Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

AIM: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. METHODS: A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. RESULTS: The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = -25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. CONCLUSIONS: The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.

Probucol Self-Emulsified Drug Delivery System: Stability Testing and Bioavailability Assessment in Human Volunteers.

BACKGROUND: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-emulsify in GIT and improve the absorption and bioavailability. Probucol (PB) is a highly lipophilic compound with very low and variable bioavailability. OBJECTIVE: The objectives of this study were to examine the stability and conduct bioavailability of the prepared Probucol Self-Emulsified Drug Delivery System (PBSEDDS) in human volunteers. METHODS: The methods included preparation of different PBSEDDS using soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (co-surfactant). The formulations were characterized in vitro for spontaneity of emulsification, droplet size, turbidity and dissolution in water after packing in HPMC capsules. The optimized formulations were evaluated for stability at different storage temperatures and human bioavailability compared with the drug dissolved in soybean oil (reference). RESULTS: The results showed that formulations (F1-F4) were stable if stored at 20 °C. The mean (n=3) pharmacokinetic parameters for stable formulations were: The Cmax, 1070.76, 883.16, 2876.43, 3513.46 and 1047.37 ng/ml; the Tmax, 7.93, 7.33, 3.96, 3.67 and 4.67 hr.; the AUC (0-t), 41043.41, 37763.23, 75006.26, 46731.36 and 26966.43 ng.hr/ml for F1, F2, F3, F4 and reference, respectively. The percentage relative bioavailability was in this order: F3> F4> F1> F2>. CONCLUSION: In conclusion, the PBSEDDS formulations were stable at room temperature. F4 showed the highest Cmax and the shortest Tmax. All the formulations showed significant enhancement of bioavailability compared with the reference. The results illustrated the potential use of SEDDS for the delivery of probucol hydrophobic compound.

Voluntary ingestion of antiparasitic drugs emulsified in honey represents an alternative to gavage in mice.

The oral route is the most frequently used method of drug intake in humans. Oral administration of drugs to laboratory animals such as mice typically is achieved through gavage, in which a feeding needle is introduced into the esophagus and the drug is delivered directly into the stomach. This method requires technical skill, is stressful for animals, and introduces risk of injury, pain and morbidity. Here we investigated another method of drug administration. The benzimidazole derivative albendazole was emulsified in commercially available honey and administered to mice by voluntary feeding or gavage. Mice that received albendazole by either gavage or honey ingestion had virtually identical levels of serum albendazole sulfoxide, indicating that uptake and metabolism of albendazole was similar for both administration techniques. In addition, dosing mice with the albendazole-honey mixture for 8 wk had antiparasitic activity comparable to earlier studies using gavage for drug administration. Compared with gavage, voluntary ingestion of a drug in honey is more rapid, less stressful to the animal, and less technically demanding for the administrator. Because of its low cost and ready availability, honey presents a viable vehicle for drug delivery.

Final amended report on safety assessment on aminomethyl propanol and aminomethyl propanediol.

Aminomethyl propanol and aminomethyl propanediol are substituted aliphatic alcohols that function as pH adjusters in cosmetic products at concentrations less than 10%; additionally, aminomethyl propanediol is a fragrance. Extensive oral toxicity data are reviewed, with fewer inhalation toxicity data. Dermal toxicity data are presented that demonstrate, for example, that a mascara with 1.92% aminomethyl propanediol does not cause dermal irritation or allergic contact sensitization, suggesting that the maximum reported use concentration of 2% in mascara would be safe. Although these ingredients are primary amines that are not substrates for N-nitrosation, they may contain secondary amines as impurities in finished products that may undergo N-nitrosation. These ingredients should not be included in cosmetic formulations containing N-nitrosating agents. The Cosmetic Ingredient Review Expert Panel concludes that aminomethyl propanol and aminomethyl propanediol are safe as cosmetic ingredients in the practices of use and concentrations as described in this safety assessment.

Assessment of dietary exposure in the French population to 13 selected food colours, preservatives, antioxidants, stabilizers, emulsifiers and sweeteners.

The results of French intake estimates for 13 food additives prioritized by the methods proposed in the 2001 Report from the European Commission on Dietary Food Additive Intake in the European Union are reported. These 13 additives were selected using the first and second tiers of the three-tier approach. The first tier was based on theoretical food consumption data and the maximum permitted level of additives. The second tier used real individual food consumption data and the maximum permitted level of additives for the substances which exceeded the acceptable daily intakes (ADI) in the first tier. In the third tier reported in this study, intake estimates were calculated for the 13 additives (colours, preservatives, antioxidants, stabilizers, emulsifiers and sweeteners) according to two modelling assumptions corresponding to two different food habit scenarios (assumption 1: consumers consume foods that may or may not contain food additives, and assumption 2: consumers always consume foods that contain additives) when possible. In this approach, real individual food consumption data and the occurrence/use-level of food additives reported by the food industry were used. Overall, the results of the intake estimates are reassuring for the majority of additives studied since the risk of exceeding the ADI was low, except for nitrites, sulfites and annatto, whose ADIs were exceeded by either children or adult consumers or by both populations under one and/or two modelling assumptions. Under the first assumption, the ADI is exceeded for high consumers among adults for nitrites and sulfites (155 and 118.4%, respectively) and among children for nitrites (275%). Under the second assumption, the average nitrites dietary exposure in children exceeds the ADI (146.7%). For high consumers, adults exceed the nitrite and sulfite ADIs (223 and 156.4%, respectively) and children exceed the nitrite, annatto and sulfite ADIs (416.7, 124.6 and 130.6%, respectively).