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The oral route is the preferred option for drug administration but contains the inherent issue of drug absorption from the gastro-intestinal tract (GIT) in order to elicit systemic activity. A pre-requisite for absorption is drug dissolution, which is dependent upon drug solubility and the variable milieu of GIT fluid, with poorly soluble drugs presenting a formulation and biopharmaceutical challenge. Multiple factors within GIT fluid influence solubility ranging from pH to the concentration and ratio of amphiphilic substances such as phospholipid, bile salt, monoglyceride and cholesterol. To aid in vitro investigation, simulated intestinal fluids (SIF) covering the fasted and fed state have been developed. SIF media is complex and statistical design of experiment (DoE) investigations have revealed the range of solubility values possible within each state due to physiological variability along with the media factors and factor interactions which influence solubility. In this research a dual level, reduced experimental number (20) DoE providing three arms covering the fasted and fed states along with a combined analysis has been investigated. The results indicate that this small scale investigation is feasible and provides solubility ranges that encompass published data in human, simulated fasted and fed fluids and published DoE results. The study also correctly identifies the major single factor or factor interactions which influence solubility but it is evident that lower significance factors are not picked up due to the lower sample number. Moreover, several approaches were made to modify drug formulation in an aim to enhance drug solubility and dissolution including sloid dispersion and the usage of excipients. In this work, examining the effect of six representative types of excipients on solubility were examined using the design of experiment. The results indicated specific drug- excipient behavior and that each excipient will have different effect on drug solubility. Smaller molecular weight or lower concentration of excipients as mannitol for example, had no impact on solubility and or dissolution. On the other hand, higher molecular weight and higher concentration of the excipient like chitosan for example, significantly reduced drug solubility. The results also indicated that the effect of the excipient on solubility will be dependent on the type of excipient under investigation, the concentration of the used excipient and on the media state (fasted or fed) under examination. This outcome improved the feasibility of the design to be used as a prognostic tool to examine the effect of excipients on solubility. Finally, dissolution testing of carvedilol in presence of excipients were carried out. The results indicated that carvedilol dissolution rate were not affected in presence of lower molecular weight excipients as mannitol for example but it significantly reduced in the presence of higher molecular weight excipients as chitosan for example. Moreover, this influence of the excipient on drug dissolution were found to be due to the interaction between the excipient with the different media components and or with the drug. The results also showed that dissolution testing correlate well with the equilibrium solubility testing where, excipients that found to affect solubility showed to affect dissolution also. These studies illustrate that these approaches therefore represent a useful initial screening tool that can guide further in depth analysis of a drug's behavior in gastrointestinal fluids and in the presence of excipients. The outputs can potentially be applied in drug formulation testing for improved bioavailability.