Okeke, Obinna Chikwado (2017) Formulation of novel buccal mucosal drug delivery systems for nicotine replacement therapy (NRT). PhD thesis, University of Greenwich.

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Abstract

Hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA) were used in the formulation of composite wafers and films for potential nicotine (NIC) replacement therapy via the buccal mucosa route. Composite blank (BK), drug loaded (DL) HPMC-SA films (optimized with 2% w/v plasticizer) and wafers (optimized by freeze drying; annealing) were formulated. Further, nicotine stabilisation using MAS (magnesium aluminium silicate) in optimised composite HPMC-SA films and wafers were undertaken. Formulation characterisation was performed using texture analyser (TA) (mechanical and mucoadhesion properties), scanning electron microscopy (SEM) (surface and internal morphology), X-ray diffractometry (XRD) (physical form), attenuated total reflectance – Fourier transform infrared (ATR-FTIR) spectroscopy (physical interactions), thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC), (thermal profiles) and high-performance liquid chromatography (HPLC) (drug loading efficiency and release). NIC stabilisation was required due to challenges of volatility and oxidative degradation associated with NIC especially for films (<35% drug loading efficiency). The incorporation of magnesium aluminium silicate (MAS) (optimum concentration; 0.25% w/v) was therefore necessary to stabilise NIC in HPMC-SA composite wafers and films. Optimized wafers and films (HPMC-SA, 1.25:0.75% w/v) were selected based on the physicochemical properties including drug loading efficiency of wafers and films (>90% NIC). The optimized formulations were used to demonstrate the effect of constituents of simulated saliva (SS) in mucoadhesion, hydration and swelling, and release of NIC, which was further compared with commercially available NiQuitin® strips. In comparison with NiQuitin® strips, optimized wafers and films containing MAS demonstrated NIC stability and a slower release from a mucoadhesive system suitable for targeted buccal drug delivery. Finally, wafers demonstrated a higher permeation flux (140.5547.55g/cm2/hr) than films (42.315.22g/cm2/hr), and can be considered safe (≥ 70% viable cells).

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	Nicotine replacement therapy; drug delivery systems; NiQuitin
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	09 Apr 2019 12:31
URI:	http://gala.gre.ac.uk/id/eprint/23500

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