Current Issue : January - March Volume : 2019 Issue Number : 1 Articles : 5 Articles
Nanocrystallization and amorphization have proven to be two effective strategies to improve\nthe bioavailability ofwater-insoluble drugs. The purpose of ourworkwas to develop a nano-formulated\ntablet of sirolimus (SRL) for enhanced dissolution. Amorphous SRL nanocomposites were prepared\nusing anti-solvent precipitation via a high-gravity rotating packed bed. Various factors that affect\nparticle size and size distribution, such as excipients, rotating speed, antisolvent/solvent flow rate,\nwere investigated. Structure, stability and in vitro dissolution of the as-prepared SRL were evaluated.\nFurthermore, the nanoparticulated SRL tablet formulawas screened to control drug release. Importantly,\nSRL tablets exhibit different dissolution profile by adjusting HPMC (hydroxypropyl methyl cellulose)\ncontent, which makes them more suitable for various formulation developments....
The aim of this study was to improve the physicochemical properties of cocoa extract (CE)\nusing hot-melt extrusion (HME) for pharmaceutical proposes. A mixture design was applied using\nthree distinct hydrophilic polymeric matrices (Soluplus, Plasdone S630, and Eudragit E). Systems\nobtained by HME were evaluated using morphologic, chromatographic, thermic, spectroscopic, and\ndiffractometric assays. The flow, wettability, and dissolution rate of HME powders were also assessed.\nBoth CE and its marker theobromine proved to be stable under heating according to thermal analysis\nand Arrhenius plot under isothermal conditions. Physicochemical analysis confirmed the stability of\nCE HME preparations and provided evidence of drugâ??polymer interactions. Improvements in the\nfunctional characteristics of CE were observed after the extrusion process, particularly in dissolution\nand flow properties. In addition, the use of a mixture design allowed the identification of synergic\neffects by excipient combination. The optimized combination of polymers obtained considering four\ndifferent aspects showed that a mixture of the Soluplus, Plasdone S630, and Eudragit E in equal\nproportions produced the best results (flowability index 88%; contact angle 47.; dispersibility 7.5%;\nand dissolution efficiency 87%), therefore making the pharmaceutical use of CE more feasible....
We present here the development of multifunctional doxorubicin (DOX)-conjugated\npoly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug release\nand targeted chemotherapy of cancer cells. In this work, we covalently conjugated DOX onto the\nperiphery of partially acetylated and folic acid (FA)-modified generation 5 (G5) PAMAM dendrimers\nthrough a pH-sensitive cis-aconityl linkage to form the G5.NHAc-FA-DOX conjugates. The formed\ndendrimer conjugates were well characterized using different methods. We show that DOX release\nfrom the G5.NHAc-FA-DOX conjugates follows an acid-triggered manner with a higher release rate\nunder an acidic pH condition (pH = 5 or 6, close to the acidic pH of tumor microenvironment) than\nunder a physiological pH condition. Both in vitro cytotoxicity evaluation and cell morphological\nobservation demonstrate that the therapeutic activity of dendrimer-DOX conjugates against cancer\ncells is absolutely related to the DOX drug released. More importantly, the FA conjugation onto\nthe dendrimers allowed a specific targeting to cancer cells overexpressing FA receptors (FAR),\nand allowed targeted inhibition of cancer cells. The developed G5.NHAc-FA-DOX conjugates may be\nused as a promising nanodevice for targeted cancer chemotherapy....
Low-dose tablet formulations were produced with excellent homogeneity based on\ndrug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning\n(SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while\npoly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) was adopted as the fiber-forming polymer.\nScanning electron microscopy (SEM) imaging was used to study the morphology of HSES and SNES\nsamples. Different homogenization techniques were compared to maximize homogeneity: mixing\nin plastic bags and in a high-shear granulator resulting in low-shear mixing (LSM) and high-shear\nmixing (HSM). Drug content and homogeneity of the tablets were measured by UV-Vis spectrometry,\nthe results revealed acceptably low-dose fluctuations especially with formulations homogenized with\nHSM. Sieve analysis was used on the final LSM and HSM powder mixtures in order to elucidate the\nobserved differences between tablet homogeneity. Tablets containing drug-loaded electrospun fibers\nwere also studied by Raman mapping demonstrating evenly distributed CAR within the corpus....
The development of a weakly basic compound is often challenging due to changes in pH\nthat the drug experiences throughout the gastrointestinal tract. As the drug transitions from the\nlow pH of the stomach to the higher pH of the small intestine, drug solubility decreases. A stomach\nwith a higher pH, caused by food or achlorhydric conditions brought about by certain medications,\ndecreases even the initial solubility. This decreased drug solubility is reflected in lower in vivo\nexposures. In many cases, a solubility-enabling approach is needed to counteract the effect of\ngastrointestinal pH changes. Solid dispersions of amorphous drug in a polymer matrix have been\ndemonstrated to be an effective tool to enhance bioavailability, with the potential to mitigate the\nfood and achlorhydric effects frequently observed with conventional formulations. Because solid\ndispersions are in a metastable state, they are particularly sensitive to processing routes that may\ncontrol particle attributes, stability, drug release profile, and bioperformance. A better understanding\nof the impacts of processing routes on the solid dispersion properties will not only enhance our ability\nto control the product properties, but also lower development risks. In this study, a weakly basic\ncompound with greatly reduced solubility in higher pHs was incorporated into a solid dispersion\nvia both spray drying and hot melt extrusion. The properties of the solid dispersion via these two\nprocessing routes were compared, and the impact on dissolution behavior and in vivo performance\nof the dispersions was investigated....
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