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“…soybean, eggs, sunflower seeds) due to their high surface active properties and biodegradability, these are extensively used in stabilizing oil-water systems. 17 (ii) Saturated lecithins showed higher risk of haemolysis that used in intravenous emulsions when compared with unsaturated lecithins. (i) Semi-synthetic mono-, di-, and triglycerides (MG, DG, and TG) are fractioned glycerides when compared to naturally occurring oils and fats, these have less variability and specified range of acceptability in their compositions.…”

Section: (C) Emulsifiersmentioning

confidence: 99%

Formulation and Evaluation of Silica Lipid Hybrid Microparticles Containing Furosemide

Kumar¹,

Habeeb²,

Mangalarapu³

et al. 2015

Int. Res. J. Pharm.

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The study of the silica-lipid hybrid (SLH) microparticles is to enhance bioavailability and efficacy of poorly water-soluble drugs after oral administration. Lipid-based delivery systems recognized as a potential strategy for improving the oral absorption. Clinical applications of any lipid-based formulations are limited by the lack of clear guidelines of incomplete understanding of absorption mechanism and invitro, invivo formulation performance. Withstanding these problems, the availability of 2-4% oral lipid based products in the pharmaceutical market worldwide has supported in addressing low bioavailability of poorly soluble drugs. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs, that has been developed for the drug, furosemide. It describes the systematic invitro characterization of dissolution and lipolysis properties. Silica-lipid hybrid microparticles include the drug solubilizing effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilization, which leads to enhanced oral bioavailability. Furosemide is mainly used in the treatment of hypertension and congestive heart failure. The role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. The formulation composed of poorly soluble drug (furosemide) and dispersion of oil phase (Soya bean oil) in lecithin (Phospholipoid 90H), surfactant and vortexed until no crystals of drug is observed and are subsequently adsorbed by Aerosol 380 (hydrophilic fumed silica) and stabilized after being transformed to powder state. Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under stimulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for furosemide formulated as SLH microparticles, when compared to that of pure drug (furosemide) and a marketed formulation. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by XRPD (X-ray powder diffraction) and FTIR (Fourier transform infrared spectroscopy) analysis confirmed non-crystalline nature and less compatibility of furosemide in silica-lipid hybrid microparticles.

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“…This is due to the bile acid in the gastrointestinal tract, which plays a key role in the solubilization of poorly soluble compounds and enhances oral absorption. 42) Thus, it is important to evaluate the aqueous solubility contained in the bile acid for poorly soluble compounds because there is the risk that their absorption is strongly affected by the effect of food. In addition, these results demonstrated that JP2-containing 20 mM GCDC was suitable to simulate fluid from fed-state intestine fluid.…”

Section: Takeda Pharmaceutical Co Ltd (Tpc) Approach For Physicochmentioning

confidence: 99%

Impact of Physicochemical Profiling for Rational Approach on Drug Discovery

Nakashima

Yamamoto

Arai

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Solid-state characterization plays a vital role in lead optimization and candidate selection with the appropriate physicochemical properties for proper oral dosage formulation. Aqueous solubility is an important parameter in the successful development of oral dosage formulation since poor aqueous solubility limits absorption. In this study, we summarized an efficient approach using a small amount of sample for solidstate characterization, including thermodynamic solubility, which is defined as physicochemical profiling. By using the physicochemical profiling results of 75 anti-cancer drugs and clinical candidates, we examined the relationship between thermodynamic solubility and molecular structural parameters and assessed the effects of thermodynamic solubility on pharmacokinetic profile for rational soluble drug design. The Log D pH 7.4 , aromatic ring count, and hydrogen bond count were good indicators for predicting sparingly soluble compounds that increase the lattice energy because of π-π stacking and hydrogen bonds, resulting in lowered thermodynamic solubility. The level of thermodynamic solubility in simulated intestinal fluid (pH 6.8) in the presence and absence of bile acid, which is required for minimal acceptable bioavailability (>30%), was 1 µg/ mL and 10 µg/mL, respectively. Physicochemical profiling, which includes thermodynamic solubility considering its solid-state properties, contributes to rational lead optimization and efficient candidate selection for drug development.

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Abstract: The expected increase in solubility as a function of bile salt concentration can be estimated on the basis of the partition coefficient and aqueous solubility of the compound.

Cited by 282 publications

References 21 publications

Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

Formulation and Evaluation of Silica Lipid Hybrid Microparticles Containing Furosemide

Impact of Physicochemical Profiling for Rational Approach on Drug Discovery

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