Formulation of Ibuprofen in Liquid Crystalline Phases and In Vitro Digestion

Abstract

Ibuprofen (IBU), a poorly water-soluble according to Biopharmaceutic Classification System (BCS) Class II drug, presented challenges in oral delivery due to its limited solubility and pH-dependent precipitation. This study investigated the use of lyotropic liquid crystalline phases (LLCPs) as lipid-based delivery systems to enhance IBU solubilization and control its release in vitro digestion. Three lipid mixtures (LMs), including lipid mixture 1 (LM1), lipid mixture 2 (LM2), lipid mixture 3 (LM3) were prepared and evaluated using a standardized in vitro digestion model with pH-stat titration.
IBU release kinetics were quantified by reversed-phase high-performance liquid chromatography (HPLC), while lipid digestion and structural evolution were assessed using Gas Chromatography-Flam Ionization Detector (GC-FID) and dynamic light scattering (DLS). All systems showed time-dependent increase in IBU release; however, release profiles differed significantly with lipid composition. LM1 (20% w/w loading) reached 86% release at 60 min, whereas LM2 (5% w/w loading) showed the highest relative release efficiency (91% at 90 min) but with pronounced non-monotonic behavior. In contrast, LM3 (10% w/w loading) demonstrated a sustained and stable release profile throughout intestinal digestion, reaching 80% at 60 min and within a comparable range (approximately 70-80%) for the rest of the 120 min, without the fluctuations seen for LM1 and LM2.
GC-FID analysis revealed different distinct fatty acid (FA) release patterns corresponding to lipid composition due to structural transitions and interfacial saturation effects. DLS analysis indicated highly polydisperse particle populations, limiting the technique’s ability to reliably resolve these complex digestion systems. Notably, incorporation of IBU appeared to influence lipid structural stability, particularly in the LM3 system, where IBU-loaded system showed less aggregation than its IBU-free control, tentatively suggesting that IBU may play a stabilizing role; this observation, however, requires confirmation by a method better suited to multimodal populations for digestive samples.
Further evaluation of LM3 under full gastrointestinal conditions showed progressive gastric release (7-62% over 120 min), followed by rapid intestinal release (78% at 0 min). Compared to that, a commercial IBU tablet showed minimal gastric release (<7%) and slower intestinal release (79% at 120 min).
These findings highlighted the importance of lipid composition in governing drug release behavior and demonstrate the potential of LLCP-based systems, for improving oral delivery of poorly water-soluble drugs.

Popular Abstract

Fat that fights for your medicine
Ibuprofen is one of the most commonly used painkillers in the world, taken for headaches, muscle pain, and inflammation. Standard tablets work well for most people, but how quickly and reliably the drug is absorbed can vary due to a simple chemical fact: ibuprofen dissolves poorly in water. Before it can be absorbed into the bloodstream, it first needs to dissolve in the fluids of the digestive tract, which can be slow and sensitive to the changing conditions along the way, particularly the strongly acidic environment of the stomach.
The project asked whether wrapping ibuprofen inside tiny fat-based particles could help it dissolve more consistently and reach the intestine where most drug absorption occurs. Three different fat mixtures were tested that kept the drug dispersed within a fatty matrix. The experiment used a laboratory model designed to mimic the conditions of human digestion, from the stomach through to the small intestine.
The results showed that fat comparison made a significant difference. One formulation had been found to maintain ibuprofen in a dissolved state throughout both the simulated stomach and intestinal phases and released it more quickly into the intestinal fluid compared to a commercial tablet under the same conditions. The tablet, by contrast, kept very little of the drug dissolved during the stomach phase, as the acidic conditions caused ibuprofen to precipitate temporarily out of solution.
These are early-stage laboratory findings, and further work would need to confirm whether these differences translate into faster or more reliable pain relief in practice. But the results suggest that the type of fat used to carry a drug could play a meaningful role in how consistently it behaves during digestion.

• author: Pham, Thuy Vy
• supervisor: Cecilia Tullberg; Patrick Adlercreutz; Eimantas Gladkauskas
• organization: Biotechnology (MSc); Biotechnology (M.Sc.Eng.)
• course: KBTM01 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: lyotropic liquid crystalline phases (LLCPs), lipid-based drug delivery, in-vitro digestion, INFOGEST 2.0, triglyceride hydrolysis, ibuprofen solubilization, lipolysis kinetics, biotechnology
• language: English
• id: 9235713
• date added to LUP: 2026-08-11 09:09:51
• date last changed: 2026-08-11 09:09:51