Home > Preparation, Characterization, in Silico Modelling and Bioavailability of Nanosuspention for Poorly Water Soluble Drugs Dexibuprofen and Domperidone
Preparation, Characterization, in Silico Modelling and Bioavailability of Nanosuspention for Poorly Water Soluble Drugs Dexibuprofen and Domperidone
The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) and domperidone nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method (APSP). Combinations of Hydroxypropyl methyl cellulose-Polyvinyl pyrrolidone and Hydroxypropyl methyl cellulose-Eudragit were shown to be very effective in producing stable dexi-nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179± 0.01, 0.182± 0.02 respectively. Produced nanocrystals of DOMP and Ethucel combination, the average particle size and polydespersity index were found to be approximately 130.00 ± 3.0 nm, 0.15 ± 0.01, moreover, the combination of hydroxyl propyl methyl cellulose and polyvinyl alcohol also found very affective to produce DOMP nanocrystals with small particle size (200.0 ±3.5nm) and PDI (0.2±0.02). The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2-8°C and 25°C were more stable than those at 40°C. The maximum recovery of dexi-nanocrystals was observed from the formulations using the combination of Hydroxypropyl methylcellulose- Polyvinyl pyrrolidone and Hydroxy propyl methyl cellulose- Eudragit, which equated to98% and 94% of the nominal active drug content respectively. In case of DOMP nanosuspensions stored at 2-8 ºC and room temperature (25 ºC) exhibited higher stability compared to the samples stored at 40 ºC. Crystallinity of the processed and unprocessed dexi and DOMP particles was confirmed using Differential Scanning Calorimetry, Powdered X-ray Diffraction and Transmission Electron Microscope. FTIR studies for both Dexi and DOMP nanocrystals confirmed that the process did not affect chemical integrity of DOMP. The DOMP nanoparticles exhibited significantly enhanced dissolution rate (P<0.05) compared to the raw counterpart. The saturation solubility of the ix dexinanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw dexi in water (51.0± 2.0μg/mL) and stabilizer solution (92.0 ± 3.0 μg/mL). Enhanced dissolution rate (P<0.05) was observed for the dexi-nanocrystals compared to the unprocessed drug substance and marketed tablets. The saturation solubility of the DOMP nanocrystals was significantly increased to 2700.0± 3.5 µg/mL compared to the raw dexi in water (952.0± 2.0μg/mL) and stabiliser solutions which include HPMC (1253.0± 3.5) and HPMC-PVA (1133.0 ± 3.5 µg/ml). DOMP nanocrystals resulted in enhanced dissolution rate (P<0.05) compared to the unprocessed drug substance. Molecular Modeling studies underpinned and substantiated the experimental studies, including the impact of polymers on nanoparticle sizes, nanocrystals recovery and stability studies of the produced dexinanocrystals. The highest potential was shown by combination ofHPMC-PVP- Dexi (-4.7) and HPMC EUD- DEXi (-4.6) . In case of DOMP, Molecular Modelling studies underpinned the molecular level understanding of the DOMP-Polymer nanocrystal interaction and substantiated the experimental studies, including the impact of polymers on nanocrystals sizes, and stability studies of the produced DOMP nanocrystals. Ethocel as single polymer showed highest binding potential (-27.26±0.24 ) for DOMP nanocrystals and HPMC-PVA was found the best dimer to effectively bind (-25.22 ± 0.79) with the nanocrystals with subsequent small particle size and high stability profile. The findings of the nociceptive assay showed that the dexinanocrystals exhibited significant analgesia, compared to the raw dexibuprofen and the control standard diclofenac sodium. The analgesic effect was, however, produced at much lower doses (5mg/kg) than that of control standard, diclofenac sodium (20mg/kg) and dexibuprofen counterparts (40 mg/kg). While theactivity results in anti-emetic assay confirmed that the nano-formulation provided significant anti-emetic effect (P< 0.05) x at a dose of 0.5 mg/kg, comparable to that of the unprocessed DOMP and the control standard Metoclopramide administered at the doses of 1.0m/kg and 30mg/kg respectively. However, DOMP nanoparticles showed the anti-emetic effect at lower doses compared to that of control standard and unprocessed DOMP. Furthermore, there was observed a substantial % increase of antiemetic potential for DOMP nanoparticles compared to the unprocessed DOMP and the standard metoclopramide.
طفیل ہوشیار پوری(۱۹۱۴ء۔۱۹۹۳ء) کا اصل نام محمد طفیل اور شہرت طفیل ہوشیار پوری کے نام سے ہوئی۔ طفیل ضلع ہوشیارپورکی تحصیل گڑھ شنکر کے ایک گاؤں بینے والی میں پیدا ہوئے۔ ۱۹۳۴ء میں ہوشیار پور سے ہجرت کر کے سیالکوٹ میں مستقل سکونت اختیار کر لی ۔یہاں انھوں نے اپنے بڑے بھائی کے ساتھ مل کر منیمی(حساب کتاب) سکول قائم کیا۔ اس سکول میں سیالکوٹ کے ممتاز تاجر ان کے شاگرد رہے ہیں۔(۶۰۷)
۱۹۴۳ء میں طفیل آل انڈیا ریڈیو سے منسلک ہو گئے۔ ۱۹۵۴ء میں ان کا ناطہ فلمی دنیا سے جڑ گیا ۔ اور آپ فلموں کے لیے گیت لکھنے لگے۔یہ گیت اردو اور پنجابی زبان میں ہیں۔۱۹۵۴ء میں ہی انھوں نے لاہور سے ایک ادبی اور علمی رسالے کا اجرا کیا جس کا نام ’’محفل‘‘ تھا۔ آپ ہفت روزہ رسالہ ’’صاف گو‘‘ کے مدیر اعلیٰ بھی رہے ہیں۔(۶۰۸)
حُب وطن پر مشتمل نظموں اور جنگی ترانوں پر مشتمل ’’میرے محبوب وطن‘‘ طفیل کا پہلا شعری مجموعہ کلام ہے۔ جوجنوری ۱۹۶۶ء میں شائع ہوا۔مولانا ابو الا علیٰ مودودی نے حرفِ اول لکھا۔ جسٹس ایس۔اے رحمان نے ’’پیشِ لفظ‘‘ سید عابد علی عابد نے ’’دیباچہ‘‘ اور سید نذیرنیازی نے ’’مقدمہ ‘‘ اور طفیل نے’’میں خود کہوں تو‘‘ کے عنوان سے اپنی قومی نظموں کا پس منظر بیان کیا ہے۔ جامِ مہتاب طفیل کا دوسرا شعری مجموعہ ہے۔ جو رباعیات و قطعات پر مشتمل ہے ۔یہ مجموعہ ۱۹۷۵ء میں شائع ہوا۔ حرفِ آغاز جسٹس ایس ۔اے رحمان نے لکھا۔’’تعارف و تقریظ‘‘ مولانا حامد علی خان نے لکھا۔ عرضِ حال کے عنوان سے طفیل نے اس کتاب میں اپنی شاعری پر روشنی ڈالی ہے۔ ڈاکٹر سید عبداﷲ نے ’’شعلہ جام پر ایک نظر‘‘ کے عنوان سے مضمون قلم بند کیا ہے۔ ڈاکٹر عبادت بریلوی نے مقدمہ لکھا ہے۔ جب کہ شاعر لکھنوی نے ’’شعلہ جام سے طفیل ہوشیار...
In the context of blasphemy issue, the present study examines the socio-cultural elements in the Moral Ethics syllabi functional at the different universities of Pakistan. As per our hypothesis, ME syllabi lack some important socio-cultural elements responsible for handling hate crimes, especially the issue of blasphemy. For testing the proposed hypothesis, available ME syllabi were collected from the official websites of different universities. Collected ME syllabi were examined through the method of content analysis. After examining literature review, necessary socio-cultural factors (SCFs) were listed and the selected syllabi were evaluated through this list of SCFs. Our study findings endorse the primary hypothesis that majority of universities has adopted the foreign model of ME syllabi without adapting them according to indigenous social and cultural needs. Additionally, the most important SCFs; knowledge of blasphemy laws (KBL) and real-life dilemmas (RLD), are mostly absent in the existing ME syllabi.
In order to produce good financial results and improve operational performance, a firm should effectively and efficiently manage its working capital. Working capital policies and practices vary from firm to firm which leads to variation in profitability. A difference in working capital practices is observed on the basis of size and location. Review of existing literature indicates that this variation in working capital management practices among various categories of firms such as small, medium, large, domestic and multinationals has not yet been adequately researched, particularly in developing countries like Pakistan. The study uses secondary data of 153 listed firms on Pakistan Stock Exchange for 10 years (2004-2013). These firms are categorized on the basis of size viz. small, medium and large; as well as location such as domestic and multinationals. R-square shows that highest explanatory power of the independent and control variables included in the model based on market to book ratio occur in multinational firms where dependent variable is explained to the extent of 41% whereas based on return on assets it is 26% in medium firms. Results show that working capital policy significantly affects firms’ performance. Multinomial logistic regression model was used to identify factors significantly affecting WC policy. Logistic regression results show that ROA and MC are the variables determining the WC policy of firms significant at 5% and 1% respectively. Overall, correct predictions for the study employing logistic regression model work out to be 71.9% showing fitness of the model used for analysis.