Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol

Abstract

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3(2) Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as Cmax, Tmax, Ke, Ka, Vd and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183 ± 2.43 nm with an entrapment efficiency of 81.4 ± 0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in Cmax (two fold, p < 0.001) and AUC (four folds, p < 0.001) of carvedilol when compared to carvedilol suspension. Car-NS were found to be stable for a period of 3 months. Thus, a stable, floating, multiparticulate GMO/Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.

Microfluidic Particle Engineering of Hydrophobic Drug with Eudragit E100─Bridging the Amorphous and Crystalline Gap

“…First, a vast majority of APIs exhibit poor powder flow properties that restrict their processability − and maximum loading in the final dosage form. − Second, a significant fraction of commercial APIs and those in discovery pipelines are hydrophobic, which limits their oral bioavailability in vivo. − Both powder flow and bioavailability of solid API are governed by the interplay of their critical quality attributes including particle morphology, − size, , and solid-state. ,,− Co-processing APIs with excipients is a promising particle engineering technique to gain control over these critical attributes and manifest superior API performance. − Excipients, although non-therapeutic, play an indispensable role in oral dosage by serving as matrices to control drug loading, , solid-state outcomes, , and tune drug release. , With the APIs being exposed to varied pH conditionshighly acidic in the stomach (1–3) to physiological values (6–7.5) in the saliva and intestinesacross the gastrointestinal tract, the use of pH-responsive excipients to modulate their release has gained significant traction in the last two decades . Eudragit E100, belonging to a class of polymethacrylate-based copolymers, is one such widely used excipient with solubility in gastric fluid up to pH 5. − E100 is reportedly non-toxic and is utilized for modulating drug release − and taste masking ,,,, in pharmaceutical formulations either on its own or in combination with other Eudragit , and non-Eudragit polymers. ,− The traditional utility of E100, however, has been heavily limited to generating amorphous solid dispersions by inhibiting precipit...…”

Poly‐L‐lactide scaffolds with super pores obtained by freeze‐extraction method

“…In addition, it was used as a nanosphere matrix to increase the bioavailability of a medication. Moreover, as a transdermal administration route because of good adhesion to skin (Alasino, Leonhard, Bianco, & Beltramo, 2012; Patil, Roy, Choudhary, & Mahadik, 2016). Recently, its mucoadhesive properties have been utilized, proving a lack of irritative properties (Porfiryeva et al, 2019).…”