Combined Self-Nanoemulsifying and Solid Dispersion Systems Showed Enhanced Cinnarizine Release in Hypochlorhydria/Achlorhydria Dissolution Model

Abstract

The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin® US2 at 1:1 and 1:2 ratios. Various CN-SDs were prepared using freeze drying and microwave technologies. The developed SDs were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). In-vitro dissolution studies were conducted to evaluate CN formulations at pH 6.8. Drug-free S-SNEDDSs showed acceptable self-emulsification and powder flow properties. DSC and XRD showed that CN was successfully amorphized into SDs. The combination of drug-free S-SNEDDS + pure CN showed negligible drug dissolution due to poor CN migration into the formed nanoemulsion droplets. CN-SDs and drug-loaded S-SNEDDS showed only 4% and 23% dissolution efficiency (DE) while (drug-free S-SNEDDS + FD-SD) combination showed 880% and 160% enhancement of total drug release compared to uncombined SD and drug-loaded S-SNEDDS, respectively. (Drug-free S-SNEDDS + SD) combination offer a potential approach to overcome the negative impact of hypochlorhydria/achlorhydria on drug absorption by enhancing dissolution at elevated pH environments. In addition, the systems minimize the adverse effect of adsorbent on drug release.

Three-Dimensional Printing of a Container Tablet: A New Paradigm for Multi-Drug-Containing Bioactive Self-Nanoemulsifying Drug-Delivery Systems (Bio-SNEDDSs)

“…The anhydrous SNEDDSs were homogeneous along with their transparent appearance. The drug-loaded SNEDDSs were prepared by dissolving the model drugs, such as CUR and LNS, in blank formulations [ 25 , 26 ]. The right amount of drugs was estimated from the subsequent equilibrium solubility studies.…”

“…The sample was freshly prepared by putting it on the carbon-coated copper grid and osmium was used to stain the lipid components. The dry sample was loaded into the TEM and viewed at different magnification levels [ 26 ].…”

Combined Curcumin and Lansoprazole-Loaded Bioactive Solid Self-Nanoemulsifying Drug Delivery Systems (Bio-SSNEDDS)

“…Each formulation was diluted in distilled water at (1:1000 w/w) ratio and subsequently evaluated for their appearance, homogeneity and spontaneity [33]. The mean droplet size and polydispersity index (PDI) of the (1:1000 w/w) diluted formulations were measured by photon correlation spectroscopy (PCS) using a Zetasizer Nano ZS analyser (Model ZEN3600, Malvern Instruments Co., Worcester-200 shire, UK).…”

“…The mean droplet size and polydispersity index (PDI) of the (1:1000 w/w) diluted formulations were measured by photon correlation spectroscopy (PCS) using a Zetasizer Nano ZS analyser (Model ZEN3600, Malvern Instruments Co., Worcester-200 shire, UK). The particle size of the aqueous dispersions was evaluated using dynamic light scattering (DLS) mode at 25 • C. Zeta potential of each formulation was evaluated by laser Doppler velocimetry (LDV) mode at 25 • C. The average particle size, polydispersity index and zeta potential were determined by taking the mean of three replicates [33,34].…”

Solubility of Cinnarizine in (Transcutol + Water) Mixtures: Determination, Hansen Solubility Parameters, Correlation, and Thermodynamics

“…CNZ is a non-efficient drug molecule due to its low solubility, stability, and poor bioavailability from a physicochemical viewpoint [1][2][3][4][5]. Various lipid-based drug delivery systems, such as self-nanoemulsifying drug delivery systems (SNEDDS) and solidified SNEDDS, have been developed to modify the physicochemical characteristics of CNZ [2,[6][7][8][9][10][11][12][13][14].…”