World View: A Philosophical and Theological Perspective

The world of today has emerged as a global village with diversity of culture, faith, religion, ideology and belief. The difference of point of view and intolerance are still left to be taken into account by the intellectuals of the world seriously with other multiple universal problems. In the present scenario, there is a need to rationalize the human existence on the face of Earth in terms of the sole objectives of human life. This study is an attempt to present a world view to the humanity through a philosophical and theological approach. Multiple questions have been raised and then answered with reference to Islamic religious philosophy of human life. It is an attempt to strengthen harmony among the world citizens.

Formulation and Evaluation of Parenteral Depot Drug Delivery of Atypical Antipsychotic Drug in the Treatment of Schizophrenia

Schizophrenia is a lifelong debilitating illness requiring extended treatment with antipsychotic agents. A novel atypical antipsychotic agent like olanzapine is required for a longer period of time to prevent relapses. Non-adherence to therapy is a very common and severe problem in these patients. Adherence to therapy can be improved by prescribing depot injectable or implant formulations in such patients to significantly reduce the dosage frequency. The purpose of this study was to develop Poly-(lactic-co-glycolic acid) (PLGA) based microsphere, Poly(N-isopropylacrylamide-co-acrylic acid) (PNA) microgels based in situ gelling system, PLGA based in situ gel and PLGA based implant formulations aimed to release the olanzapine for a period of one month or more. These dosage forms will result in increase compliance and reduce dosage frequency. Reverse phase HPLC method was also developed for in vivo studies and pharmacokinetic assessment of these dosage forms. Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency and Fourier transform infrared spectrometry. Olanzapine loaded PNA microgels were prepared and characterized by viscosity measurements, cytotoxicity assay and TEM analysis. In vitro release of olanzapine from PNA microgels was determined on different pH and temperature range. PLGA based in situ gel implant was developed on the principle of solvent exchange. Surgically implantable olanzapine loaded PLGA cylinders were prepared by using solvent extrusion method. Implant formulations were characterized by surface morphological studies, x-ray diffractometric analysis, fourier transform infrared spectrometry and differential scanning calorimetric analysis. All formulations were evaluated for in vitro release studies. For quantification of olanzapine in micro-sample rat plasma, a sensitive and validated RP-HPLC method using UV detection was developed. HPLC method was validated for precision accuracy using limits of FDA’s guidance for bioanalyitcal assay validation. In vivo studies for selected formulations were performed on Sprague-Dawley rats. Morphological results indicated that microspheres produced were having smooth surface and spherical shape. The size of microspheres was in the range from 9.71 to 19.90 μm in mean diameter with good encapsulation efficiency. In vitro release of olanzapine from PLGA 50:50 microspheres was fastest whereas release from PLGA 85:15 microspheres was slowest of all. In vitro release kinetics revealed that release of drug from olanzapine PLGA microspheres is by xxi both non-fickian diffusion and erosion of PLGA polymer. Olanzapine loaded PNA microgels were successfully prepared with drug loading efficiency of 2.14 ± 0.52 % and in vitro release was characterized by a high initial burst release up to 38.6% of the drug release within two hours. PLGA based in situ gel implant was successfully developed on the principle of solvent exchange and in vitro release profiles indicate an initial burst release from all formulation. All formulations of PLGA surgical implant showed a tri-phase in vitro release pattern. A reverse phase chromatographic column C18 hypersil-BDS was used for chromatographic separation with mobile phase consisting of 50mM phosphate buffer pH 5.5, acetonitrile and methanol (50:30:20 v/v/v) pumped at flow rate of 1.2 mL/min. Olanzapine was measured using UV detection at 214 nm with retention time of 5.0 min. Excellent linearity with concentration range 1-500 ng/mL in rat plasma was obtained with coefficient of regression i.e. r2 =0.9986. In vivo data for microspheres indicated an initial burst release and then sustained release depending on ratio of lactic to glycolic acid in copolymer PLGA, microsphere size and bulk density. Plasma concentration data for in situ gelling system shows an initial burst release for all selected formulations as expected from in vitro data. In vivo release studies of PLGA implant showed that the initial release at 11 day for 50:50, 65:35, 75:25 and 85:15 PLGA based implant was 8.9, 7.32, 6.19 and 3.25%, respectively. The study concluded that PLGA microspheres and PLGA based in situ gel can be potential candidates for 30 day depot injection drug delivery of olanzapine in treatment of non compliant schizophrenia patients. PNA microgels showed a very high initial burst release which may lead to toxicity. Olanzapine loaded PLGA based surgically implantable cylinders provided a sustained of olanzapine for more than 70 days.