مُلاّ جان محمد
افسوس ہے گذشتہ مہینہ ہمارے دومخلص قومی کارکن ملاجان محمدکلکتہ اورمولانا محمد عاقل الٰہ آباد انتقال کرگئے۔ملا صاحب کااصل وطن پشاور تھالیکن عرصہ دراز سے کلکتہ میں آبسے تھے اوراب سچ مچ وہی ان کاوطن تھا۔نہایت پُرجوش،جری اوربیباک انسان تھے۔گذشتہ نصف صدی میں کوئی قومی اور ملی تحریک ایسی نہیں ہے جس میں انہوں نے بڑھ چڑھ کراورولولہ و عزم کے ساتھ حصہ نہ لیا ہو۔ ان کی علمی زندگی کاآغاز تحریک خلافت سے ہوا اوراختتام مجلس مشاورت پر۔کلکتہ میں شاید ہی کوئی مسلم ادارہ(یہاں تک کہ محمڈن اسپورٹنگ کلب بھی) ایسا ہوجس میں ملاصاحب نے نمایاں حصہ نہ لیاہو۔اسی وجہ سے وہ کلکتہ کے لوگوں میں بے حد مقبول تھے۔ بڑے بے غرض،بے لوث اورنہایت سادہ اورمخلص مسلمان تھے۔۱۹۵۰ء میں کلکتہ کے فساد میں لوگوں نے ان کو بچوں کی طرح چیختے اور روتے دیکھا ہے۔ عمر۸۵ سال کے قریب تھی۔ [نومبر ۱۹۷۲]
هدف البحث لتفسير العلاقة القائمة بين تقنية وسائل الاتصال والقطاع الزراعي، ومدى تأثيرها في الإنتاج والإنتاجية الزراعية، بوصفها إحدى التقنيات الحديثة الواجب توفيرها لضمان تحقيق التنمية الزراعية، إذ يؤدي الاتصال الزراعي دوراً كبيراً في التأثير على المجتمع الريفي، فالإعلام الزراعي يحمل مضموناً قيماً يتمثل ببرامجه الإعلامية الزراعية، فهو يهتم عمومًا بتوجيه المعلومات البحثية العلمية والأخبار الزراعية والتوجيهات المؤسساتية، ذات العلاقة بالإنتاج الزراعي والمواد الإعلامية الزراعية، للعاملين في المجال الزراعي. وأهم النتائج تتمثل في أن للاتصالات الحديثة دورًا كبيرًا في التأثير على الإنتاج الزراعي وتطويره، وهو يواجه معوقاتٍ كبيرةً في العراق، تتمثل بضعف استخدام المؤسسات ذات العلاقة لتلك الوسائل، وعدم تحديث برامجها بما يخدم النشاط الزراعي، فضلاً عن عدم توافر أجهزة الحاسوب وخدمة الإنترنت وضعف المعرفة بها من قبل الفلاحين، اما أهم المقترَحات فتمثلت بزيادة التوجه إلى الاهتمام بهذه التقنية وتطويرها، لا سيما في المؤسسات الحكومية ذات العلاقة، وإقامة الندوات وورش عملٍ لتدريب الفلاحين على استخدامها.
The aim of any pharmaceutical dosage form designing is to formulate a product that not only provide the desired therapeutic responses but improve patient satisfaction too. For this purpose, modification in the existing dosage forms has been continued through alteration of additives and the optimization of manufacturing technique to achieve targets. Controlled release (CR) formulations have ability to maintain plasma drug concentration within the therapeutic range for longer duration of time resulting in reduced dosing. The goal of the present study was to prepare once daily valsartan CR 160 mg tablets using swellable hydrophilic and hydrophobic polymers to reduce the fluctuation in plasma level and to sustain steady state over an extended time. Being angiotensin-II receptor blocker, commonly prescribed to manage hypertension. It can also be used in patients of heart failures who cannot tolerate ACE inhibitors or others. Valsartan is commonly prescribed for treatments of left ventricular hypertrophy, isolated systolic hypertension and diabetic nephropathy. Moreover, it is considered an alternative drug to treat myocardial infarction, heart failure, coronary artery disease and systolic dysfunction. In this study different hydrophobic and hydrophilic polymers were utilized to develop valsartan controlled release formulations. They included Methocel® K4M (K4M1-K4M9), K15M (K15M1-K15M9) & K100M (K100M1-K100M9), Ethocel® Standard 7 FP (E7FP1-E7FP9), Kollidon® SR (KSR1- KSR9) and blend of Methocel® K4M & Kollidon® SR (K4M : KSR1-K4M : KSR20). These polymers were used in different concentrations to observe their influence on drug release. Each formulation contained valsartan, rate controlling polymer, Avicel PH 101 and magnesium stearate. Total sixty-five valsartan SR formulations were prepared by CCRD using software Design Expert® (ver. 7.0.). Drug-excipient compatibilities were determined using Fourier transformed-infrared spectroscopy (FT-IR) and no interactions were found between valsartan and various formulation excipients. Powder blend properties (Hausner ratio, compressibility index and angle of repose) and compressed tablets evaluation (weight variation, thickness, hardness and friability) were carried out and found to be satisfactory for formulations of Methocel® K4M (K4M2, K4M3, K4M9), Methocel® K15M (K15M3, K15M6, K15M9), Methocel® K100M (K100M2, K100M3, K100M5, K100M9), Ethocel® Standard 7 FP Premium (E7FP2, E7FP3, E7FP9), Kollidon® SR (KSR2, KSR3, KSR9) and blend of Methocel® K4M & Kollidon® SR formulations (K4M : KSR1, K4M : KSR2, K4M : KSR5, K4M : KSR11, K4M : KSR12, K4M : KSR18 and K4M : KSR20). All trial valsartan formulations were assayed using a validated spectrophotometric and HPLC methods at wavelength of 250 and 264 nm respectively. Assay results of all formulations were found within the official range of 95-105 %. In vitro dissolution of developed formulations were performed in different dissolution media including HCl pH 1.2, phosphate buffer pH 4.5 and 6.8. Desirable drug release profile was achieved by K4M9 formulation (25 % Methocel® K4M) which showed 23 %, 82 % and 100.16 % drug release in 4, 16 and 24 hrs respectively. Higher viscosity grades of Methocel® K15M (K15M3, K15M6 & K15M9) and K100M (K100M2, K100M3, K100M5 & K100M9) excessively sustained the release of valsartan. Excessive control on drug release was exhibited by hydrophobic Ethocel® based formulations (E7FP3 & E7FP9) at various concentrations not showing compliance with the criteria of CR formulation. Although KSR2 and KSR9 formulations of Kollidon® SR (25 % & 32 %) exhibited acceptable drug release (94 to 99 %) profile but having comparatively shorter shelf life in comparison to optimized K4M9 formulation. Excessive retardation in drug release was observed in valsartan CR formulations containing blend of Methocel® K4M & Kollidon® SR at various concentrations. Drug release kinetics of valsartan controlled release tablets were analyzed in various dissolution media using different mathematical models like first order, zero order, Hixon-Crowell, Higuchi, Weibull, Bakers-Lonsdale and Korsmeyer designs. DDSolver® Microsoft Excel based software was used to calculate the regression coefficients and release constants. Among all Methocel® valsartan controlled release formulations, K4M9 indicated higher linearity values for zero order, Korsmeyer-Peppas and Weibull kinetics at pH 1.2, 4.5 & 6.8. Non Fickian or anomalous diffusion release (n > 0.45) was observed showing erosion and diffusion of drug in controlled manner. β value of Weibull model was greater than 1, presenting sigmoid curve which indicated initial slower release followed by a rapid drug liberation. K4M2, K4M3 & KSR2 trial formulations exhibited higher similarity factor (f2) against K4M9 formulation, which was taken as reference due to the best physicochemical characteristics and controlled release profile. Response surface methodology was utilized to demonstrate the effect of independent variables (Polymer and Avicel PH 101 concentrations) on the responses (release of drug at 2, 8 and 16 h). Quadratic model analysis and P-value of coefficients showed strong influence of polymer on responses as compared to Avicel PH 101. Stability of controlled release formulations (K4M2, K4M3, K4M9, E7FP3, E7FP9, KSR2, KSR9 and K4M : KSR11) with desired drug release profiles were evaluated as per ICH guidelines. Samples were analyzed at long term (25±2 oC / 60±5 % RH) and accelerated (40±2 °C / 75±5 % RH) conditions. Swelling behavior of formulations containing Kollidon® SR and Methocel® K4M was also assessed. Results showed Methocel® polymer had the highest hydration ability as compared to Kollidon® SR. Methocel® and Kollidon® SR based valsartan formulations presented variable buoyancy times (< 15 h) without using any gas generating ingredients. With reference to buoyancy values, HPMC (K4M) polymers containing formulations displayed good floating lag time. Formulation K4M9 was selected as the most optimized formulation on the basis of physicochemical characteristics, desired drug release profile and zero order release kinetics among all the other formulations. Reproducibility of the complete adopted methodology was analyzed by preparing three separate lots of the optimized formulation K4M9. In vitro testing was repeated in all dissolution media and the f2 values confirmed the robustness and reproducibility of the developed formulation. A modified and validated HPLC technique was employed for the assessment of valsartan in human plasma. HPLC (LC-20A, Shimadzu, Kyoto, Japan) consisting of auto-sampler SIL-20A, column oven CTO-20A and PDA detector SPDM-20A equipped with Zorbax SB-C18 column (5 μm, 4.6 mm × 15 cm) adjusted at 40 °C was used to obtain chromatographic separation. LC solution software was used for chromatogram generation and data analysis. Mobile phase containing acetonitrile, water and glacial acetic acid in the ratio of 40 : 59 : 1 (pH 2.9) was pumped to the column with a flow rate of 1 mL/min. Each sample of valsartan was eluted at 4.1±0.2 min with a total run time of 8 min. Assay of valsartan was performed after extraction of drug with acetonitrile from plasma using precipitation method. In vivo pharmacokinetics and bioavailability studies of optimized (K4M9) controlled release valsartan tablet (160 mg) against reference immediate release (IR) brand (Diovan®) of same dose were carried out in local healthy subjects. Comparative bioavailability study of valsartan controlled release tablet with immediate release tablets was performed due to unavailability of controlled release brand in commercial market. Following FDA guidelines a single dose, open label, two treatments, two period, cross over pharmacokinetic study was conducted, comprising of twelve healthy young male subjects. The study protocol was approved by Institutional Bioethics Committee, (IBC) University of Karachi. Compartmental and non-compartmental parameters of valsartan controlled release formulations were computed by Kinetica® (version 5.1) software. Significant difference (P < 0.05) was observed between pharmacokinetics of test and reference tablets. The Cmax and Tmax of the commercial brand and the trial product (K4M9) were found to be 3.062±0.008 μg/mL, 2.396±0.016 μg/mL and 2.597±0.013 h, 5.844±0.027 h respectively. Considerable change in AUC0-t was also observed between reference (23.668±0.330 μg/mL.h) and K4M9 (50.723±0.414 μg/mL.h). The mean residence time of the currently developed formulation was found to be two folds greater than the reference IR tablets. Similarly, the T1/2Kel values of reference immediate release (Diovan®) vs. test controlled release (K4M9) were estimated as 6.023±0.473 h and 11.188±0.720 h respectively. This work focused on the designing of a quality pharmaceutical product with simple, cost effective methodology that could be beneficial for pharmaceutical industries. The findings of the current study will be helpful in the development of the controlled release valsartan tablets by direct compression method using different polymers. The pharmacokinetic evaluation of the newly designed formulation in healthy human subjects assured the steady drug plasma profile in biological system. Therefore, valsartan CR tablets will overcome the drawbacks associated with the conventional immediate release therapy resulting in better patient compliance and drug adherence." xml:lang="en_US