Development and optimization of orally disintegrating tablets containing Centella asiatica solid lipid nanoparticles for supportive therapies of Parkinson's disease

Abstract

Background: Parkinson's disease (PD) is the most common chronic progressive neurodegenerative disorder in the older population. In this work, we have developed a formulation of orally disintegrating tablets (ODTs) containing Centella asiatica (CA) encapsulated solid lipid nanoparticles (SLNs) with rapid disintegration and dissolution, thereby providing greater convenience and ease of use to older patients with PD or dysphagia. Methods: The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of CA compounds were evaluated using QikProp module of Schrödinger. CA-SLNs were prepared using hot homogenization method. The physicochemical properties and quality control of the pre-compressed powder were characterized. The direct compression method was used to prepare ODTs, and post-compression physical properties were evaluated. Results: In silico study of ADMET properties revealed the CA compounds can follow the criteria for an orally active drug and are within the standard range in terms of "Rule of Five" and "Rule of Three”. The characteristics of CA-SLNs developed in a lipid-based nanocarrier showed monodispersed particles with an average particle size of about 37.91±1.55 nm, zeta potential of -10.27±1.37 mV, encapsulation efficiency, and loading capacity of 95.07±1.14%, and 3.99±0.06%, respectively. The results obtained for the pre-compression characterization showed that the CA-SLNs powder mixture had excellent flowability properties and compressibility. Furthermore, these results affected the physical properties of CA-SLNs ODTs with a disintegration time of 14.5s, the acceptance value of content uniformity was 3.2%, and the in vitro dissolution test fulfilled the tolerance limits recommended in the United States Pharmacopeia (USP) monograph. Conclusions: Overall, these results suggest that CA-SLNs ODTs developed with lipid-based nanocarriers can be considered an alternative delivery system to protect the active compound from instability while enhancing permeability through the blood brain barrier (BBB) and can be used in the management of PD in older patients with dysphagia.