The effect of α-tocopherol on the in vitro solubilisation of lipophilic drugs

Nielsen, Poul; Müllertz, Anette; Norling, T.; Kristensen, H. G.

doi:10.1016/s0378-5173(01)00701-3

Cited by 69 publications

(34 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, a very distinct difference in degree of solubilization when long-chain lipolytic products were used to when medium-chain lipolytic products were used, has been demonstrated for the solubility of very lipophilic drugs. The use of long-chain lipolytic products was beneficial for an enhanced solubility (22). This may partly explain the high solubility found for all model drugs in early FeSSIF (6.5 mM monoolein, 40 mM oleate).…”

Section: Early Middle and Late Postprandial Mediamentioning

confidence: 99%

Postprandial Changes in Solubilizing Capacity of Human Intestinal Fluids for BCS Class II Drugs

Clarysse¹,

Psachoulias

Brouwers³

et al. 2009

Pharm Res

112

118

View full text Add to dashboard Cite

show abstract

Section: Early Middle and Late Postprandial Mediamentioning

confidence: 99%

Postprandial Changes in Solubilizing Capacity of Human Intestinal Fluids for BCS Class II Drugs

Clarysse¹,

Psachoulias

Brouwers³

et al. 2009

Pharm Res

112

118

View full text Add to dashboard Cite

show abstract

“…As seen for other poorly soluble drugs, 8,9,18,19 BS and PL increase the solubility of seocalcitol significantly, compared with the solubility in water. The solubility of seocalcitol in SIM (20 mM BS and 5 mM PL) increases more than 8000 times compared with the solubility in water (168 mg/mL vs. 20 ng/mL).…”

Section: Solubility Of Seocalcitol In Simulated Intestinal Mediamentioning

confidence: 74%

“…Solubility studies with simulated intestinal media (SIM) containing medium chain lipolytic products (MC-LP) or long chain lipolytic products (LC-LP) may give valuable information about what kind of lipids that most efficiently keep the drug substance in solution. [7][8][9] It has been shown that drug substances with low log P (approximately 2) seem to have a better solubility in media containing MC-LP, whereas the solubility of drug substances with high log P (8-9) is favored by adding LC-LP to the media. 8,9 For felodipine, having a log P of 4.8, the best solubilising capacity was found in SIM containing LC-LP 8 whereas for danazol, having a log P of 4.5, the best solubility capacity was found in SIM containing MC-LP.…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] It has been shown that drug substances with low log P (approximately 2) seem to have a better solubility in media containing MC-LP, whereas the solubility of drug substances with high log P (8-9) is favored by adding LC-LP to the media. 8,9 For felodipine, having a log P of 4.8, the best solubilising capacity was found in SIM containing LC-LP 8 whereas for danazol, having a log P of 4.5, the best solubility capacity was found in SIM containing MC-LP. 9 Thus, as to drug substances with log P values around 4-5 no clear trend is seen regarding the type of lipid that will cause the highest increase in the solubility in biorelevant media why solubility studies in SIM with LP can be used as a tool to gain information about what kind of lipid to use.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bioavailability of seocalcitol I: Relating solubility in biorelevant media with oral bioavailability in rats—effect of medium and long chain triglycerides

Grove

Pedersen

Nielsen

et al. 2005

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…The drug and excipient blend was loaded on to the core pellets with the aid of the binder solution and various process parameters were optimized using fluid bed coater that is more automated and advanced technique compared to conventional pan coating. The potential use of vitamin E preferably alpha tocopherol as antioxidant to protect plasma low density lipoproteins [5] and the use of alpha tocopherol as solubilizer for poorly soluble and highly lipophilic drug griseofulvin is well reported [6]. Owing to the dual advantages Alpha Tocopherol (AT) was selected as solubilizer for fenofibrate.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

Indira¹

2012

JBB

View full text Add to dashboard Cite

The purpose of this study was to investigate the effect of different solubilizers namely alpha tocopherol, soy phosphatidylcholine 70, Phospholipon 80H, and Phospholipon 90H on the bioavailability of sustained release fenofibrate pellets using fluid bed coating by applying Taguchi design to optimize the type and concentration of solubilizer at four levels namely 0.5%, 1%, 1.5%, and 2%. The pellets were prepared by loading the fenofibrate blended with other excipients onto the core sugar pellets with the aid of the binder solution. Taguchi experimental runs with alpha tocopherol 1% and Phospholipon 90H 2% (test) showed significant differences in in vitro dissolution behavior of drug compared to the pure drug. The pharmacokinetics of pure drug and test was evaluated in healthy male Wistar rats and found that t 1/2 was reduced significantly (4.36 and 4.02 hours) while AUC 0-t (32.14 ± 6.38 μg h/ml, 36.94 ± 6.2 μg h/ml), C max (8.7 ± 2.31 μg/ml, 9.8 ± 2.2 μg/ml) were improved markedly compared to the pure drug with t 1/2 (7.339314 ± 3.1 hours), AUC 0-t (11.89 ± 8.13 μg h/ml), and C max (5.137 ± 3.37 μg/ml). The extent of the mean plasma exposure of fenofibrate was 2.7 and 3.1 fold higher in animals treated with test. The ANOVA results revealed that type and concentration of solubilizer are crucial for enhancement of in vitro dissolution profile. Hence use of solubilizers may be the promising way to improve the oral bioavailability of fenofibrate. Enhancement of Bioavailability of MethodsDrug loading: Drug was loaded onto sugar spheres using fluidized bed processor . The sugar spheres were loaded into the fluidized bed processor and warmed for about 10 -15 minutes. Binder solution was prepared by dissolving Povidone K30 and sugar in purified water under constant stirring. Unmicronized fenofibrate which was pre blended and pulverized (0.5 mm screen pulverizer) with other excipients was incorporated intermittently into the solution under constant stirring. The obtained solution was loaded onto the circulating sugar spheres (800 μm). The wet spheres were dried simultaneously during the process of circulation in wurster chamber. The process was continued till the complete solution was consumed. The various processing variables namely inlet air temperature (40-45°C), outlet air temperature (30-33°C), product temperature (36-40°C), chamber humidity (58-60%), air flow (85 m 3 /hr), compressed air pressure (1.5-3.0 kg/cm 2 )The peristaltic pump rpm (10-35) and spray rate (2 ml/min) were optimized in the preliminary trials.Design of experiment to optimize drug loaded fenofibrate pellets: Taguchi L16 design of experiment was used to study the effect of two variables namely, type of solubilizer and concentration of solubilizer at four different levels as given in Table 1 and Table 2. All the experimental runs were analyzed using Minitab statistical software package (version 15). Characterization methodsInfrared Spectroscopy analysis of drug and excipients: FT-IR spectra were obtained using FT-IR spectrometer (Model Nic...

show abstract

The effect of α-tocopherol on the in vitro solubilisation of lipophilic drugs

Cited by 69 publications

References 12 publications

Postprandial Changes in Solubilizing Capacity of Human Intestinal Fluids for BCS Class II Drugs

Postprandial Changes in Solubilizing Capacity of Human Intestinal Fluids for BCS Class II Drugs

Bioavailability of seocalcitol I: Relating solubility in biorelevant media with oral bioavailability in rats—effect of medium and long chain triglycerides

Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

Contact Info

Product

Resources

About