Nicotine-water system

Nicotine-water system This system exhibits upper as well as lower critical solution temperatures. Within the enclosed area, the two liquids are only partially miscible and a heterogeneous system exists. (Fig. 9.14)... 

Nicotine-water system shows both an upper and lower CST. 

Due to the relative success of the pure component solubility studies, the same series of experiments were carried out using the complex seed material. Three systems were investigated to evaluate the ability of supercritical fluids to extract monocrotaline from the seeds of Crotalaria spectabilis. Pure carbon dioxide was studied with the expectation that the oils would be preferentially extracted. Ethanol was added as a co-solvent to increase the solubility of monocrotaline. Also, due to its success in the extraction of caffeine and nicotine, water was used as a co-solvent. 

Some substances exhibit both upper and lower consolute temperatures. The diagram for the system nicotine-water is shown schematically in Fig. 15.3(b). The lower consolute temperature is about 61 °C, the upper one about 210 °C. At all points in the closed loop two phases are present, while the points outside the loop represent homogeneous states of the system. 

Systems with an upper and lower critical dissolution temperature include nicotine-water (60 and 218 C, Fig. 4C). 

Key characteristics in liquid/liquid systems are the mutual solubility and the concentration of both liquid phases in the equilibrium state. The previously discussed laws of mixed phase thermodynamics can still be applied. The feasibility of a liquid/liquid extraction depends on the occurrence of a miscibility gap and its width at different temperatures. Figure 2.2-1 shows three exemplary plots of the solubility temperature vs. the mass fraction. The letter z symbolizes mass fractions in any one- or two-phased mixture. The binary mixture formic acid/benzene has an upper critical solubility temperature whereas the mixture di-n-propylamine/water features a lower critical temperature. The third example system nicotine/water shows both a lower and an upper critical temperature. From these diagrams the concentrations of... 

Conditions are often more complicated in systems of two polar liquid substances. The heats of dilution are then frequently not negligibly small. Partial miscibility is found in these systems, e.g. ether/water or nicotine/water. 

The temperature effect on solubility may have different characters depending on the molecular structure of solute. For systems of liquid-amorphous or liquid-liquid polymers, the temperature raise can cause improvement of compatibility. Such systems are considered to have the upper critical solution temperature (UCST). If the system of two liquids becomes compatible at at r ratio at the temperature below the defined critical point, the system is considered to have the lower critical solution temperature (LCST). Examples of a system with UCST are mixtures of methyl ethyl ketone-water (150°C) and phenol-water (65.8°C). An example of a system with LCST is the mixture of water-triethylamine (18°C). There are systems with both critical points, for example, nicotine-water and glyc-erol-benzyl-ethylamine. 

The third type of system gives a closed solubility curve and therefore possesses both an upper and lower critical solution temperature. The first case of this type to be established was that of nicotine and water the solubility curve is illustrated in Fig. I, 8, 3. The lower and upper consolute temperatures are 60 8° and 208° respectively below the former and above the latter the two liquids are completely miscible. 

A TLC method was developed for the estimation of nieotinie aeid and nicotinamide (Fignre 10.7) in phatmacentical preparations containing other vitamins, enzymes, herbs, and drugs, etc. [16]. The percentage recoveries for nicotinic acid and nicotinamide were 100.1 + 1.9 and 100.2 1.5, respectively, with this system. Each alcohol extract of samples or standard was pnt on sihca gel TLC plates, which were developed with distilled water. Each silica gel spot visualized under UV lamp was collected and extracted with 0.1 mol/1 HCl. The optical density of each clear extract was measured at 262 run. 

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

Nicotine in tobacco has always been used for medicinal purposes. Nicotine solutions made from soaking tobacco leaves in water have been used as pesticides for several hundred years. In modern times, numerous pharmaceutical companies have explored nicotines use for treating diseases. Nicotines most prevalent medicinal use is for smoking cessation in the form of alternate delivery systems such as gums and dermal patches. Nicotine is used medically for numerous conditions and its use is being explored in additional areas including pain relievers, attention deficit disorder medications and medications associated with Alzheimer s disease, Parkinson disease, colitis, herpes, and tuberculosis. Because of nicotines potential therapeutic use, several large tobacco companies have developed pharmaceutical divisions. 

In the hatched two-phase region of limited miscibility, the system separates heterogeneously into water-rich and nicotine-rich layers. However, at temperatures below the lower consolute point (about 61°C) or above the upper consolute point (about 210°C), the components become miscible in all proportions, resulting in a uniform homogeneous phase. The molecular-level origins of this extraordinary behavior, as well as more general aspects of consolute behavior in other (typically, hydrogen-bonded) systems, remain deeply obscure. 

The temperature composition curve for this system is shown in fig. (18). The system of nicotine and water belongs to this class. At temperatures below 60.8° and above 208°, the two liquids are completely miscible in all... 

Passive diffusion readily allows the transport of such lipid-soluble substances as oxygen and carbon dioxide, nicotine and heroin across the BBB, whereas none of the water-soluble nutrients and messenger molecules used by the brain can gain access via this route. Their access to the CNS is achieved by specialist transport systems, which selectively carry substances across the barrier. 

Thus the enthalpy of mixing is a key quantity for a system to show a UCST. For the other excess functions, e.g. VE and Cp, there are no restrictions, but generally at a UCST, Cf< 0 and VE > 0, while at a LCST, Cp > 0 and VE < 0 (Rowlinson, 1969). If Cf is negative at an LCST and remains so as the temperature increases, then HE and SE may change in such a way that the conditions for a UCST are met. Such systems show a closed solubility loop. The mixture water + nicotine is a classic example of such a system. The behaviour of another example, the mixture water + 2-butoxyethanol, is shown in Fig. 29 (Ellis, 1967). 

It should be noted that the PCL/nicotine system is somewhat unique. First is the fact that PCL is semi-crystalline at the room temperature at which the experiments were conducted. Second is the high solubility of nicotine in water, which drives the drug to partition into the aqueous regions in the matrix. A similar study with PCL and caffeine, which has a solubility of 20 mg/ml in water (i.e. 10% that of nicotine) does not show such a clear dependence of the rate of diffusion on drug loading (16). 

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