Optimization of Quality Attributes and Atomic Force Microscopy Imaging of Reconstituted Nanodroplets in Baicalin Loaded Self-Nanoemulsifying Formulations.

Géza Jakab,István Antal,Tamás Bozó,Emese Balogh,Viktor Fülöp,Miklós Kellermayer

doi:10.3390/pharmaceutics10040275

Géza Jakab, István Antal + Show 4 more

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https://doi.org/10.3390/pharmaceutics10040275

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Journal: Pharmaceutics	Publication Date: Dec 13, 2018
Citations: 23	License type: CC BY 4.0

Affiliation: Semmelweis University

Abstract

The objective of the study was to develop baicalin loaded liquid self-nanoemulsifying drug delivery systems (BSNEDDS) and to characterize them by physicochemical methods in order to optimize the composition and quality attributes. Atomic force microscopy (AFM) was utilized to evaluate the morphological characteristics and size distribution of reconstituted nanoemulsion droplets with a new sample preparation method for the elucidation of individual nanodroplets without any signs of coalescence. Response surface methodology and desirability approach was used to select the optimized composition related to droplet size, zeta-potential, polydispersity index (PDI), and turbidity characteristics. Droplet size distribution measured by dynamic light scattering method was highly desirable with 52.87 ± 0.5322 nm, which was confirmed by AFM imaging. The optimized formula contains Peceol® (14.29%, w/w), Kolliphor® EL (57.14%, w/w), and Transcutol® P (28.57%, w/w). Long-term stability analysis did not show any significant change in droplet size or PDI over the investigated period. More than 40.5-times solubility improvement was achieved with the optimized BSNEDDS correlated to solubility of baicalin in distilled water. In vitro dissolution studies at pH 1.2 and pH 6.8 were performed and revealed that the optimized BSNEDDS formula showed pH independent drug dissolution, and 100% of incorporated baicalin dissolved within five minutes in rapidly dispersing nanodroplets.

Highlights

Scutellaria baicalensis Georgi (S. baicalensis G.) is one of the fundamental herbs in traditional Chinese herbal medicine known as Huang Qin [1]
Baicalin belongs to Class IV of the Biopharmaceutical Classification System (BCS) due to the extremely low water solubility (0.054 mg/mL) and lipophilicity (Papp = 0.037 × 10−6 cm/s, logP = 1.29) [5]
Different ATP-binding cassette (ABC) transporters were identified, which interfere in the enterohepatic recirculation of baicalin [10]

Summary

Introduction

Scutellaria baicalensis Georgi (S. baicalensis G.) is one of the fundamental herbs in traditional Chinese herbal medicine known as Huang Qin [1]. Baicalin belongs to Class IV of the Biopharmaceutical Classification System (BCS) due to the extremely low water solubility (0.054 mg/mL) and lipophilicity (Papp = 0.037 × 10−6 cm/s, logP = 1.29) [5]. It is a weak acidic compound, with pKa values of 7.6 and 10.1 [6]. The absolute bioavailability of baicalin was 2.2 ± 0.2% after intravenous and oral administration to intact rats. It undergoes extensive intestinal glucuronidation and the fraction of baicalin and its conjugated metabolites excreted in urine appear to be negligible compared with the biliary excretion [9]. A baicalin-loaded nanohydrogel formulation showed promising performances in the topical treatment of skin wounds [12]

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