Bilayer tablet formulations containing immediate release layer and sustained release layer has gained substantial attention among researchers and in pharmaceutical industries. Bilayer tablets have various advantages in contrast to conventional tablets and can surmount the limitation observed in single layer tablet. Cardiovascular diseases extensively cover hypertension and ischemic heart diseases that requires blood pressure monitoring. High blood pressure is one of the biggest contributors of global death. Furthermore, high serum cholesterol and elevated low density lipoprotein are important risk factor associated with cardiovascular disease. Combination formulations of anti-hyper-lipidemic agents and antihypertensive agents minimized various hypertensive symptoms of hyper-lipidemic patients. It has been reported that two or more drug given in combined form has been found to be more effective in multiple therapies than single drug and provides patient compliance. In some cases, combination drugs are available as single pill proving to be less expensive and convenient in long term treatment and saves person time and effort in their daily routine. The objective of the present study is to develop bilayer tablet of sustained release layer of nicorandil 80 mg and immediate release layer of atorvastatin 20 mg using double compression technique. Sustained release nicorandil formulations were developed and optimized by direct compression method using different hydrophilic and hydrophobic polymers. Nicorandil is a novel compound associated with the class of potassium channel activators employed for the management of cardio vascular ailments such as hypertension and angina pectoris. Nicorandil has a short half-life and the usual oral dosage regimen is 5 to 40 mg taken 2 to 4 times a day. Pharmaceutical literature reviews has repeatedly emphasized therapeutic and pharmacological benefits of controlled release dosage forms of compounds with short half-lives. One of challenge to researcher is to develop highly water soluble drug sustained release dosage form which can release constantly at a definite rate. Successful treatment of cardiovascular diseases can be accomplished through blood pressure maintenance at a normal physiological level that requires steady and consistent supply of drug. Recurrent dose administration at intermission of 6 to 8 hours is problematic for a hypertensive patient or a patient with angina, ultimately leads to patient nonconformity. Nicorandil with all evident advantages proved to be a suitable candidate for development of a controlled-release dosage form because of relatively small daily dose, short half-life and rapid absorption from the GIT. Therefore, once daily nicorandil sustained release formulation is needed that requires drug to be released constantly throughout twenty four hour period. Atorvastatin calcium is a BCS class II drug used as a lipid lowering agent. In the present study, nine different immediate release atorvastatin formulations was developed using central composite design. Formulations were prepared through incorporation of superdisintegrant crospovidone along with sodium carbonate as an alkalizer that can facilitates drug solubility and hence drug dissolution. Nicorandil sustained release formulations were developed through direct compression method. Central composite design was used for developing nine different formulations using different hydrophilic and hydrophobic polymers combination. Formulations F1-F9 comprised of polyox and ethyl cellulose polymer combination. Formulations F10-F18 consisted of HPMC K100M and eudragit® and F19-F27 formulations included HPMC K100M and ethyl cellulose as hydrophilic and hydrophobic polymers. Response surface graphs were plotted with design expert® software version 7.0.0 to assess the effect of different polymer combination in formulation on dependent variables such as disintegration and dissolution at 2 hours and 12 hours. Pre-compressional and post compressional pharmacopoeial and non-pharmacopoeial test parameters were applied to ensure compressed tablets quality. Micromeritic evaluation, FT-IR studies and blending time was determined. Micromeritic results showed that powder blends complying the B.P standard categorization of passable to excellent were selected for formulation development by direct compression method. FT-IR studies were also performed and nicorandil showed no interaction. Blending time was found to be 9 minutes. Formulation F3, F6, F9, F11, F17, F18, F20, F26 and F27 formulations showed better results among their respective formulations. Drug content was found to be within pharmacopoeial limit as determined by developed and validated method. Swelling studies for all the nicorandil sustained release formulations were determined and it was found that formulation that contained less percentage of HPMC as demonstrated by F14 containing HPMC-eudragit® combination and F21 and F23 formulations that composed of HPMC-EC combination swelled less. Dissolution profile was studied in phosphate buffer at pH 4.5, pH 6.8 and 0.1 N HCl (pH 1.2). An efficient sustained release formulation preferably must release drug content at determined time period to attain desired level in plasma. Theoretical release profile determination is one of the important aspects to ascertain release at a definite rate in a reproducible manner. The dissolution study of formulation F18 and F20 showed sustained-release pattern was comparable to theoretical release profile. DDSolver® excel based Add in program was used for the application of model dependent and independent approach to the dissolution profile. Formulation F20 was considered as reference owing to its best physicochemical attributes. All the formulations were found similar to formulation F20 except formulations F1, F5, F7, F10, F14 and F25 were found dissimilar in contrast with formulation F20. The sustained release nicorandil formulations showed release kinetics that was best fitted for Higuchi model for all sustained release nicorandil formulations. For the confirmation of release mechanism, the dissolution profile was fitted to Korsmeyer equation. The regression values indicated that drug release followed anomalous drug release kinetics among all formulations. The selected formulations were subjected to long term stability testing at 25°C/60% RH for duration of 12 months and accelerated studies at 40°C/75% RH for duration of 6 months according to ICH guidelines. Selected formulations physicochemical attributes were determined for the determination of most stable formulation. Long term stability results showed F6, F18 and F20 represent a shelf life of 17.85, 17.56 and 17.4 months using Minitab®17.1.0 software and accelerated stability studies showed good pharmaco-technical attributes and proved as the best designed formulation having shelf life of 12.05 months, 13.164 months and 13.776 months respectively. Therefore, formulation F18 and F20 can be considered as most stable and optimized formulation. Immediate release atorvastatin formulation development through central composite design using crospovidone (1.37-5%), sodium carbonate (1.58-4.41%) along with magnesium stearate 2% and avicel was added to attain a tablet average weight of 150 mg. Micromeritic evaluation, FT-IR studies and blending time were carried out. Physicochemical attributes of the developed formulation were determined as per pharmacopoeial standard that includes tablet hardness, weight variation, disintegration, diameter variation, friability and assay. All formulation had a disintegration time of less than 1 minute. Formulation A7 failed hardness test. Dissolution profile study was performed on pH 1.2 and phosphate buffer at pH 4.5 and pH 6.8. DDsolver® excel based Add in program was used for the application of model dependent and independent approach to the dissolution profile. It was found that formulation A6, A8 failed f2 test in pH 1.2 while A2 failed f2 test in all pH. Formulations A1, A3, A5, A7 and A9 were found similar to market innovator brand M1 in all pH. The lowest mean dissolution time (MDT) values were shown by formulation A1and A3 and A9 owing to the presence of higher proportion of superdisintegrant. Furthermore, those formulations containing lesser proportion of superdisintegrant corresponds to higher MDT values as is the case of A2 formulation. % DE was applied to all immediate release atorvastatin formulation and it was found that A2 and A6 did not comply %D.E test in pH 1.2 while all formulations were considered equivalent to innovator brands as difference of dissolution efficiency is within desired limit. Model dependent studies result showed that the dissolution release followed First order and Weibull model kinetics. The long term and accelerated study were carried out as per ICH guide lines. Different physicochemical parameters such as friability test, disintegration test, % drug release, hardness test and % assay for selected atorvastatin immediate release formulations was determined according to pharmacopoeial standards. The shelf life of selected formulations when subjected to long term stability was in the range from 20-23 months using Minitab®17.1.0 software. The estimated shelf life of selected formulations A1, A3, A5 and A9 after accelerated studies was in the range from 15 - 23 months. A9 was considered to be most stable formulation among selected formulation owing to longer shelf life. Bilayer tablet of nicorandil and atorvastatin was developed from the optimized formulation of sustained release nicorandil (F18 and F20) and immediate release atorvastatin (A9) formulations. Therefore, two bilayer tablets were formulated, B1 formulation contained immediate release layer of atorvastatin (A9) and sustained release nicorandil layer (F18) and B2 bilayer tablet was prepared with immediate release atorvastatin layer (A9) and sustained release nicorandil layer (F20). Both of the optimized formulations powder containing API and excipients were blended separately and their bilayer tablets were prepared through double compression technique. Assessment of physicochemical attributes of bilayer tablet was determined using pharmacopoeial standards. Accelerated stability studies on the developed formulation was performed and the study result revealed that formulation B1 and B2 complied with all standard requirement but formulation B2 was preferred from economic point of view. In present research a reproducible, robust, simple high performance liquid chromatographic method was developed for assessment of nicorandil and atorvastatin in bulk and combined dosage form utilizing Waters Spherisorb® column (4.6×200 mm, 10 μm ODS), acetonitrile: phosphate buffer (pH 4.5) in proportion of 55:45 as a mobile phase with flow rate of 1ml/min and discreet peaks were identified using UV–VIS detector at 262 nm. Method validation encompasses parameter such as specificity, system suitability, linearity, accuracy, precision, limit of detection and limit of quantification were determined. The calibration curves for nicorandil and atorvastatin demonstrated an excellent linearity with R2 = 0.9999 in range of 0.3125-80 μg/ml and 0.156-80 μg/ml respectively. The developed and validated method showed satisfactory accuracy and precision characteristics. The developed method short run time (7 minutes) with the with the with the with the with the with the retention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minutretention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minutretention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minutretention time of approximately 3 minutretention time of approximately 3 minut retention time of approximately 3 minut retention time of approximately 3 minut es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and es (mean ± SD=3.047 0.119) for nicorandil and 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin 5.37 minutes (mean ± SD=5.373 0.209) for atorvastatin and less injection volume (20 μl) enables the method‘s successful utilization in QA/QC laboratories. The pharmaceutical equivalence of different nicorandil and atorvastatin tablets available locally were purchased from local store of Karachi. Brand A was considered as innovator brand for nicorandil and M1 was selected as reference brand for atorvastatin due to its excellent physicochemical attributes as per pharmacopoeial standard. Quality attributes such as diameter, hardness, thickness, weight variation and friability were analyzed as per pharmacopoeial standard. Marketed brands showed acceptable result as per pharmacopoeial standard. Dissolution profile was studied at 0.1 N HCl (pH 1.2), phosphate buffer at pH 4.5 and pH 6.8. Model dependent and independent method was carried out using DDSolver® excel based add in program for analysis for dissolution profile. In case of nicorandil, all brands except brand D passed f1, f2 test and %D.E was within acceptable limit of ±10% in all three dissolution medium while in case of atorvastatin M5 and M6 passed f1, f2 test and their difference in %D.E was within ±10% in all three FDA recommended dissolution medium. Nicorandil and atorvastatin release kinetics followed First order release kinetics. Hence, only brand D from nicorandil brands does not complied with pharmaceutical quality test while M5 and M6 atorvastatin brands was found to pharmaceutically equivalent to innovator brand and can be used interchangeably." xml:lang="en_US
شاعری کے لیے کچھ نہیں کرنا پڑتا یہ کھڑے کھڑے ہو جاتی ہے۔ بعض اوقات تو سوئے سوئے بھی سر زد ہو جاتی ہے کہ اس کا تعلق آمد سے ہے جس کے لیے جامد ہونے کی قطعاً ضرورت نہیں۔ لیکن نثر کا معاملہ الگ ہے۔ اس کے لیے باقاعدہ اکڑوں ہو کے بیٹھنا پڑتا ہے۔ یعنی یہ وہ ریاضت ہے جو حالت رکوع میں کی جاتی ہے۔
نثری اصناف میں سفر نامہ تو اور بھی جوکھم کا کام ہے کہ اس کی طلب میں سفر بھی کرنا پڑتا ہے جو بسا اوقات انگریزی کا Suffer ثابت ہوتا ہے۔ گویا یہ ادب کی ایسی صنفِ گراں بار ہے جس کو صنفِ نازک کی طرح قابو کرنا آسان نہیں ہوتا۔ اس کے حصول کے لیے شدید مارا ماری اور بے تحاشا جتن کرنے پڑتے ہیں۔ پہلے سفر کرنے کا سلیقہ اور پھر اسے بیان کرنے کا قرینہ ہونا چاہیے۔
ہمارے دوست ڈاکٹر یوسف میر کی محبت کہ ڈاکٹر الطاف یوسف زئی کا مصری سفر نامہ ارسال کیا۔ مشاہدہ عام ہے کہ یوسف نام کے لوگ خوب صورت ہوتے ہیں۔ پھر بندہ ذات کا بھی یوسف زئی ہو اور مصر سے محبت نہ ہو یہ کیسے ممکن ہے۔ پس یہ طے ہے کہ یہ سفر نامہ سراسر فطری محبت کا شاخسانہ ہے۔ اگر یقین نہ آئے تو پڑھ کر دیکھ لیجیے۔
کچھ سفر نامے تو محض سفر کی صعوبت برادشت کرنے کی خاطر لکھے جاتے ہیں جن کے پڑھنے سے قاری کو بھی شدید تھکاوٹ ہوتی ہے۔ اس قبیل کے سفر نامے یوں شروع ہوتے ہیں۔
Human is the combination of body and spirit, Islām pays attention to the balanced growth and construction of the human personality considering the health of both body and spirit. As Muslims, we believe that Islām is the perfect code of life, which provides guidance for the solutions of all individual and collective problems of human beings. Therefore, we believe that Islām has a complete system of instructions for the development and reformation of spirit on the one hand, and, on the other hand, it has prescribed guidelines for the upkeeping and maintenance of the body. Reproductive and sexual health is one of the major problems of human beings. Eastern societies are comparatively shy to discuss this problem, unless necessary, while the western societies have introduced sex education in their schools to teenagers. We being Muslims tend to look towards our religion to guide us in such a way, that it may educate us, on the one hand, and on the other, it may guide us to adopt the required attitude to avoid the negativity of its awareness. Although the issue of reproductive health is considered as the specialty of the modern age, however, Islamic instructions very obviously discuss them from the beginning. In this article, the author has explored and elaborated Islamic teachings regarding the reproductive health and sexual instructions and discussed them in order to prove that Islām has the full capacity to solve the current social problems of reproductive health and sexual health.
The enormous and unprecedented spread of English has made it difficult for the so- called ‘Native Speakers of English’ to exercise their control over it. The non-native varieties of English are establishing their niche alongside the standard varieties of English. A paradigm shift can be noticed from ‘EFL, ESL, ENL’ to EIL paradigm. The non-native varieties of English have initiated their codification and description. In this scenario, this research studies Pakistani English as a non-native institutionalized variety and aims at identifying various features of it. The lexico-grammatical features of noun phrase in Pakistani English have been explored from six aspects. A corpus of written Pakistani English (PWE), 2.1 million words, has been compiled as a research tool. PWE comprises 29 text categories to enhance the representativeness of the corpus. PWE has been used to identify the features on the basis of actual instances or corpus evidence. BoE, BNC, Brown, Frown, LOB, and FLOB corpora have been used as reference corpora. This investigation is mainly a corpus driven research and the components of this research are based on corpus evidence observed during the study. One inference can be drawn from all the components of the present research that the differences between Pakistani English and the Standard varieties of English are not so wide as to create any serious problems in mutual intelligibility. But the differences seem wider than those between the British and American Englishes. The chapter 1 introduces the research and chapter 2 explores the theoretical undercurrents related to World Englishes and Pakistani English. It discusses the spread of English and the emergence of non-native varieties, conflicting standards among varieties, role of English in non-native context, the impact of pluricintricity, language policy and which model Pakistani English should follow etc. Chapter 3 is the survey of literature and links the present research with the research already done in the areas of Pakistani English, corpus linguistics, collocations, lexico-grammar, and noun phrase. Chapter 4 discusses the steps taken in the compilation of the corpus and introduces the corpus (PWE). Methodological framework has been kept separate from methodology. Chapter 5 describes the methodological framework of the research and explores the paradigm this research is II aligned with. Due to the complex methodology of the six components of the research, the methodology (a guide for the replication of the research) has been discussed in each component of the noun phrase before analysis in Chapter 6. The sixth chapter comprises six components of research and presents their analysis. The first component deals with mechanics i.e. hyphenated compounds in PWE, and highlights the differences from BNC and also addresses the importance of such issues in the context of Non-native varieties of English. The second component, Urduization, is the study of Urdu words in PWE and tabulates the data in various domains to show how Pakistani English as a non-native variety of English is bound in socio-cultural make up of the community. The third component, Noun Noun Compounds explores nine trends in the noun compounds and reveals hundreds of examples to identify trends in PWE. The fourth component, Modifying Adjectives, uses Yibin Ni’s (2004) model to explore lexico- grammatical and semantic categories of the modifying adjectives of 50 nouns selected on the basis of frequency and detailed consistency. The quantitative differences of this component have been further explored in the fifth component of the research. The same 50 nouns have been used as nodes of concordance lines to study the 1R and 1L collocates. These collocates have been grouped into lexical fields. The results of this component loudly pronounce that the real differences between Pakistani English and other varieties of English are mainly of collocations. One hundred nouns in PWE, which have been identified as vocabulary differences between British and American Englishes by Davies (2005), have been studied in the final component of the research. Chapter 7 concludes the research and shares some observations I made during the research. Chapter 8 is forward looking and introduces various researchable areas the present research has identified. In the light of the detailed discussion on theoretical undercurrents, it can be assumed that the results obtained in the data analysis are significant for description of Pakistani English and establishing the status of Pakistani English. Moreover, the results are insightful in ELT because they can show the difference between what is taught and what is being used. The information obtained as the results of the data analysis can be used in lexicographical activities. A supplement can be added to the already existing dictionaries.