سید ابوالنظر رضوی
افسوس ہے ہمارے حمیم صمیم سید ابو النظر رضوی کا۸/اپریل کوکراچی میں انتقال ہوگیا۔موصوف امروہہ ضلع مراد آباد کے شرفا اورنامور رؤسا میں سے تھے، بلا کے ذہین اور طباع تھے۔درس نظامی کا بڑا حصہ مدرسہ امدادیہ مرادآباد میں پڑھا تھااورپھر آخر میں ایک سال دارالعلوم دیوبند میں رہ کر تکمیل کی تھی۔اردو کے صاحب طرزانشاء پرداز اورادیب تھے۔طبیعت میں روانی غضب کی تھی۔تقسیم سے پہلے برہان میں اُن کے مقالات اکثر نکلتے رہتے تھے۔اس کے علاوہ دوسرے ادبی اورعلمی رسالے بھی مرحوم کے مضامین فخر سے شایع کرتے تھے۔ ۱۹۴۸ء میں یکایک اپنی تمام جائیدادواملاک چھوڑ چھاڑ کرکرا چی چل دیے۔بڑی تمناؤں اورآرزؤں کولے کر گئے تھے لیکن ایک بھی پوری نہیں ہوئی اورہزاروں روپیہ ماہوار کاخرچ رکھنے والا وہاں عسرت وتنگدستی کاشکارہوکر رہنے لگا۔ان پیہم ناکامیوں اورمایوسیوں کانتیجہ یہ ہواکہ تپ دق میں مبتلا ہوگئے۔مرنے سے چندماہ پہلے ایک خط میں کس حسرت سے لکھتے ہیں:’’قدرت کے کارخانے بھی عجیب ہیں۔ جب میرے پاس ریاست تھی،دولت تھی اورطاقت تھی اس وقت مجھ کویہ موذی مرض نہ دیاکہ میں اس کامقابلہ کرسکتا تھا، اب اس غریب الوطنی اورتنگدستی میں مجھ کو اس بیماری میں مبتلا کرکے سوائے اس کے کہ قدرت’’گربہ و موش‘‘ کا تماشا دکھانا چاہے اورکیا فائدہ ہے؟‘‘
بعض خاص اسباب کی بناپر مذہبی خیالات میں عدم توازن پیداہوگیا تھا اور قرآن مجید میں بعض عجیب طرح کی تاویلات و توجیہات کرنے لگے تھے۔ یوں نہایت شریف، بامروت،دوست نواز،بے حد خلیق اورملنسار تھے۔مہماں نوازی بڑی عالی ظرفی سے کرتے تھے۔ اﷲ تعالیٰ اُن کی لغزشوں اورغلطیوں سے درگزر فرماکر ان کو مغفرت وبخشش کی نعمت سے نوازے۔آمین [مئی۱۹۵۶ء]
Background: Hypertension is a growing medical and public health issue. The United States and European treatment guidelines have been issued to attain smooth control of hypertension in various categories of patients. It is a need of time to unveil safe combination therapies in various populations. Objectives: (i) To determine the efficacy of valsartan and hydrochlorothiazide versus valsartan and amlodipine (ii) To determine the safety and tolerability of both combinations. Materials & Methods: This experimental study was conducted at Shalamar Hospital Lahore. 126 patients with stage 2 hypertension were recruited from the medical outdoor of Shalamar Hospital Lahore after getting informed consent. In group A, 63 patients were given valsartan and hydrochlorothiazide. In group B, 63 patients were given valsartan and amlodipine. Blood pressure (BP) of both study groups was recorded on day zero, 2nd, 4th, and 8th weeks and the readings were entered on a Proforma. The efficacy of drug combinations was accessed in both groups by recording the change in mean systolic blood pressure (MSBP) and mean diastolic blood pressure (MDBP). The safety and tolerability of the drug combinations were assessed in terms of side effects and laboratory findings. Results: In group A, there was a 39±7mmzHg and 18±1mmHg decrease in MSBP and MDBP, respectively, from baseline BP. In group B, there was a 26.7±4mmHg and 14±2 mmHg decrease in MSBP and MDBP, respectively, from baseline BP. Both combinations were safe, and no significant difference in the efficacy of both combinations was observed after 8-week of treatment. Conclusion: Both combinations are effective for control of BP, but the valsartan and hydrochlorothiazide combination (group A) appears to have better tolerability and greater effect in decreasing BP as compared to the combination of valsartan and amlodipine (group B), although this difference is not statistically significant.
Oral drug delivery system is the most preferred route of drug administration due to ease of administration; handling, longer shelf-life compared with the other dosage form and cost effectiveness. The drug release from the Fast Dispersible Tablets is rapid compared with the conventional tablets. These tablets can be grouped as; I) Orally Disintegrating Tablets 2) Effervescent Tablets. Prokinetic drugs enhance gastric emptying, prevent reflux of gastric content and relieve the symptoms of dyspepsia. Prokinetic drugs are commonly used for treatment of various GIT diseases like Gastro Esophageal Relux Disease, Functional Dyspepsia and Diabetic Gastroparisis and for control of emesis of varyying etiology. Prokinetic drugs have motility enhancing effect on upper part of GIT, whereas no clinically significant effects on motility of large intestine have been reported. While taking prokinetic drugs, dose of drugs with inhibitory effects on GIT motility should be reduced without increasing dose of prokinetic drugs as higher doses bear the risk of iatrogenic inhibition of gastric motility. In the present study, Orally Disintegrating Tablets and Effervescent Tablets of Domperidone and Itopride HCl, prokinetic drugs, were formulated and evaluated. The project was accompolished in three steps; i. Pre formulation studies ii. Development of formulations iii. Evaluation of the formulations. Pre formulation studies included drug excipients compatibility study, characterization of drug and excipients as per SeDeM and SeDeM-ODT experts system and development of method of UV-Visible Spectrophotometric and RP-HPLC methods analysis for Domperidone and Itopride HCl. Binary mixture approach was applied for drug excipients compatibility study using 1g of each material. Samples were prepared in 1:1 with and without moisture and subjected to stress conditions (75 ± 5% R.H and 45 ± 2 o C) for 90 days. Each sample was evaluated for drug content (using HPLC method of analysis), physical state and FTIR spectra. Suitability of the both APIs and excipients for preparation of fast dispersible tablets by direct compression was determined on the basis of SeDeM/SeDeM-ODT profile. Basic parameters were determined for each powder according to the official and reported methods. Experimental values were converted to “r” values by applying specific factors and Index of Good Compressibility and Bucco dispersibility (IGCB) was calculated according to SeDeM-ODT experts system. Two types of methods analysis (UV Visible Spectrophotometric method and HPLC method) were developed and validated for each drug. HPLC method of analysis was developed for simultaneous determination of domperidone and itopride HCl using water and acetonitrile (65:35) as mobile phase. pH of the water was adjusted to 3.00 with O-phosphoric acid and Tenofavir was used as internal standard. The taste of Itopride HCl is bitter and prior to formulation as Fast Dispersible Tablets taste of the drug was masked using different excipients (Eudragit, HPMC, PVP, PEG and Cetostearyl alcohol). Taste masking was carried out by granulation technique, solid dispersion technique and micro encapsulation technique. Orally disintegrating tablets were prepared by direct compression by using super disintegrants and sublimation method. Cross carmellose sodium and sodium starch glycolate were used as disintegrant alone and in combination with starch maize. Menthol and ammonium bicarbonate were used in different concentrations as sublimating agents and heat was applied for sublimation. ODTs of domperidone were compressed on 10.00 mm oval shallow concave punches by adjusting the compression weight to 200 mg. Taste masked ODTs of itoprideHCl were compressed on 10.50 mm round shallow concave punches (compression weight was 350 mg). Effervescent tablets of both drugs (Domperidone and Itopride HCl) were compressed on 13.00 mm round flat punches under compression weight of 650 mg. Prior to compression bulk density, tapped density, Carr’s index, Hausner ratio, angle of repose and flow ability of powder blends for all the formulations were evaluated. Tablets were subjected to in-vitro and in-vivo evaluation. In-vitro evaluation included determination of the physical characteristics; mechanical strength, disintegration behavior and in-vitro drug release. In-vivo evaluation comprised of preclinical evaluation (pharmacokinetic evaluation) and clinical evaluation. The in-vivo drug release and pharmacokinetics were studied in healthy male rabbits and clinical evaluation was carried out in patients taking anti cancer chemotherapy. Clinical evaluation was carried out in the hospital under the supervision of the physician following the approval from the Health Regulatory Authorities and Hospital Ethical Committee. UV visible spectrophotometric method of analysis was accurate and specific for both drugs (Domperidone and Itopride HCl). Methods of analysis were quiet linear for both drugs, having R 2 values of 0.998 for domperidone and 0.999 for itopride HCl. Regression equations were 0.039 x + 0.051 and 0.068 x + 0.0168 for domperidone and itopride HCl, respectively. HPLC-UV method of analysis for simultaneous determination of domperidone and itopride HCl using tinofavir as internal standard was developed and validated. The method had LLOQ values of 10 ng/ml and 15 ng/ml for domperidone and itopride HCl, respectively. The method was applied for drug excipients compatibility study and in-vivo analysis of both drugs. The excipients intended to be used in formulation of Fast Dispersible Tablets were found compatible with both drugs. Drug content, physical consistency and FTIR spectra of all the samples remained un-affected by exposure to stress conditions (45 ± 5 o C and 75 ± 5% R.H) for 90 days. On the basis of SeDeM experts system, both the APIs were found deficient in most of parameters required for direct compression. Taste masking of itopride HCl improved most of the parameters, making it suitable for direct compression. Microcrystalline cellulose and Tablettose- 80 were used as diluents in combination. In combination both the excipients resulted in a diluents system with all the characteristics required for direct compression. Itopride HCl is a bitter tasting drug with taste threshold of 80μg/ml. Different excipients and methods were used for the taste masking of the itopride HCl, however the best results were obtained using HPMC processed by granulation technique. Drug release was retarded below its taste threshold in 1:3 (drug to polymer ratio). Granulation technique was rapid and simple technique of taste masking without any advanced machinery involvement. At pre-compression level, all formulations exhibited good rheological characteristics; the angle of repose, flow ability, Hausner ratio and Carr’s index were found within the range of better flow for all the formulations. Orally disintegrating tablets with better mechanical strength and rapid disintegration were obtained by sublimation technique and using super disintegrants. Compared with the sublimation technique, mechanical strength of the tablets prepared using super disintegrants was higher. Higher peak plasma concentration was achieved with both types of Fast Dispersible Tablets (ODTs and Effervescent Tablets) in rabbits compared to conventional tablets. Rate of absorption was higher with both the fast dispersible tablets as T max was achieved very quickly. The clinical evaluation showed the effective control of the emesis by ODTs in patients undergoing chemotherapy compared with the conventional tablets and better patient compliance. Almost all the patients enrolled in the study preferred to take ODTs in comparison with the conventional tablets due to ease of administration, better taste and mouth feel. The present studies showed the good mechanical strength and drug release behavior of the ODTs. The in-vivo drug release and pharmacokinetic data in the rabbits also support the appropriate drug release from the ODTs. The better patient’s compliance and control of the emesis by the ODTs compared with the conventional tablets showed that the ODTs can play an effective role in the control of emesis." xml:lang="en_US