The term ‘solubility’ is defined as an excess amount of solute that can be incorporated in a given amount of solvent. Solubility of poorly water-soluble drugs is one of the most emerging issue associated with these drugs to form a suitable dosage form that will provide desired pharmacological response. Their low solubility causes elimination of most of the drug from body as such, and desired therapeutic levels are not achieved. In recent years, a large number of drugs have been developed, but nearly 70% of new drugs have poor water solubility. Major part of the human body is made up of water. Therefore, drugs must be having a certain aqueous solubility. The solubility of drugs ultimately has strong impact on their bioavailability. Rosuvastatin calcium (RST) belongs to the Biopharmaceutics Classification System class II having low solubility and high permeability. It is a poorly water-soluble 3-hydroxy-3-methyl glutaryl CoA (HMG- CoA) reductase inhibitor. Efforts have been made to enhance solubility of these drugs. Different techniques have been used to enhance solubility of these poorly water soluble drugs such as reduction in particle size to increase surface area, thus increasing the dissolution rate of drug, solubilization in surfactant systems, formation of water-soluble complexes, drug derivatization such as strong electrolyte salt forms that usually have higher dissolution rate, producing liquisolid formulations, manipulation of the solid state of a drug substance to enhance drug dissolution i.e. by decreasing crystallinity of the drug substance through formation of solid solutions, solid dispersion formulations. Polymers are major players in these formulations to enhance solubility e.g., chitosan, polyvinyl pyrolidone, polyvinyl alcohol, β-cyclodextrin, etc. β-Cyclodextrin is one of the most efficient polymer among all of these to work as a carrier for these drugs to enhance solubility. In present work, fast disintegrating tablets (FDT’s) of rosuvastatin calcium were prepared by using β-cyclodextrin as polymer along with different super disintegrants such as kyron T 134 and sodium starch glycolate and microparticles were prepared by using β- cyclodextrin as polymer to enhance solubility. Microparticles were prepared by using solvent evaporation (solid dispersions), kneeding technique (inclusion complexes) and XXIfree radical polymerization to prepare hydrogel microparticles. Prepared formulations were evaluated by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermo Gravimetric Analysis (TGA), dissolution studies, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), zeta size and zeta potential, transmission electron microscopy (TEM), and stability studies to confirm enhancement in solubility. FDT’s were further characterized by wetting time, wetting volume, disintegration time, dispersion time etc. Different in vitro kinetic models such as zero order, first order, Higuchi, and Korsmeyer–Peppas were applied to determine the release behavior of drug from prepared formulations. Results were also statistically analyzed by mean, one-way analysis of variance (ANOVA), and p value was determined to check significant results. Results of FTIR and DSC of prepared formulations had revealed that stable complex was formed between drug and polymer. SEM study of formulations had shown that small openings were present on their surfaces. These openings facilitated the penetration of water and rapid release of drug. From PXRD study it was observed that drug had changed from crystalline to amorphous form. Internal morphology of TEM images had shown that drug was present inside of FDT’s and microparticles. Zeta size and zeta potential studies confirmed that microparticles had micron size and net charge was neutral. Wetting time, wetting volume, disintegration time, dispersion time, water absorption ratio of FDT’s were 43±1.15-96±1.5 seconds, 80±0.5-22±1.50 seconds, 3±1.50-77±1.50 seconds, 29±0.58-57±0.58 seconds and 1.10±0.01-2.00±0.02, respectively. FDT’s and microparticles dissolution studies had shown that FDT’s released 91- 97% (p=0.025) of drug while inclusion complexes and solid dispersions released 71-92% (p=0.15) of drug and hydrogel microparticles released upto 92% of drug (p=0.02). In contrast to prepared formulations, drug released from commercially available tablets of Rosuvastatin calcium was very less (43%). Due to acidic nature of Rosuvastatin calcium drug was more soluble at higher pH value i.e., at 6.8 as compared to 1.2 pH. Hydrogel microparticles containing Acrylamido-2-methyl propane sulphonic acid (AMPS) as monomer had shown pH independent swelling and shown better release than methacrylic acid (MAA) containing hydrogel microparticles. AMPS containing hydrogel microparticles released drug at both pH values but it was better at 6.8 than 1.2. Solubility studies revealed that prepared formulations had greater solubility at 6.8 pH phosphate buffer, 1.2 pH HCl buffer and in pure water than alone drug. All three types of formulations had enhanced solubility of Rosuvastatin calcium but it was highest at 6.8 pH phosphate buffer. FDT’s enhanced solubility of Rosuvastatin calcium 7.42 folds in HCl buffer of 1.2 pH, while in phosphate buffer of 6.8 pH 11.71 folds and in pure water 9.05 folds solubility was enhanced. Microparticles prepared by solvent evaporation had enhanced solubility 3.32 folds, 8.54 folds and 5.86 folds at 1.2 pH, 6.8 pH and in pure water, respectively. Hydrogel microparticles prepared by AMPS had enhanced solubility 7.53 folds, 10.66 folds and 7.30 folds at 1.2 pH, 6.8 pH and in pure water, respectively. In case of hydrogel microparticles containing MAA had no greater impact on solubility of Rosuvastatin calcium (RST) at 1.2 pH, while these enhanced solubility upto 9.59 folds and 6.9 folds at pH 6.8 and in pure water. From findings it was observed that solubility of Rosuvastatin calcium was enhanced by using these techniques. Pharmacokinetic data had also depicted that C max and AUC 0-24 were also greater for prepared formulations in contrast to RST commercially available tablets. Elimination half-life of drug was reduced upto 4 hours in our formulations. Toxicology data also shown that no toxic effects were observed from hematological, biochemical and histological studies. From findings of this study it was concluded that solubility of Rosuvastatin calcium was successfully enhanced by using techniques. Prepared formulations were found stable during stability studies of 6 month period. Thus, we can conclude that solubility of BCS class drugs can be enhanced by using these techniques with improved bioavailability.
سردار پٹیل افسوس ہے کہ گذشتہ ۱۵؍ دسمبر کو ہماری قومی عمارت کا ایک آہنی ستون گرگیا، اور سردار پٹیل ہم سے جدا ہوگئے، ملک و قوم کی راہ میں ان کی بڑی قربانیاں اور بڑی خدمات ہیں، وہ جنگ آزادی کے نامور ہیرو گاندھی جی کے دست راست اور جدید ہندوستان کے رکن اعظم تھے، گو قومی نقطہ نظر سے ان کے بعض خیالات صحیح نہیں تھے، جس سے ملک کو نقصان پہنچا، لیکن اس غلطی کے احساس اور اس کے برے نتائج دیکھنے کے بعد انہوں نے اس کی تلافی کی بھی پوری کوشش کی، فرقہ پرستی کی بھڑکتی ہوئی آگ کو انہی نے بجھایا، اور نہرو لیاقت پیکٹ کو انہی نے کامیاب بنایا، اگر ان کی تائید حاصل نہ ہوتی، تو ہندوستان اور پاکستان کی اقلیتوں پر دونوں ملکوں کی سرزمین تنگ ہوجاتی، اور آخر میں وہ اقلیتوں کے تحفظ، ملک میں قیامِ امن و پاکستان سے مفاہمت کے مسائل میں بڑی حد تک جواہر لال کے ہم نوا ہوگئے تھے، اور ملک کے ضبط و نظام اور امن و امان کا دارومدار انہی پر تھا، ان کا سب سے نمایاں وصف ان کا کوہ وقار عزم و استقلال تھا، وہ بولتے کم تھے، مگرجو کچھ کہتے یا چاہتے تھے، اس کو پورا کر کے رہتے تھے، ان کا سب سے بڑا کارنامہ ریاستوں کا انضمام ہے، جو انگریزوں سے بھی نہ ہوسکا تھا، انہوں نے تاریخ میں پہلی مرتبہ ہندوستان کو ایک متحدہ ملک بنایا آیندہ ہندوستان میں اس عزم و ارادہ کا انسان مشکل سے پیدا ہوگا ، اور اس کی تاریخ میں ان کانام ہمیشہ روشن رہے گا۔ (شاہ معین الدین ندوی، جنوری ۱۹۵۱ء)
NAC transcription factors are considered as main family of transcriptional regulators in plants. NAC gene family members play significant contribution in regulating transcriptional reprogramming in plants related to plant stress response. These proteins possess highly conserved DNA binding domains and play a diverse functions in several plants. NAC gene is related to several stress factors including biotic and abiotic factors. NAC transcription factors controls several interrelated processes and their protein products can function as negative or positive regulators in many cellular processes. These regulatory functions are also controlled by NAC proteins such as auto and cross regulation. These regulatory proteins are regarded as a central regulator for the interaction of phytohormones in various stress signaling pathways. This review highlights the role of NAC transcription factors in modulating gene expression and their role in various biotic and abiotic stress tolerance in plants.
A very fast, economical and simple direct spectrophotometric method was investigated for Paracetamol (PC) determination in aqueous medium without using any reagent. The method is based on the photo activation of the analyte at 243 nm after dissolution in water. The change in structure of PC after addition of water was studied by comparing the corresponding FTIR spectra. Optimization studies were conducted by using a 5 μg ml-1 standard solution of the analyte. Various parameters studied include, time for stability and measurement of spectra, effect of HCl, NaOH, CH3COOH and NH3 for change in absorbance and shift in spectra, interference by some analgesic drugs and some polar solvents and temperature effect. After optimization, Beer’s law was obeyed in the range of 0.3–20 μg ml-1 PC solution with a correlation coefficient of 0.9999 and detection limit of 0.1 μg ml-1 for 3/1 S/N ratio. The newly developed method was successfully applied for PC determination in some locally available tablets and urinary samples. The proposed method is very useful for quick analysis of various types of solid and liquid samples containing PC. Another spectrophotometric work describes a simple, sensitive, rapid and economical analytical procedure for direct spectrophotometric evaluation of Diclofenac Sodium (DS) using aqueous medium without using a chemical reagent. Parameters like time, temperature, acidic and basic conditions and interference by analgesic drugs was studied for a 5μg ml-1 solution of DS at 276 nm. Under optimized parameters, a linear working range of 0.1–30 mg ml-1 with regression coefficient of 0.9998 and lower detection limit of 0.01 mg ml-1 was obtained. The method was applied for DS contents in tablets, serum and urine samples. v A new method was developed for the determination of paracetamol by differential pulse voltammetry (DPV) at carbon film electrode (CFE). The experimental parameters, such as pH of Britton-Robinson buffer and potentials for regeneration of electrode surface were optimized. Under optimized conditions in Britton-Robinson buffer pH 4.0 a linear calibration curve was obtained in the range 0.02–100 μmol L-1. The limit of determination was 0.034 μmol L-1 which showed high sensitivity of developed method. The method was applied for the quantitative determination of Paracetamol in pharmaceutical formulations as well as urine samples. A rapid, reliable and economical analytical procedure for the estimation of ibuprofen in pharmaceutical formulations and human urine samples was developed using transmission Fourier Transform Infrared (FT-IR) spectroscopy. For the determination of ibuprofen, a KBr window with 500 μm spacer was used to acquire the FT-IR spectra of standards, pharmaceuticals as well as urine samples. The Partial Least Squares (PLS) calibration model was developed based on carbonyl region (C=O) from 1807-1461 cm−1 in the range from 10- 1000 ppm. The developed model was checked by cross-validation steps to diminish standard error of the models, such as root mean square error of calibration (RMSEC), root mean square error of cross validation (RMSECV) and root mean square error of prediction (RMSEP). The good coefficient of determination (R2) was achieved 0.999 with minimum standard errors RMSEC, RMSECV and RMSEP 1.89, 1.956 and 1.38, respectively. The other method was based on indirect determination of acetylsalicylic acid (aspirin) utilizing differential pulse voltammetry at carbon film electrode as working electrode. The theory of indirect determination of ASA is based on the hydrolysis of aspirin in salicylic acid (SA) for detection. Moreover, we optimized conditions such as pH of Britton-Robinson buffer, potentials for regeneration and activation of electrode surface, amplitude and scan rate. Under optimized conditions in Britton-Robinson buffer pH 2.0 a linear calibration curve was obtained in the range 0.2 – 100 μmol L-1. The limit of determination was 0.15 μmol L-1 which showed high sensitivity of developed method. The method for indirect determination of ASA was thus developed for the quantification of pharmaceutical formulations as well in human urine model samples.