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

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

Thesis Info

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External Link

Author

Pervaiz, Fahad

Program

PhD

Institute

The Islamia University of Bahawalpur

City

Bahawalpur

Province

Punjab

Country

Pakistan

Thesis Completing Year

2015

Thesis Completion Status

Completed

Subject

Applied Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/6844/1/Fahad%20Pervaiz%20PhD%20thesis.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726228687

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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.
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۔غزل

شبہ بچھڑنے کا ہونے نہیں دیا اُس نے
نہیں ہے خواب کوئی بھی تھکن سے لپٹا ہوا
وہ ایک زخم مرے شوق کی نشانی تھا
نہیں یہ کم تو نہیں ہے کہ مدتوں مجھ کو
یہ میرے اشک بجھا دیں گے آگ اندر کی

 

ستم کِیا ہے کہ رونے نہیں دیا اُس نے
میں کہہ رہا ہوں کہ سونے نہیں دیا اُس نے
وہ ایک زخم جو دھونے نہیں دیا اُس نے
ہجومِ وقت میں کھونے نہیں دیا اُس نے
اُسے پتہ تھا جو رونے نہیں دیا اُس نے

The Existence of Gorontalo Muhammadiyah University in Increasing the Income of the East Pentadio Village Community

The purpose of this research was to determine the existence of the Muhammadiyah University of Gorontalo in increasing the income of the people of East Pentadio Village. This research uses a descriptive qualitative research approach, using interview instruments with various informants. The results using Samuelson's theory about the factors that influence income, show that the existence of the Muhammadiyah University of Gorontalo is able to increase the income of the people of East Pentadio Village. However, the current existence of the campus has not been fully utilized by the community in increasing the income of the people of East Pentadio Village. There are still many outsiders who take advantage of the opportunity of the existence of the Muhammadiyah University of Gorontalo by making larger businesses in the campus area so that community businesses that are built simply with little capital experience competition. The low level of education of rural communities makes the business that is built still not optimal and makes the community less creative and innovative in entrepreneurship. This also causes people to easily give up when experiencing losses.

Simulation Study for Optimized Demand Side Management in Smart Grid

Simulation Study for Optimized Demand Side Management in Smart Grid Smart grid is envisioned to meet the 21st century energy requirements in a sophisticated manner with real time approach by integrating the latest digital communications and advanced control technologies to the existing power grid. It will dynamically connect all the stake holders of smart grid through enhanced energy efficiency awareness corridor. Smart Homes (SHs), Home Energy Management Systems (HEMS) and effect of home appliances scheduling in smart grid are now familiar research topics in electrical engineering. Peak load management and reduction of Peak to Average Ratio (PAR) and associated methods are under focus of researchers since decades. These topics have got new dimensions in smart grid environment. This dissertation aims at simulation study for effective Demand SideManagement (DSM) in smart grid environment. This work is mainly focused on optimal load scheduling for energy cost minimization and peak load reduction. This work comprehensively reviews the smart grid applications, communication technologies, load management techniques, pricing schemes and related topics in order to provide an insight to the environment required for dynamic DSM. Various network attributes such as Internet Protocol (IP) support, power usage, data rate etc. are considered to compare the communications technologies in smart grid context. Techniques suitable for Home Area Networks (HANs) such as ZigBee, Bluetooth, Wi-Fi, 6LoWPAN and Z-wave are discussed and compared in context of consumer concerns and network attributes. A similar approach in context of utilities’ concerns is adopted for wireless communications techniques for Neighborhood Area Networks (NANs), which include WiMAX and GSM based cellular standards. Issues and challenges regarding dynamic DSM in smart grid have been discussed briefly. DSM is supposed to have a vital role in future energy management systems and is one of the hot research areas. This study presents detailed review and analytical comparison of DSM techniques along with related technologies and implementation challenges in smart grid. It also covers consumers and utilities concerns in context of DSM to enhance the readers’ intuition about the topic. Two major types of DSM schemes, incentive based and dynamic pricing based, have been discussed and compared analytically. Dynamic pricing based HEMS are emphasized as important tools for peak load reduction and consumers’ energy cost minimization. Dynamic pricing based HEMS and their associated optimization techniques along with analytical comparison of the latest schemes have been described. Comparison of DSM techniques and study of latest HEMS scheme provided the base for new ideas of partial baseline load and reserved interrupting load to formulate two unique energy cost minimization problems. These models resulted the following two solutions in which scheduling has been carried out through many different algorithms to reduce peak load and consequently the PAR. This work includes novel appliance scheduling solution named; Comprehensive Home Energy Management Architecture (CHEMA), with multiple integrated scheduling options in smart grid environment. Multiple layers of enhanced architecture are modeled in Simulink with embedded MATLAB code. Single Knapsack is used for scheduling and four different cases for cost reduction are modeled. Fault identification and electricity theft control have also been added along with the carbon foot prints reduction for environmental concerns. Simulation results have shown the peak load reduction of 22.9% for unscheduled load with Persons Presence Controller (PPC), 23.15% for scheduled load with PPC and 25.56% for flexible load scheduling. Similarly total cost reduction of 23.11%, 24% and 25.7% has been observed, respectively. Smart grid interface layer and load forecasting layers are not implemented in current work and will be focused in future work. Another novel comparative approach has also been proposed in this research, which investigates the effect of multiple pricing schemes and optimization techniques for cost minimization and peak load reduction. The proposed model uses multiple pricing schemes including Time of Use (ToU), Real Time Pricing (RTP) day ahead case and Critical Peak Pricing (CPP). Proposed optimization problem has been solved with multiple optimization techniques including Knapsack, Particle Swarm Optimization (PSO) and Genetic Algorithm (GA). Knapsack is used with two options of limited slots scheduling and whole day scheduling. Comparative results of the multiple pricing and optimization schemes have been discussed. Results show that the best combination achieved with GA and CPP with 39.9223% cost reduction. PSO showed the 43.73% cost reduction with all the pricing schemes. The proposed schemes have many applications for peak load reduction and energy cost minimization to benefit consumers and utilities. A user can schedule his load using one of the options provided in CHEMA according to his preferences. Similarly, maintenance activities can be accommodated without disturbing the pre-defined schedule by using reserved interrupting slots. In large buildings, reserved slots can be used to schedule heavy loads without generating a peak.