**6. References**

Abosi AO, Raseroka BH: In vivo antimalarial activity of *Vernonia amygdalina. Br J Biomed Sci*  2003;60:89–91.

Adzu B, Abbah J, Vongtau H, Gamaniel K: Study on the used of *Cassia singueana* in malaria ethnopharmacy. *J Ethnopharmacol* 2003;88:261–267.

systemic toxicity on oral LD50 values, recommended by the organization for Economic Cooperation and Development (Walum et al,1986). It has, however, been reported, that the median lethal dose is not an absolute value but is an inherently variable biologic parameter that cannot be compared to constants such as molecular weight or melting point (Oliver, 1986). The adverse signs of gaiting, reduction in stereotypic activities and deaths were

 In the sub-chronic study, the hematologic parameter shows a decrease in the RBC counts and an increased neutrophil in the treated groups. The serum chemistry parameter shows an increase in the direct and total bilirubin value. In several organs, mainly heart and liver, cell damage is followed by increased levels of a number of cytoplasmic enzymes in the blood, a phenomenon that provides the basis for clinical diagnosis of heart and liver diseases . For example, liver enzymes are usually raised in acute hepatotoxicity but tend to decreased with prolonged intoxication due to damage to the liver cells (Orisakwe et al, 2004). In this study, the extract did not exert significant effects on the serum chemistry parameters, the increased in bilirubin levels were probably due to the decrease RBC values. Since the traditional healers reported use of the drug as prophylactics against malaria, male rats were exposed to the extract for 6 weeks. No extract-related deaths occurred, the clinical condition of the animals, body weight gain, and food consumption were unaffected. Clinical pathology parameters (hematology, serum chemistry) exhibited no treatment-related effect. Organ weight changes can be sensitive indicators of target organ toxicity, and significant changes in organ weights may occur in the absence in changes in other pathology parameters (Bailey,S.A., 2004 ), for example, increased liver weight associated with hepatic cytochrome P450 induction is a common finding in toxicology studies. Liver weight increases of up to 20% relative to control without microscopic evidence of hepatocellular hypertrophy or changes in serum chemistries (Amacher, et al., 2000). Similarly modest doserelated changes in kidney weight commonly occur in toxicology studies without

In conclusion, the results of this study showed analgesic activity of the extract with clear and significant antiplasmodial effects in mice, no indication of toxicity in rats, incidental findings below or above standard reference levels were all within control values based on historical reference ranges. This might explain the pharmacological basis for the successes in

This study received financial support from Innovation at Makerere Committee (I@mak.com) grant. The authors are grateful to Prof. F.I.B. Kayanja (Mbarara University of Science and Technology) for his valuable input. We also thank The Rukararwe Traditional Medicine

Abosi AO, Raseroka BH: In vivo antimalarial activity of *Vernonia amygdalina. Br J Biomed Sci* 

Adzu B, Abbah J, Vongtau H, Gamaniel K: Study on the used of *Cassia singueana* in malaria

pain and malaria treatment claimed by traditional healers who use *V. amygdalina.*

Health Center in Bushenyi District for providing plant material for the study.

ethnopharmacy. *J Ethnopharmacol* 2003;88:261–267.

histopathologic evidence of cellular alteration (Greaves, P. 2000).

however seen in high doses.

**5. Acknowledgments** 

2003;60:89–91.

**6. References** 


**9** 

*Iran* 

**Experimental and Computational** 

*1Drug Applied Research Center and Faculty of Pharmacy, 2Liver and Gastrointestinal Diseases Research Center,* 

*Tabriz University of Medical Sciences, Tabriz,* 

**Methods Pertaining to Drug Solubility** 

Solubility of a drug is one of its important physico-chemical properties. More attention has been paid to the aqueous solubility since water is the unique solvent of biological systems. It is obvious that a drug should be reached to its receptors in the body through the aqueous and non-aqueous media. The chance of a low water soluble drug to be appeared in the market place is very low and nearly 40 % of the drug candidates fail to reach higher phases of the drug trials simply because of their low water solubility. The solubility in non-aqueous solvents is not too important from clinical viewpoint however these solubilities play curious roles in drug discovery and development investigations. Most of drugs are synthesized in non-aqueous media and/or extracted from natural sources using non-aqueous extracting solvents. Different polymorphs of some drugs could be produced from their crystallization

There are various methods for solubility determination of drugs which is discussed in this chapter. The experimental determination is tedious and time-consuming process and sometimes there is restrictions in the availability of enough amount of a drug candidate to be used in the solubility measurements, especially in the early stages of drug discovery investigations in which only small amount of a drug is synthesized/extracted and large number of preliminary biological tests should be carried out. To cover this limitation, and in order to provide a faster and easier tool, mathematical models have been developed to correlate/predict the solubility of drugs. These models are discussed in this chapter to provide an overall view for a pharmaceutical scientist who is working in the research and development department of a company and/or a research laboratory within academia. In addition to the accurate calculations which are expected from these models, the simplicity of the required computations is another parameter which should be taken into account, since more complex computations did not attract more attention in the pharmaceutical industry.

When talking about solubility, there are two concepts which might be confused with each other: solubility and dissolution. The term solution (i.e. thermodynamic solution) is used to define the state which is thermodynamically stable and shows the neat result of an

**1. Introduction** 

using organic solvents.

**1.1 Solubility and dissolution** 

Abolghasem Jouyban1 and Mohammad A. A. Fakhree2

