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اے قتادہؓ ! جو عطا دستِ یدُاللہ نے کی
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سامنے آنکھوں کے عرفانؔ! جب آئے غم خوار
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رحمتِ کون و مکاں نے ہی سنبھالا آکر
جس گھڑی خود سے بھی عرفانؔ سنبھالے نہ گئے
Increasing the creative economy during the pandemic is very urgent, as an effort to stabilize the economy in ASEAN. The character of the creative economy is characterized by economic activities that are based on the exploration and exploitation of creative ideas that have high selling value. All tourism ministers from ASEAN countries to strengthen tourism cooperation, one of the economic sectors hardest hit in the pandemic. Intelligent marketing is needed in order to know the strengths of our competitors and market tastes, because in the era of globalization, war is actually a war in the economic field and the creative economy is the main weapon. Strong cooperation in efforts to jointly handle the impact of COVID-19 in the tourism sector in the ASEAN region. All ASEAN members to jointly enhance cooperation not only in dealing with pandemic problems but also in terms of developing the creative economy.
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.