Low bioavailability of the drugs is often the consequence of their poor water solubility and low dissolution rate. There are many different approaches available to increase solubility and dissolution rate of poorly water-soluble drugs, and nanotechnological approaches, including the design and fabrication of polymer nanofibers, are becoming increasingly relevant. The nanofibers are characterized by specific properties, which can have a significant impact on the solubility and dissolution rate of the incorporated drugs. The dissolution of poorly soluble drugs is enhanced due to the particle size reduction, the formation of solid dispersions, the modification of the drug crystal form, the amorphization, and/or the solubilization effect of the excipients used. Preparation of nanofibers offers endless possibilities for combinations of formulation, process, and environmental parameters, and thus enables production of nanofibers with desired properties and controlled solubility and/or dissolution of incorporated poorly soluble drugs. Drug-delivery systems made of nanofibers are extensively used to achieve preferred drug release and consequently the desired therapeutic effects at the target location and timing. The properties of nanofibers, that are exploited to achieve immediate drug release are large surface-to-volume ratio, high interfibrilar porosity and the use of suitable water-soluble polymers.
In our work, we proposed a new idea of exploiting amphiphilic polymers poloxamers as key excipients in electrospun nanofibers to improve solubility and increase dissolution rate of poorly soluble drugs. A new nanofiber-based drug delivery system for carvedilol was developed based on amphiphilic polymer poloxamer 407 and hydrophilic polymer polyethylene oxide as fiber-forming polymer. Various liquid carvedilol dispersions, such as carvedilol (nano)suspensions and ethanol solution, were electrospun to obtain different nanofiber samples, which all exhibited comparable morphologies with different mean fiber diameters (170–450 nm). Polymer films, prepared as a reference samples from the same dispersions, exhibited slower dissolution rates of carvedilol compared to its dissolution from nanofibers. The crystalline carvedilol was not detected in nanofibers, electrospun from ethanol solution, which resulted in the highest carvedilol dissolution rate. In the first 5 min more than 90% of the drug was dissolved. In all other nanofibers, crystalline carvedilol form II or III was detected. The ability of nanofibers to retain the drug in the initial non-crystalline form was shown in a 1-year physical stability study. Nanofibers based on poloxamers are thus a promising formulation to improve dissolution and to achieve immediate release of poorly soluble drugs. The method of electrospinning is typically used to incorporate oxidatively stable drugs since the emerging nanofibers are exposed to the external conditions during the electrospinning. In the scope of our study, we have shown that the method is suitable also to incorporate the drugs with low oxidative stability, such as lovastatin, when the appropriate excipients are used. Nanofibers with lovastatin were electrospun from poloxamer 188/Soluplus – based ethanol solutions with polyethylene oxide added as fiber-forming polymer. The nanofibers exhibited lower lovastatin content than theoretically expected right after the preparation, indicating the oxidative degradation of lovastatin during the electrospinning process. The chemical stability of lovastatin during the electrospinning process and in the electrospun nanofibers was improved after the addition of antioxidants buthylhydroxyanisole and ascorbic acid. In the case of Soluplus-based nanofibers, where no crystalline lovastatin was observed, the fastest dissolution and the highest solubility of lovastatin were determined. The lovastatin solubility was thus ~3.5-fold higher compared to its physical mixture. The accelerated stability study revealed that lovastatin content was gradually decreasing in Soluplus-based nanofibers with the addition of antioxidants, whereas in poloxamer-based nanofibers with antioxidants the lovastatin content was preserved. Nonetheless, it is expected that appropriate packaging and the storage of the Soluplus-based nanofibers with antioxidants under normal conditions would improve its chemical stability. We have thus demonstrated that formulation of nanofibers to increase the solubility and the dissolution rate of poorly soluble drugs is suitable approach also for oxidatively unstable drugs.
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