Bioavailability Of Ibuprofen Research Articles

New Ibuprofen Cystamine Salts With Improved Solubility and Anti-Inflammatory Effect.

Two novel ibuprofen cystamine salts (IBU-CYS 1 and IBU-CYS 2) are synthesized by coupling the anion of ibuprofen with cystamine dihydrochloride in 1 : 1 and 2 : 1 ratio to improve the solubility and bioavailability of ibuprofen. The salts are characterized by 1HNMR, FT-IR and UV-Vis spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TGA, DTA) and X-ray diffraction measurements. IBU-CYS 1 and IBU-CYS 2 show higher solubility (6.11 and 7.81 mg/mL) compared to ibuprofen (0.04 mg/mL) in water. IBU-CYS2 was encapsulated into 2-hydroxyethyl methacrylate: poly (ethylene glycol) acrylate hydrogels for enhanced delivery. The in vitro studies in PBS (pH 7.4) indicate that the salts are effective in relieving inflammatory responses induced by lipopolysaccharide in RAW264.7 macrophage cells (nitrite inhibition percentages of IBU-CYS 1, IBU-CYS 2 and ibuprofen: approximately 34.29, 27.03 and 31.50 respectively) while indicating no cytotoxicity. Therefore, these salts may be promising candidates for the development of effective formulations of this drug.

In Vitro and In Vivo Evaluation of Dark Chocolate as Age-appropriate Oral Matrix

Swallowing difficulties encountered by geriatric patients who undergo polypharmacy represent a significant challenge that hampers patient compliance and therapeutic management. As an appealing and sensory-pleasing, chocolate-based formulations have emerged as a potential alternative oral dosage form suitable for both the elderly and paediatric populations. However, the extent to which the incorporation of drugs into a chocolate matrix affects their oral availability remains unclear. Therefore, the objective of this investigation was to explore the in vitro and in vivo performance of an ibuprofen-based chocolate dosage form. A matrix based on dark chocolate and the model drug was prepared at two distinct temperatures: 50 and 80 °C. In vitro release studies revealed that ibuprofen formulated through co-melting at 80 °C exhibited a statistically significant slower drug release (p < 0.05) compared to formulations prepared at 50 °C in both FaSSGF (fasted-state simulated gastric fluid) and lipolysis media. The enzymatic degradation of chocolate in the presence of lipase accelerated in vitro ibuprofen release from chocolate matrices. To delve deeper into the bioavailability of ibuprofen within the chocolate formulations, we conducted an in vivo assessment, comparing the pharmacokinetic profiles of ibuprofen in its conventional suspension form with our chocolate-based dosage forms. A notable drop (p < 0.05) in the maximum serum concentration of ibuprofen when incorporated into co-melted or solid-suspension chocolate matrices. However, no significant differences in plasma exposure were observed between the two formulations. These findings shed a light on the potential of chocolate to extend of ibuprofen when integrated into various chocolate matrices, showcasing the potential held by these innovative formulations.

Pembuatan dan Karakterisasi Self Emulsifying Drug Delivery Systems(SEDDS) Ibuprofen Secara Oral

Self emulsifying drug delivery systems (SEDDS) dikembangkan sebagai metode untuk meningkatkan kelarutan obat lipofilik seperti ibuprofen, serta untuk meningkatkan absorpsi dan laju disolusi obat. Oleh karena itu penelitian ini bertujuan untuk mengembangkan formulasi SEDDS ibuprofen yang memenuhi syarat secara farmasetik dan meningkatkan bioavailabilitas ibuprofen. Formula SEDDS diperoleh dari uji kelarutan ibuprofen dan optimasi formula pada berbagai konsentrasi minyak, surfaktan dan kosurfaktan. Asam oleat, cremophor RH 40 dan propilenglikol masing-masing terpilih sebagai minyak, surfaktan dan kosurfaktan dengan perbandingan fase minyak : (surfaktan + kosurfaktan) 1:9 dan pebandingan surfaktan : kosurfaktan (3:2). Formula SEDDS optimum dievaluasi meliputi pengukuran persen transmitan, pengujian dispersibilitas, pengujian robustness, pengujian stabilitas (sentrifugasi, heating cooling cycle, freeze thaw cycle), penentuan ukuran partikel dan uji laju disolusi. Formula SEDDS ibuprofen terbaik memenuhi persyaratan persen transmitan (99,7% ± 0,872), waktu dispersibilitas (41,48 detik ± 1,3), stabil pada pengujian robustness, tidak terjadi pemisahan fasa pada pengujian stabilitas, serta memiliki ukuran globul dalam kisaran mikrometer yaitu 114,7 ± 0,692 nm. Hasil uji laju disolusi in vitro pada menit ke-10 menunjukkan bahwa sediaan SEDDS ibuprofen lebih tinggi dibandingkan dengan serbuk ibuprofen murni, yaitu masing-masing sebesar 90,04 ± 1,764% dan 59,30 ± 1,638%.

Preparation, in vitro and in vivo Evaluation of Thermosensitive in situ Gel Loaded with Ibuprofen-Solid Lipid Nanoparticles for Rectal Delivery.

BackgroundIbuprofen (IBU), a nonsteroidal anti-inflammatory drug, shows poor gastrointestinal absorption due to its low solubility, which limits its clinical application.ObjectiveIn the present study, we aimed to develop thermosensitive gel-mediated ibuprofen-solid lipid nanoparticles (IBU-SLN-ISG) to improve the dissolution and bioavailability of IBU after rectal delivery.MethodsIBU-loaded SLNs (IBU-SLNs) were developed and optimized applying Box-Behnken design. The optimized IBU-SLNs were characterized by physicochemical parameters and morphology. Then, the optimized IBU-SLNs was incorporated into the gel and characterized for gel properties and rheology and investigated its release in vitro, pharmacokinetics in vivo, rectal irritation and rectal retention time.ResultsThe optimized SLNs had an EE of 90.74 ± 1.40%, DL of 11.36 ± 1.20%, MPS of 166.77 ± 2.26 nm, PDI of 0.27 ± 0.08, and ZP of −21.00 ± 0.59 mV. The FTIR spectra confirmed successful encapsulation of the drug inside the nanoparticle as only peaks responsible for the lipid could be identified. This corroborated well with XRD spectra, which showed a completely amorphous state of the IBU-SLNs as compared to the crystalline nature of the pure drug. The gelation temperature of the prepared IBU-SLN-ISG was 33.30 ± 0.78°C, the gelation time was 14.67 ± 2.52 s, the gel strength was 54.00 ± 1.41 s, and the mucoadhesion was (11.54±0.37) × 102dyne/cm2. The in vitro results of IBU-SLNs and IBU-SLN-ISG showed a biphasic release pattern with initial burst release followed by sustained release. More importantly, IBU-SLN-ISG produced much better absorption of IBU and improved bioavailability in rats. In addition, IBU-SLN-ISG caused no irritation or damage to rectal tissues, and could be retained in the rectum for a long time.ConclusionThermosensitive in situ gel loaded with IBU-solid lipid nanoparticles might be further developed as a more convenient and effective rectal dosage form.

Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug.

Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by 1H, 13C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients.

Ibuprofen-loaded centrifugally spun microfibers for quick relief of inflammation in rats

The conventional dosage forms (tablets, capsules) of ibuprofen have less potential in the suppression of pain and inflammation due to their slow dissolution rates and lower bioavailability. The aim of this study was to fabricate fibrous solid dispersion of ibuprofen for improved dissolution rate and quick therapeutic action. Drug-loaded microfibers were fabricated using centrifugal melt spinning (CMS) technique from the physical mixture of sucrose, ibuprofen and a hydrophilic polymer, PVP. These fibers were characterized by SEM, PXRD, DSC, and FTIR spectroscopy. The selected formulation was also pressed into tablets by direct compression method followed by its in vitro and in vivo characterization. The production yield of fibers was 75 ± 2% with an average diameter of 15 ± 5 µm. The drug loading efficiency (DLE) was 85 ± 5%. The tablets dissolved rapidly (<40 s). In vitro dissolution studies have shown >85% of ibuprofen dissolved from tablet within first 2 min which was ∼5 times quicker than drug alone. Dissolution efficiency has improved from 0.63 of ibuprofen to 0.95 of that in fibers with ∼7 times reduction in mean dissolution time. PXRD, and DSC have shown the amorphous state of ibuprofen in the formulation and FTIR spectra demonstrated no interaction of drug with excipients. In vivo anti-inflammatory studies using rabbits revealed a significant (p < 0.05) reduction in paw volume (mm) in the groups treated with fibrous formulation. This study concludes that microfibers produced by centrifugal melt spinning have improved dissolution rates and bioavailability of ibuprofen. Incorporation of polymer in the formulations improves the production yield and drug loading efficiency of microfibers.

In vivo evaluation of toxicity and anti-inflammatory activity of iron oxide nanoparticles conjugated with ibuprofen.

Aim: The low solubility and consequent poor bioavailability of ibuprofen (IBU) is a major drawback that can be overcome by anchoring IBU on ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) as effective multifunctional carriers for drug delivery. Methods: USPIONs were conjugated with glycerol phosphate (USPION-GP) and also co-conjugated with IBU (USPION-GP/IBU), and their in vivo toxicity and anti-inflammatory effects investigated. Phosphate buffer saline (control), IBU, USPION-GP and USPION-GP/IBU were intravenously administered 15min before lipopolysaccharide-induced peritonitis in male Balb/c mice. Results: 4h later, USPION bioconjugates did not appear to have caused toxicity to blood leukocytes or caused alterations in the spleen, liver or kidneys. Also, they inhibited lipopolysaccharide-induced neutrophil mobilization into the peritoneum. Conclusion: The absence of systemic toxicity and the unexpected anti-inflammatory action of USPION bioconjugates indicates that they could be a novel and effective approach to administer IBU and warrant further investigation.

Incomplete cocrystalization of ibuprofen and nicotinamide and its interplay with formation of ibuprofen dimer and/or nicotinamide dimer: A thermodynamic analysis based on DFT data.

Cocrystallization of ibuprofen and nicotinamide in hot melt extrusion process has been subject of many studies addressing low ibuprofen bioavailability. However, it is observed that the process of cocrystal formation of ibuprofen and nicotinamide might be incomplete. We hypothesized that formation of dimers of ibuprofen-ibuprofen or dimers nicotinamide- nicotinamide might be the cause of such poor cocrystalization process by altering the phase behaviour of the mixture. This paper addresses the molecular thermodynamics of mixtures of ibuprofen and nicotinamide, with special focus on the possibility of formation of these dimers and their corresponding interplay with mixture phase behaviour. For this purpose, density functional theory calculations are used to calculate electron donor-acceptor sizes on each molecule and accordingly possible dimers of each molecule are analysed. The free energies and phase diagram are determined for (1) when a dimer is formed or (2) no dimer is formed, over a wide operating temperature range of 273.15K-390K. The binding and solvation energies are calculated to identify/rank dimers. Calculations showed that formation of dimers requires an energy input which can be accessible noting to the external heating in hot melt extrusion process. The calculated solvation energies of the dimers suggest that addition of liquid binder (water) can mitigate the risk of dimer formations. Addition of proper binder/excipient is an easy route to compensate such dimer formation and to engineer ibuprofen and nicotinamide cocrystallization behaviour.

Phase I Pharmacokinetic Study of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in Healthy Adult and Adolescent Populations

IntroductionA fixed-dose combination (FDC) of ibuprofen and acetaminophen has been developed that provides greater analgesic efficacy than either agent alone at the same doses without increasing the risk for adverse events.MethodsWe report three clinical phase I studies designed to assess the pharmacokinetics (PK) of the FDC of ibuprofen/acetaminophen 250/500 mg (administered as two tablets of ibuprofen 125 mg/acetaminophen 250 mg) in comparison with its individual components administered alone or together, and to determine the effect of food on the PK of the FDC. Two studies in healthy adults aged 18–55 years used a crossover design in which subjects received a single dose of each treatment with a 2-day washout period between each. In the third study, the bioavailability of ibuprofen and acetaminophen from a single oral dose of the FDC was assessed in healthy adolescents aged 12–17 years, inclusive.ResultsA total of 35 and 46 subjects were enrolled in the two adult studies, respectively, and 21 were enrolled in the adolescent study. Ibuprofen and acetaminophen in the FDC were bioequivalent to the monocomponents administered alone or together. With food, the maximum concentration (Cmax) for ibuprofen and acetaminophen from the FDC was reduced by 36% and 37%, respectively, and time to Cmax (i.e. tmax) was delayed. Overall drug exposure to ibuprofen or acetaminophen in the fed versus fasted states was similar. In adolescents, overall exposure to acetaminophen and ibuprofen was comparable with that in adults, with a slightly higher overall exposure to ibuprofen. Exposure to acetaminophen and ibuprofen in adolescents aged 12–14 years was slightly higher versus those aged 15–17 years. Adverse events were similar across all treatment groups.ConclusionsThe FDC of ibuprofen/acetaminophen 250/500 mg has a PK profile similar to its monocomponent constituents when administered separately or coadministered, indicating no drug–drug interactions and no formulation effects. Similar to previous findings for the individual components, the rates of absorption of ibuprofen and acetaminophen from the FDC were slightly delayed in the presence of food. Overall, adolescents had similar exposures to acetaminophen and ibuprofen as adults, while younger adolescents had slightly greater exposure than older adolescents, probably due to their smaller body size. The FDC was generally well tolerated.

Development and validation of a liquid chromatography-tandem mass spectrometry method for determination of ibuprofen in human plasma

Ibuprofen is widely used to reduce fever, pain, and inflammation and in the treatment of patent ductus arteriosus (PDA) in preterm infants. However, to study the impact of pharmacokinetics of ibuprofen on the rate of ductus arteriosus closure in humans, a quantitative method is required. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a highly sensitive, accurate, reliable, fast, and simple bioanalytical method. In this study, we developed and utilized an LC-MS/MS method to determine ibuprofen bioavailability. One of the novel aspects of this work is the small specimen volume required for the analysis (i.e., 50 µL). The calibration curve was linear across a concentration range of 0.15–50 μg/mL. The coefficient of variation for intra-day and inter-day precision was within 0.78%–7.21% and accuracy was within 97.52%–107.21% of the nominal values for low, medium, and high quality control (QC) concentration levels—QCL, QCM, and QCH (0.45, 9.0, and 40.0 μg/mL, respectively). For ibuprofen concentrations at the lower limit of quantitation (LLOQ), intra-day and inter-day accuracy were 98.11% and 99.81%, respectively; however, the intra-day and inter-day precision were 1.89% and 5.37%, respectively. The pharmacokinetic study involved 18 neonatal subjects who were grouped into low- or high-dose ibuprofen groups. The median maximum concentration for low- and high-dose regimens were 16.05 (14.21–19.32) and 24.10 (20.63–32.03) µg/mL, respectively, and the median elimination rate constant was 0.041 (0.026–0.047) and 0.071 (0.050–0.073) h−1, respectively. Thus, the fully validated LC-MS/MS method was determined to be suitable for analyzing unknown plasma samples for ibuprofen pharmacokinetic, bioavailability, and bioequivalence studies.

Formulation, Characterization and Stability of Ibuprofen-Loaded Self-Nano Emulsifying Drug Delivery System (SNEDDS)

Ibuprofen is a poorly water-soluble drug with analgesic, antipyretic and anti-inflammatory effects. Self-Nano Emulsifying Drug Delivery System (SNEDDS) formulation is a solution to improve the solubility and bioavailability of ibuprofen. This research purposed to perform a formulation, characterization, and stability studies of ibuprofen-loaded Self-Nano Emulsifying Drug Delivery System (SNEDDS). Screening of ibuprofen SNEDDS was prepared by ternary diagrams for the chosen co-surfactants, surfactants, and oil. The following was characterizations of droplet size, zeta potential, and clarity. The solubility test for the determination of co-surfactant, surfactant, and oil obtained Propylene glycol monocaprylate (Capryol-90), Polysorbate 20 (Tween 20) and PEG 400. The screening of SNEDDS showed nine formulas (compositions) in the range concentration of Propylene glycol monocaprylate (1-3 mL), Polysorbate 20 (4-8 mL), and PEG 400 (1-3 mL). The composition of Propylene glycol monocaprylate (1-2 mL), Polysorbate 20 (5-8 mL) and PEG 400 (1-3 mL) passed the thermodynamic stability test. The test of robustness to dilution and stability study indicated that the formula with Propylene glycol monocaprylate, Polysorbate 20 and PEG 400 with the ratio of 1: 8: 1 and 1: 7: 2 was more stable. In conclusion, the stable ibuprofen SNEDDS could be prepared with Propylene glycol monocaprylate, Polysorbate 20, and PEG 400.

Polyelectrolyte complex nanoparticles based on chitosan and methoxy poly(ethylene glycol) methacrylate-co-poly(methylacrylic acid) for oral delivery of ibuprofen.

In this study, the copolymer of methoxy poly(ethylene glycol) methacrylate-co-poly(methylacrylic acid) [poly(mPEGMA-co-MAA)] was synthesized via radical polymerization. Based on this copolymer, novel chitosan-modified poly(mPEGMA-co-MAA) nanoparticles (CS/NPs) were developed to improve the bio-availability of ibuprofen (IBU). Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectra were used to confirm the synthesis of the copolymers. The morphology of CS/NPs was investigated with transmission electron microscopy (TEM). Thermogravimetric analysis (TGA) was used to reveal the thermodynamic properties of the CS/NPs. The cytotoxicity of CS/NPs was assessed by the cell viability of 293T cells. FTIR and 1H NMR spectra confirmed the synthesis of the novel copolymer. TEM photographs showed that the CS/NPs had a core-shell structure. High cell viability indicated that the CS/NPs were nontoxic. The in vitro release profiles suggested that the CS/NPs released IBU in pH 7.4 buffer in a continuous manner. Furthermore, the IBU-CS/NPs showed a long antifebrile effect. Animal experiments showed that the IBU-CS/NPs had obvious antifebrile effects. Therefore, CS/NPs could reduce the dosing frequency of IBU, and improve its bio-availability.

In vitro and In vivo Studies on a Novel Bioadhesive Colloidal System: Cationic Liposomes of Ibuprofen.

The objective of this study was to develop an ocular drug delivery system built on the cationic liposomes, a novel bioadhesive colloidal system, which could enhance the precorneal residence time, ocular permeation, and bioavailability of ibuprofen. The optimal formulation of cationic liposomes prepared by ethanol injection method was ultimately confirmed by an orthogonal L9 (33) test design. In addition, γ-scintigraphic technology and the microdialysis technique were utilized in the assessment of in vivo precorneal retention capability and ocular bioavailability individually. In the end, we acquired the optimal formulation of ibuprofen cationic liposomes (Ibu-CL) by orthogonal test design, and the particle size and entrapment efficiency (EE%) were 121.0±3.5nm and 72.9±3.4%, respectively. In comparison to ibuprofen eye drops (Ibu-ED), Ibu-CL could significantly prolong the T max to 100min and the AUC to 1.53-folds, which indicated that the Ibu-CL could improve the precorneal retention time and bioavailability of ibuprofen. Consequently, these outcomes designated that the ibuprofen cationic liposomes we researched probably are a promising application in ocular drug delivery system.

The binary complex of poly(PEGMA-co-MAA) hydrogel and PLGA nanoparticles as a novel oral drug delivery system for ibuprofen delivery

To improve the bioavailability of ibuprofen (IBU), we developed a novel binary complex of poly(PEGMA-co-MAA) hydrogel and IBU-loaded PLGA nanoparticles (IBU-PLGA NPs@hydrogels) as an oral intestinal targeting drug delivery system (OIDDS). The IBU-loaded PLGA NPs and pH-sensitive hydrogels were obtained via the solvent evaporation method and radical polymerization, respectively. The final OIDDS was obtained by immersing the hydrogel chips in the IBU-loaded PLGA NPs solutions (pH 7.4) for 3 d. The size distribution and morphology of cargo-free NPs were studied by laser granularity analyzer and transmission electron microscope (TEM). The inner structures of the pH-sensitive hydrogel chips were observed with an S-4800 scanning electron microscope (SEM). The distribution states of IBU in the OIDDS were also studied with X-ray diffraction (XRD) and differential scanning calorimetry (DSC). TEM photographs illustrated that the PLGA NPs had a round shape with an average diameter about 100 nm. Fourier transform infrared spectrum (FTIR) confirmed the synthesis of poly(PEGMA-co-MAA) hydrogel. The SEM picture showed that the final hydrogel had 3D net-work structures. Moreover, the poly(PEGMA-co-MAA) hydrogel showed an excellent pH-sensitivity. The XRD and DSC curves suggested that IBU distributed in the OIDDS with an amorphous state. The cumulated release profiles indicated that the final OIDDS could release IBU in alkaline environment (e.g. intestinal tract) at a sustained manner. Therefore, the novel OIDDS could improve the oral bioavailability of IBU, and had a potential application in drug delivery.

Evaluation of pharmacokinetics and in vitro/in vivo correlation of ibuprofen with essential oils as penetration enhancer following transdermal administration

The study was carried out to investigate the pharmacokinetics and in vitro/in vivo correlation of ibuprofen with essential oils as penetration enhancers (PE) following transdermal administration. With Azone as the positive control, ibuprofen hydrogels containing Chuanxiong oil, Angelica oil or Cinnamon oil as PE were prepared and administered to the rat abdominal skin. Then the pharmacokinetics of ibuprofen following transdermal administration were investigated and compared. In comparison with negative control (no PE was added), the relative bioavailability values with the addition of Chuanxiong oil, Angelica oil, Cinnamon oil and Azone as PE were determined to be 161.87%, 171.05%, 151.37% and 148.66%, respectively. In vitro/in vivo correlation analysis was performed by deconvolution method and the results demonstrated a good correlation between in vitro and in vivo percutaneous absorption studies. The correlation coefficients were measured to be 0.999 7, 0.995 2 and 0.999 4 for Chuanxiong oil, Angelica oil and Cinnamon oil respectively. In summary, Chuanxiong oil, Angelica oil and Cinnamon oil as PE could significantly enhance the bioavailability of ibuprofen following transdermal administration. A satisfactory in vitro/in vivo correlation could be obtained by using hydrogel as the dosage form.

Supramolecular Complex of Ibuprofen with Larch Polysaccharide Arabinogalactan: Studies on Bioavailability and Pharmacokinetics.

In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen's bioavailability and decrease its effective dose after oral administration. The complex with mass ratio as IBU:AG 1:10 was obtained by mechanochemical synthesis and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. Different animal models of pain and inflammation was used to investigate IBU:AG biological effects. Plasma concentration of IBU and its pharmacokinetic parameters were evaluated after oral introduction. It was found that ibuprofen's effective analgesic and anti-inflammatory dose decreased twofold after its introduction as a complex with AG. The reason of this difference is due to the increase of ibuprofen concentration in rats' plasma: C max of IBU at doses of 20 and 40mg/kg was found as 0.088 and 0.132μg/ml, whereas C max of IBU in the complex form was 0.103 and 0.160μg/ml, respectively. Thus, we have shown that complexation of the IBU with AG results in its bioavailability increase, reduction of the effective dose and should decrease toxic side effects.

Development of mucoadhesive and thermosensitive eyedrops to improve the ophthalmic bioavailability of ibuprofen

Topical ophthalmic formulations prepared with nanostructured lipid carriers (NLC) exhibit low bioavailability. Specific physicochemical properties of the ocular tissues, namely, temperature, pH and electrolyte composition of the pre-corneal region, can be exploited to enhance the bioavailability of colloidal nanocarriers using in situ gelling systems. The aim of this study was to enhance the ophthalmic bioavailability of NLC dispersions through the addition of a thermoresponsive polymer (Pluronic® F-127) and a mucoadhesive polymer (chitosan). Simulating the physiological conditions, the addition of Pluronic® F 127 (PF 127) caused the sol-gel transition of the colloidal dispersion upon contact with the ocular surface temperature, while the addition of chitosan (CS) led to the establishment of electrostatic interactions with the mucin present in the ocular tissues. The results also suggested that NLC–based hydrogels were biocompatible with no significant cytotoxicity observed in the Y-79 human retinoblastoma cell line. The addition of PF 127 and CS to NLC dispersions can enhance the bioavailability and the therapeutic efficacy of topical ophthalmic formulations.

Optimized mixed oils remarkably reduce the amount of surfactants in microemulsions without affecting oral bioavailability of ibuprofen by simultaneously enlarging microemulsion areas and enhancing drug solubility

The toxicity and irritation associated with high amounts of surfactants restrict the extensive utilization of microemulsions. To address these shortcomings, employing mixed oils to enlarge microemulsion areas therefore reducing surfactant contents is a promising strategy. However, what kinds of mixed oils are more efficient in enlarging microemulsion areas still remains unclear. In this research, we found that the chain length and degree of unsaturation of oils play a key role in enlarging microemulsion areas. The combination of moderate chain saturated oil caprylic/capric triglyceride (GTCC) with long chain unsaturated oil glycerol trioleate significantly increased the microemulsion areas. Solubility of ibuprofen in the mixed oils was unexpectedly and remarkably increased (almost 300mg/mL) compared with that (around 100mg/mL) of the single oil (GTCC), which also resulted in greatly increased solubility of ibuprofen in mixed oils-containing microemulsions. By optimizing the mixed oil formulation, the absolute amount of surfactant in drug-loaded microemulsions was reduced but increased drug oral bioavailability in rats was maintained. It could be concluded that the combined use of moderate chain oils and long chain unsaturated oils could not only acquire enlarged microemulsion areas but also enhanced drug solubility, therefore doubly reducing surfactant amount, which is extremely beneficial for developing safe microemulsions.

Optimizing surfactant content to improve oral bioavailability of ibuprofen in microemulsions: just enough or more than enough?

Microemulsions show excellent potential as drug delivery systems, but the surfactants used to prepare them can cause side effects. Researchers have explored various strategies to expand microemulsion area and thereby reduce the surfactant content necessary, but how these strategies affect drug oral bioavailability has not been investigated in detail. Microemulsions were prepared using 16% or 24% mixed surfactant Tween 80-Cremophor EL-PEG400 (1:1:2) and either 6% caprylic/capric triglyceride oil (GTCC) or 6% or 15% mixed oil (Maisine™ 35-1 with GTCC). Some microemulsions contained just enough surfactant based on ternary phase diagrams, while others had excess surfactant. All empty and ibuprofen-loaded microemulsions were clear or translucent with a slight blue color, and they remained stable after dilution and centrifugation. In experiments with rats, oral bioavailability (AUC0⟶t) of ibuprofen in the microemulsions was similar for the different formulations (6779.0-7413.3 min μg/mL) and significantly higher than that of an ibuprofen suspension (4830.9 min μg/mL). The different formulations behaved similarly in a cellular uptake assay with Caco-2 cells. These results suggest that excess surfactant does not increase oral bioavailability or cellular uptake of ibuprofen. Therefore, to minimize side effects, using just enough surfactant to ensure microemulsion stability and drug solubility may be an appropriate strategy.

Preparation of Micronized Ibuprofen Substance and Assessment of Its Bioavailability

A Buchi B-290 mini spray dryer (Switzerland) designed to dry aqueous solutions or suspensions was used to prepare micronized ibuprofen substance, which differed from the starting substance in terms of decreased crystal size. The bioavailability of ibuprofen given as oral capsules containing micronized ibuprofen substance (crystal size 30 μm) and capsules containing commercial ibuprofen substance (crystal size 150 μm) was studied in Chinchilla rabbits. Concentrations of unaltered ibuprofen were measured by reverse-phase HPLC with spectrophotometric detection at 220 nm. Ibuprofen was extracted from rabbit serum by liquid:liquid extraction and averaged 78 %. The detection limit was 0.1 μg/ml. The bioavailability of micronized ibuprofen was more than twice that of the commercial substance (mean crystal size 150 μm). There were no differences in the rates of absorption or elimination of ibuprofen from the systemic circulation.