scholarly journals Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

ADMET & DMPK ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 183-195 ◽  
Author(s):  
Asami Ono ◽  
Naoya Matsumura ◽  
Takahiro Kimoto ◽  
Yoshiyuki Akiyama ◽  
Satoko Funaki ◽  
...  
Keyword(s):  
Shake Flask ◽  
Water Soluble ◽  
Equilibrium Solubility ◽  
Poorly Water Soluble Drugs ◽  
Solubility Measurement ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Proprietary Protocol

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP.

scholarly journals The effect of drug ionization on lipid-lased formulations for the oral delivery of anti-psychotics

ADMET & DMPK ◽  
2020 ◽  
Author(s):  
Tahlia R Meola ◽  
Kara Paxton ◽  
Paul Joyce ◽  
Hayley B Schultz ◽  
Clive A Prestidge
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Fold Increase ◽  
Water Soluble ◽  
Equilibrium Solubility ◽  
Poorly Water Soluble Drugs ◽  
Physiochemical Properties ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Rate Limiting

<p class="ADMETabstracttext">Lipid-based formulations (LBFs) are well-known to improve the oral bioavailability of poorly water-soluble drugs (PWSDs) by presenting the drug to the gastrointestinal environment in a molecularly dispersed state, thus avoiding the rate-limiting dissolution step. Risperidone and lurasidone are antipsychotics drugs which experience erratic and variable absorption, leading to a low oral bioavailability. The aim of this research was to develop and investigate the performance of risperidone and lurasidone when formulated as an emulsion and silica-lipid hybrid (SLH). Lurasidone and risperidone were dissolved in Capmul® MCM at 100% and 80% their equilibrium solubility, respectively, prior to forming a sub-micron emulsion. SLH microparticles were fabricated by spray-drying a silica stabilised sub-micron emulsion to form a solid powder. The performances of the formulations were evaluated in simulated intestinal media under digesting conditions, where the emulsion and SLH provided a 17-fold and 23-fold increase in LUR solubilisation, respectively. However, the performance of RIS was reduced by 2.2-fold when encapsulated within SLH compared to pure drug. Owing to its pKa, RIS adsorbed to the silica and thus, dissolution was significantly hindered. The results reveal that LBFs may not overcome the challenges of all PWSDs and physiochemical properties must be carefully considered when predicting drug performance.</p>

scholarly journals Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update

2016 ◽  
Vol 19 (2) ◽  
pp. 208 ◽  
Author(s):  
Meiyan Yang ◽  
Wei Gong ◽  
Yuli Wang ◽  
Li Shan ◽  
Ying Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Formulation Development ◽  
Equilibrium Solubility ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Soluble ◽  
Poorly Water Soluble

The formulation development for poorly soluble drugs still remains a challenge. Supersaturating drug delivery systems (SDDS) or drug delivery systems based on supersaturating provide a promising way to improve the oral bioavailability of poorly water-soluble drugs. In supersaturable formulations, drug concentration exceeds the equilibrium solubility when exposed to gastrointestinal fluids, and the supersaturation state is maintained long enough to be absorbed, resulting in compromised bioavailability. In this article, the mechanism of generating and maintaining supersaturation and the evaluation methods of supersaturation assays are discussed. Recent advances in different drug delivery systems based on supersaturating are the focus and are discussed in detail.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shivarani Eesam ◽  
Jaswanth S. Bhandaru ◽  
Chandana Naliganti ◽  
Ravi Kumar Bobbala ◽  
Raghuram Rao Akkinepally
Keyword(s):  
Aqueous Solubility ◽  
Sem Analysis ◽  
Water Soluble ◽  
High Permeability ◽  
Poorly Water Soluble Drugs ◽  
Drug Discovery And Development ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Dissolution In Vitro

Abstract Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs

2016 ◽  
Vol 105 (9) ◽  
pp. 2864-2872 ◽  
Author(s):  
Sara B.E. Andersson ◽  
Caroline Alvebratt ◽  
Jan Bevernage ◽  
Damien Bonneau ◽  
Claudia da Costa Mathews ◽  
...  
Keyword(s):  
Water Soluble ◽  
Small Scale ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Interlaboratory Validation ◽  
Poorly Water Soluble

Development of biodegradable porous starch foam for improving oral delivery of poorly water soluble drugs

2011 ◽  
Vol 403 (1-2) ◽  
pp. 162-169 ◽  
Author(s):  
Chao Wu ◽  
Zhongyan Wang ◽  
Zhuangzhi Zhi ◽  
Tongying Jiang ◽  
Jinghai Zhang ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Water Soluble ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

scholarly journals Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Wei Xu ◽  
Peixue Ling ◽  
Tianmin Zhang
Keyword(s):  
Drug Delivery ◽  
Residence Time ◽  
Oral Delivery ◽  
Polymeric Micelles ◽  
Water Soluble ◽  
Gi Tract ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Accepted Form

Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

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