Purpose: Solidification of lipid formulations using adsorbents became a well-known technique attracting great interests due to its favourable properties including flexibility in dose division, reduction of intra-subject and inter-subject variability, improvement in efficacy/safety profile and enhancement of physical/chemical stability. The current study aims to convert liquid self-emulsifying/nanoemulsifying drug delivery systems (SEDDS/SNEDDS) into solid SEDDS/SNEDDS and investigate how the adsorption of drug onto an inorganic high surface area material Neusilin® grade US2 (NUS2) and SYLOID (SYL) affects in vitro dissolution performance.
Methods: Four Liquid SEDDS/SNEDDS formulations were designed for the model anti-histaminic drug cinnarizine (CN). Self-emulsification assessment studies were conducted to evaluate the liquid SEDDS/SNEDDS performance. NUS2 and SYL were used to solidify the liquid SEDDS/SNEDDS. The solidified drug loaded formulation powder were characterized using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). In vitro dissolution studies were conducted to evaluate the liquid SEDDS/SNEDDS formulations and investigate the influence of solidification by adsorption on CN release.
Results: Liquid formulation containing mixed glycerides and coconut oil fatty acid (COFA) showed excellent self-emulsification performance with turbid and transparent appearance, respectively. On the other hand, formulations containing capric and caprylic acid showed poor self-emulsification with non-dispersible flakes. Solidification studies showed that use of 50% (w/w) adsorbent in the liquid formulation yield free flowing powder with no agglomeration but Neusilin® produced smooth granules than Syloid® and kept the drugs stable is amorphous state. In vitro dissolution studies of liquid formulations showed that mixed medium chain glycerides provided high dissolution efficiency and reproducibility. On the other hand, formulation containing capric and caprylic acid showed high variability and significant drug precipitation against time. COFA showed reproducible but lower dissolution efficiency compared to medium chain glyceride counterparts. Solidification of liquid SEDDS with NUS2 and SYL led to significant inhibition of CN release from the formulation. However, NUS2 showed higher dissolution efficiency compared to SYL.
Conclusion: In the present study, solidified powder formulations of CN from liquid SEDDS/SNEDDS were successfully prepared using NUS2/SYL as adsorbent carrier. The overall results from the characterization and in vitro dissolution studies confirmed that liquid formulations containing mixed glycerides and its conversion using NUS2 showed enhanced efficiency/release rate compared to free fatty acids.