Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide

Abstract

ObjectiveThe current study sought to design a quickly dissolving, high drug loading nanocrystal-based solid dispersion (NC-SD) in order to improve the dissolution of poorly soluble drugs.MethodsThe NC-SD was prepared by means of combination of homogenization and spray-drying. Polymer hydroxypropylmethylcellulose (HPMC) was used as baseline dispersant for NC-SD of the model drug – andrographolide (AG). Three superdisintegrants cohomogenized with HPMC were used as codispersant for AG-NC-SD and compared to common water-soluble dispersants – mannitol and lactose. The dissolution characterization and oral bioavailability of AG-NC-SD were evaluated.ResultsThe AG-NC-SD with the higher concentration of HPMC exhibited fast dissolution due to the enhanced wettability of HPMC. The water-soluble codispersants (mannitol and lactose) did not completely prevent AG-NC from aggregation during spray-drying. To achieve much faster AG release, cohomogenized superdisintegrants at a level of 20% must be used along with 25% HPMC. Compared with water-soluble dispersants like mannitol and lactose, superdisintegrants with high swelling capacity were much more effective dispersants for enhancing fast redispersion/dissolution of AG-NC-SD via a swelling-triggered erosion/disintegration mechanism. Surfactant-free AG-NC-SD with 15% cohomogenized sodium carboxymethyl starch combined with 15% HPMC and 10% lactose enhanced the dissolution further, without comprising drug loading, exhibited a barely compromised dissolution rate compared to precursor NC suspensions (f2>50), and possessed drug loading up to 67.83%±1.26%. The pharmacokinetics results also demonstrated that the AG-NC-SD significantly improved the bioavailability in vivo of AG (P<0.05), compared with to the coarse AG.ConclusionThis study illustrates that a quickly dissolving, high drug load, surfactant-free NC-SD can be prepared by using a superdisintegrant as codispersant, and provides a feasible strategy to improve the oral bioavailability of poorly soluble drugs.

Oral Bioavailability Enhancement and Anti-Fatigue Assessment of the Andrographolide Loaded Solid Dispersion

“…As depicted in Figure 3a, AG's diffraction pattern was highly crystalline in its natural state, as indicated by the numerous peaks. The results resemble those of Ma et al [19]. The powdered PVP K30 was amorphous where no prominent peaks were detected ( Figure 3b).…”

“…Various formulations have been proposed to improve the solubility, dissolution, and bioavailability of AG. These formulation approaches for AG included solid dispersion (SD) [16][17][18][19][20], liposomes [21], niosomes [22], and solid lipid nanoparticles (SLN) [23] and focused on in vitro characterization for delivery systems and assessing their effects on diverse cell models. The inclusion complex composed of AG and hydroxypropyl-β-cyclodextrin has been proposed to elevate the bioavailability of AG by 1.6-fold [14].…”

“…However, pharmacokinetic data for the above systems are lacking; thus, their effects on the absorption of AG cannot be confirmed. Nanocrystal-based SD prepared by Ma et al [19] and AG-solid self-nanodispersion delivery system developed by Xu et al [20] have exhibited a fast dissolution rate and significantly improved the bioavailability of AG. Nevertheless, several steps containing homogenization and spray-drying technology render the optimization of their preparation process complicated and time-consuming.…”

Andrographolide solid dispersions formulated by Soluplus to enhance interface wetting, dissolution, and absorption

“…Comparing with the oral administration of pure ADG, we found that the mean C max and AUC values of ADG for ADG‐Soluplus solid dispersion were approximately increased 1.96‐ to 2.53‐fold, confirming the superiority of Soluplus as ADG solid dispersion carrier owing to the strong binding affinity between ADG and Soluplus. Compared to other ADG solid dispersions, the ADG‐Soluplus solid dispersion 1:7 had significant high oral bioavailability . Other solid dispersion, including ADG‐PEG 6000, ADG‐PVP VA64, and ADG‐F68, showed little effect on AGD absorption.…”

“…Solid dispersion is designed as drug dispersion system that drug is highly dispersed in a suitable solid carrier, which can effectively change drug physical state from crystalline to amorphous phase owing to the advantages of carriers in enlarging area surface and interacting with drug molecules . Many polymers, such as polyoxyethylene pyrrolidone K30, polyethylene glycol, Eudragit series, hydroxy propyl cellulose, poloxamer, and Soluplus, have been considered as excipients for forming solid dispersion.…”