Formulation solution

The thermal method is based on the much higher solubiUty of KCl in hot water as compared to the solubiUty of NaCl. The KCl is recovered in vacuum crystallizers, filtered or centrifuged, dried, and sometimes granulated by compaction. Product from the thermal beneficiation method usually is of relatively high purity and is particularly suitable for use in formulating solution-type fertilizers. Guaranteed K2O content of this product is usually 62%... 

Historical prelude Kepler s laws Historical prelude Maxwell Theory Axiomatic teaching of Quantum Mechanics Problem lack of reference points Problem imprecise boundaries Problem inaccurate formulation Solution reference points from a journey Solution precise boundaries Solution accurate formulation Intuitive teaching of Quantum Mechanics Conclusion... 

Wang TF, Kasting GB, Nitsche JM (2006) A multiphase microscopic diffusion model for stratum comeum permeability. 1. Formulation, solution, and illustrative results for representative compounds. J Pharm Sci 95 620-647. 

This deformation variable determines the strain and subsequent overall stress state. The overall stress state, in turn, is related (through Eqs. 13.11 and 13.12) to the fiber stresses. As in the sequential compaction formulation, solutions for fiber position and fiber volume fraction are found numerically. 

Potassium sorbate has both antimicrobial and antifungal properties in formulations below pH 6. Generally, it is used at concentrations of 0.1% to 0.2% in oral formulations (solutions, syrup, and suspensions), and is used much more than sorbic acid because of its higher solubility and stability in water. However, some loss of antimicrobial activity occurs in the presence of nonionic surfactants and some plastics. 

Mujtaba (1999) considered the conventional configuration of BED processes for the separation of binary close boiling and azeotropic mixtures. Dynamic optimisation technique was used for quantitative assessment of the effectiveness of BED processes. Two distinct solvent feeding modes were considered and their implications on the optimisation problem formulation, solution and on the performance of BED processes were discussed. A general Multiperiod Dynamic Optimisation (MDO) problem formulation was presented to obtain optimal separation of all the components in the feed mixture and the recovery of solvent while maximising the overall profitability of the operation. 

Anesthetic (Trade Name) Formulation (% Solution) Onset of Action (min) Duration of Action (hr) Maximum Dose (mg) ... 

Throughout the course of these studies, multiple batches of the same formulation were exposed to either full ICH exposure conditions or only the visible component of ICH light. Substantial variation was observed between different preparations of the formulation. One major trend appears to be that older formulation solutions are more photosensitive than recently prepared solutions (vide supra). After ICH visible exposure, a three-month-old solution has about 0.1% levels of phenol and a 13-month-old solution forms 0.4% phenol, whereas a 23-month-old solution forms 1.2% phenol. The large magnitude of the variation in photosensitivity observed for different manufactured batches as well as for bench top preparations (Table 3) argue that the photodegradation is not a function of a component that is intentionally controlled in the formulation. 

Table 6 Impurity Profiles of Borosilicate Glass and Corresponding ppb Levels of Elements Found in 3-mo-old and 23-mo-old 0.57mM Drug A, lOmM Citrate (pH 6), 136mM Sodium Chloride Formulation Solutions Measured by Inductively Coupled Plasma-Mass Spectroscopy...

None of the transition metals examined except iron showed increased formation of phenol compared to the unspiked sample of formulation one. Thus, it appears likely that iron levels will remain highly correlated with the photosensitivity of initially prepared drug A formulation solutions. 

The photodegradation of drug A formulation solutions at a fixed iron content was also examined for a series of 10 mM poly- and monocarboxylate buffers (oxalate, succinate, maleate, tartrate, and formate). The general photocatalysis was observed for all systems examined and varied from 0.40% to 17.6% loss of drug A for solutions containing 50ppb iron (Table 11). 

Oliyai et al. [23] studied an Asn-hexapeptide (Val-Tyr-Pro-Asn-Gly-Ala) in lyophilized formulation as a function of pH of the bulk solution, temperature, and residual moisture content in a factorial study. A statistically significant two-factor interaction indicated that the pH of formulation solution determined the extent to which this peptide stability depends on moisture level and temperature. 

When the formulated solution contains essentially saline or organic solutes that crystallize easily, the interstitial phase will crystallize out abruptly as an eutectic or a mixture of eutectics. The crystallization results in an immediate hardening of the frozen system, which becomes fully rigid. At this point, the system has reached its maximum temperature for complete... 

When the formulated solution predominantly contains polyols, sugars, or polymers, the interstitial phase does not usually crystallize out upon cooling but increases progressively in viscosity as a glass-like system. In the case where the interstitial phase has effectively the structure of a glass, the frozen system becomes fully rigid once the glass transition temperature (Fg) is reached. In contrast, some amorphous systems may show no such definite transition, but they eventually become very stiff at low temperature, as shown by electrical resistance studies. 

Regardless of the freezing behavior of the formulated solution, it is essential to make sure that the temperature of the product is decreased below the temperature where complete solidification is observed. If this condition is not respected, the incompletely frozen interstitial phase will boil or induce pellet partial melting or collapse during lyophilization. 

Despite these precautions, a slow freezing process is not always sufficient to ensure a dimensionally stable pellet of good cosmetic appearance. In this respect, formulated solutions that produce interstitial metastable glasses on cooling are sometimes a source of problems. In such systems, devitrification followed by partial erratic recrystallization of the excipient may occur during lyophilization, thereby generating a pellet of poor powdery appearance. 

Liquid samples should be taken at the critical stages of the process, e.g., bulk material, formulated solution before and after filtration, filling solution, filled vials or ampoules at the beginning, middle, and end of filling. When traces of material are to be assayed, care should be taken that the collecting test tubes or containers do not adsorb significant amounts of drug or leach out impurities in the formulated solution. 

To conclude this section, it is worth noting that the process qualification based on liquid samples, although necessary, is not sufficient to qualify all aspects of the stability of the formulated solution. For example, it may happen that the formulated solution has to be stored in the filling tank for a few hours longer than usual. The behavior of the solution during this extra time cannot be safely predicted from the above in-process data. In order to release the batch produced, it is necessary to have a documented study about the stability of the filling solution at different temperatures, over an adequate period of time, e.g., 24 hours. 

Providing the product is reconstituted in a small volume of diluent, the resulting solution is more concentrated than the formulated solution before freeze-drying. It is therefore easier to assay minute amounts of drug or impurities and the analytical methods used for QC release can be implemented. 

When a child has febrile convulsions the decision to embark on continuous prophylaxis is serious for the child, and depends on an assessment of risk factors, e.g. age, nature and duration of the fits. Most children who have febrile convulsions do not develop epilepsy. Prolonged drug therapy, e.g. with phenytoin or phenobarbitone, has been shown to interfere with cognitive development, the effect persisting for months after the drug is withdrawn. Parents may be supplied with a specially formulated solution of diazepam for rectal administration (absorption from a suppository is too slow) for easy and early administration, and advised on managing fever, e.g. use paracetamol at the first hint of fever, and tepid sponging. 

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