Revealing the mechanism of morphological variation of amorphous drug nanoparticles formed by aqueous dispersion of ternary solid dispersion

2021 ◽  
pp. 120984
Author(s):  
Zhijing Zhao ◽  
Kenjirou Higashi ◽  
Keisuke Ueda ◽  
Kunikazu Moribe
Keyword(s):  
Solid Dispersion ◽  
Morphological Variation ◽  
Aqueous Dispersion ◽  
Drug Nanoparticles ◽  
Ternary Solid Dispersion ◽  
Amorphous Drug

scholarly journals Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 206 ◽  
Author(s):  
Rajiv Bajracharya ◽  
Sang Hoon Lee ◽  
Jae Geun Song ◽  
Minkyoung Kim ◽  
Kyeong Lee ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous State ◽  
Weight Ratio ◽  
Acid Methyl Ester ◽  
Systemic Exposure ◽  
Aqueous Solubility ◽  
Poloxamer 407 ◽  
Cancer Resistance ◽  
Ternary Solid Dispersion

LW6 (3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-benzoic acid methyl ester) is a potent inhibitor of drug efflux by the breast cancer resistance protein (BCRP). However, its poor aqueous solubility leads to low bioavailability, which currently limits in vivo applications. Therefore, the present study aimed to develop ternary solid dispersion (SD) formulations in order to enhance the aqueous solubility and dissolution rate of LW6. Various SDs of LW6 were prepared using a solvent evaporation method with different drug/excipient ratios. The solubility and dissolution profiles of LW6 in different SDs were examined, and F8-SD which is composed of LW6, poloxamer 407, and povidone K30 at a weight ratio of 1:5:8 was selected as the optimal SD. The structural characteristics of F8-SD were also examined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In the acidic to neutral pH range, F8-SD achieved rapid dissolution with a drug release of 76–81% within 20 min, while the dissolution of pure LW6 was negligible. The XRPD patterns indicated that F8-SD probably enhanced the solubility and dissolution of LW6 by changing the drug crystallinity to an amorphous state, in addition to the solubilizing effect of the hydrophilic carriers. Furthermore, F8-SD significantly improved the oral bioavailability of topotecan, which is a BCRP substrate, in rats. The systemic exposure of topotecan was enhanced approximately 10-fold by the concurrent use of F8-SD. In conclusion, the ternary SD formulation of LW6 with povidone K30 and poloxamer 407 appeared to be effective at improving the dissolution and in vivo effects of LW6 as a BCRP inhibitor.

scholarly journals Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers

2007 ◽  
Vol 57 (3) ◽  
pp. 287-300 ◽  
Author(s):  
Ravindra Dhumal ◽  
Shamkant Shimpi ◽  
Anant Paradkar
Keyword(s):  
Hydrogen Bonding ◽  
Solid Dispersion ◽  
Dissolution Profile ◽  
Scanning Calorimetry ◽  
Unit Operations ◽  
Bonding Interaction ◽  
Amorphous Drugs ◽  
The Stability ◽  
Amorphous Drug ◽  
Spray Dried

Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizersThe purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.

Amorphization Strategy Affects the Stability and Supersaturation Profile of Amorphous Drug Nanoparticles

2014 ◽  
Vol 11 (5) ◽  
pp. 1611-1620 ◽  
Author(s):  
Wean Sin Cheow ◽  
Tie Yi Kiew ◽  
Yue Yang ◽  
Kunn Hadinoto
Keyword(s):  
Drug Nanoparticles ◽  
The Stability ◽  
Amorphous Drug

Enhancement of solubility and oral bioavailability of manidipine by formation of ternary solid dispersion with d-α-tocopherol polyethylene glycol 1000 succinate and copovidone

2017 ◽  
Vol 43 (12) ◽  
pp. 2064-2075 ◽  
Author(s):  
Benchawan Chamsai ◽  
Sontaya Limmatvapirat ◽  
Srisagul Sungthongjeen ◽  
Pornsak Sriamornsak
Keyword(s):  
Polyethylene Glycol ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Polyethylene Glycol 1000 ◽  
Ternary Solid Dispersion

scholarly journals Enhancement of docetaxel solubility using binary and ternary solid dispersion systems

2015 ◽  
Vol 41 (11) ◽  
pp. 1847-1855 ◽  
Author(s):  
Sue May Lim ◽  
Zyu Wenn Pang ◽  
Hwei Yuin Tan ◽  
Mohsin Shaikh ◽  
Gorajana Adinarayana ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Dispersion Systems ◽  
Ternary Solid Dispersion

Formulation and Evaluation of Carbamazepine Tablets using Biosurfactant in Ternary Solid Dispersion System

2020 ◽  
Vol 54 (2) ◽  
pp. 302-309
Author(s):  
Uday Baburao Bolmal ◽  
Ramnathkar Prajakta Subhod ◽  
Anand Panchaxari Gadad ◽  
Archana Sidagouda Patill
Keyword(s):  
Solid Dispersion ◽  
Dispersion System ◽  
Ternary Solid Dispersion
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