ABSTRACT
The content of latanoprost, a therapeutic drug for glaucoma, is likely to decrease in solution. In a previous study, we confirmed that this was associated with latanoprost adsorption to the container and hydrolysis of latanoprost, and established a formulation of latanoprost eye drop solution that can be stored at room temperature. In addition, we clarified that a surfactant added to the formulation stabilized latanoprost by forming complex micelle. In this study, we investigated the influence of structure of surfactants in the stabilization of latanoprost. Non-ionic surfactants involving the polyoxyethylene chain (additive mol number: 20 or more) and the straight-chain alkyl group, with an HLB of 15.0 or more, markedly inhibited a decrease in the latanoprost content and its degradation. These surfactants are soluble in the formulation of eye drop solution, leading to micelle formation even at a low concentration, and they are not influenced by the temperature. Therefore, they may exhibit marked stabilization effects. In addition, there was no influence on the stability of latanoprost when adding benzalkonium chloride, as a preservative, to a formulation involving these surfactants.
Subject(s)
Ophthalmic Solutions/chemistry , Prostaglandins F, Synthetic/chemistry , Surface-Active Agents/chemistry , Adsorption , Benzalkonium Compounds/chemistry , Drug Packaging , Drug Stability , Latanoprost , Polyethylene/chemistry , Preservatives, Pharmaceutical/chemistryABSTRACT
The content of latanoprost is likely to decrease in solution because of the adsorption to eye drop containers and hydrolysis. We reduced these problems and established a formulation of latanoprost eye drops which is stable at room temperature. We assume that the additive surfactants form micelles and stabilize latanoprost in this formulation. In this study, we elucidated the latanoprost stabilization mechanism. It was revealed by Arrhenius analysis that the adsorption to eye drop containers and hydrolysis of latanoprost were temperature-dependent. In addition, polyethylene glycol monostearates inhibited the adsorption and hydrolysis of latanoprost at 1 mg/mL, which exceeded the critical micelle concentration. By the fluorescent probe method, it was suggested that the surfactants were associated with benzalkonium chloride and formed complex micelles consisting of about 10 molecules, and latanoprost interacted with the micelles at 1:1. By (1)H NMR, it was revealed that adsorption was inhibited by arranging the hydrophobic group toward the center of complex micelles and that hydrolysis was inhibited by interaction between the ester group and the complex micelles. It was shown that the latanoprost is stabilized by the interaction with complex micelles. It was effective for the inhibition of both adsorption and degradation.
Subject(s)
Antihypertensive Agents/chemistry , Prostaglandins F, Synthetic/chemistry , Surface-Active Agents/chemistry , Adsorption , Antihypertensive Agents/administration & dosage , Benzalkonium Compounds/chemistry , Drug Packaging , Drug Stability , Hydrolysis , Hydrophobic and Hydrophilic Interactions , Latanoprost , Magnetic Resonance Spectroscopy , Micelles , Ophthalmic Solutions , Prostaglandins F, Synthetic/administration & dosage , Spectrometry, Fluorescence , TemperatureABSTRACT
In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration. Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences. Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein (P-gp) is one of the major factors in drug-drug interactions, we focused on this transporter. We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/drug effects , Ubiquinone/analogs & derivatives , Vitamins/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/physiology , Biological Transport/drug effects , Caco-2 Cells , Digoxin/pharmacology , Drug Interactions , Humans , Intestinal Mucosa/metabolism , Quinidine/pharmacology , Rhodamine 123/pharmacology , Ubiquinone/pharmacokinetics , Ubiquinone/pharmacologyABSTRACT
Coenzyme Q10 (CoQ10) is widely consumed as a food supplement because of its recognition as an important nutrient in supporting human health. Absorption of compounds from the gastrointestinal tract is one of the important determinants of oral bioavailability. However, the absorption of dietary CoQ10 is slow and limited due to its hydrophobicity and large molecular weight. The absorption of orally applied compounds can be enhanced by interactions with food or food components. Thus, we investigated the effect of food intake on the absorption of CoQ10 after oral supplementation. In this study, we demonstrated that food intake enhanced the intestinal absorption of CoQ10. In order to improve intestinal absorption of CoQ10 after oral supplementation, we developed an emulsion formulation. Intestinal absorption of CoQ10 after administration of the emulsion formulation was also enhanced by food intake. Moreover, the peak concentration and the extent of absorption after administration of the emulsion formulation were greater than those after administration of a suspension formulation. It is possible that administration of CoQ10 in an emulsion formulation enhances the pharmacological effects of CoQ10.
