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Home > Development and Evaluation of Microspheres of Model Drug Prepared With Methacrylate Derivatives and Ethyl Cellulose for Controlled Drug Release

Development and Evaluation of Microspheres of Model Drug Prepared With Methacrylate Derivatives and Ethyl Cellulose for Controlled Drug Release

Thesis Info

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Author

Majeed, Abdul

Program

PhD

Institute

Bahauddin Zakariya University

City

Multan

Province

KPK

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Pharmaceutics

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/10305/1/Abdul%20Majeed_Pharmaceutics_2018_BZU_Secrecy.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725857583

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Purpose of the study The objective of current research work was to develop and evaluate microspheres for controlled drug delivery. These pH dependent polymeric microspheres were designed to deliver drug in a controlled release fashion, to minimize dosing frequency, to increase bioavailability and minimize drug toxicity. Methodologies In this study various polymeric microsphere formulations were prepared using methacrylate derivatives and ethyl cellulose (EC) by oil-in-oil (O/O) solvent evaporation method. Span 80 was used as an emulsifier. Ivabradine HCl (IBH), anti-anginal was used as a model drug. IBH was encapsulated into microspheres by in-situ method in all formulations. A series of formulations with three different polymeric combinations i.e., eudragit L100-55-EC (Formulation code FA1-FA7), eudragit FS30D-EC (formulation codes FB1-FB7) and Kollicoat MAE 100P-EC (formulations codes FC1-FC7) were developed. Prepared microspheres of all formulations were characterized by recovery of microspheres, percentage yield, percentage drug loading, encapsulation efficiency and swelling studies. Optical and scanning electron microscopy (SEM) was used to examine the morphology and size of microspheres. Particle size distribution analysis was performed by Zetasizer. Rheological properties were conducted to measure the flow properties of resultant microspheres. Chemical stability of IBH loaded microspheres was confirmed by fourier transform infrared spectroscopy (FTIR), x-ray diffractometry (X-RD), differential scanning calorimetery (DSC) and thermal gravimetric analysis (TGA). In-vitro drug release studies were performed in phosphate buffer solution of pH 1.2, 5.5, 6.0 and 7.4. On the basis of results of in-vitro dissolution studies optimized formulations (FA7, FB7 and FC7) were selected for in-vivo studies on rabbits. Results and Discussion All formulations were synthesized and characterized successfully. Rheological studies showed that the formed microspheres were free flowing in nature. SEM images confirmed that resultant microspheres were spherical and smooth surfaces. SEM images showed that microspheres were in the size range of 20-80 μm with spherical shape. Zeta size analysis showed all formulation were in micromeritic range with narrow size distribution. FTIR spectra confirmed the presence of drug in pure form and reflected no interaction between drug and polymers. DSC and X-RD xx determined that the nature of drug in drug-loaded microspheres was in amorphous form. X-RD clearly indicated that drug particles were uniformly distributed in the polymeric matrix. TGA indicated that prepared microspheres showed much better thermal stability than pure drug. The microspheres executed pH dependent swelling behavior. The Maximum percentage entrapment efficiency of IBH was found upto 81 ± 2.15, 45.1% and 82 ± 2.11 for developed microspheres of eudragit L100-55-EC, eudragit FS30D-EC and Kollicoat MAE100P-EC respectively. Maximum percentage yield of eudragit L100-55-EC, eudragit FS30D-EC and Kollicoat MAE100P-EC microspheres was found 88± 2.65, 71.66 ± 2.12 % and 89 ± 3.31 respectively. In-vitro studies revealed that all formulations (FA1-FA7, FB1-FB7 and FCI-FC7) showed pH responsive drug release. All polymeric carrier presented negligible cumulative drug release in buffer solution of pH 1.2. The Maximum drug release 94.5%, 95.9% and 90% of optimised formulation (FA7, FB7 and FC7) was observed at pH 7.4 which demonstrated that all formulations had a pH-dependent drug release. Maximum controlled release effect was observed in formulations (FA7, FB7 and FC7) containing 50:50 of eudragit and EC due to reduction in swelling of microspheres. Results showed that high concentration of EC results in a longer diffusional path length, so drug release is extended and drug release mechanism gradually transfer from diffusion to erosion. Cumulative drug release data of all formulations were analyzed by using different kinetic models. The result showed that first order was best fit to the data and followed by drug release. By applying Korsmeyer-peppas model the value of (n) for release of drug was calculated. The value of (n) was found between 0.435- 0.830 which indicates that diffusion mechanism was non-fickian. High-performance liquid chromatographic (HPLC) method was developed and validated for analysis of IBH in mobile phase and rabbit plasma as per ICH-guidelines. The separation was performed on HSC18 (25 cm x 4.6 mm, 5μm) column with Acetonitrile: Buffer pH 6.0), 40:60 v/v) as mobile phase and a flow rate of 1.0 ml/min in the isocratic mode. A well-defined chromatographic peak of IBH was exhibited with a retention time of 4.062 minutes and tailing factor of 1.658.The linear regression analysis data for calibration plots showed good linear relationship with R=0.9998 in the concentration range of 1.56-100 μg/ml both in mobile phase and in plasma. The method was validated for precision, recovery and robustness. Intra and inter-day precision were less than 2%. The method showed the mean recovery of 96% to 102% and relative standard deviation (RSD) < 1% in Mobile phase and rabbit plasma. HPLC method was found to be highly precise, sensitive and accurate for determination of IBH in xxi pharmaceutical dosage form successfully applied to the commercial tablets without any interference of excipients. Optimized polymeric formulations were selected on the basis of in-vitro results and further studied for biological evaluation in rabbits in order to validate their effectiveness up to a considerable extent. After administration of single oral dose of drug solution and selected microspheres were subjected to in-vivo studies to calculate pharmacokinetics parameters. Pharmacokinetic parameters (pk) were calculated by Phoenix WinNonLin® Version 6.3 software the linear trapezoidal method was used to calculate AUC from time versus plasma concentration. All the polymeric microspheres (FA7, FB7 and F7C) had significantly prolonged Tmax, mean residence time (MRT), lower maximum plasma drug concentration (Cmax) had higher area under curve (AUC) in comparison to oral drug solution. Statistical analysis was performed by using one-way analysis of variance (ANOVA) in order to determine statistical significant and non-significant interpretation. The P value was < 0.05 which indicates a significant difference in results. Conclusion In short, pH dependent polymeric carriers; eudragit L100-55-EC, eudragit FS30D-EC and Kollicoat MAE100P-EC microspheres having potential to release drug in a controlled fashion, have been developed successfully. The results of in-vitro and in-vivo studies confirmed that microspheres entrapped IBH and prolonged its pharmacological effects due to increase of biological half-life. Collectively, these in-vivo results manifested that pH-dependent microspheres had a reasonable controlled release. This polymeric microspheres system can be further explored for the drug targeted delivery with maximum therapeutic efficacy and minimum adverse effects.
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110. An-Nasr/Help

110. An-Nasr/Help

I/We begin by the Blessed Name of Allah

The Immensely Merciful to all, The Infinitely Compassionate to everyone.

110:01
a. When Allah’s help arrives and HE opens up your way to victory after victory,

110:02
a. then you see people entering Allah’s Religion of Islam en-mass, in swarming crowds.

110:03
a. So glorify your Rabb - The Lord with HIS Praise,
b. and seek HIS Forgiveness.
c. Surely HE is the Acceptor of Repentance and Ever-Pardoning.

سیرت طیبہ صلی اللہ علیہ وآلہ وسلم کا عدلیاتی پہلو: ایک تحقیقی جائزہ A Research Review of the Prophetic Justiceﷺ

Islam is a religion of peace and it has provided a strong system of justice for the establishment of peace and order, the practical picture of which is available to the Muslim Ummah in the form of Sira-e-Taiba of the Holy Prophetﷺ. On which the seal of beauty has been recorded by Allah Himself. Therefore, the system of justice of Islam can be used only when the solution of all issues is sought from Sira-e-Taiba because Heﷺ has eliminated the distinction between rich and poor in the supremacy of law. The Holy Prophet ﷺ has set great and enlightening examples of justice for humanity, the pursuit of which leads to peace and tranquility of social life. In his Supreme Court, the Qur'an and Sunnah and consensus and analogy were of fundamental importance. In the Qur'an and Hadith, Sira-e-Taiba had the status of Shāri' and Legislator, while in consensus and speculation, Sira-e-Taiba has promoted thinking and counseling. The center and axis of Islamic law is your caste. He ﷺ has established justice, supremacy, and law in every field of worship, affairs, disputes, and crime. Therefore, in this article, the judicial aspect of His ﷺ Sira-e-Taiba has been explained in the light of the Qur'an and Hadith, the Sahabah and the followers, and the edicts of the Imams and jurists.

Mathematical Modeling and Analysis of Ciliary Induced Flow of Newtonian and Non-Newtonian Fluids

The present thesis deals with a mathematical study of ciliary induced flows of various non- Newtonian fluids through a planar channel and in an axially symmetric tube. The main motivation of the present research work is concerned with an investigation of the propulsion mechanics of ciliary induced flows of some biological fluids through certain physiological systems of the human body. In particular, we want to study the role.of ciliary movement in the transport of spermatic fluids through the ductuli efferentes of male reproduction system in the human beings through mathematical modeling. The spermatic fluids or the efferent duct materials are assumed as Casson, Carreau, micropolar, hydromagnetic conducting Newtonian fluids and the geometry of the ductus efferentes of the human male reproduction system is approximated with a planar channel of uniform dimensions and an axially symmetric uniform cylinderical tube. The mathematical equations governing the flow of the present problem are formulated in Cartesian and axisymmetric cylindrical coordinate systems. These are highly nonlinear and coupled partial differential equations. However, implication of the well known creeping flow approximation along with the long wavelength assumption permits us to obtain closed form exact solutions for the resulting simplifying system of equations governing the flow problems. This is a valid approach for the low Reynolds number flows and is widely used in the literature of physiological dynamics. The flow is produced under the action of ciliary beating that generates a metachronal wave and the analysis is made in the wave frame travelling at the speed of metachronal wave in the direction of flow. Exact solutions for velocity components, axial. pressure.gradient and the stream. function are obtained. For Carreau fluid model the governing system of equations is.reduced to a.system of nonlinear but ordinary differential equations by employing the creeping flow i.e., the low Reynolds number assumption along with the long wavelength approximation. In this case, we utilize the well known regular perturbation method to tackle the nonlinear.terms of the governing system of equations. Consequently, series form solutions for the stream.function, the velocity.distributions and the pressure.gradient are computed. In last two chapters, we have investigated the magnetohydrodynamics (MHD) effects on the ciliary induced flows by assuming that the efferent duct material is a conducting fluid. The applications of magnetohydrodynamics principles in physiological-type flows have been the subject of intensive research and study during the last few years. The study of MHD effects on the flow of spermatic fluids through the ductus efferents is a relatively new aspect of the problem. We have studied the problem theoretically through a mathematical model. The quantities of physical interest like the pumping characteristics, the ciliary trapping phenomenon, the axial pressure gradient, the velocity distribution and the volume flow rates are discussed in this study. Extensive analytical and numerical computations are carried out to obtain the results of various flow characteristics of physiological interest. The influence of pertinent parameters on the analytical results obtained by these models are analyzed and discussed through graphs. The numerical values of the volumetric flow rate obtained by the proposed models of our study are ix also compared with the experimentally estimated value of the flow rate of the human semen, 6´10-3 mlh . This estimated value was suggested by Lardner and Shack [1] in human based on the flow rates in the ductus efferentes in the other animals, e.g., rat, ram and bull. These values are found to be in excellent agreement with the estimated value as compared to the value obtained by the Newtonian model of Lardner and Shack which was0.12´10-3 mlh-1 .