Improved Dissolution Rate of Oxcarbazepine by Centrifugal Spinning: In-Vitro and In-Vivo Implications

Amjad Hussain,Muhammad Sohail Arshad,Sidra Nasir,Nasir Abbas,Jahanzeb Mudassir,Fahad Hussain,Nadeem Irfan Bukhari,Abid Ali,Sumera Latif

doi:10.3390/iecp2020-08702

Amjad Hussain, Muhammad Sohail Arshad + Show 7 more

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https://doi.org/10.3390/iecp2020-08702

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Abstract

Low dissolution rates of poorly soluble drugs are the factor afflicting their bioavailability. The aim of this study is to prepare a centrifugal spinning-based formulation of a poorly soluble drug, oxcarbazepine, for the improvement of dissolution rate and hence quick action. Sucrose-based microfibers of oxcarbazepine were prepared by a centrifugal melt spinning technique using a cotton candy machine. The prepared microfibers were characterized using Scanning electron microscopy (SEM), PXRD, Differential Scanning Calorimetry (DSC) and FTIR. The optimum formulation was molded into tablets and tested for in vitro drug release and in vivo pharmacokinetic studies using rabbits as test animals. The results indicated that the centrifugal spinning rapidly produced dissolving microfibers (diameter are <10 µm and dissolve in few seconds). In these fibers, ~20% oxcarbazepine was loaded, and both the yield and drug loading efficiency were improved by incorporating polyvinypyrolidine (PVP) in the formulations. The dissolution studies have revealed >90% of the drug was dissolved in just 2 min as compared with drug alone that shows only 15% dissolution at this time interval. XRD and DSC analyses have shown the amorphous state of the drug in the fibers while the FTIR analysis showed chemical stability of oxcarbazepine in the fibers. In vivo studies have revealed a 2 h reduction in tmax of drug in the rabbits treated with microfibers as compared with controlled group which was given pure oxcarbazepine. The study concludes the potential of the centrifugal spinning technique for the production of drug loaded fibers that can significantly enhance the dissolution rates of poorly soluble drugs and thus produce formulations for quick action of such drugs. Furthermore, the sucrose-based formulation can enhance the palatability with the intention of attracting pediatric patients.

Highlights

Majority of newly developed active pharmaceutical ingredient (APIs) are poorly soluble owing to their lipophilic nature [1]. This leads to low dissolution rate and in turn poor bioavailability of these drugs [2]
Manipulations based on enhancement of surface area or solubility, both could be opted for the enhancement of dissolution rate of poorly soluble drugs
Percentage yield of up to 80% and drug loading efficiency up to 90 ± 5% was obtained with different OXC/ excipient combinations (Table 1)

Summary

Introduction

Majority of newly developed active pharmaceutical ingredient (APIs) are poorly soluble owing to their lipophilic nature [1]. This leads to low dissolution rate and in turn poor bioavailability of these drugs [2]. Manipulations based on enhancement of surface area or solubility, both could be opted for the enhancement of dissolution rate of poorly soluble drugs. One such useful approach is to make fibrous solid dispersion of hydrophobic drug in a hydrophilic carrier [6,7]. This fabrication of solid dispersions into microfibers with increased surface area is a developing drift in Pharma industry

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