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۵۲۔ محرومیوں کی گٹھڑی

محرومیوں کی گٹھڑی

بیس برس کا تنہا سفر

بیس برس کی محرومیاں

 جو بچپن کے برہنہ پیڑ تلے

 میرے ساتھ رینگتی رہیں

دوست بن کر کھیلتی رہیں

شام ہوتے لوٹ جاتی تھیں

پیڑ اپنے دامن میںپرندے لپیٹ کے سو جاتا

میں اداسی کی چادر اوڑھے

دن بھر کی تنہائی کندھے پہ اٹھائے

خواہشوں کے جگنو پکڑتے گھر لوٹتا

From Jihad to Salam in Pursuit of Political Change: A Perspective based on Qur’ānic Sources

The political reality of many countries in the Muslim World is untenable and reforms and change is absolutely necessary. This article argues that use of force and violence for political change is making things worse as one can witness in Syria and Iraq. The article advances a Qur’ānic perspective on the desirability of peace as a goal and peaceful means as instruments of change. The article acknowledges that the Qur’ānic sanction for use of force to defend religious freedom prcludes the advocacy of pacifism but nevertheless the article does make a strong case for privileging peace over use of force.

Development of Modified Release Polymeric Formulations of Venlafaxine and in Vitro–In Vivo Evaluation

Purpose of the Study This study was designed to prepare, characterize and evaluate new polymeric formulations (hydrogels, microparticles) for sustained delivery of a hydrophilic drug. For this purpose, a highly water soluble anti-depressant; venlafaxine hydrochloride was employed as a model drug. Methodologies In this study, various hydrogel formulations were synthesized by aqueous free radical graft copolymerization and microparticles were prepared using aqueous free solvent evaporation method. Results and Discussions 1. Hydroxypropyl Methylcellulose Graft Acrylic Acid (HPMC-g-AA) Hydrogels Hydroxypropyl methylcellulose graft acrylic acid (HPMC-g-AA) hydrogels were prepared using ammonium persulphate (APS) and sodium metabisulphite (SMBS) as redox pair and tetra ethylene glycol dimethacrylate (TEGDMA) was used as crosslinker. Hydrogels were characterized by FT-IR and SEM. All formulations executed a pH dependent swelling behaviour. Venlafaxine was loaded into hydrogels through imbibition. Swelling ratio and drug loading increased with increase of AA contents and decreased on increase of TEGDMA contents. Formulation A4, having highest content of AA showed superior behaviour in terms of drug loading (171.5 mg/0.45 g gel) and extent of drug release (79.45 %) in 12 h dissolution. Lowest quantity of drug loading (69.5 mg/ 0.45 g gel) and extent of drug release (27.29 %) was observed for T4, having highest content of TEGDMA (1.4 %w/w). All formulations showed sustained release behaviour and burst effect was negligible. Cross-linked network structure of new polymer does not permit free diffusion of water excluding the possible burst effect of highly water soluble venlafaxine. Mechanism of drug release was Fickian diffusion at pH 1.2 and non-Fickian at higher pH buffers. Based on highest values of correlation coefficients, Higuchi model was the best fit model followed by Zero order. 2. Hybrid Copolymer Polyvinylalcohol (H-PVA) Hydrogels A series of hybrid copolymer poly vinyl alcohol hydrogel (H-PVA) formulations were developed using AA, 2-acryl amido-2-methyl propane sulfonic acid (AMPSA) and ethylene glycol dimethacrylate (EGDMA) was used as crosslinking agent. Hybrid hydrogels were characterized by FT-IR, TGA and SEM. SEM analysis reveals the development of a three dimensional porous network structure. TGA findings prove a slight increase in thermal stability of venlafaxine loaded hydrogel. FT-IR analysis proved successful grafting of AA and AMPSA on backbone of PVA. Swelling and diffusion coefficient increased with increase of monomers (AA, AMPSA) ratios and decreased on increasing ratio of crosslinker. Highest amount of drug: (135.67 mg/0.4 g hydrogel disc) was incorporated in E1 having lowest amount of crosslinker (0.2 %w/w). Drug loading and release were associated with hydrogel composition. Drug loading increased with increase of AA, AMPSA and decreased on increase of EGDMA. 100 % drug release was achieved from A1, A2, A3, S1 and E1 in 24 h dissolution study in buffer of pH 7.4. However, cumulative drug release remained below 25 % in pH 1.2. Gel fraction increased with increasing ratio of AA, AMPSA and EGDMA. All formulations exhibited sustained release of venlafaxine up to 24 h, sufficient to be employed for once daily dosing. Pattern of drug release was best explained by Zero order equation followed by Higuchi model. 3. Hydroxypropyl Methylcellulose-co-Methacrylic Acid (HPMC-co-MA) Hydrogels Controlled release hydrogel formulations based on modification of HPMC were synthesized using benzoyl peroxide (BPO) as free radical initiator. Thermal based aqueous copolymerization was carried out in the presence of methylene bisacrylamide (MBA) as crosslinker and methacrylic acid (MA) was monomer. FT-IR analysis confirmed grafting of monomer and SEM analysis proved the synthesis of mesh type solid network. Gel fraction, absorptivity, polymer volume fraction, diffusion coefficient, drug loading and extent of drug release profiles were evaluated. Swelling of new crosslinked polymer increased on increasing ratio of HPMC due to its hydrophilic nature of the polymer. Amount of drug incorporated in hydrogel network increased with increasing ratio of HPMC and decreased on increasing degree of crosslinking. Highest amount of drug entrapment; 157.89 mg/0.5 g gel was found for Y1 having the lowest degree of crosslinking (0.1 %w/w). Y1 also showed highest value of diffusion coefficient. Y4 having highest degree of crosslinking (0.7 %w/w), showed the lowest value of drug entrapped as well as diffusion coefficient. High degree of crosslinking results into development of tightly crosslinked compact structure having less porosity. Highly crosslinked network structure restricts diffusion of water as well as drug molecules. Drug release gradually increased on increase of pH from 3.0 to 7.0. All polymeric formulations showed a negligible cumulative drug release in buffer of pH 1.2. But rate and extent of drug release was increased steadily at pH 7.0 reaching to 100 % in 24 h dissolution experiments. Most of HPMC-co-MA hydrogel formulations followed Zero order release based on highest values of correlation coefficient. 4. Poly(hydroxyethyl Methacrylate-co-Itaconic Acid (HEMA-co-IA) Hydrogels New polymeric formulations based on TEGDMA crosslinked hydroxyethyl methacrylate- co-itaconic acid (HEMA-co-IA) were synthesized using APS and tetramethylethylenediamine (TEMEDA) as redox pair. Development of new copolymer was confirmed by FT-IR spectra. TGA analysis revealed increased stability of venlafaxine loaded HEMA-co-IA hydrogel. HEMA-co-IA hydrogels were subjected to in-vitro and in-vivo performance. Gel fraction of hydrogels increased on increasing fraction of IA and TEGDMA in hydrogel formulations. Mass equilibrium swelling ratio of hydrogels increased on increase of IA contents and decreased sharply on increasing degree of crosslinking. Highest swelling ratio (63.34) was found for T1 gel having lowest quantity of crosslinker. T1 also showed highest value of diffusion coefficient (3.37×102cm2/sec) and drug loading (86.35 mg/0.2 g gel). The pH of dissolution media is another important parameter that affects rate and extent of drug release. T1 showed a faster release and 100 % cumulative drug release was achieved in 16 h in buffer of pH 7.4. However, at pH 1.2, drug release was less than 25 % even after 24 h dissolution. Equilibrium swelling and extent of drug release was restricted in low pH and on increasing ratio of crosslinker. Formulation T1 showing the rapid but sustained release, was further evaluated in-vivo in rabbits. HEMA-co-IA hydrogels possess well-established biocompatibility profile, therefore was selected for in-vivo evaluation. For this purpose, gel pieces were carefully cut having venlafaxine equivalent to 12 mg. Oral solution of drug containing 12 mg of venlafaxine was used as reference to calculate relative bioavailability. Values of Cmax were 19.11 ng/mL and 11.45 ng/mL for oral solution and oral hydrogel, respectively. Tmax was 180 min and 600 min for oral solution and oral hydrogel, respectively. Mean residence time (MRT) was 272.23 min and 850.33 min for oral solution and oral hydrogel, respectively. AUC extrapolated was 2.1 times greater for oral hydrogel than that of oral solution. 5. Biodegradable Microspheres of Venlafaxine PCL is a hydrophobic, biodegradable, biocompatible and FDA approved polymer. O/O solvent evaporation method was used to prepare microspheres of venlafaxine. PCL and venlafaxine were dissolved in dichloromethane and dropped slowly to 120 mL corn oil containing span 85. The corn oil was stirred continuously at 600 rpm until whole dichloromethane was evaporated. Microparticles were collected by vacuum filtration and oil was removed by washing with n-heptane. No new peak was present in FT-IR spectra of venlafaxine loaded microspheres indicating good compatibility of venlafaxine with PCL. SEM analysis showed the development of smooth and spherical shape microparticles. Thermal analysis of EC and venlafaxine indicated increase in stability of drug loaded microspheres. Particle size of microspheres was increased steadily with increasing contents of PCL. Product yield was greater than 90 % and drug entrapment efficiency increased slightly with increase of PCL. All formulations of biodegradable microspheres showed a burst effect. Burst effect was reduced on increasing amount of PCL. However, more than 49 % of entrapped drug was released in first hour of dissolution experiment. Drug release was accomplished suddenly from P1, P2 and P3. Only P5 formulation was able to extend the release up to 8 h. Drug release from P5 was best explained by Higuchi equation and mechanism of release was Fickian diffusion. 6. Non-biodegradable Microparticles of Venlafaxine Ethyl cellulose is an inert, biocompatible, hydrophobic, non-biodegradable and FDA approved polymer used extensively in development of sustained release formulations. EC, venlafaxine and magnesium stearate were dissolved in methyl acetate. The solution containing polymer and drug was slowly added to 120 mL paraffin oil. Paraffin oil was stirred continuously at 600 rpm. Stirring was continued for 6 h to ensure complete removal of organic solvent. Microparticles of EC were collected on filter paper under vacuum and washed with n-heptane to remove adhered paraffin oil. Washed microparticles were dried and stored in oven at 45 °C. Microparticles prepared in this way were again dispersed in 120 mL paraffin oil. Same polymer was again dissolved in methyl acetate without drug. The polymer solution was again added drop by drop to paraffin oil containing suspended drug loaded microparticles and stirred at 600 rpm. The process took another six h for complete evaporation of methyl acetate. SEM analysis showed the formation of spherical microparticles with slightly rough surface due to second coat. FT-IR analysis of drug loaded microparticles exhibited good compatibility as no new peak was seen in spectra of loaded microparticles. EC microparticles showed good packing and flow properties. The objective for preparation of double layered microparticles (inner core containing drug and outer core of same hydrophobic polymer without drug) was to achieve better control over initial sudden liberation of highly water soluble drug. Burst effect was reduced to 31.78 % in E5 having a thick outer layer without drug compared to 73.34 % from E1 in first hour of release study. However, after initial sudden liberation, E5 maintained a sustained release effect up to 10 hours. All loaded drug was released in 4 h from E1. Second coating of microparticles provides a thick wall and restricts water penetration resulting into reduced burst. Conclusion As a whole, crosslinked polymers showed better sustained release properties than that of microspheres. Therefore, the crosslinked hydrogels having better controlled release potential should be considered suitable oral drug carriers for hydrophilic drugs." xml:lang="en_US
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