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.
Highlights
Hypochlorhydria, a major public health problem which is characterized by diminished or even absent gastric acid secretion [1]
Preparation and Optimization of Solid self-nanoemulsifying drug delivery systems (SNEDDS) and solid dispersion (SD). Both drug-free and drug-loaded solid SNEDDS prepared by adsorption onto Neusilin®
The absence of CN from the solid SNEDDS did not have any adverse effect on the solidified powder flow outcomes
Summary
Hypochlorhydria, a major public health problem which is characterized by diminished or even absent (achlorhydria) gastric acid secretion [1]. The most common cause of spontaneous hypochlorhydria is chronic atrophic gastritis, which can be caused by either. More than 30% of individuals aged over 60 years are affected by chronic gastritis which implies that hypochlorhydria is one of the most common pathologies in the aged population. Prolonged use of proton pump inhibitors substantially increases the prevalence of hypochlorhydria, especially in the elder population. Hypochlorhydria is common in patients with gallbladder disease and patients with gallstones [2]. Bariatric surgery significantly reduces gastric capacity leading to significant drop in gastric acid secretions and causing elevated pH level within the remaining gastric pouch [3,4]
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