Preparation and In Vitro–In Vivo Evaluation of Sustained-Release Matrix Pellets of Capsaicin to Enhance the Oral Bioavailability

Abstract

Abstract. Capsaicin has multiple pharmacological activities including antioxidant, anticancer, and antiinflammatory activities. However, its clinical application is limited due to its poor aqueous solubility, gastric irritation, and low oral bioavailability. This research was aimed at preparing sustained-release matrix pellets of capsaicin to enhance its oral bioavailability. The pellets comprised of a core of soliddispersed capsaicin mixed with microcrystalline cellulose (MCC) and hydroxypropyl cellulose (HPMC) and subsequently coating with ethyl cellulose (EC) were obtained by using the technology of extrusion/ spheronization. The physicochemical properties of the pellets were evaluated through scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). Besides, the in vitro release, in vivo absorption, and in vitro-in vivo correlation were also assessed. More importantly, the relative bioavailability of the sustained-release matrix pellets was studied in fasted rabbits after oral administration using free capsaicin and solid dispersion as references. The oral bioavailability of the matrix pellets and sustained-release matrix pellets of capsaicin was improved approximately 1.98-fold and 5.34-fold, respectively, compared with the free capsaicin. A good level A IVIVC (in vitro-in vivo correlation) was established between the in vitro dissolution and the in vivo absorption of sustainedrelease matrix pellets. All the results affirmed the remarkable improvement in the oral bioavailability of capsaicin owing to the successful preparation of its sustained-release matrix pellets.

Premium ethylcellulose polymer based architectures at work in drug delivery

“…with the exception of drug carriers characterized by larger surface areas such as pellets and granules in which cases, the release kinetics tend to be significantly more rapid. Besides, drug release from formulations such as ethylcellulose coated microcapsules may also be a function of the capsular wall thickness in addition to the surface area (Grund et al, 2014, Muschert et al, 2009, Rowe et al, 2009, Zhang et al, 2016a, Zhang et al, 2016b).…”

“…As an ofloxacin-loaded floating bioadhesive multiparticulate delivery system (Fig. 5(a)), ethylcellulose in the form of Surelease® E-7-19040 combined with Eudragit® NE 30D were used to achieve optimal weight gain for robust pellet core structures and as coating which aided an extended release characteristic (Zhang et al, 2016a, Zhang et al, 2016b). Muschert et al (2009) developed multi-layered pellet delivery systems (Fig.…”

“…Ethylcellulose aqueous dispersion NF (Aquacoat®) was employed as an external coat layer and it was discovered that amongst other applied excipients layers, it was dominant for exhibited sustained release characteristics, minimized potential effects of pellet core type and nature of the surrounding bulk fluid.

Fig. 5(a) Morphological differences exhibited by Ethocel™ based (a) ofloxacin-loaded floating bioadhesive multiparticulate delivery system (adapted from Zhang et al, 2016a, Zhang et al, 2016b), (b) multi-layered pellets (adapted from Muschert et al, 2009), (c) tacrolimus containing extended release granules (adapted from Tsunashima et al, 2016), (d) rough surfaced pellets (adapted from Priese et al, 2015), (e) osmotic theophylline pellets (adapted from Kazlauske et al, 2017), (f) reservoir type extended release multiparticulates (adapted from Franc et al, 2016), (g) wax based floating sustained-release dispersion pellets (adapted from Yan et al, 2016).

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Capsaicin Loaded Solid SNEDDS for Enhanced Bioavailability and Anticancer Activity: In-Vitro, In-Silico, and In-Vivo Characterization

“…7 Capsaicin (305.41 g/mol), an alkaloid is a homovanillic acid derivative & being a major component of Capsicum annuum (Solanaceae) responsible for its spicy & pungent taste. 8,9 Since its discovery, Capsaicin has loads of activities to its credits such as analgesic & anti-inflammatory, anti-pruritis, gastro-protection, antiemetabolic syndrome effects, etc. 8e11 Furthermore, capsaicin has showed prominent effect against gastric, 12 lung 13 bladder, breast, 14 and prostate cancer cells.…”

Development of a HPLC Method for the Quantitative Determination of Capsaicin in Collagen Sponge

“…LC-MS/MS and HPLC methodology were reported for the determination of capsaicin in different applications such as liposomes, pellets [16–18]. As far as we know, there were no reports about the collagen sponge capsaicin loaded.…”