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کبھی نگاہوں کی چلمنوں سے نہ راز کہنا، فضا سے کہنا

کبھی نگاہوں کی چلمنوں سے نہ راز کہنا، فضا سے کہنا
غمِ جہاں کو تو زندگی بھر پڑے گا سہنا، فضا سے کہنا

رفاقتوں کا ہے دعویٰ تم کو تو اپنے دعوے کی لاج رکھنا
زماں، مکاں کی حدوں سے آگے بھی ساتھ رہنا، فضا سے کہنا

قدم قدم پر ہے خطرۂ جاں، وہ عزم اپنا بلند رکھے
یہ عشق دریا ہے اس کی فطرت ہے الٹا بہنا، فضا سے کہنا

وہ شوخ آنکھیں غزال جن پہ ہیں صدقے واری، مَیں کیوں نہ واروں
یہ چاند، بادل، دھنک، بہاریں، یہ حسن گہنا، فضا سے کہنا

گلوں نے کلیوں نے کترے دامن، قزح بھی آنکھیں چھپا رہی ہے
یہ نازکی کا لباس تم نے غضب ہے پہنا، فضا سے کہنا

عیسائیت پر لکھی گئی منتخب اردو کتب کا تجزیاتی مطالعہ

Christianity is the religion from the Hazrat Essa (A.S) the Holy Prophet of Allah. Christians believe that Christianity is a perfect religion and this religion save them from hell, and this religion is revealed from Allah. Christian knows that their ideology based upon Hazrat Essa (A.S) and they relate themselves towards Hazrat Essa (A.S). Different books in different languages have written on the Christianity like English, Arabic, Persian and other languages there are many books written on Christianity in Pakistani national language Urdu and the books written in many languages have translated in Urdu. The analysis put forward on Christianity in Urdu written books, one thing is clear that which author writes a good, topic on Christianity and on the other hand by studying Christianity students and readers feel easy and will understand about these books easily and search the relevant material easily. This article shows the analytical study of books written on Christianity in Urdu and translation from other languages nominated Urdu books.

Formulation Development of Fast Dispersible Aceclofenac 100Mg Tablets

Fast dispersible tablets are classic example of novel drug delivery system. This dosage form is particularly designed to facilitate the patients suffering from dysphagia (i.e. difficulty in swallowing). Multiple benefits have been reported with the use of fast dispersible tablets. Amongst all benefits, the most important one is the rapid dispersion of tablet for initiating quick therapeutic response. Model drug used in this research study was the Aceclofenac which has been safely used as analgesic and anti-inflammatory throughout the world. It belongs to BCS class II which shows low solubility and high permeability. Since it is indicated for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and low back pain which are common problems of geriatircs. Therefore aged patients have good palatability towards fast dispersible Aceclofenac tablet than convnetional dsage form due to rapid drug action. It is also indcated for the treatment of dysmenorrhea and dental pain, thus patients of different age groups can equally get benefit form it. In the presented study fast dispersible formulations were designed by suitable selection of excipients and manufactured by i) direct compression and ii) compaction of pellets (manufactured through extrusion -spheronization technique). Tablet manufacturing by direct compression is the easiest approach and widely applicable. In the making of fast dispersible tablets, use of superdisintegrant is most common. Selection of superdisintegrant in appropriate concentration requires careful consideration. In this study ac-di-sol was used in different concentrations in both methods of tablet manufacturing. Fast dispersible directly compressed (i.e. FDDC) formulations were comprised of avicel PH102 (20 -35%), mannitol (10 -25%), ac-di-sol (1 – 3%), aspartame (2%), talc (2%) and vanilla flavor (1%). Twenty formulations were designed through Design Expert® using “6” central point. Eight formulations (A-H) were compressed to make tablets, depending upon the satisfactory micromeritic properties of powder blends. On the other hand compaction after extrusion-spheronization was adopted to make this novel dosage form more palatable. In this method bitterness of medicament was masked, and a creamy taste was imparted to the tablets. However, superdisintegrant was also added in the making of pellets to quickly disintegrate the tablets. Compacted pelletized formulations were comprised of Aceclofenac (100mg) sucrose (20-25%), ac-di-sol (2-5 %), mannitol (20%), aspartame (2%) and pine apple flavor (1%). For designing the fast dispersible Aceclofenac pellets Design Expert® was used using “6” central point. Only five formulations i.e. P1-P5 were pelletized (through extrusion-spheronization) and finally compressed by direct compression method depending upon the satisfactory results of micromeritic properties of powder blends and appropriate tablet weight. Blending rate constant was determined at 6 minutes for mixing all formulations. Micromeritic properties of all powder blends were assessed. Mean values of fast dispersible directly compressed formulations for Carr’s index were between 11.18 – 27.46%, for angle of repose 33.43o - 47.66o and for Hausner’s ration were 1.13 - 1.38 which shows good flowability of powder blends. Mean values of fast dispersible pellet for Carr’s index were found 2.71- 4.30%, for angle of repose 4.00 – 6.72 o and for Hausner’s ration were 1.02 – 1.07. Tapped densities and bulk densities of the pellets were found to be in the range of 0.73-0.77 g/mL and 0.70-0.73 g/mL respectively. Spherical shaped pellets were analysed and area was found: 8713-12909, Feret diameter: 111.66-136.19, aspect ratio: 1.02-1.05, perimeter: 359.69-445.61and roundness: 0.94- 0.97 respectively. Fast dispersible Aceclofenac formulations were evaluated for physicochemical properties according to official and un-official standards. These tests include tablet weight variation, hardness variation, thickness and diameter variation, disintegration time, % friability, dissolution, assay and content uniformity of tablets. Compressional behavior of directly compressed formulations was also evaluated. All formulations’ weights were found within the specified limits (i.e. ± 7.5%). Average weight of formulations (A-H) was found in the range of 155.03 ± 0.76 - 214.66 ± 0.81mg. Whereas, average weight of the compacted pellets (P1-P5) was found: 181.93 ± 0.78 – 211.73 ± 0.87 mg. Average thickness and diameter of the tablets and compacted pellets were controlled within ± 5% limit. Mean thickness and diameter of formulations A-H was found to be 2.61 ± 0.05 – 2.78 ±0.04mm and 8.46 ± 0.01 – 8.49 ±0.01mm respectively. Average thickness and diameter of compacted pellets (P1-P5) was found in the range of: 2.62 ± 0.05 – 2.83 ± 0.04mm and 8.60 ± 0.06 – 8.85 ± 0.04mm respectively. The mechanical strength of tablets is determined by its hardness and % friability. A tablet should be sufficiently hard to withstand during manufacturing, shipping and transportation. Although fast dispersible tablets; prepared by direct compression, are usually deficient of potent binders but their recommended hardness range is 3-8 Kg. In this study tablet hardness of formulations A-H was found to be 3.63 ± 0.18 – 5.20± 0.23 kg and for compacted pellets (P1-P5) hardness was found to be: 4.32 ± 0.21 – 6.22 ± 0.45 Kg. The friability of formulations A-H was observed 0.29 - 0.76% and for compacted pellets was observed: 0.20 – 0.35%. None of the tablets showed lamination or capping during friability testing. All formulations satisfactorily qualify the dispersion test of tablets. Wetting time of formulations A-H was found to be 08-19 sec and for compacted pellets wetting time was: 15-22 sec. Disintegration time of formulations A-H and compacted pellets was found in the range: 12-27 sec and 29-42 sec respectively. Analysis and content uniformity results of formulations A-H and P1-P5 were found in the range: 98.63 ± 0.80 – 100.58 ± 1.68%; 99.88 ± 1.23 – 100.40 ± 0.97 and98.71±1.12 – 99.89 ± 0.28%; 99.26 ± 0.54 – 101.37 ± 0.57 respectively. Compressional behavior of fast dispersible directly compressed formulations was examined through Heckel and Kawakita equations. For this purpose formulations A-H were compressed under recommendation conditions of weight and dimensions (i.e. within ± 0.01mg and within ± 0.01mm). The applied compressional pressure was ranged from: 7.72, 23.16, 30.88, 38.0, 46.32, 54.04, 61.76, 69.48 and 77.2 MN/m2. Heckel plots of formulation B and D showed more plastic behavior and such formulations do not show difficulty during compression even at minimum compressional pressure. Kawakita analysis of formulations A and B exhibited their more plastic behavior having least PK values whereas formulations E and F were found more elastic. From Heckel and Kawakita analysis optimized formulation B was found to be more plastic among all formulations. Dissolution profile comparison of reference formulation and all test formulations (A-H and P1-P5) was conducted in three different medium (0.1NHCI, phosphate buffer pH 4.5 and pH 6.8). Reference product was purchased from market. DD solver® was used to analyze the data through model dependent and model independent approaches. Release kinetics of all fast dispersible formulations in 0.1N HCl followed Weibull model and r2 value for formulations A-H were observed as : 0.919 – 0.963 and for P1-P5: 0.924 – 0.941. In phosphate buffer of pH 4.5 all formulations followed First–order, Higuchi, Hixson Crowell and Weibull model with r2> 0.9. However, for Weibull model; values of r2 were found highest i.e. formulations A-H: 0.982- 0.991 and formulations P1-P5: 0.983 – 0.990. In phosphate buffer of pH 6.8 all formulations followed the Weibull > Hixson > First order model and comparatively low r2 value for Higuchi model. The release kinetics of directly compressed formulations (A-H) and compacted pellets (P1-P5) was found similar in terms of model dependent approach. Model-independent approach was used to calculate similarity factor f2 by making a comparison of all test formulations with the reference formulation. Formulations A-H showed dissimilarity in all three medium with f2 values 38-43 in 0.1NHCI, 41 - 44 in buffer solution of pH 4.5 and 46 – 49 in buffer solution of pH 6.8. Similarly all compacted pelletized formulations (P1-P5) showed lack of similarity in all dissolution medium with the reference and f2 values in 0.1NHCI, phosphate buffer solution of pH 4.5 and 6.8 were found to be: 37 - 40, 40 - 43 and 45 – 48 respectively. Formulation B with average weight 212.14± 0.60 mg, disintegration time of 21 sec only, friability 0.34%, mean hardness 3.85± 0.14 kg, content uniformity: 100.04 ± 1.2% and estimated shelf life 38 months (on the basis of long-term stability testing), was chosen for in-vivo study. Compacted pelletized formulation P5 also produced satisfactory results, with average weight 211.73 ± 0.87 mg, disintegration time 29 sec, friability 0.35%, average hardness 4.32± 0.21kg, content uniformity 100.44 ± 0.74% and 36 months shelf life (estimated during long-term stability testing). Based on satisfactory results of physicochemical properties of formulation “B” and “P5” were considered successful. Hence these formulations were selected for in-vivo study. It is mandatory to quantify the drug in plasma prior conducting the in-vivo study in human volunteers. For this purpose bio-analytical method was developed and validated on HPLC by following the FDA guidelines. Linearity, accuracy, precision, specificity, and reproducibility of analytical method were examined in mobile phase and plasma and satisfactory results were obtained. Linearity in mobile phase and plasma was established at concentration range 0.1 - 40μg.mL-1 with mean r2 value of 0.999 in both medium. Absolute analytical recovery of analyte was calculated in the mobile phase: 103.1%, 101.2%, 101.17% and in healthy human plasma: 96.1%, 98.98% and 99.63% using concentrations 1, 20, and 35μg.mL-1. The intraday accuracy was determined at concentration: 1, 5, 10, and 20 μg.mL-1 using 5 replicates of each concentration and mean results were found to be: 99.94%, 99.90%, 101.72% and 98.00% respectively. Interday accuracy was determined at concentration: 1, 10, 15 and 20 μg.mL-1 and mean results of each concentration were found to be: 99.93%, 100.04%, 99.68% and 98.80%. The LOD (i.e. lower limit of detection) was 0.05 μg mL-1 and LLOQ (i.e. lower limit of quantification) was 0.1 μg mL-1. Stability of plasma samples was evaluated through 3 freeze and thaw cycles at lower concentration such as 1 μg mL-1 and higher concentration for instance 35 μg mL-1. All formulations were also subjected to accelerated stability testing for 6 months and long term stability testing for 12 months. Physical and chemical testing of the formulations was carried out, such as tablet appearance, disintegration time, percentage drug dissolution and assay. All formulations showed better stability over testing period and their shelf lives were estimated through Minitab software (version: 17.0) program. Shelf life of optimized formulation B by accelerated stability testing was reported as 28 months and through long-term stability testing it was found to be 38 months. Whereas estimated shelf life of optimized formulation P5 through accelerated stability was 25 months and through long-term stability testing was 36 months. Pharmacokinetic and bioequivalent study was conducted in 12 healthy human volunteers as per FDA guidelines. Volunteers were selected after taking ethical approval from NBC Pakistan and their informed consent were documented. This study design was single dose, open label, randomized, two-way, cross over and conducted in three phases after washout period of two, two week for reference and test formulations. A marketed product (core immediate release Aceclofenac 100 mg tablet) was used as reference for evaluating the pharmacokinetic parameters. Blood sampling was carried out at time points 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 14 and 16 hours interval after reference tablet intake. Plasma was separated by centrifugation and preserved for analysis by validated procedure as discussed above. After two weeks washout period, formulation B was administered to same volunteers and their blood samples were collected and analyzed in same pattern. Same protocol of wash out period was followed before administering the formulation P5. After analysis of plasma samples of reference and test formulations B and P5, the drug concentration in plasma was used to analyze the compartmental and non-compartmental parameters. For this purpose Kinetica® (5.10) software was used. Using compartmental model the mean Cmax values for reference was: 8.796 ± 0.021 μg/mL, for formulation B: 8.64 ± 0.022 μg/mL and for formulation P5 was: 8.803 ±0.032 μg/mL. Mean Tmax values for reference, formulation B and P5 were: 1.412± 0.004 hr, 1.20 ± 0.003hr and 1.227 ± 0.007 hr respectively. Mean values of AUC for reference, formulations B and P5 by compartmental analysis were: 21.409 ± 0.072 mg/L×hr, 25.400 ± 0.155 mg/L×hr and 26.073 ± 0.288 mg/L×hr respectively. Drug absorption and elimination are crucial stages of fast dispersible formulations. Mean values of T1/2Ka (absorption half-life) and T1/2Kel (elimination half-life) of reference and formulations B and P5were calculated as: 0.298 ± 0.022hr, 0.518 ± 0.033hr, 0.428 ± 0.041hr and 0.736 ± 0.051 hr, 0.829 ± 0.050hr and 0.847 ± 0.110hr respectively. Mean values of absorption rate constant Ka and elimination rate constant Kel for reference 2.33 ± 0.219hr-1 and 0.945 ± 0.055hr-1. Mean results of these parameters for test formulation B and P5 were found to be: 1.95 ± 0.03hr-1, 0.838 ± 0.053hr-1 and 1.958 ± 0.019hr-1, 0.791 ± 0.004hr-1. Mean clearance (Cl) and volume of distribution at terminal phase (Vz) for reference, and test formulation B and P5 were: 4.671 ± 0.016L.hr-1, 3.937 ± 0.024 L.hr-1, 3.836 ± 0.043L.hr-1 and 14.640 ± 0.631L, 11.711± 2.610L and 11.082 ± 2.54L respectively. Non-compartmental analysis yielded mean Cmax values for reference, formulation B and P5: 8.620 ± 0.015 μg/mL, 8.471 ± 0.0130 μg/mL and 8.612 ± 0.010 μg/mL respectively. Whereas mean Tmax values for reference: 1.5 ± 0.00hr and for both formulations B and P5 were found to be: 1.0 ± 0.00hr. The mean AUClast and AUCtot by non-compartmental analysis for reference, formulation B and P5 were: 22.213 ± 0.061 mg/L×hr, 22.375 ± 0.064 mg/L×hr; 26.254 ± 0.042 mg/L×hr, 26.363 ± 0.083 mg/L×hr; and 26.384 ± 0.006 mg/L×hr, 26.938 ± 0.088 mg/L×hr respectively. Estimated mean values of AUMC for reference and test formulations B and P5 were: 80.396 ± 0.843, 67.343 ± 1.50 and 68.286 ± 3.329 mg/Lx (h)2 respectively. Whereas mean values of AUMClast and AUMCtot were found to be: 76.719 ± 0.532, 73.085 ± 0.361, 74.713 ± 0.329, 79.852 ± 0.616, 75.209 ± 1.423, and 76.700 ± 1.398 mg/Lx(h)2 respectively. The mean residence time of the reference and test formulations were: 3.569 ± 0.018, 2.853 ± 0.045hr (for B) and 2.847 ± 0.045 hr (for P5). Pharmacokinetic parameters of reference and test formulations; such as Cmax, Tmax, AUC, AUClast and AUCtot were compared by two way ANOVA test and Schirmann’s two one sided t test in the form of log-transformed and non-log transformed data to conclude bioequivalence by Kinetica®. For log-transformed data based on the reference and formulation B, the geomean ratio (Test/Reference) of Cmax, Tmax, AUC, AUCtot and AUClast were: 0.982246, 0.849749, 1.1864, 1.17824 and 1.18193 respectively. The standard 90% confidence interval for these parameters were found as: 0.98034 - 0.98416, 0.84829- 0.85122, 1.1823 - 1.1905, 1.1759 - 1.1806 and 1.1801 - 1.1837 respectively. For non-log transformed data of reference Vs test formulation (B) geomean ratio of Cmax, Tmax, AUC, AUCtotand AUClast was found to be: 0.982246, 0.849747, 1.18642, 1.18193, and 1.18193 respectively. The 90% confidence interval of Cmax, Tmax, AUC, AUCtot and AUClast was lying in following ranges: 0.98032- 0.98418, 0.8481- 0.8514, 1.1825- 1.1903, 1.1803-1.1835, and 1.1803- 1.1835 respectively. For bioequivalence study of test and reference formulation P5, using log-transformed data the geometric mean ratio of Cmax, Tmax, AUC, AUCtot and AUClast was found to be: 1.00081, 0.869467, 1.21778, 1.20395 and 1.18778 respectively. The 90% standard confidence interval for these parameters were found as: 0.99858 - 1.003, 0.86653 - 0.87241, 1.2117 - 1.2239, 1.202 - 1.2059 and 1.1861- 1.1895 respectively. For non-log transformed data of reference and test formulation P5 the geomean ratio of Cmax, Tmax, AUC, AUCtotand AUClast was calculated as: 1.00081, 0.869474, 1.21784, 1.20396, and 1.18778 respectively. The 90% confidence interval of Cmax, Tmax, AUC, AUCtot and AUClast was calculated: 0.99859 - 1.003, 0.86638 - 0.87257, 1.2117-1.2239, 1.2021-1.2058, and 1.1864 - 1.1892 respectively. Results of bioequivalence parameters such as Cmax, Tmax, AUC, AUCtot and AUClast concluded that test and reference formulations B and P5 are bioequivalent according to FDA criteria. Hence presented study could be considered to make novel fast dispersible tablets of Aceclofenac with increased palatability. It will produce ease of administration to the patients of all age groups and particularly useful for geriatrics. Use of superdisintegrant has proven improved bioavailability and faster onset of drug action than conventional dosage form. The designed formulations have also shown bioequivalence with the reference product and therefore they could be used to attain rapid analgesic and anti-inflammatory effects." xml:lang="en_US
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