Dissolution, problems

Adsorbent Life. Long term stability under rugged operating conditions is an important characteristic of an adsorbent. By their nature 2eohtes are not stable in an aqueous environment and must be specially formulated to enhance their stabiUty in order to obtain several years of service. Polymeric resins do not suffer from dissolution problems. However, they are prone to chemical attack (52). 

Greenberg RR, Kingston HM, Waiters Jr RL, and Pratt KW (1990) Dissolution problems with botanical reference materials. Fresenius Anal Chem 338 394-398. 

I Ullah, GJ Wiley, SN Agharkar. Analysis and simulation of capsule dissolution problem encountered during product scale-up. Drug Dev Ind Pharm 18 895-910, 1992. 

The chemiluminescence reaction of esters of oxalic acid can proceed within a wider pH range than for luminol. However, the most efficient oxalate derivatives are only soluble in organic solvents such as ethyl acetate, acetonitrile, dioxane or dimethoxyethane and dissolution problems of these solvents in aqueous media are encountered. This can limit the use of this chemiluminescence reaction for a direct coupling to an H202-generating enzymatic reaction. 

D S involves a lot of guesswork. An alternative to D S as a yardstick for compounds still early in development is to use a solubility of 100 pg/mL as a criterion. In our experience, few compounds with aqueous solubilities >100 pg/mL across the pH range of interest exhibit dissolution problems in vivo. 

Another idea for resolving the cathode dissolution problem is to formulate a milder cell environment This leads to the approach of using additives in the electrolyte to increase its basicity. Small amounts of additives provide similar voltages to those without additives, but larger amounts adversely affect performance (39). Table 6-2 quantifies the limiting amounts of additives. 

Some convective crystal dissolution problems can be treated by combined consideration of dissolution kinetics and hydrodynamics. Hydrod5mamic consideration is necessary because it is necessary to know how rapidly the interface fluid is removed. In considering the problems, steady state is assumed. Irregular and unsteady convection is not treated. The following problems have been tackled ... 

Harding et al. (33) proposed mixing in a Turbula high intensity mixer as a predictive stress test to determine the likelihood of encountering a dissolution problem on scale-up due to lubricant over-mixing. They found a... 

It is the authors experience that with a formulation compressed without a forced feeder in R D, the scale-up in a different country, but by gravity feed and without a forced feeder, was perfect. In a second country, however, all production presses operated with forced feeders, and the target tablet hardness was not achieved. It was possible to conclude that press speed was not the cause of the problem but it was much later (and based on laboratory experiments) that it was possible to conclude that the lubricant was ovennixed on the tablet press, resulting in a softer tablet. Fortunately, the drug was very soluble and no dissolution problem resulted, but slower dissolution could be a problem with a drug of low solubility. 

In ionic block copolymers, micellization occurs in a solvent that is selective for one of the blocks, as for non-ionic block copolymers. However, the ionic character of the copolymer introduces a new parameter governing the structure and properties of micellar structures. In particular, the ionic strength plays an important role in the conformation of the copolymer, and the presence of a high charge density leads to some specific properties unique to ionic block copolymers. Many of the studies on ionic block copolymers have been undertaken with solvents selective for the ionic polyelectrolyte block, generally water or related solvents, such as water-methanol mixtures. However, it has been observed that it is often difficult to dissolve ionic hydrophilic-hydrophobic block copolymers in water. These dissolution problems are far more pronounced than for block copolymers in non-aqueous selective solvents, although they do not always reflect real insolubility. In many cases, dissolution can be achieved if a better solvent is used first and examples of the use of cosolvents are listed by Selb and Gallot (1985). 

A rate of less than 0.1 mg/min/chalmost always indicates a dissolution problem, and intermediate rates are borderline. More recently, a solubility of 0.1 mg/mL or less has been identiLed as a general rule for ascertaining the importance of dissolution rate in predicting the oral absorption (Dressman et al., 1985). 

In order to achieve and sustain therapeutic blood levels by peroral administration of drugs, several hurdles have to be overcome. Besides well-known barriers such as enzymatic degradation, dissolution problems, mucus barrier and others,... 

The cotton and rayon used as fillers in solid oral dosage form containers may not meet pharmacopeial standards, but through appropriate tests and acceptance criteria for identification and moisture content, their adequacy should be shown. For example, rayon has been found to be a potential source of dissolution problems for gelatin capsules and gelatin-coated tablets. 

The presence of carbonaceous material in the ore precipitates the gold in cyanide solutions, thus resulting in an increase of gold content in the cyanidation residue. For such complex gold-bearing ores, a roasting operation oxidizes the carbonaceous matter and thereby makes the ore more amenable to cyanidation. However, the alteration of the associated minerals presents new dissolution problems which must be solved. 

Aqueous solutions, syrups, elixirs, and emulsions do not present a dissolution problem and generally result in fast and often complete absorption as compared to solid dosage forms. Due to their generally good systemic availability, solutions are frequently used as bioavailability standards against which other dosage forms are compared. 

Presence of these impurities can result in gelatin cross-linking and possible dissolution problems or in undesired changes in the product appearance over time. 

Table 1 lists some of the examples where dissolution problems have been reported with hard gelatin capsules. Fig. 7 depicts the behavior in one such case. Hard capsules normally contain 13%-16% water, which acts as a plasticizer and imparts flexibility. The moisture variations in the range of 12%-18% do not seriously impair the shell structure, however, below 12%, the shells beeome brittle and get easily ruptured. The capsules beeome moist, soft, and distorted when... 

Table 3 gives a summary of the known dissolution problems with sugar-coated tablets. The progressive decrease in disintegration and dissolution has been ascribed to adherence of gelatin subcoat to the tablet core. This was also a conclusion made in a study where most of the core tablets were found to be dry even at the end of the dissolution test. " Fig. 9 shows an example of sugar-coated chloroquine phosphate tablets exposed to 40°C and 75% RH. Clearly, the dissolution rate decreases with time. ... 

Dissolution problems for rectally administered medications because of lower fluid volume in the rectum than in the stomach, duodenum, etc... 

On the other hand, coordination complexes or organometallic compounds can be solubilized in ionic liquids, especially hydrophobic or anionic complexes [71, 78], It has been pointed out earlier that there are tricks to circumvent dissolution problems such as dissolving a metal salt and the IL in an organic solvent followed by solvent evaporation. Furthermore, the viscosity, which is much higher in ILs than in conventional solvents, will dramatically reduce mass transfer, which in turn will lead to a much slower metal salt dissolution [71]. 

Initial dissolution of primary silicates is typically incongruent that is, the stoichiometric ratio of elements released to solution is not the same as that found in the bulk phase of the mineral. An excellent example of incongruent dissolution (Fig. 7-13) is presented by Chou and Wollast (1984). They reacted albite with aqueous solutions in a fluidized bed reactor and maintained solution concentrations of the reaction products below saturation for potential secondary products. Even so, the molar ratio of Na/Si initially released to solution was almost an order of magnitude higher than that of the bulk albite. Dissolution incongruence has posed a particularly difficult theoretical problem for researchers working on mineral dissolution problems. 

The dissolution problem can readily be reduced to the consideration of one species (Cu2+ in this particular case) by experimentally setting the conditions such that the counterion (SO -) concentration remains essentially constant, i.e., is buffered, during a measurement. For the CuS04-5H20 dissolution experiments, this was achieved by making measurements in aqueous sulfuric acid solutions (carefully avoiding concentrations that would promote the dehydration of the crystal), which additionally serves as a supporting electrolyte. 

A solution presented to this fast dissolution problem is partial protection with an acid-labile lipophilic group, which will be described in detail later. 

These diagrams lie at the heart of the continuum dissolution problem... 

---