolution testing of the capsules was conducted utilizing the USP apparatus 2 (paddle) with a neutral pH dissolution medium. Unexpectedly, the lower‐strength capsules exhibited slower dissolution than the higher‐strength capsules filled with the same stock granulation. Higher variability was also observed for the lower‐strength capsules. This was found to be mainly caused by a low fill weight in a relatively large size hard gelatin capsule shell. Instead of bursting open, some gelatin capsule shells softened and collapsed onto the granulation, which delayed the release of the active drug. The problem was aggravated by the use of coil sinkers which hindered the medium flow around the capsules. Switching from the gelatin capsule shells to the HPMC (hydroxypropyl methylcellulose) shells reversed the dissolution rate ranking between the two capsule strengths. However, both dissolved at a slower rate initially than the gelatin capsules due to the inherent dissolution rate of the HPMC shells at pH 6.8. Notably, the HPMC shells did not occlude the granulation as observed with the gelatin shells. The study demonstrated that the dissolution of capsule formulations in neutral pH media was significantly affected by the fill weight, sinker design, and capsule shell type. Careful selection of these parameters is essential to objectively evaluate the in vitro drug release.

자가유화 약물전달시스템을 이용한 이부프로펜의 용출개선 및 흰쥐에서의 생체이용률 평가

A self-microemulsifying drug delivery system(SMEDDS) composed of Cremophor , and Lauroglycol was prepared for the enhancement of solubility, dissolution rate and bioavailability of ibuprofen(IBP), which is water-insoluble but soluble in oils and surfactants. Phase diagram with various regions including microemulsion area was depicted. The SMEDDS was encapsulated in soft gelatin capsules and their dissolution characteristics in various media were observed in comparison to the generic products commercially available in the market. Soft capsules of SMEDDS formulation showed better dissolution profiles, especially in acidic condition, than the others. For the period of 1 hr dissolution in pH 1.2 medium, it reached over 70% dissolution from soft capsules, compared to less than 40% dissolution from commercial reference tablets. On the other hand, in vivo pharmacokinetic parameters were obtained after oral administrations of different IBP preparations to Sprague Dawley rats. SMEDDS formulation showed higher and greater than the suspension of reference tablet or IBP powder. Therefore, it is possible to conclude that a newly developed soft capsules employing SMEDDS provides an alternative preparation to improve oral bioavailability of IBP.

General properties of silated hydroxyethylcellulose for potential biomedical applications.

The general properties of hydroxyethylcellulose (HEC) grafted with 3-glycidoxypropyltrimethoxysilane (GPTMS) or 3-glycidoxypropylmethyldiethoxysilane (GPDMS) were studied for potential biomedical applications. The graft involved a Williamson reaction between the free hydroxyl function of HEC and the epoxy function of the two silanes. As the grafted silanes are in ionic form (sodium silanolate), this product remains in gel form at basic pH (>12.3) in aqueous solution. When pH decreases, sodium silanolate is transformed into silanol (2 or 3 silanol functions are carried by silicon, depending on the silane grafted). The silanols interreact, and the gel is transformed into a cross-linking form at room or body temperature. Studies were conducted to optimise this product for specific uses. Steam sterilization was used to compare self-hardening as a function of the silane grafted. Our previous work indicated that HEC grafted with GPTMS has good reactivity, but requires high pH for dissolution, whereas dissolution occurs at lower pH with GPMDS. The rate of silanol condensation for silated HEC was then determined as a function of pH, temperature, type of silane, and the percentage grafted. Condensation rates were ascertained by the viscosity method, and gels were neutralized by different solutions to obtain buffered forms at various pH. The time required to obtain 10(5) mPa x s, with an initial state of 2500 mPa x s, was then calculated. Condensation was catalysed in acid or basic medium at a lower rate at pH 5.5-6.5, and a temperature rise increased the condensation rate, regardless of the pH or silane studied. Silanetriol was more reactive than silanediol. However, as HEC lost considerable viscosity after sterilization, further studies will be conducted to develop new polysaccharides grafted with silane.

A novel pH- and time-based multi-unit potential colonic drug delivery system. I. Development

A novel delivery system was developed for delivering drugs to the colon by selecting polymethacrylates with appropriate pH dissolution characteristics for the distal end of the small intestine and relying upon the relatively constant transit time of the small intestine. Pellets were prepared by powder layering of 5-aminosalicylic acid (5-ASA) on nonpareils (0.5–0.6 mm) in a conventional coating pan. Drug-layered pellets were coated with an inner layer of a combination of two pH-independent polymers Eudragit ® RL and RS (2:8), and an outer layer of a pH-dependent polymer, Eudragit FS. Scanning electron micrograph (SEM) pictures of the coated pellets showed the uniformity of both the coatings. The release profile of 5-ASA was studied in three phosphate buffers after a simulated gastric pre-soak for 2 h in pH 1.2 media. There was no drug release for 12 h at pH 6.5. There was a sustained release of 5-ASA for over 12 h both at pH 7.0 and 7.5 after a lag time at pH 7.0 and no lag time at pH 7.5. The release rate was faster at pH 7.5 than at pH 7.0. The delivery system demonstrated its potential for colonic delivery by resisting drug release until pH 6.5 and the combination of Eudragit RL and RS proved successful for the sustained delivery of 5-ASA at the expected pH of the colon.

Divisability of Diltiazem Matrix Sustained-Release Tablets

The objective of this work was to study the possibility of a solid sustained-release dosage form, like a tablet, be divided without changing its release characteristics. Diltiazem hydrochloride Sustained-Release (SR) tablets with a standard groove on one face, were tested and the following dissolution parameters were evaluated: t10%, t25%, and t50% dissolution time, and dissolution efficiency at t120, and at t360. To analyze the release mechanism, several release models were tested such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull, and Korsmeyer-Peppas. The similarities between two in vitro dissolution profiles were assessed by the difference factor (f1), the similarity factor (f2) and the Rescigno index (ξi). The in vitro release kinetics of diltiazem hydrochloride tablets were evaluated using USP apparatus 4. Using a one-way ANOVA (α = 0.05), statistically significant differences were found for t10%, t25%, and t50% dissolution times with a constant and with a variable pH dissolution fluid. The variation coefficient for the divisibility assay (Portuguese Pharmacopoeia VI) was lower than the limit value of 10%. The diltiazem release rate from this pharmaceutical system was not constant, and diminished with the square root of time (Higuchi model) showing that the phenomenon controlling drug release was the diffusion occurring inside the swelled polymeric matrix. Diltiazem release rate was a function of the area in direct contact with the dissolution fluid and not of the pharmaceutical matrix volume. The results obtained permit us to conclude that the division, in this case, affects the drug release characteristics.

Does the site of intestinal delivery of oleic acid alter the ileal brake response?

Previous work has demonstrated that high doses of oleic acid can activate the ileal brake but the importance of site of delivery has yet to be investigated. The objective of this study was to use modified release capsules to release oleic acid in different regions of the intestine. When tested by in vitro dissolution in pH 6.8 phosphate buffer, one batch released the contents almost immediately, another after around 30 min and the last batch after around 60–70 min. The effect of oleic acid release site on the ileal brake was assessed by the measurement of transit time of radiolabelled non disintegrating tablets by γ scintigraphy. The results demonstrated that the transit of tablets could be slowed down by oleic acid and therefore it appears the ileal brake can be activated along the entirety of the small intestine.

Mineralogical and morphological changes of fly ashes with leaching phenomenon

In this study, three Fly Ashes (FA) from Spanish Power Plants with CaO contents between 2-30% in weight were examined. They were leached using a variation on EPA-EP leaching test, checking the influence of the leaching process on FA. Leaches were analyzed by ICP. XRD and SEM-EDX technique were used to analyze the leached FA. The study carried out was mainly centered in following the evolution of the most soluble elements and the formation of new secondary crystalline phases. The relationship between dissolution pH and the percentage of the extracted element was also confirmed.

Corrosion of Al–Cu–Fe quasicrystals and related crystalline phases

Corrosion of quasicrystalline and related crystalline phases in the Al–Cu–Fe system was investigated by anodic polarization in acid and alkaline solutions at room temperature. Corrosion products as well as surface morphology were measured by means of X-ray diffraction, scanning and transmission electron microscopy. During polarization of icosahedral quasicrystals in a strong alkaline solution a two-layered film is formed: an inner layer with reduced Al content which consists of quasicrystals and a bcc phase and an nanocrystalline oxide layer with a needle-like morphology. At low pH (<2) dissolution of the quasicrystalline phases was observed to precede deposition of a porous Cu film. In a strong alkaline medium icosahedral quasicrystals have a smaller corrosion resistance than neighboring crystalline phases, e.g. the β-phase (Al50Cu30Fe20); in strong acid solution other crystalline phases (for example Al2Cu) show less corrosion. The open circuit potentials have been observed to vary in a similar manner.

Conversion of proteins to diazeniumdiolate-based nitric oxide donors.

Michael reaction of the methoxymethyl-protected monodiazeniumdiolate of piperazine (MOM-PIPERAZI/NO) with 4-maleimidobutyric acid followed by its conversion to the N-hydroxy-succinimido ester produces a reagent capable of transferring the nitric oxide (NO)-donating diazeniumdiolate group to the terminal amines of the lysine residues contained in proteins. The reagent has been used to produce diazeniumdiolated bovine serum albumin (D-BSA) and diazeniumdiolated human serum albumin (D-HSA) containing 22 and 19 modified lysyl groups, respectively. Upon dissolution in pH 7.4 phosphate buffer at 37 degrees C, these albumin derivatives gradually released all of their contained NO (approximately 40 mol/mol of protein) with initial rates of about 30-40 pmol/min/mg and half-lives on the order of 3 weeks. This methodology is now available for use in exploiting the unique specific metabolic interactions of proteins to target NO therapy to specific physiological processes in vivo.

Weathering detected by Raman spectroscopy using Al-ordering in albite

Albite samples from Ontario, Canada, laboratory weathered in HCl solutions at pH 1 have been analysed and compared to unreacted mineral samples with the same crystal orientation using Raman microspectrometry. The study was focused on Raman bands reflecting Al-ordering because destabilisation of Al–O bonds with subsequent release of Al is well recognised to be a major factor in low pH dissolution of albite. Analyses of unweathered samples reveal that most bands in the albite spectra show variations in intensities for different crystal orientations in the wavenumber range 100 to 1200 cm −1. A well-defined crystal orientation is therefore essential to a successful investigation of weathered samples. Unweathered albite has two bands; 455 and 976 cm −1 in the spectrum normal to the (001) face, which have been related to Al-ordering in the structure. In spectra of weathered albite crystals, with the same orientation, the band most sensitive to alteration is 976 cm −1. This band is very strong for unreacted albite, but diminishes in intensity relative to the other bands at the initial stage of weathering. When dissolution continued, the structural information in the range 700 to 1200 cm −1 was completely lost, shown as a bandbroadening of a less organised structure, while the characteristic albite bands still could be observed in the range 100 to 600 cm −1.

Development of cellulose derivatives as novel enteric coating agents soluble at pH 3.5-4.5 and higher.

Hydroxypropyl methylcellulose (HPMC) was selected as a base polymer to develop novel enteric coating agents for acid protection which can dissolve at pH around 4, and was modified with trimellitic acid or maleic acid at various degrees of substitution. These carboxylic acids have higher dissociation constants and higher solubility in water than the carboxylic acids of existing enteric coating polymers. The synthesized polymers were micronized and dispersed in aqueous medium to determine their pKa values by potentiometric titration. The pH of dissolution and the water vapor permeability of the cast films prepared from organic solutions were also evaluated. Hydroxypropyl methylcellulose trimellitate (HPMCT) showed good acid resistance, and the pH at which it dissolves can be controlled in the range of pH 3.5 to 4.5 by varying the content of trimellityl groups and the methoxyl substitution of the base polymer.

Continuous Monitoring of Salivary Flow Rate and pH at the Surface of the Dentition following Consumption of Acidic Beverages

Use of a splint-mounted flexible pH electrode has allowed reliable continuous monitoring of pH at the surface of the dentition whilst still enabling subjects to drink normally. pH was monitored at the palatal upper left central incisor and upper right first permanent molar sites after drinking 1% (w/v) citric acid. A maximal decrease in pH to values of 2-3 was observed after 1 min followed by a slower recovery which was above pH 5.5 within 2 min at the former site and in 4-5 min at the latter site. A sharp rise in parotid saliva flow rate was seen at 1 min after drinking the same concentration of citric acid by glass, straw or feeder cup, which returned to resting levels within 6 min although the fall-off of flow rate was slower with the feeder cup. Thus, after dietary acid intake the pH at the surface of the dentition is below the critical pH for enamel dissolution for shorter periods than previously suggested, which is probably a reflection of salivary neutralisation and washing.