Orally Fast Disintegrating Cyclodextrin/Prednisolone Inclusion-Complex Nanofibrous Webs for Potential Steroid Medications

Abstract

Prednisolone is a widely used immunosuppressive and anti-inflammatory drug type that suffers from low aqueous solubility and bioavailability. Due to the inclusion complexation with cyclodextrins (CDs), prednisolone's drawbacks that hinder its potential during the administration can be eliminated effectively. Here, we have early shown the electrospinning of free-standing nanofibrous webs of CD/prednisolone inclusion complexes (ICs) in the absence of a polymer matrix. In this study, hydroxypropylbeta-CD (HPβCD) has been used to form ICs with prednisolone and generate nanofibrous webs with a drug loading capacity of ∼10% (w/w). Pullulan/prednisolone nanofibrous webs have been also fabricated as a control sample having the same drug loading (∼10%, w/w). It has been demonstrated that prednisolone has been found in an amorphous state in the HPβCD/prednisolone nanofibrous web due to inclusion complexation, while it has retained its crystal structure in the pullulan/prednisolone nanofibrous web. Therefore, the HPβCD/prednisolone IC nanofibrous web has shown a faster and enhanced release profile and superior disintegration feature in artificial saliva than the pullulan/ prednisolone nanofibrous web. The complexation energy calculated using ab initio modeling displayed a more favorable interaction between HPβCD and prednisolone in the case of a molar ratio of 2:1 than 1:1 (CD: drug). Here, the HPβCD/prednisolone IC nanofibrous web has been developed without using a toxic component or solvent to dissolve drug molecules and boost drug loading in amorphous nature. The investigation of IC nanofibrous webs has been conducted to formulate a promising alternative to the orally disintegrating tablet formulation of prednisolone in the market. The nanofibrous structure and the improved physicochemical properties of prednisolone arising with the complexation might ensure a faster disintegration and onset of action against commercially available and orally disintegrating delivery systems during the desired treatment.

Rapid Sublingual Delivery of Piroxicam from Electrospun Cyclodextrin Inclusion Complex Nanofibers

“…The time-dependent drug release from the nanofibers was achieved as reported before . Briefly, the fiber samples (5 mg) were placed in a PBS solution (pH: 7.4) and shaken in an incubator at 150 rpm at 37 °C.…”

“…The time-dependent drug release from the nanofibers was achieved as reported before. 46 Briefly, the fiber samples (5 mg) were placed in a PBS solution (pH: 7.4) and shaken in an incubator at 150 rpm at 37 °C. Then, 200 μL aliquots were taken from the solutions at set time intervals and replaced by the fresh PBS buffer.…”

“… 40 Thus, polymer-free HP-β-CD-based nanofibers have been used as a carrier of many drugs molecules, but not for piroxicam. 41 − 46 …”

“…The formation of inclusion complexation with CD molecules will boost the bioavailability of drugs, − while masking the bitter and disgusting taste of drugs. − Moreover, HP-β-CD received FDA approval as a vehicle for drug delivery and was incorporated into the FDA’s list of Inactive Pharmaceutical Ingredients . Thus, polymer-free HP-β-CD-based nanofibers have been used as a carrier of many drugs molecules, but not for piroxicam. − …”

Green Electrospinning of Chitosan/Pectin Nanofibrous Films by the Incorporation of Cyclodextrin/Curcumin Inclusion Complexes: pH-Responsive Release and Hydrogel Features

“…These starch-derived molecules can form noncovalent interactions with a variety of active agents, and this makes them the main source of attention as an encapsulation agent. As a result of inclusion complexation with CD, the aqueous solubility, stability, and bioavailability of bioactive compounds can be enhanced noticeably. , Even the highly water-soluble hydroxypropylated derivative of CDs and their inclusion complexes can be electrospun into freestanding nanofibrous films without using an additional polymeric matrix or toxic chemicals. − In this study, highly water-soluble hydroxypropyl-γ-CD (HPγCD) (>500 mg/mL) was used as a carrier matrix to generate nanofibrous films from chitosan and chitosan/pectin blend systems. HPγCD is a hydroxypropylated version of native γCD, and it has been approved by the U.S. Food and Drug Administration (FDA) as an inert excipient that can be used in topical products .…”