Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid

Ma, Ying; Zhang, Zeng-Zhu; Li, Gang; Zhang, Jing; Xiao, Hanyang; Li, Xian-Fei

doi:10.3109/10837450.2014.982822

Cited by 22 publications

(9 citation statements)

References 18 publications

(19 reference statements)

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“…13,115,116 Several formulations of UDCA have been developed to try to increase colonic delivery, including conjugation with glutamate, nanosuspensions/nanoparticles, and microbial derivation. [116][117][118] The UDCA-glutamate prevents absorption and biotransformation in the small intestine but takes advantage of the peptide bond cleavage within the colonic brush boarder enzymes to remove the glutamate thus allowing for colonic delivery of UDCA. 116 UDCA nanosuspensions encapsulate this bile acid and allow for increased colonic transit time.…”

Section: Ursodeoxycholic Acid Modulation Of Microbiota-bile Acid-hostmentioning

confidence: 99%

“…116 UDCA nanosuspensions encapsulate this bile acid and allow for increased colonic transit time. 117,118 UDCA could also be microbially derived from administration of UDCA-producing bacteria, such as Clostridium baratii or Ruminococcus gnavus N53 (Figure 3). 61,90 Additional research is required to investigate the use of UDCA-producing bacteria in vivo.…”

Section: Ursodeoxycholic Acid Modulation Of Microbiota-bile Acid-hostmentioning

confidence: 99%

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Diversification of host bile acids by members of the gut microbiota

2019

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Bile acid biotransformation is a collaborative effort by the host and the gut microbiome. Host hepatocytes synthesize primary bile acids from cholesterol. Once these host-derived primary bile acids enter the gastrointestinal tract, the gut microbiota chemically modify them into secondary bile acids. Interest into the gut-bile acid-host axis is expanding in diverse fields including gastroenterology, endocrinology, oncology, and infectious disease. This review aims to 1) describe the physiologic aspects of collaborative bile acid metabolism by the host and gut microbiota; 2) to evaluate how gut microbes influence bile acid pools, and in turn how bile acid pools modulate the gut microbial community structure; 3) to compare species differences in bile acid pools; and lastly, 4) discuss the effects of ursodeoxycholic acid (UDCA) administration, a common therapeutic bile acid, on the gut microbiota-bile acid-host axis.

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Section: Ursodeoxycholic Acid Modulation Of Microbiota-bile Acid-hostmentioning

confidence: 99%

Section: Ursodeoxycholic Acid Modulation Of Microbiota-bile Acid-hostmentioning

confidence: 99%

Diversification of host bile acids by members of the gut microbiota

2019

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“…6,7 However, the main challenge is that dried NC-aggregated particles must have the ability to recover their original nanosuspensions and improve the dissolution of poorly soluble drugs. [8][9][10] Combinations of soluble polymers, sugars, and surfactants have been shown to be effective in stabilizing drug nanosuspensions. 11 This combination allowed for fast recovery of drug NCs from NC-aggregated particles.…”

Section: Introductionmentioning

confidence: 99%

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

Ma¹,

Yang²,

Xie³

et al. 2018

IJN

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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.

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“…Figure 5 shows the RDI of the lyophilized NS. The RDI did not change significantly after one month with and without cryoprotectants [73].…”

Section: Lyophilization and Redispersity Index (Rdi)mentioning

confidence: 76%

Pharmacokinetics and Anti-Diabetic Studies of Gliclazide Nanosuspension

et al. 2022

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Gliclazide (GCZ), an antidiabetic medication, has poor solubility and limited oral bioavailability due to substantial first-pass metabolism. Thus, the purpose of the current study was to optimize and formulate a GCZ nanosuspension (NS) employing the antisolvent precipitation technique. A three-factor, three-level Box–Behnken design (BBD) was used to examine the impact of the primary formulation factors (drug concentration, stabilizer, and surfactant %) on particle size. The optimized NS contains 29.6 mg/mL drug, 0.739% lecithin, and 0.216% sodium dodecyl sulfate (SDS). Under scanning microscopy, the topography of NS revealed spherical particles. Furthermore, NS had a much better saturation solubility than the pure material, which resulted in a rapid dissolving rate, which was attributed to the amorphous structure and smaller particle size of the NS particles. Studies on intestinal permeability using the in vitro noneverted intestinal sac gut method (duodenum, jejunum, and ileum) and single-pass intestinal permeability (SPIP) techniques showed that the effective permeability was also increased by more than 3 fold. In the pharmacokinetic study, the Cmax and AUC0–t values of NS were approximately 3.35- and 1.9-fold higher than those of the raw medication and marketed formulation (MF). When compared to plain drug and commercial formulations, the antidiabetic efficacy of NS demonstrated that it had a significant impact on lowering glucose levels.

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Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid

Cited by 22 publications

References 18 publications

Diversification of host bile acids by members of the gut microbiota

Diversification of host bile acids by members of the gut microbiota

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

Pharmacokinetics and Anti-Diabetic Studies of Gliclazide Nanosuspension

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