Behnaz was Currently a graduate student Dubai Pharmacy College at Dubai
Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. Extensive hepatic first pass metabolism is one of the principal reasons for poor oral bioavailability of drugs. It is a mechanism whereby detoxification of drugs and their conversion to their water soluble forms occurs which facilitates convenient excretion through kidneys. However, it prevents required amounts of the drug to reach systemic circulation leading to a need of higher doses to achieve minimum effective plasma concentrations. This results in dose related side effects and thus poor patient compliance. The resulting metabolites may possess equal pharmacological activity or may have modified activity leading to increased or decreased effect. The metabolites produced in many cases are also reported to be toxic compared to the parent drug. Thus, hepatic first pass effect may or may not lead to loss of pharmacological action of drugs. Various formulation approaches for inhibition of hepatic first pass metabolism are employed in order to enhance the oral bioavailability. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. various nano-carriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs. These include its co-administration with another drug (which gets preferentially metabolized), use of prodrugs, and promoting drug absorption via lymphatic route (avoiding portal circulation). Novel Drug Delivery systems e.g. microemulsion, SMEDDS, nanoparticles and liposomes are used widely for avoidance of hepatic first pass effect. This review focuses on oral formulation strategies by which reduction of hepatic first pass metabolism, and thus, enhancement of systemic availability of drugs can be achieved. These strategies result in improved bioavailability, reduction in dose and side effects ultimately leading to enhanced patient compliance.
Foziah Ali Al-Saif is Associate Professor of Inorganic Chemistry, Department of Chemistry, Faculty of Science, Princes Nourah bint Abdulrahman University Kingdom of Saudi Arabia. She has variety of experience after years of work in research, teaching and administration of university. Her research area is metal-drug interaction. She has participated in three projects funded by Princess Nourah University and now she is principle investigator of research group named Chemistry of Metal-drug Complexes and it’s Biological Applications.
New six cobalt (II) complexes 1-6 with four generation of quinolone drugs (nalidixic acid (Nal), oxolonic acid (Oxo), pipemidic acid (Pip), lomefloxacin (Lom), pefloxacin mesylate (Pef) and levofloxacin (Lev)) have been synthesized in methanol medium and the general formula was designed as [Co(L)2(Cl)2(H2O)2].4H2O (L=Nal (1), Oxo (2), Pip (3), Lom (4), Pef (5) and Lev (6)). The Co (III) complexes were identified using microanalytical, FTIR spectroscopy, conductance data, effective magnetic moments, electronic UVvis spectra and thermal analyses. The six quinolone drug chelates acts as unidentate via nitrogen atom of pyridone/piperazyl moiety. Electronic spectroscopic tools are in agreement with an octahedral geometrical structure. Thermal degradation analyses TGDTG in nitrogen gas environmental are discussed the number and location of water molecules. The thermal decomposition process is completely in 34 steps, that the first step is responsible to loss of four uncoordinated water molecules. The stabilities of Co (II) complex 16 were studied dependent on activations of energy E, entropy ΔS, enthalpy ΔH and Gibbs free energy ΔG that have been estimated using CoatsRedfern and HorowitzMetzeger nonisothermal methods. Molecular docking was used to predict the binding between some quinolone drugs with the receptor of breast cancer mutant 3hb5-oxidoreductase. The structural view of the synthesized cobalt (II)-quinolone nanoparticles has been documented with the help of transmission electron microscope (TEM). The synthesized metal chelates have been screened in vitro antibacterial activity against bacteria, gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) and two strains of fungus (Aspergillus flavus and Candida albicans). The cobalt (II) chelates were shown to possess more antibacterial activity than the free chelates.